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Leflunomide (LEF), a disease-modifying anti-rheumatic drug, has been widely explored for its anti-inflammatory potential in skin disorders such as psoriasis and melanoma. However, its poor stability and skin irritation pose challenges for topical delivery. To surmount these issues, LEF-loaded solid lipid nanoparticles (SLNs) integrated with hydrogels have been developed in the present investigation. SLNs developed by microemulsion techniques were found ellipsoidal with 273.1 nm particle size and -0.15 mV zeta potential. Entrapment and total drug content of LEF-SLNs were obtained as 65.25 ± 0.95% and 93.12 ± 1.72%, respectively. FTIR and XRD validated the successful fabrication of LEF-SLNs. The higher stability of LEF-SLNs ( p < 0.001) compared to pure drug solution was observed in photostability studies. Additionally, in vitro anti-inflammatory activity of LEF-SLNs showed good potential in comparison to pure drugs. Further, prepared LEF-SLNs loaded hydrogel showed ideal rheology, texture, occlusion, and spreadability for topical drug delivery. In vitro release from LEF-SLN hydrogel was found to follow the Korsmeyer-Peppas model. To assess the skin safety of fabricated lipidic formulation, irritation potential was performed employing the HET-CAM technique. In conclusion, the findings of this investigation demonstrated that LEF-SLN hydrogel is capable of enhancing the photostability of the entrapped drug while reducing its skin irritation with improved topical delivery characteristics.

The efficacy of topical antifungal therapy in onychomycosis has been hindered by the failure of the antimycotic to permeate the nail plate. This research aims to design and develop a transungual system for the effective delivery of efinaconazole utilizing constant voltage iontophoresis. Seven prototype drug-loaded hydrogel formulations (E1-E7) were prepared to assess the influence of solvent (ethanol) and cosolvent (Labrasol ® ) on transungual delivery. Optimization was performed to evaluate the effect of three independent variables; voltage, solvent-to-cosolvent ratio, and penetration enhancer (PEG 400) concentration on critical quality attributes (CQAs), such as drug permeation and loading into the nail. The selected hydrogel product was characterized for pharmaceutical properties, efinaconazole release from the nail, and antifungal activity. Preliminary data indicates ethanol, Labrasol ® , and voltage influence the transungual delivery of efinaconazole. Optimization design indicates a significant impact by applied voltage ( p -0.0001) and enhancer concentration ( p -0.0004) on the CQAs. Excellent correlation between selected independent variables and CQAs was confirmed by the high desirability value (0.9427). A significant ( p < 0.0001) enhancement in the permeation (~78.59 µg/cm 2 ) and drug loading (3.24 µg/mg) was noticed in the optimized transungual delivery with 10.5 V. FTIR spectral data indicates no interaction between the drug and excipients, while the DSC thermograms confirmed the amorphous state of the drug in the formulation. Iontophoresis produces a drug depot in the nail that releases above the minimum inhibitory concentration level for an extended period, potentially reducing the need for frequent topical treatment. Antifungal studies further substantiate the release data and have shown remarkable inhibition of Trichophyton mentagrophyte . Overall, the promising results obtained here demonstrate the prospective of this non-invasive method for the effective transungual delivery of efinaconazole, which could improve the treatment of onychomycosis.

Clinical application of treprostinil in pulmonary arterial hypertension is hampered by adverse effects caused by its high dosing frequency. The objective of this investigation was to Formulate an adhesive-type transdermal patch of treprostinil and evaluate it both in vitro and in vivo. A 3 2 -factorial design was utilized to optimize the selected independent variables (X 1 : drug amount, X 2 : enhancer concentration) on the response variables (Y 1 : drug release, Y 2 : transdermal flux). The optimized patch was evaluated for various pharmaceutical properties, skin irritation, and pharmacokinetics in rats. Optimization results signify considerable influence ( p < 0.0001) of X 1 on both Y 1 and Y 2 , as compared to X 2 . The optimized patch possesses higher drug content (>95%), suitable surface morphology, and an absence of drug crystallization. FTIR analysis revealed compatibility of the drug with excipients, whereas DSC thermograms indicate that the drug exists as amorphous in the patch. The adhesive properties of the prepared patch confirm adequate adhesion and painless removal, while the skin irritation study confirms its safety. A steady drug release via Fickian diffusion and greater transdermal delivery (~23.26 µg/cm 2 /h) substantiate the potential of the optimized patch. Transdermal therapy resulted in higher treprostinil absorption ( p < 0.0001) and relative bioavailability (237%) when compared to oral administration. Overall, the results indicate that the developed drug in the adhesive patch can effectively deliver treprostinil through the skin and could be a promising treatment option for pulmonary arterial hypertension.

