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The work aimed to enhance chrysin (CHR) water solubility, dissolution, and in vitro antibacterial as well as cell viability. Chrysin binary, as well as ternary inclusion complex, were prepared using the spray drying method. The influence of an auxiliary component (poloxamer; PLX) was also assessed after being incorporated into the chrysin HP βCD complex (CHR-BC) and formed as a chrysin ternary complex (CHR-TC). The phase solubility investigation was carried out in order to assess the complexation efficiency and stability constant. The samples were assessed for the dissolution test, physicochemical evaluation, antibacterial activity, and cell viability tests were also assessed. The results of the phase solubility investigation showed that the stability constant for the binary system (268 M−1) was lower than the ternary system (720 M−1). The complex stability was validated by the greater stability constant value. The dissolution results showed that pure CHR had a limited release of 32.55 ± 1.7% in 60 min, while prepared CHR-TC and CHR-BC both demonstrated maximum CHR releases of 99.03 ± 2.34% and 71.95 ±2.1%, respectively. The dissolution study's findings revealed that the release of CHR was much improved over that of pure CHR. A study using a scanning electron microscope showed that CHR-TC contains more agglomerated and amorphous components. The higher conversion of crystalline CHR into an amorphous form is responsible for the structural alterations that are observed. After complexation, the distinctive peaks of pure CHR changed due to the complexation with HP βCD and PLX. The antimicrobial and cell viability results revealed improved antimicrobial activity as well as a lower IC50 value than pure CHR against the tested anticancer cell line (MCF7). [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer is a unique subtype among breast cancers. Management includes a neoadjuvant chemotherapy regimen. Psychiatric complications of the regimen have not been reported before. We present a case of acute psychosis after the second cycle of chemotherapy in a 42-year-old woman with triple-negative breast cancer. The patient presented with sudden irritability, agitation, disorganization in speech and behavior, and paranoia involving her coworkers conspiring against her and causing her trouble with the law for 4 days. She was in her usual state of health until after her second cycle of chemotherapy. This was the first presentation of psychotic symptoms in her life. She was conscious and oriented. There were no neurologic deficits. She denied any change in her mood and any features of hallucinations. She was uncooperative, restless, had flight of ideas, and persecutory delusions. The remainder of the examination was normal. An autoimmune process, nervous system infection, or psychosis secondary to the chemotherapy were suspected. Serum electrolytes and other biochemical parameters were normal. Imaging of the brain showed no signs of acute brain insults or intracranial metastasis. Cerebrospinal fluid analysis and culture showed no abnormality or growth. The work-up revealed that neurologic, infectious, or autoimmune causes of her psychotic symptoms were less likely. Thus, a diagnosis of psychosis secondary to chemotherapy was considered. Treatment was with paliperidone, risperidone, clonazepam, and sertraline. Over the course of treatment, she showed substantial improvement and completed all of the chemotherapy sessions without adverse effects. In summary, we report a case of a patient whose initial chemotherapy course was complicated by psychosis. Since the neurotoxic and psychiatric effects of chemotherapeutics are not yet sufficiently elucidated, our case emphasizes that early signs of behavioral changes in patients receiving chemotherapy should trigger comprehensive psychiatric evaluation and monitoring of the patient's mental state. [ABSTRACT FROM AUTHOR]

Mole fraction solubilities of tadalafil (3) in aqueous mixtures of Transcutol® and PEG 400 at temperatures from 298.15 to 333.15 K were analysed following Hildebrand solubility parameters. Cosolvency models for representing tadalafil solubility at various temperatures were also provided for correlation/prediction purposes. Apparent thermodynamic quantities for tadalafil dissolution processes were calculated based on van't Hoff and Gibbs equations. Non-linear enthalpy–entropy compensation was observed for tadalafil transfer from more polar to less polar solvent systems. Preferential solvation parameters of tadalafil at 298.15 and 313.15 K were determined by means of the inverse Kirkwood-Buff integrals (IKBI). Tadalafil is preferentially solvated by water in water-rich mixtures of Transcutol® but preferentially solvated by Transcutol® in mixtures of 0.12 < x1 < 1.00. In the former case, this result could be due to hydrophobic hydration around the non-polar moieties of tadalafil. Otherwise, tadalafil is preferentially solvated by PEG 400 in all the aqueous mixtures. [ABSTRACT FROM AUTHOR]

The study aimed to develop a new reverse-phase high-performance liquid chromatography (RP-HPLC) method with diode array detection (DAD) detection for simultaneous estimation of escitalopram (EST) and clonazepam (CZP) in tablet dosage forms with a quality by design (QbD) approach. The chromatographic conditions were optimized by Box-Behnken design (BBD) and developed method was validated for the linearity, system suitability, accuracy, precision, robustness, sensitivity, and solution stability according to International Council for Harmonization (ICH) guidelines. EST and CZP standard drugs peaks were separated at retention times of 2.668 and 5.046 min by C-18 column with dimension of 4.6 × 100 mm length and particle size packing 2.5 µm. The mobile phase was methanol: 0.1% orthophosphoric acid (OPA) (25:75, v/v), with a flow rate of 0.7 mL/min at temperature of 26 °C. The sample volume injected was 20 µL and peaks were detected at 239 nm. Using the standard calibration curve, the % assay of marketed tablet was founded 98.89 and 98.76 for EST and CZP, respectively. The proposed RP-HPLC method was able to detect EST and CZP in the presence of their degradation products, indicating the stability-indicating property of the developed RP-HPLC method. The validation parameter's results in terms of linearity, system suitability, accuracy, precision, robustness, sensitivity, and solution stability were in an acceptable range as per the ICH guidelines. The newly developed RP-HPLC method with QbD application is simple, accurate, time-saving, and economic. [ABSTRACT FROM AUTHOR]

Butin has a strong antioxidant plus anti-inflammatory action and it is reported to be protective in oxidative stress-induced mitochondrial dysfunction. Butin has been shown to protect the mouse hippocampus HT22 cells from glutamate-induced neurotoxicity. The current investigation was planned to assess anti-Huntington's effect of butin in 3-nitropropionic acid-treated rats. A total of 32 Wistar rats (200–240 g) were equally segregated into four groups. Groups I and II were treated with vehicle (0.3 ml/100 g) and groups III and IV received butin 25 and 50 mg/kg for 15 days. Daily 1 h post above oral treatments, 3 ml/kg of normal saline was injected (i.p.) to group I animals and 10 mg/kg of 3-NP was injected (i.p.) to II and IV groups for 15 days. During the experimental schedule, behavioral tests were conducted for animals. On day 15, after behavioral parameters, animals were sacrificed and brains were removed for biochemical tests. Systemic administration of 3-NP induced neurobehavioral deficits which resulted in reduced spontaneous locomotor activity, motor incoordination, learning ability, and memory in the animals. Moreover, 3-NP depleted endogenous antioxidants (GSH, catalase, and SOD), mitochondrial complexes activities (I, II, IV, and MTT assay), elevated LDH, MDA, nitrite, and AchE. Administration of butin significantly improved neurobehavioral impairments, nitrative and oxidative stress, activities of mitochondrial enzyme complex, and reduced AchE levels in rat brain. [ABSTRACT FROM AUTHOR]

The present research work is designed to prepare and optimize butenafine (BT) loaded poly lactic co glycolic acid (PLGA) nanoparticles (BT-NPs). BT-NPs were prepared by emulsification probe sonication method using PLGA (A), PVA (B) as polymer and stabilizer, respectively. The optimum composition of BT-NPs was selected based on the point prediction method given by the Box Behnken design software. The optimized composition of BT-NPop showed a particle size of 267.21 ± 3.54 nm with an entrapment efficiency of 72.43 ± 3.11%. The optimum composition of BT-NPop was further converted into gel formulation using chitosan as a natural polymer. The prepared topical gel formulation (BTNPopG) was further evaluated for gel characterization, drug release, permeation study, irritation, and antifungal studies. The prepared BT-NPopG formulation showed optimum pH, viscosity, spreadability, and drug content. The release and permeation study results revealed slow BT release (42.76 ± 2.87%) with significantly enhanced permeation across the egg membrane. The irritation study data showed negligible irritation with a cumulative score of 0.33. The antifungal study results conclude higher activity than marketed as well as pure BT. The overall conclusion of the results revealed BT-NPopG as an ideal delivery system to treat topical fungal infection. [ABSTRACT FROM AUTHOR]