Poor aqueous solubility besides extensive hepatic first effect significantly decreases the oral absorption of levosulpiride, which in turn minimizes its therapeutic effectiveness. Niosomes have been extensively investigated as a transdermal vesicular nanocarrier to increase the delivery of low permeable compounds into and across the skin. This research work was to design, develop and optimize levosulpiride-loaded niosomal gel and to evaluate its prospects for transdermal delivery. The Box-Behnken design was used to optimize niosomes by analyzing the impact of three factors (cholesterol; X 1 , Span 40; X 2 , and sonication time; X 3 ) on the responses (particle size, Y 1 , and entrapment efficiency, Y 2 ). Optimized formulation (NC) was incorporated into gel and evaluated for pharmaceutical properties, drug release study, ex vivo permeation, and in vivo absorption. The design experiment data suggest that all three independent variables influence both response variables significantly ( p < 0.01). Pharmaceutical characteristics of NC vesicles showed the absence of drug excipient interaction, nanosize (~102.2 nm), narrow distribution (~0.218), adequate zeta potential (-49.9 mV), and spherical shape, which are suitable for transdermal therapy. The levosulpiride release rates varied significantly ( p < 0.01) between niosomal gel formulation and control. Greater flux ( p < 0.01) was observed with levosulpiride-loaded niosomal gel than with control gel formulation. Indeed, the drug plasma profile of niosomal gel was significantly higher ( p < 0.005), with ~3 folds higher C max and greater bioavailability (~500% higher; p < 0.0001) than its counterpart. Overall, these findings imply that the use of an optimized niosomal gel formulation can increase the therapeutic efficacy of levosulpiride and may represent a promising alternative to conventional therapy.

Natural plants and their products continue to be the major source of phytoconstituents in food and therapeutics. Scientific studies have evidenced the benefits of sesame oil and its bioactives in various health conditions. Various bioactives present in it include sesamin, sasamolin, sesaminol, and sesamol; among these, sesamol represents a major constituent. This bioactive is responsible for preventing various diseases including cancer, hepatic disorders, cardiac ailments, and neurological diseases. In the last decade, the application of sesamol in the management of various disorders has attracted the increasing interest of the research community. Owing to its prominent pharmacological activities, such as antioxidant, antiinflammatory, antineoplastic, and antimicrobial, sesamol has been explored for the above-mentioned disorders. However, despite the above-mentioned therapeutic potential, its clinical utility is mainly hindered owing to low solubility, stability, bioavailability, and rapid clearance issues. In this regard, numerous strategies have been explored to surpass these restrictions with the formulation of novel carrier platforms. This review aims to describe the various reports and summarize the different pharmacological activities of sesamol. Furthermore, one part of this review is devoted to formulating strategies to improve sesamol's challenges. To resolve the issues such as the stability, low bioavailability, and high systemic clearance of sesamol, novel carrier systems have been developed to open a new avenue to utilize this bioactive as an efficient first-line treatment for various diseases.