Tinea is a common superficial infection caused by keratinophylic fungi called dermatophytes. The objective of the current investigation was to develop and optimize a self-nanoemulsion drug delivery system (SENDDs) using clove oil loaded with naftifine (NF). Clove oil possesses good anti-inflammatory and antifungal properties that can support naftifine action. Box-Behnken designs were used to prepare plain and naftifine loaded SENDDs. The plain SENDDs were evaluated for their globule size. The medicated formulations (NF-CO-SENDDs) were characterized by measuring their globular size, ex vivo % NF permeated, level of interleukin-31 in rats, and antifungal activity. The optimum clove oil level was found to be 10-17%, while NF-CO-SENDDs formulations displayed globular sizes ranging from 119 to 310nm. The statistical design confirmed the synergistic effect of clove oil and NF in the treatment of fungal infections, confirming that the anti-inflammatory effect of clove oil can counteract the side effects of NF. The optimized formulation composed of 14% clove oil, 12.5mg Naftifine, and prepared with an Smix ratio equaling 3:1, exhibited good antifungal and anti-inflammatory activity, achieving up to 2-, 3-, 5.75-, and 2.74-fold increases in the amount of permeated NF, steady-state flux, permeability, and diffusion coefficients, respectively, compared with a commercial product. Moreover, the optimum formulation revealed an adequate zeta potential value of 28.31 ± 1.37mV and showed reasonable stability with no or mild signs of skin sensitivity. Therefore, the designed nanoemulsions containing a combination of clove oil and naftifine could be considered promising delivery systems for the treatment of tinea. [ABSTRACT FROM AUTHOR]

The aim of this work was to solubilize simvastatin (SIM) using different micellar solutions of various non-ionic surfactants such as Tween-80 (T80), Tween-20 (T20), Myrj-52 (M52), Myrj-59 (M59), Brij-35 (B35) and Brij-58 (B58). The solubility of SIM in water (H2O) and different micellar concentrations of T80, T20, M52, M59, B35 and B58 was determined at temperatures T = 300.2 K to 320.2 K under atmospheric pressure p = 0.1 MPa using saturation shake flask method. The experimental solubility data of SIM was regressed using van't Hoff and Apelblat models. The solubility of SIM (mole fraction) was recorded highest in M59 (1.54 x 10−2) followed by M52 (6.56 x 10−3), B58 (5.52 x 10−3), B35 (3.97 x 10−3), T80 (1.68 x 10−3), T20 (1.16 x 10−3) [the concentration of surfactants was 20 mM in H2O in all cases] and H2O (1.94 x 10−6) at T = 320.2 K. The same results were also recorded at each temperature and each micellar concentration of T80, T20, M52, M59, B35 and B58. "Apparent thermodynamic analysis" showed endothermic and entropy-driven dissolution/solubilization of SIM in H2O and various micellar solutions of T80, T20, M52, M59, B35 and B58. [ABSTRACT FROM AUTHOR]

In the last few decades, solid dispersion (SD) technology had been studied as an approach to produce an amorphous carrier to enhance the solubility, dissolution rate, and bioavailability of poorly water-soluble drugs. The use of suitable carrier and methodology in the preparation of SDs play a significant role in the biological behavior of the SDs. SDs have been prepared using a variety of pharmaceutically acceptable polymers utilizing various novel technologies. In the recent years, much attention has been paid toward the use of novel carriers and methodologies in exploring novel types of SDs to enhance therapeutic efficacy and bioavailability. The use of novel carriers and methodologies would be very beneficial for formulation scientists to develop some SDs-based formulations for their commercial use and clinical applications. In the present review, current literature of novel methodologies for SD preparation to enhance the dissolution rate, solubility, therapeutic efficacy, and bioavailability of poorly water-soluble drugs has been summarized and analyzed. Further, the current status of SDs, patent status, and future prospects have also been discussed. [ABSTRACT FROM AUTHOR]

Solubility and thermodynamic data of apigenin (APG) in binary {2-(2-ethoxyethoxy)ethanol (Transcutol ® ) + water} mixtures were obtained in this work. The mole fraction solubilities ( x e ) of APG in binary {Transcutol ®  + water} mixtures were measured at temperature T  = 298.15 K to318.15 K and atmospheric pressure p  = 0.1 MPa. Solubility values of APG determined in this study were fitted well with four different computational models namely “van’t Hoff, Apelblat, Yalkowsky and Jouyban-Acree” models with root mean square deviations of <4.0%. The maximum x e value of APG was recorded in neat Transcutol ® (0.382 at T  = 318.15 K). However, the minimum x e value of APG was recorded in neat water (1.01 × 10 −6 at T  = 298.15 K). The values of activity coefficients were also determined for the evaluation of solute-solvent molecular interactions and results suggested higher solute-solvent molecular interaction in APG-Transcutol in comparison with other combinations studied. Apparent thermodynamic analysis suggested endothermic and entropy-driven dissolution of APG in all binary {Transcutol ®  + water} mixtures studied. Enthalpy-entropy compensation analysis suggested enthalpy-driven mechanism as the main mechanism for solvation behavior of APG. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to assess the effect of anemia on subjective sleep quality in patients with iron deficiency anemia (IDA). Methods: The present study is a prospective and cross-sectional study which has been carried out at King Abdulaziz hospital between November 2016 and April 2017. Fifty-two patients diagnosed with iron deficiency anemia and 40 healthy individuals, who are gender and age matched, were involved in the study. All participants were requested to fill 3 forms: a socio-demographic form (age, gender, marital status, income level and educational status), hospital anxiety and depression (HAD) scale and Pittsburgh sleep quality index (PSQI). Results: According to the HAD scale, the average anxiety score was found 9.31±2.41 in patients and 7.62±2.11 in controls. And, the average depression score was 7.49±2.08 in patients and 6.39±2.73 in controls. The total sleep quality score was 6.68±2.99 in patients and 4.27±1.71 in controls. There was a statistically significant difference in terms of anxiety, depression and sleep quality scores. Linear regression analysis showed no association between anxiety and depression with poor sleeping. Conclusion: IDA affects sleep quality irrespective of psychological symptoms such as depression and anxiety. [ABSTRACT FROM AUTHOR]

In this study, the solubility, molecular interactions and mixing thermodynamic properties of a poorly water soluble bioactive compound piperine in twelve different pure solvents namely “water, methanol, ethanol, isopropyl alcohol (IPA), ethylene glycol (EG), propylene glycol (PG), 1-butanol, 2-butanol, ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and 2-(2-ethoxyethoxy) ethanol [Transcutol®]” were evaluated. The solubility of piperine was determined at temperatures “ T = 298.2 K to 318.2 K” and pressure “ p = 0.1 MPa”. The experimental solubility values of piperine were determined using a static equilibrium method by high-performance liquid chromatography at 254 nm. The solubility data of piperine obtained in this study was regressed using “van't Hoff and Apelblat models” with root mean square deviation values of < 5.0%. The solubilities of piperine in mole fraction were obtained maximum in Transcutol (9.17 × 10 − 2 ) followed by PEG-400 (7.88 × 10 − 2 ), DMSO (3.59 × 10 − 3 ), 2-butanol (2.25 × 10 − 2 ), 1-butanol (2.20 × 10 − 2 ), IPA (1.82 × 10 − 2 ), EA (1.54 × 10 − 2 ), PG (1.47 × 10 − 2 ), ethanol (1.34 × 10 − 2 ), methanol (7.91 × 10 − 3 ), EG (6.70 × 10 − 3 ) and water (1.52 × 10 − 5 ) at “ T = 318.2 K”. Based on the results of activity coefficient, the solute-solvent interaction was seen maximum in piperine-Transcutol and piperine-PEG-400 in comparison with other solute-solvent combination studied. Mixing thermodynamic properties of piperine were determined by activity coefficient model and results indicated spontaneous and entropy-driven dissolution of piperine in most of the pure solvents studied. [ABSTRACT FROM AUTHOR]

As part of the Saudi energy sustainability plan in Vision 2030, the Kingdom of Saudi Arabia has decided to rely on multiple sources of clean energy, and one of the Kingdom's sustainable choices was nuclear fission energy. There has been a lack of published papers discussing nuclear energy initiatives in the Kingdom, and this motivates our research work. This paper will consider nuclear power initiatives in KSA, at first a discussion on the Saudi energy sector in Vision 2030 and how nuclear energy can be a leader of the sector. A brief description of the international requirements for building a nuclear energy program will be discussed. This will be followed by recommendations on what should be done to achieve an outstanding nuclear power program. Furthermore, suggestions to ensure a sustainable nuclear program are discussed, focusing on multiple challenges in the educational sector, such as societal views, expert development, training, and research centers. Moreover, discussions are on regulating technical support organizations (TSO), nuclear power plant safety, safeguards, and security. Additional topics like the nuclear fuel cycle, reactor site location, and lessons learned from similar countries, like the UAE, are discussed in the paper. [ABSTRACT FROM AUTHOR]

Cabozantinib malate (CBZM), a new anticancer medication, has been studied for its solubility and thermodynamic properties in a variety of {dimethyl sulfoxide (DMSO) + water (H2O)} mixtures at 298.2–318.2 K and 101.1 kPa. Using the shake flask technique, the solubility of CBZM was assessed and the results were correlated to the van't Hoff, Apelblat, Buchowski–Ksiazczak λh, Yalkowsky–Roseman, Jouyban–Acree, and Jouyban–Acree-van't Hoff models. There was a significant correlation between the experimental CBZM solubility data and all computational models, as evidenced by the error values for all computational models being less than 5.0%. Temperature and DMSO mass percentage improved the CBZM mole fraction solubility in the cosolvent solutions of {DMSO + H2O}. At 318.2 K, pure DMSO had the highest mole fraction solubility of CBZM (4.38 × 10−2), whereas pure H2O had the lowest mole fraction solubility (2.24 × 10−7 at 298.2 K). The positive values of computed thermodynamic parameters indicated that the dissolution of CBZM was endothermic and entropy-driven in all of the {DMSO + H2O} solutions investigated. It was found that the CBZM solvation in {DMSO + H2O} solutions is governed by enthalpy. When compared to CBZM-H2O, CBZM-DMSO showed the highest molecular interactions. The findings of this investigation demonstrated that DMSO has a great deal of potential for CBZM solubilization in H2O. [ABSTRACT FROM AUTHOR]

The solubility data of poorly soluble anti-inflammatory drug flufenamic acid (FFA) are scarce in literature. Therefore, in the current study, the solubility of FFA in eleven different neat solvents including “water, methanol, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), 1-butanol, 2-butanol, dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol ® ” was measured and correlated at temperatures “ T = 298.2 K to 318.2 K” and pressure “ p = 0.1 MPa”. The solubilities of FFA in mole fraction were measured using a static equilibrium method and correlated with “van't Hoff and Apelblat equations”. The mole fraction solubilities of FFA were obtained maximum in DMSO (2.86 × 10 − 1 ), followed by Transcutol (2.78 × 10 − 1 ), 2-butanol (1.79 × 10 − 1 ), 1-butanol (1.77 × 10 − 1 ), IPA (1.44 × 10 − 1 ), ethanol (1.12 × 10 − 1 ), methanol (6.29 × 10 − 2 ), PEG-400 (6.16 × 10 − 2 ), EG (1.20 × 10 − 2 ), PG (1.81 × 10 − 2 ) and water (1.60 × 10 − 6 ) at “ T = 318.2 K” and similar trends were also recorded at each temperature studied. Activity coefficients were also calculated in order to evaluate the molecular interactions between solute and solvent molecules and results showed higher solute-solvent molecular interactions in FFA-DMSO, FFA-Transcutol, FFA-2-butanol, FFA-1-butanol, FFA-IPA and FFA-ethanol in comparison with other solute-solvent combinations. “Apparent thermodynamic analysis” showed an “endothermic and entropy-driven dissolution” of FFA in all neat solvents studied. [ABSTRACT FROM AUTHOR]

The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs. [ABSTRACT FROM AUTHOR]

In the current study, the solubility of a poorly water-soluble bioflavonoid apigenin in twelve different neat solvents including “water, methanol, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), 1-butanol, 2-butanol, ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol ® ” was measured at temperatures “ T = 298.2 K to 318.2 K” and pressure “ p = 0.1 MPa”. The experimental solubilities of apigenin were measured by a static equilibrium method using ultra performance liquid chromatography at 336 nm. The measured solubilities of apigenin in mole fraction were correlated with “van't Hoff and Apelblat models”. Good correlation was observed with both models with root mean square deviation values of < 3.0% in all solvents evaluated. The solid state characterization of apigenin was performed using differential scanning calorimetry and thermal gravimetric analysis. The solubilities of apigenin in mole fraction were obtained highest in PEG-400 (4.27 × 10 − 1 ) followed by DMSO (4.18 × 10 − 1 ), Transcutol (3.83 × 10 − 1 ), PG (1.50 × 10 − 2 ), EG (8.22 × 10 − 3 ), 1-butanol (9.18 × 10 − 4 ), 2-butanol (8.90 × 10 − 4 ), IPA (6.29 × 10 − 4 ), ethanol (4.86 × 10 − 4 ), EA (4.46 × 10 − 4 ), methanol (2.96 × 10 − 4 ) and water (3.08 × 10 − 6 ) at “ T = 318.2 K” and similar trend was recorded at each temperature evaluated. The solute-solvent interaction was described based on the polarity and activity coefficient. Apparent standard thermodynamic parameters of apigenin in twelve different neat solvents were determined using “apparent thermodynamic analysis” and results showed an “endothermic and entropy-driven dissolution” of apigenin in each solvent evaluated. Based on these results, PEG-400, DMSO and Transcutol were selected as the best solvents and water and methanol were selected as the anti-solvents for apigenin. [ABSTRACT FROM AUTHOR]

The information regarding thermodynamic parameters on solid-liquid equilibrium (SLE) of itraconazole (ITR) in different neat solvents is essential for its pharmaceutical and industrial applications. The SLE of ITR in different neat solvents had not been studied previously in literature. Hence, in this study, the SLE of ITR in various neat solvents including “water, ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), n -butanol, ethyl acetate (EA), dimethyl sulfoxide (DMSO), polyethylene glycol-400 (PEG-400) and Transcutol®” was determined and correlated at temperatures “ T = 298.2 K to 318.2 K” and pressure “ p = 0.1 MPa”. The experimental solubilities of ITR in mole fraction were determined by shake flask method and correlated with “Van't Hoff and Apelblat models”. The measured solubility values of ITR in mole fraction were correlated well with “Van't Hoff and Apelblat models” with root mean square deviation values of < 5.0%. The mole fraction solubility values of ITR were increasing with increase in temperature in all neat solvents investigated. The solubility of ITR was obtained highest in Transcutol (9.80 × 10 − 4 ) followed by DMSO (8.79 × 10 − 4 ), PEG-400 (4.62 × 10 − 4 ), EA (3.35 × 10 − 4 ), ethanol (4.84 × 10 − 5 ), n -butanol (4.46 × 10 − 5 ), IPA (3.58 × 10 − 5 ), PG (2.12 × 10 − 5 ), EG (9.85 × 10 − 6 ) and water (8.12 × 10 − 8 ) at T = 318.2 K. The solubilities of ITR were obtained in similar magnitude in Transcutol and DMSO, PEG-400 and EA and ethanol, IPA and n -butanol. The results of “apparent thermodynamic analysis” showed an “endothermic and entropy-driven dissolution” of ITR in each solvent evaluated. [ABSTRACT FROM AUTHOR]

The solubility and solution thermodynamics of isotretinoin (ITN) (3) in numerous {dimethyl sulfoxide (DMSO) (1) + water (H2O) (2)} combinations were studied at 298.2–318.2 K under fixed atmospheric pressure of 101.1 kPa. A shake flask methodology was used to determine ITN solubility, and correlations were made using the "van't Hoff, Apelblat, Buchowski-Ksiazczak λh, Yalkowsky-Roseman, Jouyban-Acree, and Jouyban-Acree-van't Hoff models". In mixtures of {(DMSO (1) + H2O (2)}, the solubility of ITN in mole fractions was enhanced with the temperature and DMSO mass fraction. The mole fraction solubility of ITN was highest in neat DMSO (1.02 × 10−1 at 318.2 K) and lowest in pure H2O (3.14 × 10−7 at 298.2 K). The output of computational models revealed good relationships between the solubility data from the experiments. The dissolution of ITN was "endothermic and entropy-driven" in all of the {(DMSO (1) + H2O (2)} mixtures examined, according to the positive values of measured thermodynamic parameters. Enthalpy was discovered to be the driving force behind ITN solvation in {(DMSO (1) + H2O (2)} combinations. ITN-DMSO displayed the highest molecular interactions when compared to ITN-H2O. The outcomes of this study suggest that DMSO has a great potential for solubilizing ITN in H2O. [ABSTRACT FROM AUTHOR]

We prepared apigenin (APG)-loaded bilosomes (BLs) and evaluated them for vesicle size, zeta-potential and encapsulation efficiency. The formulations were prepared with cholesterol (CHL), sodium deoxy cholate (SDC), Tween 80 (T80) and phosphatidylcholine (PC) using solvent evaporation method. The prepared formulations showed the optimum result was coated with much mucoadhesive polymer chitosan (CH, 0.25 and 0.5% w/v). The chitosan-coated bilosomes (CH-BLs) were further evaluated for surface morphology, drug–polymer interaction, mucoadhesion, permeation, antimicrobial activity and cell viability. The prepared APG-BLs showed nano-metric size (211 ± 2.87 nm to 433 ± 1.98 nm), polydispersibility index <0.5, negative zeta potential (−15 to −29 mV) and enhanced encapsulation efficiency (69.5 ± 0.93 to 81.9 ± 1.3%). Based on these findings, selected formulation (F2) was further coated with chitosan and showed a marked increase in vesicle size (298 ± 3.56 nm), a positive zeta potential (+17 mV), superior encapsulation efficiency (88.1 ± 1.48%) and improved drug release (69.37 ± 1.34%). Formulation F2C1 showed significantly enhanced permeation and mucoadhesion (p < 0.05) compared to formulation F2 due to the presence of CH as a mucoadhesive polymer. The presence of CH on the surfaces of BLs helps to open the tight membrane junctions and leads to enhanced permeation. A TEM study revealed non-aggregated smooth surface vesicles. The antimicrobial and cell viability assessment revealed better effects in terms of zone of inhibition and cell line assessment against two different cancer cell line. From the study, it can be concluded that APG-CHBLs could be a superior alternative to conventional delivery systems. [ABSTRACT FROM AUTHOR]