Glycyrrhiza glabra L. (belonging to the family Leguminosae), commonly known as Licorice, is a popular medicinal plant that has been used in traditional medicine worldwide for its ethnopharmacological efficacy in treating several ailments. Natural herbal substances with strong biological activity have recently received much attention. The main metabolite of glycyrrhizic acid is 18β-glycyrrhetinic acid (18βGA), a pentacyclic triterpene. A major active plant component derived from licorice root, 18βGA has sparked a lot of attention due to its pharmacological properties. The current review thoroughly examines the literature on 18βGA, a major active plant component obtained from Glycyrrhiza glabra L. The current work provides insight into the pharmacological activities of 18βGA and the potential mechanisms of action involved. The plant contains a variety of phytoconstituents such as 18βGA, which has a variety of biological effects including antiasthmatic, hepatoprotective, anticancer, nephroprotective, antidiabetic, antileishmanial, antiviral, antibacterial, antipsoriasis, antiosteoporosis, antiepileptic, antiarrhythmic, and anti-inflammatory, and is also useful in the management of pulmonary arterial hypertension, antipsychotic-induced hyperprolactinemia, and cerebral ischemia. This review examines research on the pharmacological characteristics of 18βGA throughout recent decades to demonstrate its therapeutic potential and any gaps that may exist, presenting possibilities for future drug research and development.

Dolutegravir's therapeutic effectiveness in the management of neuroAIDS is mainly limited by its failure to cross the blood-brain barrier. However, lipid-based nanovesicles such as nanoemulsions have demonstrated their potential for the brain targeting of various drugs by intranasal delivery. Thus, the purpose of this study was to develop a Dolutegravir-loaded nanoemulsion-based in situ gel and evaluate its prospective for brain targeting by intranasal delivery. Dolutegravir-loaded nanoemulsions were prepared using dill oil, Tween ® 80, and Transcutol ® P. Optimization of the nanoemulsion particle size and drug release was carried out using a simplex lattice design. Formulations (F1-F7 and B1-B6) were assessed for various pharmaceutical characteristics. Ex vivo permeation and ciliotoxicity studies of selected in situ gels (B1) were conducted using sheep nasal mucosa. Drug targeting to the brain was assessed in vivo in rats following the nasal delivery of B1. The composition of oil, surfactant, and cosurfactant significantly ( p < 0.05) influenced the dependent variables (particle size and % of drug release in 8 h). Formulation B1 exhibits pharmaceutical characteristics that are ideal for intranasal delivery. The mucosal steady-state flux noticed with BI was significantly greater ( p < 0.005) than for the control gel. A histopathology of nasal mucosa treated with BI showed no signs of toxicity or cellular damage. Intranasal administration of B1 resulted in greater C max (~six-fold, p < 0.0001) and AUC 0-α (~five-fold, p < 0.0001), and decreased T max (1 h) values in the brain, compared to intravenous administration. Meantime, the drug level in the plasma was relatively low, suggesting less systemic exposure to Dolutegravir through intranasal delivery. In summary, the promising data observed here signifies the prospective of B1 to enhance the brain targeting of Dolutegravir by intranasal delivery and it could be used as a feasible and practicable strategy for the management of neuroAIDS.

The objective of the present study was to evaluate the potential of solid dispersion adsorbate (SDA) to improve the solubility and bioavailability of rivaroxaban (RXN). SDA of RXN was developed by fusion method using PEG 4000 as carrier and Neusilin as adsorbent. A 3 2 full factorial design was utilized to formulate various SDAs. The selected independent variables were the amount of carrier (X 1 ) and amount of adsorbent (X 2 ). The responses measured were the time required for 85% drug release (Y 1 ) and saturated solubility (Y 2 ). MTT assay was employed for cytotoxicity studies on Caco-2 cells. In vivo pharmacokinetics and pharmacodynamic evaluations were carried out to assess the prepared SDA. Pre-compression evaluation of SDA suggests the prepared batches (B1-B9) possess adequate flow properties and could be used for compression of tablets. Differential scanning calorimetry and X-ray diffraction data signified the conversion of the crystalline form of drug to amorphous form, a key parameter accountable for improvement in drug dissolution. Optimization data suggests that the amount of carrier and amount of adsorbent significantly (P < 0.05) influence both dependent variables. Post-compression data signifies that the compressibility behavior of prepared tablets was within the official standard limits. A significant increase (P < 0.0001) in the in vitro dissolution characteristics of RXN was noticed in optimized SDA (> 85% in 10 min) as compared to the pure drug, marketed product, and directly compressible tablet. Cytotoxicity studies confirmed the nontoxicity of prepared RXN SDA tablets. RXN SDA tablets exhibited 2.79- and 1.85-fold higher AUC in comparison to RXN suspension and Xarelto tablets respectively indicating improved oral bioavailability. Higher bleeding time and percentage of platelet aggregation noticed with RXN SDA tablets in comparison to RXN suspension further substantiate the efficacy of the prepared formulation. In summary, the results showed the potential of RXN SDA tablets to enhance the bioavailability of RXN and hence can be an alternate approach of solid dosage form for its development for commercial application., (© 2022. Controlled Release Society.)

Sesamol (SES) possesses remarkable chemotherapeutic activity, owing to its anti-inflammatory and antioxidant potential. However, the activity of SES is mainly hampered by its poor physicochemical properties and stability issues. Hence, to improve the efficacy of this natural anti-inflammatory and cytotoxic agent, it was loaded into β-cyclodextrin nanosponges (NS) prepared using different molar ratios of polymer and crosslinker (diphenyl carbonate). The particle size of SES-laden NS (SES-NS) was shown to be in the nano range (200 to 500 nm), with a low polydispersity index, an adequate charge (-17 to -26 mV), and a high payload. Field emission scanning electron microscopy, thermogravimetric analysis, and Fourier transform infrared spectroscopy were used to characterize the bioactive-loaded selected batch (SES-NS6). This batch of nanoformulations showed improved solubilization efficacy (701.88 µg/mL) in comparison to bare SES (244.36 µg/mL), polymer (β-CD) (261.43 µg/mL), and other fabricated batches. The drug release data displayed the controlled release behavior of SES from NS. The findings of the egg albumin denaturation assay revealed the enhanced anti-inflammatory potential of SES-NS as compared to bare SES. Further, the cytotoxicity assay showed that SES-NS was more effective against B16F12 melanoma cell lines than the bioactive alone. The findings of this assay demonstrated a reduction in the IC 50 values of SES-NS (67.38 μg/mL) in comparison to SES (106 μg/mL). The present investigation demonstrated the in vitro controlled release pattern and the enhanced anti-inflammatory and cytotoxic activity of SES-NS, suggesting its potential as a promising drug delivery carrier for topical delivery.

Healing wounds is an important attempt to keep the internal higher organs safe. Complications in topical wound healing may lead to the formation of scars, which can affect the patient's quality of life. Although several approaches are ongoing in parallel in the exploration of natural compounds via advanced delivery, in this article, an attempt has been made to highlight tocotrienol. Tocotrienol is a natural form of vitamin E and has shown its potential in certain pharmacological activities better than tocopherol. Its antioxidant, anti-inflammatory, cell signal-mediating effects, angiogenic properties, management of scar, and promotion of wound environment with essential factors have shown potential in the management of topical wound healing. Therefore, this review has aimed to focus on recent advances in topical wound healing through the application of tocotrienols. Challenges in delivering tocotrienols to the topical wound due to its large molecular weight and higher logP have also been explored using nanotechnological-based carriers, which has made tocotrienol a potential tool to facilitate the closure of wounds. Exploration of tocotrienol has also been made in human volunteers for biopsy wounds; however, the results are yet to be reported. Overall, based on the current findings in the literature, it could be inferred that tocotrienol would be a viable alternative to the existing wound dressing components for the management of topical wounds.