Bionanotechnology is a branch of science that has revolutionized modern science and technology. Nanomaterials, especially noble metals, have attracted researchers due to their size and application in different branches of sciences that benefit humanity. Metal nanoparticles can be synthesized using green methods, which are good for the environment, economically viable, and facilitate synthesis. Due to their size and form, gold nanoparticles have become significant. Plant materials are of particular interest in the synthesis and manufacture of theranostic gold nanoparticles (NPs), which have been generated using various materials. On the other hand, chemically produced nanoparticles have several drawbacks in terms of cost, toxicity, and effectiveness. A plant-mediated integration of metallic nanoparticles has been developed in the field of nanotechnology to overcome the drawbacks of traditional synthesis, such as physical and synthetic strategies. Nanomaterials′ tunable features make them sophisticated tools in the biomedical platform, especially for developing new diagnostics and therapeutics for malignancy, neurodegenerative, and other chronic disorders. Therefore, this review outlines the theranostic approach, the different plant materials utilized in theranostic applications, and future directions based on current breakthroughs in these fields. [ABSTRACT FROM AUTHOR]

• Solubility of PDP-6 vs. Hildebrand parameter of Transcutol + water mixtures. • Solubility of PDP-6 vs. Hildebrand parameter of PEG 400 + water mixtures. • Jouyban-Acree-van't Hoff model correlating PDP-6 solubility. • PDP-6 is preferentially hydrated in water-rich mixtures of aqueous-Transcutol system. Reported equilibrium mole fraction solubility values of 6-phenyl-4,5-dihydropyridazin-3(2 H)-one (PDP-6) (3) in {Transcutol (1) + water (2)} and {PEG 400 (1) + water (2)} mixtures at five temperatures from T = (293.15 to 313.15) K were analyzed based on the Hildebrand solubility parameter of the respective aqueous mixtures. Cosolvency models for representing the equilibrium solubility of PDP-6 in both binary solvent systems at various temperatures were also provided for correlation/prediction purposes. Moreover, the preferential solvation parameters of PDP-6 in these aqueous-cosolvent mixtures at T = (298.15 and 313.15) K were determined by means of the "inverse Kirkwood-Buff integrals" (IKBI). PDP-6 is preferentially solvated by water in water-rich mixtures of {Transcutol (1) + water (2)} system but preferentially solvated by Transcutol in mixtures of 0.13 < x 1 < 1.00. In the former case this result could be due to hydrophobic hydration around the non-polar moieties of PDP-6. Otherwise, PDP-6 is preferentially solvated by PEG 400 in all the aqueous mixtures. Moreover, in the systems where preferentially solvation of PDP-6 by cosolvents are observed, these results could be due to the Lewis acidic behavior of PDP-6 in front of Transcutol or PEG 400 molecules because these cosolvents exhibit higher Lewis basic behavior than water. [ABSTRACT FROM AUTHOR]

The investigation aimed to evaluate the favourable effects of rosinidin in lipopolysaccharide (LPS)-induced learning and memory impairment in rats. Adult Wistar rats (150–200 g) were segregated equally into four different groups and treated as below: Group 1 (normal) and Group 2 (LPS control) were administered orally with 3 mL of 0.5% SCMC (vehicle); Group 3 and Group 4 were test groups and orally administered with rosinidin lower dose (10 mg/kg) and higher dose 20 mg/kg. Daily, 1 h post-offer mentioned treatments, Group 1 animals were injected with normal saline (i.p.) and groups 2–4 were treated with 1 mg/kg/day of LPS. This treatment schedule was followed daily for 7 days. During the treatment, schedule rats were evaluated for spontaneous locomotor activity, memory, and learning abilities. The biochemical assessment was carried out of acetylcholine esterase (AChE), endogenous antioxidants (GSH, SOD, GPx, and catalase), oxidative stress marker MDA, neuroinflammatory markers (IL-6, IL-1β, TNF-α, and NF-κB), and BDNF. LPS-induced reduced spontaneous locomotor activity and memory impairment in the animals. Moreover, LPS reduced GSH, SOD, GPx, and catalase levels; altered activities of AChE; elevated levels of MDA, IL-6, IL-1β, TNF-α, and NF-κB; and attenuated the levels of BDNF in brain tissue. Administration of rosinidin to LPS-treated animals significantly reduced LPS-induced neurobehavioral impairments, oxidative stress, neuroinflammatory markers, and reversed the Ach enzyme activities and BDNF levels towards normal. Results demonstrated that rosinidin attenuates the effects of LPS on learning memory in rats. [ABSTRACT FROM AUTHOR]

The excellent therapeutic potential of a variety of phytochemicals in different diseases has been proven by extensive studies throughout history. However, most phytochemicals are characterized by a high molecular weight, poor aqueous solubility, limited gastrointestinal permeability, extensive pre-systemic metabolism, and poor stability in the harsh gastrointestinal milieu. Therefore, loading of these phytochemicals in biodegradable and biocompatible nanoparticles (NPs) might be an effective approach to improve their bioactivity. Different nanocarrier systems have been developed in recent decades to deliver phytochemicals. Among them, NPs based on chitosan (CS) (CS-NPs), a mucoadhesive, non-toxic, and biodegradable polysaccharide, are considered the best nanoplatform for the oral delivery of phytochemicals. This review highlights the oral delivery of natural products, i.e., phytochemicals, encapsulated in NPs prepared from a natural polymer, i.e., CS, for improved bioavailability and bioactivity. The unique properties of CS for oral delivery such as its mucoadhesiveness, non-toxicity, excellent stability in the harsh environment of the GIT, good solubility in slightly acidic and alkaline conditions, and ability to enhance intestinal permeability are discussed first, and then the outcomes of various phytochemical-loaded CS-NPs after oral administration are discussed in detail. Furthermore, different challenges associated with the oral delivery of phytochemicals with CS-NPs and future directions are also discussed. [ABSTRACT FROM AUTHOR]

• Solubility of sinapic acid vs. Hildebrand parameter of DMSO + water mixtures. • Solubility of sinapic acid vs. Hildebrand parameter of Carbitol + water mixtures. • Sinapic acid is preferentially solvated by water in water-rich mixtures. • Jouyban-Acree model with Hansen parameters correlating sinapic acid solubility. Reported equilibrium mole fraction solubilities of sinapic acid (3) in {DMSO (1) + water (2)} and {Carbitol (1) + water (2)} mixtures at several temperatures were analyzed in terms of the Hildebrand solubility parameter of these aqueous mixtures. Moreover, the preferential solvation parameters of sinapic acid in these aqueous saturated mixtures at (298.15 and 313.15) K were determined based on the inverse Kirkwood-Buff integrals (IKBI) as widely described in the literature. Sinapic acid is preferentially solvated by water in water-rich mixtures, i.e. (0.00 < x 1 < 0.21 in {DMSO (1) + water (2)}) and (0.00 < x 1 < 0.12 in {Carbitol (1) + water (2)}) but preferentially solvated by the cosolvents in the other mixtures composition. In the former cases these results could be interpreted as a consequence of hydrophobic hydration around the non-polar moieties of sinapic acid. Moreover, in the last cases, the observed trends could be due to the Lewis acidic behavior of sinapic acid in front of DMSO or Carbitol molecules because both cosolvents exhibit higher Lewis basic character than water, as indicated by the respective solvatochromic parameters. A single cosolvency model for representing the equilibrium solubility of sinapic acid in binary solvents at various temperatures was also provided based on a combination of Hansen solubility parameters and Jouyban-Acree model. [ABSTRACT FROM AUTHOR]

[Display omitted] • The spectrofluorimetric approach is based on the quenching of Acid red 87 at an acidic medium. • The approach is compatible with green chemistry criteria. • The technique was applied successfully for the assay of eletriptan in dosage form assay and plasma. • The approach was validated in concordance with ICH directives. Eletriptan (ETR), a selective pharmaceutical agent agonist of the 5-hydroxytryptamine1 receptor subtype, are primarily used to treat acute migraine attacks. ETR is a triptan-class medication that works by narrowing cerebral blood vessels and reducing chemicals that produce headache pain, light and sound sensitivity, and nausea. Due to its effectiveness in reducing migraine symptoms, it is a worthwhile choice for those looking for quick and efficient treatment. A green, raid, one-pot and straightforward fluorescence spectrometric method was employed to evaluate ETR in tablets and biological samples. By introducing the ETR drug and the fluorescent ligand, Acid red 87, in an acidic buffer, a quenching of the ligand native fluorescent was promptly produced. The quenching action was simply attributed to the selective ion-pair complex generation between the cationic target and the selected ligand. An increase in ETR concentration was linearly proportional to the quenching response in the 50.0 – 500.0 ng/mL range. The optimal configurations for adjusting the system's variable parameters were determined by examining the ETR–Acid red 87 system's response. Additionally, the sensor that was developed met the standards set by the International Council for Harmonisation of Technical Requirements of Pharmaceuticals for Human Use. The sensitivity thresholds of the approach were 13.8 and 42.0 ng/mL for the detection and quantification parameters, respectively, LOD and LOQ. This approach proficiently evaluated the pharmaceutical and biological samples of ETR. Finally, the proposed approach not only simplifies the analysis process but also limits the bad impact on the environment, making it a promising technique for analytical applications. [ABSTRACT FROM AUTHOR]