Hepatic ischemia/reperfusion (HIR) is the most common type of liver injury following several clinical situations. Modulating oxidative stress and inflammation by Nrf2/HO-1 and TLR4/MYD88/NF-κB pathways, respectively, is involved in alleviating HIR injury. Paeonol is a natural phenolic compound that demonstrates significant antioxidant and anti-inflammatory effects. The present study explored the possible protective effect of paeonol against HIR injury and investigated its possible molecular mechanisms in rats. Rats were randomly divided into four groups: sham-operated control, paeonol-treated sham-operated control, HIR untreated, and HIR paeonol-treated groups. The results confirmed that hepatic injury was significantly aggravated biochemically by elevated serum levels of alanine transaminase and aspartate transaminase, as well as by histopathological alterations, while paeonol reduced the increase in transaminases and alleviated pathological changes induced by HIR. Additionally, paeonol inhibited the HIR-induced oxidative stress in hepatic tissues by decreasing the upraised levels of malondialdehyde and nitric oxide and enhancing the suppressed levels of reduced glutathione and superoxide dismutase activity. Furthermore, paeonol activated the protective antioxidative Nrf2/HO-1 pathway. The protective effect of paeonol was associated with inhibiting the expression of the inflammatory key mediators TLR4, MYD88, NF-κB, and TNF-α. Finally, paeonol inhibited the increased mRNA levels of the pro-apoptotic marker Bax and enhanced the reduced mRNA levels of the anti-apoptotic marker Bcl-2. Taken together, our results proved for the first time that paeonol could protect against HIR injury by inhibiting oxidative stress, inflammation, and apoptosis.

The second most common cause of mortality among women is breast cancer. A variety of natural compounds have been demonstrated to be beneficial in the management of various malignancies. Resveratrol is a promising anticancer polyphenolic compound found in grapes, berries, etc. Nevertheless, its low solubility, and hence its low bioavailability, restrict its therapeutic potential. Therefore, in our study, we developed a thermosensitive hydrogel formulation loaded with resveratrol nanoemulsion to enhance its bioavailability. Initially, resveratrol nanoemulsions were formulated and optimized utilizing a central composite-face-centered design. The independent variables for optimization were surfactant level, homogenization speed, and time, while the size and zeta potential were the dependent variables. The optimized nanoemulsion formulation was converted into a sensitive hydrogel using poloxamer 407. Rheological studies proved the formation of gel consistency at physiological temperature. Drug loading efficiency and in vitro drug release from gels were also analyzed. The drug release mechanisms from the gels were assessed using various mathematical models. The effect of the optimized thermosensitive resveratrol nanoemulsion hydrogel on the viability of human breast cancer cells was tested using MCF-7 cancer cell lines. The globule size of the selected formulation was 111.54 ± 4.16 nm, with a zeta potential of 40.96 ± 3.1 mV. Within 6 h, the in vitro release profile demonstrated a release rate of 80%. According to cell line studies, the produced hydrogel of resveratrol nanoemulsion was cytotoxic to breast cancer cells. Overall, the results proved the developed nanoemulsion-loaded thermosensitive hydrogel is a promising platform for the effective delivery of resveratrol for the management of breast cancer.

A series of 2,3-dihydroquinazolin-4(1 H )-one derivatives ( 3a - 3m ) was screened for in vitro whole-cell antitubercular activity against the tubercular strain H37Rv and multidrug-resistant (MDR) Mycobacterium tuberculosis (MTB) strains. Compounds 3l and 3m with di-substituted aryl moiety (halogens) attached to the 2-position of the scaffold showed a minimum inhibitory concentration (MIC) of 2 µg/mL against the MTB strain H37Rv. Compound 3k with an imidazole ring at the 2-position of the dihydroquinazolin-4(1 H )-one also showed significant inhibitory action against both the susceptible strain H37Rv and MDR strains with MIC values of 4 and 16 µg/mL, respectively. The computational results revealed the mycobacterial pyridoxal-5'-phosphate (PLP)-dependent aminotransferase (BioA) enzyme as the potential target for the tested compounds. In vitro, ADMET calculations and cytotoxicity studies against the normal human dermal fibroblast cells indicated the safety and tolerability of the test compounds 3k - 3m . Thus, compounds 3k - 3m warrant further optimization to develop novel BioA inhibitors for the treatment of drug-sensitive H37Rv and drug-resistant MTB.