Background: Neurodegenerative diseases primarily afflict the elderly and are characterized by a progressive loss of neurons. Oxidative stress is intricately linked to the advancement of these conditions. This study focuses on Phoenix dactylifera (P. dactylifera; Family: Arecaceae), commonly known as "Ajwa," a globally cultivated herbal plant renowned for its potent antioxidant properties and reported neuroprotective effects in pharmacological studies. Method: This comprehensive systematic review delves into the antioxidant properties of plant extracts and their phytochemical components, with a particular emphasis on P. dactylifera and its potential neuroprotective benefits. Preferred reporting items for systemic reviews and meta-analysis (PRISMA) were employed to review the articles. Results: The study includes 269 articles published in the literature and 17 were selected after qualitative analysis. The growing body of research underscores the critical role of polyphenolic compounds found in P. dactylifera, which significantly contribute to its neuroprotective effects through antioxidant mechanisms. Despite emerging insights into the antioxidant actions of P. dactylifera, further investigation is essential to fully elucidate the specific pathways through which it confers neuroprotection. Conclusions: Like many other plant-based supplements, P. dactylifera's antioxidant effects are likely mediated by synergistic interactions among its diverse bioactive compounds, rather than by any single constituent alone. Therefore, additional preclinical and clinical studies are necessary to explore P. dactylifera's therapeutic potential comprehensively, especially in terms of its targeted antioxidant activities aimed at mitigating neurodegenerative processes. Such research holds promise for advancing our understanding and potentially harnessing the therapeutic benefits of P. dactylifera in neuroprotection. [ABSTRACT FROM AUTHOR]

The present research work is designed to prepare and evaluate piperine liposomes and piperine–chitosan-coated liposomes for oral delivery. Piperine (PPN) is a water-insoluble bioactive compound used for different diseases. The prepared formulations were evaluated for physicochemical study, mucoadhesive study, permeation study and in vitro cytotoxic study using the MCF7 breast cancer cell line. Piperine-loaded liposomes (PLF) were prepared by the thin-film evaporation method. The selected liposomes were coated with chitosan (PLFC) by electrostatic deposition to enhance the mucoadhesive property and in vitro therapeutic efficacy. Based on the findings of the study, the prepared PPN liposomes (PLF3) and chitosan coated PPN liposomes (PLF3C1) showed a nanometric size range of 165.7 ± 7.4 to 243.4 ± 7.5, a narrow polydispersity index (>0.3) and zeta potential (−7.1 to 29.8 mV). The average encapsulation efficiency was found to be between 60 and 80% for all prepared formulations. The drug release and permeation study profile showed biphasic release behavior and enhanced PPN permeation. The in vitro antioxidant study results showed a comparable antioxidant activity with pure PPN. The anticancer study depicted that the cell viability assay of tested PLF3C2 has significantly (p < 0.001)) reduced the IC50 when compared with pure PPN. The study revealed that oral chitosan-coated liposomes are a promising delivery system for the PPN and can increase the therapeutic efficacy against the breast cancer cell line. [ABSTRACT FROM AUTHOR]

The goal of this study was to optimize and formulate apigenin (APG)-loaded pegylated chitosan nanoparticles (PEGylated-CNPs) via ionic gelation techniques using the Box–Behnken design (BBD). Three individual variables, X1(chitosan: TPP concentration), X2 (PEG-400 concentration), and X3 (sonication time), were investigated for their influence on response variables (Y1—particle size (PS); Y2—drug entrapment efficiency (DEE); and Y3—zeta potential (ZP). The optimized formula of APG-PEGylated CNPs was picked from the statistical design and was then examined for physical, morphological, release characterization, anti-oxidant, and anti-tumor potential. The average PS, PDI, %DEE, and ZP were found to be 139.63 ± 5.67 nm, 0.296 ± 0.014, 79.55 ± 3.12%, and 24.68 ± 1.84 mV, respectively. The optimized APG formulation was chosen and reformulated based on the desirability function. Results of the observed and predicted values of responses through the BBD process were found to be nearly identical. The resulting APG-PEGylated CNPs were spherical and smooth, according to surface morphology studies. The release study revealed that PEGylated-CNPs exhibited biphasic release patterns distinguished by an initial burst release of APG only at early phases accompanied by a delayed release near 24 h. Furthermore, APG-PEGylated CNPs demonstrated statistically increased antioxidant activities and cytotoxicity against MCF-7 cells compared to pure APG. Based on the findings, it is possible to conclude that BBD was efficient in optimizing the PEGylated CNPs formulation and recognizing the impacts of formulation variables. In conclusion, the developed formulation has a significant potential for anticancer therapy. [ABSTRACT FROM AUTHOR]

Recently, drug delivery using natural biological carriers has emerged as one of the most widely investigated topics of research. Erythrocytes, or red blood cells, can act as potential carriers for a wide variety of drugs, including anticancer, antibacterial, antiviral, and anti-inflammatory, along with various proteins, peptides, enzymes, and other macromolecules. The red blood cell-based nanocarrier systems, also called nanoerythrosomes, are nanovesicles poised with extraordinary features such as long blood circulation times, the ability to escape immune system, the ability to release the drug gradually, the protection of drugs from various endogenous factors, targeted and specified delivery of drugs, as well as possessing both therapeutic and diagnostic applications in various fields of biomedical sciences. Their journey over the last two decades is escalating with fast pace, ranging from in vivo to preclinical and clinical studies by encapsulating a number of drugs into these carriers. Being biomimetic nanoparticles, they have enhanced the stability profile of drugs and their excellent site-specific targeting ability makes them potential carrier systems in the diagnosis and therapy of wide variety of tumors including gliomas, lung cancers, breast cancers, colon cancers, gastric cancers, and other solid tumors. This review focuses on the most recent advancements in the field of nanoerythrosomes, as an excellent and promising nanoplatform for the novel drug delivery of various drugs particularly antineoplastic drugs along with their potential as a promising diagnostic tool for the identification of different tumors. [ABSTRACT FROM AUTHOR]

Early detection, right therapeutic intervention, and simultaneous effectiveness mapping are considered the critical factors in successful cancer therapy. Nevertheless, these factors experience the limitations of conventional cancer diagnostics and therapeutics delivery approaches. Along with providing the targeted therapeutics delivery, advances in nanomedicines have allowed the combination of therapy and diagnostics in a single system (called cancer theranostics). This paper discusses the progress in the pre-clinical and clinical development of therapeutics, diagnostics, and theranostics cancer nanomedicines. It has been well evident that compared to the overabundance of works that claimed success in pre-clinical studies, merely 15 and around 75 cancer nanomedicines are approved, and currently under clinical trials, respectively. Thus, we also brief the critical bottlenecks in the successful clinical translation of cancer nanomedicines. [ABSTRACT FROM AUTHOR]

This study examines the solubility and thermodynamics of febuxostat (FBX) in a variety of mono solvents, including "water, methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), ethyl acetate (EA), Transcutol-HP (THP), and dimethyl sulfoxide (DMSO)" at 298.2–318.2 K and 101.1 kPa. The solubility of FBX was determined using a shake flask method and correlated with "van't Hoff, Buchowski-Ksiazczak λh, and Apelblat models". The overall error values for van't Hoff, Buchowski-Ksiazczak λh, and Apelblat models was recorded to be 1.60, 2.86, and 1.14%, respectively. The maximum mole fraction solubility of FBX was 3.06 × 10−2 in PEG-400 at 318.2 K, however the least one was 1.97 × 10−7 in water at 298.2 K. The FBX solubility increased with temperature and the order followed in different mono solvents was PEG-400 (3.06 × 10−2) > THP (1.70 × 10−2) > 2-BuOH (1.38 × 10−2) > 1-BuOH (1.37 × 10−2) > IPA (1.10 × 10−2) > EtOH (8.37 × 10−3) > EA (8.31 × 10−3) > DMSO (7.35 × 10−3) > MeOH (3.26 × 10−3) > PG (1.88 × 10−3) > EG (1.31 × 10−3) > water (1.14 × 10−6) at 318.2 K. Compared to the other combinations of FBX and mono solvents, FBX-PEG-400 had the strongest solute-solvent interactions. The apparent thermodynamic analysis revealed that FBX dissolution was "endothermic and entropy-driven" in all mono solvents investigated. Based on these findings, PEG-400 appears to be the optimal co-solvent for FBX solubility. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to improve the aqueous solubility, dissolution, and antioxidant activity of the water-insoluble drug piperine (PIP). The study was performed by preparing PIP binary inclusion complex (PIP BIC) and piperine ternary inclusion complex (PIP TIC) by different methods. The effect of a hydrophilic auxiliary substance (TPGS) was assessed with addition to PIP and hydroxypropyl beta cyclodextrin (HP β CD) complex. The phase solubility study was performed to evaluate the complexation efficiency and stability constant. The aqueous solubility, dissolution, physicochemical assessment, antioxidant activity, antimicrobial activity, and molecular docking were further evaluated to check the effect of the complexation of PIP. The stability constant (Ks) value was found to be 238 and 461 M−1 for the binary and ternary inclusion complex. The dissolution study results showed a marked enhancement of release in comparison to pure drug. XRD and SEM studies revealed the presence of more agglomerated and amorphous structures of PIP, which confirmed the formation of complexes. The results of DPPH radical scavenging and antimicrobial activity showed a significant (p < 0.05) enhancement in scavenging activity for PIP TIC (microwave irradiation (MI)). The docking studies have revealed that the binding affinity of TPGS at the PIP-HP β CD complex was −5.2 kcal/mol. [ABSTRACT FROM AUTHOR]