The clinical efficacy of antiretroviral therapy in NeuroAIDS is primarily limited by the low perfusion of the drug to the brain. The objective of the current investigation was to design and develop an in situ mucoadhesive gel loaded with darunavir to assess the feasibility of brain targeting through the intranasal route. Preliminary batches (F1−F9) were prepared and evaluated for various pharmaceutical characteristics. A full factorial design of the experiment was applied to optimize and assess the effect of two influencing variables (Carbopol 934P (X1) and Poloxamer 407 (X2)) on the response effects (gelation temperature (Y1) and % drug release (Y2) at 8 h). The data demonstrate that both influencing variables affect the response variables significantly (p < 0.05). The optimized formulation (F7) exhibited favorable rheological properties, adequate mucoadhesion, sustained drug release, and greater permeation across the nasal mucosa. An in vitro ciliotoxicity study confirms the nontoxicity of the optimized in situ gel (D7) on the nasal mucosa. An in vivo pharmacokinetic study in rats was performed to assess drug targeting to the brain following the nasal application of the selected in situ gel (D7). Significantly higher (p < 0.0001) Cmax (~4-fold) and AUC0-α (~3.5-fold) values were noticed in the brain after nasal application, as compared to the intravenous route. However, less systemic exposure to darunavir was noticed with nasal therapy, which confirms the low absorption of the drug into the central compartment. Overall, the data here demonstrate that the optimized in situ mucoadhesive nasal gel is effective in targeting darunavir to the brain by the nasal route and could be a viable option for the treatment of NeuroAIDS.

This study investigated the protective effect of extracts from flowers of Brassica oleracea L. var. italica Plenck on type 2 diabetes mellitus and its associated disorders. Three different doses of each extract (petroleum ether, ethanol, and aqueous) were administered orally for 42 days. Biochemical parameters, behavioral studies, and histological studies were measured at different periods. Mortality was found to be nil up to 2,000 mg/kg. Statistically significant ( P <0.001) improvement in serum glucose level was observed in the groups receiving 400 mg/kg of petroleum ether, aqueous, or ethanol extracts compared with the negative control group. Insulin level was decreased by aqueous extracts, whereas lipid profiles were improved by aqueous and ethanol extracts. A reduction in transfer latency was observed in treatments of all three extract types. Ethanol extract treatment (400 mg/kg) showed maximum percentage inhibition in a lipid peroxidation assay. Additionally, the aqueous and ethanol extract treatments markedly reduced tumor necrosis factor-α, interleukin-6, and glycosylated hemoglobin levels. Histological results showed that high doses of extracts alleviated the damages induced by type 2 diabetes mellitus in various organs and bones. Based on the results of this study, it can be concluded that B. oleracea has the potential to alleviate type 2 diabetes mellitus., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (Copyright © 2022 by The Korean Society of Food Science and Nutrition. All rights Reserved.)

Due to complicated anatomical and physical properties, targeted drug delivery to ocular tissues continues to be a key challenge for formulation scientists. Various attempts are currently being made to improve the in vivo performance of therapeutic molecules by encapsulating them in various nanocarrier systems or devices and administering them via invasive/non-invasive or minimally invasive drug administration methods. Biocompatible and biodegradable lipid nanoparticles have emerged as a potential alternative to conventional ocular drug delivery systems to overcome various ocular barriers. Lipid-based nanocarrier systems led to major technological advancements and therapeutic advantages during the last few decades of ocular therapy, such as high precorneal residence time, sustained drug release profile, minimum dosing frequency, decreased drug toxicity, targeted site delivery, and, therefore, an improvement in ocular bioavailability. In addition, such formulations can be given as fine dispersion in patient-friendly droppable preparation without causing blurred vision and ocular sensitivity reactions. The unique advantages of lipid nanoparticles, namely, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, and liposomes in intraocular targeted administration of various therapeutic drugs are extensively discussed. Ongoing and completed clinical trials of various liposome-based formulations and various characterization techniques designed for nanoemulsion in ocular delivery are tabulated. This review also describes diverse solid lipid nanoparticle preparation methods, procedures, advantages, and limitations. Functionalization approaches to overcome the drawbacks of lipid nanoparticles, as well as the exploration of new functional additives with the potential to improve the penetration of macromolecular pharmaceuticals, would quickly progress the challenging field of ocular drug delivery systems.