Temperature-dependent solubility data and other physicochemical parameters of sunitinib malate (SM) are scarce in literature. Therefore, in this research, the solubility, various solubility parameters and dissolution thermodynamic properties of SM in six cosolvents {i.e., ethanol, isopropanol (IPA), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400) and Transcutol-HP (THP)}, water and various THP + water mixtures at " T = 298.2 K to 318.2 K" and " p = 0.1 MPa" were determined. The experimental solubilities of SM were validated using five different computational models such as "van't Hoff, Apelblat, Yalkowsly-Roseman, Jouyban-Acree and van't Hoff-Jouyban-Acree models". All the studied models performed good correlation and validation. Various solubility parameters of SM, cosolvents, water and different THP + water mixtures were estimated to select the best solvent for SM solubility/miscibility. The mole fraction solubilities of SM were obtained maximum in pure THP (1.87 × 10−2) followed by PEG-400, IPA, ethanol, PG, EG and water (1.05 × 10−5) at " T = 318.2 K". The similar trends of solubility were also found at " T = 298.2, 303.2, 308.2 and 313.2 K". Most of the solubility parameters of SM were found to very close with pure THP. Apparent thermodynamic analysis suggested an endothermic and entropy-driven dissolution of SM in six different cosolvents, water and all THP + water mixtures. The maximum interactions at molecular level were found in SM-THP in comparison with other SM-cosolvents and SM-water combinations. Based on these results, THP has been chosen as the best cosolvent for solubility/miscibility of SM. Unlabelled Image • Solubility of sunitininb malate (SM) in various cosolvents/mixtures was determined. • The mole fraction solubilities of SM were found highest in neat Transcutol (THP). • Experimental solubilities of SM were correlated well with five computational models. • The dissolution of SM was found as endothermic and entropy-driven in all samples. • The driven mechanism for SM solvation was found enthalpy-driven. [ABSTRACT FROM AUTHOR]

Gefitinib (GFT) is an anticancer drug which shows poor aqueous solubility and bioavailability. The quantitative solubility data of GFT in any aqueous, organic or the mixture of aqueous and organic solvents have not been reported in literature. Therefore, various experimental and computational approaches for solubility determination of GFT in different organic solvents were used in the proposed research. The solubility of GFT in various organic solvents namely "methanol, ethanol, isopropanol (IPA), 1-butanol, 2-butanol, ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), dimethyl sulfoxide (DMSO) and Transcutol-HP (THP)" at " T = 298.2 K to 318.2 K" and " p = 0.1 MPa" was determined using an isothermal saturation shake flask method. Experimental solubilities of GFT were validated and correlated with "van't Hoff and Apelblat models". Various solubility parameters for GFT and different organic solvents were also determined by "HSPiP software" in order to obtain the best solvents for GFT. Experimental mole fraction solubilities of GFT were recorded highest in DMSO (3.50 × 10−2) followed by THP (3.28 × 10−2), PEG-400 (3.01 × 10−2), 2-butanol (4.62 × 10−3), 1-butanol (3.80 × 10−3), IPA (2.94 × 10−3), ethanol (2.07 × 10−3), PG (1.64 × 10−3), EG (1.44 × 10−3) and methanol (9.23 × 10−4) at " T = 318.2 K". Similar results were also observed at " T = 298.2 K, T = 303.2 K, T = 308.2 K and T = 313.2 K". Various solubility parameters of GFT were found to be closet with "DMSO, THP and PEG-400". The results of activity coefficients suggested maximum solute-solvent interactions in "GFT-DMSO, GFT-THP and GFT-PEG-400". Based on these results, "DMSO, THP and PEG-400" were optimized as the best organic solvents for miscibility/solubility of GFT. • Solubility of gefitinib (GFT) in various organic solvents was determined. • The maximum mole fraction solubilities of GFT were recorded in DMSO. • Experimental solubilities of GFT were correlated well with calculated ones. • The dissolution of GFT was recorded as endothermic and entropy-driven. [ABSTRACT FROM AUTHOR]

The current research work was performed to evaluate the solubilization behavior, solution thermodynamics, and solvation behavior of poorly soluble pyridazinone derivative i.e., 6-phenyl-pyridazin-3(2H)-one (PPD) in various binary solvent systems of dimethyl sulfoxide (DMSO) and water using experimental and various computational approaches. The solubility of PPD in various binary solvent system of DMSO and water was investigated within the temperature range T = 298.2 K to 318.2 K at constant air pressure p = 0.1 MPa, by employing an isothermal technique. The generated solubility data of PPD was computationally represented by five different cosolvency models including van't Hoff, Apelblat, Yalkowsky–Roseman, Jouyban–Acree, and Jouyban–Acree–van't Hoff models. The performance of each computational model for correlation studies was illustrated using root mean square deviations (RMSD). The overall RMSD value was obtained <2.0% for each computational model. The maximum solubility of PPD in mole fraction was recorded in neat DMSO (4.67 × 10−1 at T = 318.2 K), whereas the lowest one was obtained in neat water (5.82 × 10−6 at T = 298.2 K). The experimental solubility of PPD in mole fraction in neat DMSO was much higher than its ideal solubility, indicating the potential of DMSO for solubility enhancement of PPD. The computed values of activity coefficients showed maximum molecular interaction in PPD-DMSO compared with PPD-water. Thermodynamic evaluation showed an endothermic and entropy-driven dissolution of PPD in all the mixtures of DMSO and water. Additionally, enthalpy–entropy compensation evaluation indicated an enthalpy-driven mechanism as a driven mechanism for the solvation property of PPD. [ABSTRACT FROM AUTHOR]

A simple scheming summarizing the planned method and giving overall picture about the article concerns, CPX-Erythrosine B coupled product suggested mechanism, system spectra, and method's greenness and whitness evaluation. [Display omitted] • The article introduces a facile green/white/blue spectroscopic method to analyze the CPX drug. • The method lacks the extraction process, reduced analysis time, and reduced cost. • The article presents a dye-drug product that relied on the RRS response strategy. • The method was applied to determine the drug in its raw and dosage forms. • The system was validated and studied from the greenness, whiteness, and blueness viewpoints using various tools. The proposed research adheres to a certain methodology to ensure that the technique used for analyzing the centrophenoxine drug is sustainable and green. It is important to highlight that several tools that have been recently developed were utilized as potential indicators of environmental sustainability and applicability. The present research presents a novel and entirely innovative method utilizing ultrasensitive spectrofluorimetry for the detection of centrophenoxine (CPX) drug. The employed methodology in this study involved the utilization of one-step, one-pot, and direct spectrofluorimetric technique, which was found to be both efficient and environmentally sustainable in the validation and assessment of the drug. Simply, when CPX and erythrosine B reagent were combined in an acidic environment, the highly resonance Rayleigh scattering product was immediately produced. The sensitivity limits were observed to be within the range of 15–47 ng mL−1, whereas the linearity was assessed to be in the range of 50–2000 ng mL−1. The optimal settings for all modifiable parameters of the system were ascertained through an analysis of centrophenoxine-erythrosine B complexes. Moreover, the system demonstrated compliance with International Council for Harmonization (ICH) specifications without encountering any issues. The suggested process was then rated on different recent environmental safety measuring metrics to see how good it was for the environment. Fortunately, the WAC standards that combine ecological and functional elements utilizing the Green/Red/Blue (RGB 12) design also acclaimed the current analytical technique as a white one. Additionally, a new applicability evaluation tool (BAGI) was employed to estimate the practicability of the planned method in the analytical chemistry field. [ABSTRACT FROM AUTHOR]

The present research work was designed to develop dorzolamide-loaded chitosan-coated polycaprolactone nanoparticles (DRZ-CS-PCL-NPs) for improved ocular delivery. The nanoparticles were prepared by single-step emulsification technique and optimized using the three-factor three-level Box-Behnken design. The optimized DRZ-CS-PCL-NPs prepared with the composition of polycaprolactone (60 mg), chitosan (0.6%) and polyvinyl alcohol (1.5%). The particle size, polydispersity index, zeta potential and encapsulation efficiency of optimized DRZ-CS-PCL-NPs were found to be 192.38 ± 6.42 nm, 0.18 ± 0.04, +5.21 ± 1.24 mV, and 72.48 ± 5.62%, respectively. The dependent and independent response variables showed excellent correlation and signifying the rationality of the optimized DRZ-CS-PCL-NPs. The DRZ release from CS-PCL-NPs showed biphasic behaviour with initial burst release for 2 h after that sustained-release up to 12 h of study. The corneal flux experiment showed many fold enhancement in permeation across goat cornea. DRZ-CS-PCL-NPs exhibited 3.7 fold higher mucoadhesive strength compared to the control. Furthermore, the histopathological assessment and HET-CAM study revealed that the DRZ-CS-PCL-NPs were non-irritant and safe for ocular administration. Therefore, from the present study, it can be concluded that the optimized DRZ-CS-PCL-NPs are safe and have the potential for successful ocular delivery and improved therapeutic efficacy. [ABSTRACT FROM AUTHOR]