Background & Objectives: Low penetration efficiency and retention time are the main therapeutic concerns that make it difficult for most of the drugs to be delivered to the intraocular tissues. These challenging issues are often related to those drugs, which have low or poor solubility and low permeability. The goal of this study was designed to develop nanostructured lipid carriers (NLCs) loaded with itraconazole (ITZ) with the objective of enhancing topical ocular permeation and thereby improving clinical efficacy., Materials and Methods: ITZ-loaded NLCs were fabricated by a high-speed homogenization technique using surfactant (Poloxamer 407), and lipids (stearic acid and oleic acid). Optimization of formulations was performed by 3 level factorial design and the selected formulation (F6) was evaluated by differential scanning calorimetry and transmission electron microscopy. Antifungal activity was assessed by measuring the zone of inhibition and irritation potential using the HET-CAM test., Results: The independent variables (lipid ratio-X 1 and percentage of emulsifier-X 2 ) have a positive impact on percentage entrapment efficiency (Y 2 ) and percentage release (Y 3 ) but have a negative impact on particle size (Y 1 ). Based on the better entrapment efficiency (94.65%), optimum particle size (150.67 nm), and percentage cumulative drug release (68.67%), batch F6 was selected for further evaluation. Electron microscopic images revealed that the prepared particles are spherical and have nano size. Antifungal studies demonstrated enhancement in the zone of inhibition by formulation F6 as compared to a commercial eye drop. The non-irritancy of optimized formulation (F6) was confirmed with a zero score., Interpretation & Conclusion: In summary, the optimized NLCs seem to be a potent carrier for the effective delivery of itraconazole in ocular therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: Curcumin, a natural polyphenol from Curcuma longa, is known to possess diversified pharmacological roles including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic properties; however, its bioavailability is severely limited due to its poor solubility, poor absorption, rapid metabolism, and significant elimination. Hydrazinocurcumin (HZC), a novel analogue of curcumin has been reported to overcome the limitations of curcumin and also possesses multiple pharmacological activities. The present study aimed to evaluate the unexplored pharmacokinetic profile of this agent in experimental rats., Methods: Drug formulations were administered to the experimental animals via oral, intravenous and intraperitoneal routes. Blood samples were collected at different pre-determined time intervals to determine the pharmacokinetic parameters. To understand the biodistribution profile of HCZ, tissue samples were isolated from different groups of Sprague-Dawley rats at different time points. The pharmacokinetic parameters of HZC were evaluated after administration through oral (100 mg/kg), intraperitoneal (100 mg/kg) and intravenous (10 mg/kg) routes., Results: Significantly (p < 0.05) higher total AUC along with maximum concentration were evident with intraperitoneal administration when compared to the results of oral administration at a similar dose. In addition, shorter time to peak was observed with intraperitoneal administration. These results revealed a faster rate and longer duration of absorption with intraperitoneal administration, which further resulted in enhanced absolute bioavailability of HZC (29.17%) when compared to 5.1% upon oral dosing. The obtained data from the pharmacokinetic study indicated that HZC was instantaneously distributed and moderately eliminated from body fluids., Conclusion: Based on the findings, it could be concluded that absorption of HZC is much higher via intraperitoneal route of administration compared to the oral administration., (© 2021. Maj Institute of Pharmacology Polish Academy of Sciences.)

Asenapine, an atypical antipsychotic agent, has been approved for the acute and maintenance treatment of schizophrenia and manic episodes of bipolar disorder. However, the extensive hepatic metabolism limits its oral bioavailability. Therefore, the objective of the current investigation was to develop sublingual film containing asenapine to enhance the therapeutic efficacy. Sublingual films containing asenapine were fabricated using polyethylene oxide and hydroxypropyl methylcellulose by solvent casting method. Design of experiment was used as a statistical tool to optimize the proportion of the film-forming polymers in order to establish the critical quality attributes of the drug formulation. The process was studied in detail by assessing risk of each step as well as parameters and material attributes to reduce the risk to a minimum. A control strategy was defined to ensure manufacture of films according to the target product profile by evaluation of intermediate quality attributes at the end of each process step. Results of optimized formulations showed rapid disintegration, adequate folding endurance, good percentage elongation, tensile strength, and viscosity. Besides, the results from the in vitro dissolution/ex vivo permeation studies showed rapid dissolution (100% in 6 min) and higher asenapine permeation (~ 80% in 90 min) through the sublingual epithelium. In vivo study indicates greater asenapine absorption (31.18 ± 5.01% of administered dose) within 5 min and was comparable with marketed formulation. In summary, the designing plan to develop asenapine formulation was successfully achieved with desired characteristics of the delivery tool for sublingual administration., (© 2021. American Association of Pharmaceutical Scientists.)