A library of natural sesquiterpene and phenolic compounds from Petasites japonicus are being investigated through different computational techniques to study their ability to target BMP. Lipinski rule, ADMET, molecular docking studies and metabolism were used to reach promising candidates with proposed activity against BMP. Four sesquiterpenes (kablicin, petisinol, bakkenolide D and bakkenolide IIIa) and four phenolic compounds exhibited drug-like properties (caffeic acid, petasiphenol, petasitesin A and petasitesin B), so they deserve further clinical exploration as bone loss modulators. The phenolic compounds specially fukinolic acid and petasiphenol showed lower binding energy with both BMPRIA and BMPRII than Icariin agonist and sesquiterpenes. Bakkenolide IIIa showed dual potential on both BMPRIA and BMPRII with binding energies equal – 7.82 and – 9.9 Kcal/mol respectively, which is more better score than Betulinic acid agonist. This research is focusing on plant-human interactions and exploring the ability of plant constituents to modulate a human protein such as BMP. [ABSTRACT FROM AUTHOR]

The current work was performed to estimate the solubility and Hansen solubility parameters of a poorly soluble corticosteroid hydrocortisone (HCN) in various components of nanoemulsion and to enhance the skin permeation rate of HCN using nanoemulsions as potential vehicles. Screening studies suggested the use of Capryol‐90 (oil), Triton‐X100 (surfactant) and Transcutol‐HP (cosurfactant) in the preparation of HCN nanoemulsions. HCN nanoemulsions were developed using low energy emulsification technique and characterized for droplet size, plolydispersity index (PDI), zeta potential (ZP), refractive index (RI), percent of transmittance (% T) and transmission electron microscopy (TEM) and evaluated for drug release behavior. Selected nanoemulsions and control (HCN suspension) were subjected to in vitro skin permeation studies. Optimized formula HSN8 showed droplet size of 52.6 nm, PDI of 0.109, ZP of −33.72 mV, RI of 1.337 and % T of 97.68%. TEM confirmed spherical‐shaped droplets in nanometer range. In vitro drug release evaluation suggested significant release of HCN from optimized nanoemulsion (98.52%) compared with control (35.85%). Skin permeation profile of HCN from optimized nanoemulsion was also significant compared with control. These results suggested the potential of nanoemulsion in enhancing the transdermal delivery of HCN via rat skin. [ABSTRACT FROM AUTHOR]

A new ultra-high performance liquid chromatography-mass spectrometry-mass spectrometry (UHPLC-MS/MS) system has been formulated for the resolution of closely related drugs apigenin (API, a bioflavinoid) and prednisolone (PRD) from their mixture. This developed method comprised of a "BEH™ C 18 column (50 mm × 2.1 mm, 1.7 μm)" using acetonitrile and 0.1% formic acid (35:65 v/v) at a supply rate of 0.25 mL·min−1 as eluent. It was found that selected eluent provided short run time (≤2.5 min) as well as better peak symmetry. Satisfactory values of chromatographic parameters such as resolution (Rs = 2.5), capacity factor (k; 13.6 and 23.4 for API and PRD respectively, selectivity (α = 1.72) and number of theoretical plates (N; 3789 and 42,435 for API and PRD respectively) indicate the efficiency of the developed method. The obtained separation was then exploited for the detection and measurement of API in rat plasma sample by means of PRD as an "internal standard" (IS). The eluted compounds in plasma were identified by tandem mass spectrometry by means of tandem quadrupole (TQ) detector ("Waters Corp., Milford, MA") fortified with an "electrospray ionisation (ESI)" source functioning in positive ionization mode. The determination of API in plasma was accomplished by means of "multiple reactions monitoring (MRM)" mode. Assortment of "ionization pairs" (m / z) was displayed in the following manner: API: 270.99 → 152.9 ("cone voltage" 57 V, "collision energy" 34 V), PRD: 403.172 → 385.224 ("cone voltage" 42 V, "collision energy" 13 V). The calibration curves followed linearity in concentration range of 05–1000 ng mL−1 with limit of detection "LOD" and limit of quantification "LOQ" of 7.30 and 22.77 ng mL−1, respectively. The developed method was validated taking into consideration various test conditions and satisfactory values of various parameters such as linearity (r2 ± SD = 0.9995 ± 0.0005), interday accuracy (88–120%), interday precision % RSD = 3.30–13.65% whereas intraday accuracy (91–118%) intraday precision % RSD = 1.18–5.83) indicated its validity. The validation outcomes fulfilled the standards of united states food and drug administration "USFDA" in addition Scientific Working Group for Forensic Toxicology "SWGTOX" guiding principles and were not beyond the tolerable constraint. The process developed in plasma was efficaciously harnessed in the pharmacokinetic investigation of various formulations of API after oral administration in rats. Unlabelled Image • Validated "UPLC–MS/MS" assay for the quantification of apigenin in rat plasma sample • Satisfies the validation criteria of USFDA and "SWGTOX" guidelines • Developed process was effectively applied in the pharmacokinetic investigation of various formulations of apigenin. [ABSTRACT FROM AUTHOR]

The aim of this study was to prepare, characterize, and evaluate apigenin in a solid dispersion system to improve the dissolution rate and bioavailability of such poorly soluble drug. Apigenin was dissolved in organic solvent with micelle forming polymer Pluronic F-127 (PL-F127). Solid dispersion of apigenin-PL F-127 was developed using spray drying technique. Physicochemical and in vitro characterization of the produced solid dispersion particles were conducted using scanning electron microscopy, differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffractometry and dissolution study. In addition, in vivo study was performed for the spray dried versus pure and marketed apigenin. C max was found to be around 5 folds higher for spray dried product compared to non spray dried materials. The prepared drug:polymer formulation showed elongated particles and complete lack of crystallinity at 1:4 ratio. The change in the vibrational wave numbers strongly suggested the formation of hydrogen bonding between apigenin and PL F-127. Significant increase in the dissolution rate and bioavailability of the spray dried apigenin showed the potential of solid dispersion system to overcome problem related to BCS II drugs . [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate solubility, thermodynamic properties and solute-solvent molecular interactions of poorly water-soluble bioactive compound luteolin (LUT) in various pure solvents namely water (H 2 O), ethylene glycol (EG), propylene glycol (PG), polyethylene glycol-400 (PEG-400), methanol (MeOH), ethanol (EtOH), isopropanol (IPA), 1-butanol (1-BuOH), 2-butanol (2-BuOH), ethyl acetate (EA), dimethyl sulfoxide (DMSO) and Transcutol® (THP) at temperatures “ T  = 298.2 K to 318.2 K” and pressure “ p  = 0.1 MPa”. The solubility values of LUT at equilibrium were determined using a shake flask technique with the help of ultra-performance liquid chromatography technique at 348 nm. The solid state of LUT in pure and equilibrated form was characterized using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) techniques. The solubilities of LUT measured by shake flask method were correlated with “van't Hoff and Apelblat models”. The DSC and PXRD spectra of pure and equilibrated LUT were similar, suggesting no transformation of LUT during equilibrium. Good correlation was recorded between experimental and calculated solubilities of LUT. The solubility values of LUT (mole fraction) were obtained maximum in PEG-400 (1.27 × 10 −1 ) followed by DMSO (7.15 × 10 −2 ), THP (4.01 × 10 −2 ), 2-BuOH (5.53 × 10 −3 ), 1-BuOH (5.36 × 10 −3 ), EA (5.11 × 10 −3 ), IPA (4.14 × 10 −3 ), PG (3.89 × 10 −3 ), EtOH (3.08 × 10 −3 ), EG (2.38 × 10 −3 ), MeOH (8.16 × 10 −4 ) and H 2 O (4.17 × 10 −6 ) at “ T  = 318.2 K” and similar trend was obtained at each temperature studied. The physical values of activity coefficients were determined with the help of ideal solubilities of LUT. Based on the physical values of activity coefficients, maximum solute-solvent interactions were observed in LUT-PEG-400, LUT-DMSO and LUT-THP. Apparent thermodynamic analysis suggested endothermic and entropy-driven dissolution of LUT in each pure solvent studied. [ABSTRACT FROM AUTHOR]

This article sheds light on the various scaffolds that can be used in the designing and development of novel synthetic compounds to create DPP-4 inhibitors for the treatment of type 2 diabetes mellitus (T2DM). This review highlights a variety of scaffolds with high DPP-4 inhibition activity, such as pyrazolopyrimidine, tetrahydro pyridopyrimidine, uracil-based benzoic acid and esters, triazole-based, fluorophenyl-based, glycinamide, glycolamide, β-carbonyl 1,2,4-triazole, and quinazoline motifs. The article further explains that the potential of the compounds can be increased by substituting atoms such as fluorine, chlorine, and bromine. Docking of existing drugs like sitagliptin, saxagliptin, and vildagliptin was done using Maestro 12.5, and the interaction with specific residues was studied to gain a better understanding of the active sites of DPP-4. The structural activities of the various scaffolds against DPP-4 were further illustrated by their inhibitory concentration (IC50) values. Additionally, various synthesis schemes were developed to make several commercially available DPP4 inhibitors such as vildagliptin, sitagliptin and omarigliptin. In conclusion, the use of halogenated scaffolds for the development of DPP-4 inhibitors is likely to be an area of increasing interest in the future. [ABSTRACT FROM AUTHOR]

Introduction: Isotretinoin is a synthetic vitamin A derivative, administered off-label as maintenance therapy for neuroblastoma. This report addresses the challenge of administering isotretinoin to children, given its availability as soft gelatin capsules only. Case report: A 3-year-old boy diagnosed with stage IV neuroblastoma has undergone multimodal therapy, including six cycles of chemotherapy, followed by tumor resection and radiotherapy. Later, he was initiated on immunotherapy and prescribed isotretinoin 50 mg orally twice daily for two weeks, before each immunotherapy cycle. Isotretinoin is not available in liquid formulation and the patient could not swallow isotretinoin capsules. Therefore, pharmacist counseling was required to ensure appropriate administration of the drug. Management and outcomes: The patient's parents were instructed to pierce prescribed capsules, and empty and dilute their contents into a small glass containing olive oil after taking safety measures. Isotretinoin's stability in olive oil for 72 h was compared using high-performance liquid chromatography to its stability in soybean oil. The recovery rates were 98.62% and 98.3%, respectively. Drug miscibility was not an issue as isotretinoin is lipophilic. Therefore, it could be administered easily without considerable remaining on the interior wall of the glass. Discussion: To the best of our knowledge, this is the first report that suggests a practical method for administering isotretinoin in liquid form, particularly in pediatric oncology patients. Isotretinoin was noted to be stable in olive oil and its exposure to light and oxygen would not be an issue given the short time from preparation to administration and the low emphasis on exposure by the manufacturer when such a method is recommended. [ABSTRACT FROM AUTHOR]

BCS class II molecules suffer from low oral bioavailability because of their poor permeability and sub-optimal aqueous solubility. One of the approaches to enhance their bioavailability is using cyclodextrin-based nanosponges. This study aimed to optimise and evaluate the feasibility of a microwave-assisted approach to synthesise nanosponges and improve domperidone's solubility and drug delivery potential. In the production process, microwave power level, response speed, and stirring speed were optimised using the Box-Behnken approach. Ultimately, the batch with the smallest particle size and highest yield was chosen. The optimised method of synthesis of the nanosponges resulted in a product yield of 77.4% and a particle size of 195.68 ± 2.16 nm. The nanocarriers had a drug entrapment capacity of 84 ± 4.2% and a zeta potential of −9.17± 0.43 mV. The similarity and the difference factors demonstrated proof-of-concept, showing that the drug release from the loaded nanosponges is significantly greater than the plain drug. Additionally, spectral and thermal characterisations, such as FTIR, DSC, and XRD, confirmed the entrapment of the drug within the nanocarrier. SEM scans revealed the porous nature of the nanocarriers. Microwave-assisted synthesis could be used as a better and greener approach to synthesise these nanocarriers. It could then be utilised to load drugs and improve their solubility, as seen in the case of domperidone. [ABSTRACT FROM AUTHOR]

Lumpy skin disease is a fatal emerging disease of cattle, which has started to gain extensive attention due to its rapid incursions across the globe. The disease epidemic causes economic loss and cattle morbidity. Currently, there are no specific treatments and safe vaccines against the lumpy skin disease virus (LSDV) to halt the spread of the disease. The current study uses genome-scan vaccinomics analyses to prioritize promiscuous vaccine candidate proteins of the LSDV. These proteins were subjected to top-ranked B- and T-cell epitope prediction based on their antigenicity, allergenicity, and toxicity values. The shortlisted epitopes were connected using appropriate linkers and adjuvant sequences to design multi-epitope vaccine constructs. Three vaccine constructs were prioritized based on their immunological and physicochemical properties. The model constructs were back-translated to nucleotide sequences and codons were optimized. The Kozak sequence with a start codon along with MITD, tPA, Goblin 5′, 3′ UTRs, and a poly(A) tail sequences were added to design a stable and highly immunogenic mRNA vaccine. Molecular docking followed by MD simulation analysis predicted significant binding affinity and stability of LSDV-V2 construct within bovine immune receptors and predicted it to be the top-ranked candidate to stimulate the humeral and cellular immunogenic responses. Furthermore, in silico restriction cloning predicted feasible gene expression of the LSDV-V2 construct in a bacterial expression vector. It could prove worthwhile to validate the predicted vaccine models experimentally and clinically against LSDV. [ABSTRACT FROM AUTHOR]

In the present study, orally administered Osimertinib nanostructured lipid carriers (OSM-NLCs) was prepared by the hot-melt emulsification and sonication method. The formulations were optimized by Box-Behnken design to get the optimum composition. The optimized formulation (OSM-NLCop) was further evaluated for in-vitro, ex-vivo parameters as well as in-vitro cytotoxicity evaluation against lung cancer cell line. The selected OSM-NLCop has shown a particle size of 162.6 ± 3.5 nm, PDI 0.25, entrapment efficiency 80.2 ± 3.9% with the negative zeta potential (− 24.7 mV). OSM-NLCop showed significant (p < 0.05) high drug release (82.52 ± 5.4%) as compared to pure OSM (24.7 ± 3.6%). Drug release profile from OSM-NLCop displayed Fickian release kinetic with Korsmeyer-Peppas release model. It also exhibited significantly high permeation with 4.8-fold enhancement in the permeation flux than pure OSM dispersion. OSM-NLCs also depicted (p < 0.05) lesser cytotoxicity against the tested lung cancer cell and reduced IC50 value as compared to pure OSM. From the findings, it can be concluded that NLCs are promising carriers for the delivery of OSM and may improve the therapeutic efficacy against lung cancer cell lines. [ABSTRACT FROM AUTHOR]

The quantification of a natural bioactive compound, pterostilbene (PTT), in commercial capsule dosage form, solubility, and stability samples was carried out using a rapid and sensitive high-performance liquid chromatography (HPLC) approach. PTT was quantified on a Nucleodur (150 mm × 4.6 mm) RP C18 column with a particle size of 5 µm. Acetonitrile and water (90:10 v/v) made up the mobile phase, which was pumped at a flow speed of 1.0 mL/min. At a wavelength of 254 nm, PTT was detected. The developed HPLC approach was linear in 1–75 µg/g range, with a determination coefficient of 0.9995. The developed HPLC approach for PTT estimation was also rapid (Rt = 2.54 min), accurate (%recoveries = 98.10–101.93), precise (%CV = 0.59–1.25), and sensitive (LOD = 2.65 ng/g and LOQ = 7.95 ng/g). The applicability of developed HPLC approach was revealed by determining PTT in commercial capsule dosage form, solubility, and stability samples. The % assay of PTT in marketed capsules was determined to be 99.31%. The solubility of PTT in five different green solvents, including water, propylene glycol, ethanol, polyethylene glycol-400, and Carbitol was found to be 0.0180 mg/g, 1127 mg/g, 710.0 mg/g, 340.0 mg/g, and 571.0 mg/g, respectively. In addition, the precision and accuracy of stability samples were within the acceptable limit, hence PTT was found to be stable in solution. These results suggested that PTT in commercial products, solubility, and stability samples may be routinely determined using the established HPLC method. [ABSTRACT FROM AUTHOR]

An accurate, precise and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) bioanalytical approach was developed for the simultaneous estimation of cinnarizine (CIN) and domperidone (DOM) in rat plasma using irbesartan (IRB) as an internal standard (IS). The proposed RP-HPLC approach was validated as per the latest ICH M10 guidelines. The analytes (CIN and DOM) and IS were extracted from plasma samples using the protein precipitation strategy. Chromatographic separation is accomplished by a C18 SunfireTM (5 µm, 250 mm × 4.6 mm) analytical column, using an isocratic mobile phase consisting of acetonitrile-methanol in 30:70 proportions at a flow rate of 1 mL/min. The detection of all three constituents was recorded at a wavelength of 270 nm with a UV detector. DOM, CIN and IS were eluted at 3.2, 4.5 and 6.1 min, respectively, utilizing a total run time of 10 min. The lower limit of quantification (LLOQ) was 5 ng/mL for CIN and DOM in rat plasma. The proposed RP-HPLC approach was linear in the 5–200 ng/mL range for CIN and DOM. The recovery of the method was greater than 95%, and the relative uncertainty was less than 2%, indicating that the proposed bioanalytical approach was accurate and precise. The limit of detection was established as 1.1 ng/mL for CIN and 1.7 ng/mL for DOM. The created approach was found to be robust and passed all validation criteria; thus, the proposed RP-HPLC approach can be employed successfully for the simultaneous assessment of CIN and DOM in rat plasma. [ABSTRACT FROM AUTHOR]