The current study was aimed to ascertain the effect of blood lead level on brain tissues in patients with type 2 diabetes. A total of 300 human participants ages 27 to 60 years with type 2 diabetes (n = 150) and healthy individuals (n = 150) were included in this study. The serum samples were used for measuring HbA1c and fasting blood glucose. Blood lead level was measured using flame atomic absorption spectrophotometer. Magnetic resonance imaging sub-analysis was used to assess the brain hyperintensities. Brain hyperintensities were found in 55% of patients with diabetes and 6% of non-diabetic control group subjects. The deep white matter hyperintensities were observed in 45% of diabetic patients, while the subcortical hyperintensities were noted in 10% of cases. Entorhinal cortex changes (31%) and hippocampus changes (42%) were noted in diabetic patients with brain hyperintensities. Diabetic patients with brain hyperintensities showed higher blood lead levels, HbA1c, and fasting blood sugar (p < 0.0001) as compared with healthy volunteers. A higher correlation (R 2  = 0.8922) was found between deep white matter hyperintensities' size and blood lead levels. In nutshell, persistence of high blood lead level in diabetic patients may progress to brain hyperintensities which may consequently lead to cognitive, behavioral changes and Alzheimer's disease.

Being a candidate of BCS class II, dolutegravir (DTG), a recently approved antiretroviral drug, possesses solubility issues. The current research was aimed to improve the solubility of the DTG and thereby enhance its efficacy using the solid dispersion technique. In due course, the miscibility study of the drug was performed with different polymers, where Poloxamer 407 (P407) was found suitable to move forward. The solid dispersion of DTG and P407 was formulated using solvent evaporation technique with a 1:1 proportion of drug and polymer, where the solid-state characterization was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffraction. No physicochemical interaction was found between the DTG and P407 in the fabricated solid dispersion; however, crystalline state of the drug was changed to amorphous as evident from the X-ray diffractogram. A rapid release of DTG was observed from the solid dispersion (>95%), which is highly significant (p<0.05) as compared to pure drug (11.40%), physical mixture (20.07%) and marketed preparation of DTG (35.30%). The drug release from the formulated solid dispersion followed Weibull model kinetics. Finally, the rapid drug release from the solid dispersion formulation revealed increased C max (14.56 μg/mL) when compared to the physical mixture (4.12 μg/mL) and pure drug (3.45 μg/mL). This was further reflected by improved bioavailability of DTG (AUC: 105.99±10.07 μg/h/mL) in the experimental Wistar rats when compared to the AUC of animals administered with physical mixture (54.45±6.58 μg/h/mL) and pure drug (49.27±6.16 μg/h/mL). Therefore, it could be concluded that the dissolution profile and simultaneously the bioavailability of DTG could be enhanced by means of the solid dispersion platform using the hydrophilic polymer, P407, which could be projected towards improved efficacy of the drug in HIV/AIDS.

Background: Inflammation is a complex response to noxious stimuli promoted by the release of chemical mediators from the damaged cells. Metabolic products of arachidonic acid, produced by the action of cyclooxygenase and lipoxygenase, play important roles in this process. Several non-steroidal anti-inflammatory drugs act as cyclooxygenase inhibitors. However, almost all of them have undesired side effects., Methods: Prediction of the anti-inflammatory action of the compounds was performed using PASS Program. The anti-inflammatory activity was evaluated by the carrageenan paw edema test. COX and LOX inhibitory actions were tested using ovine COX-1, human recombinant COX-2 and soybean LOX-1, respectively. Docking analysis was performed using Autodock., Results: All designed derivatives had good prediction results according to PASS and were synthesized and experimentally evaluated. The compounds exhibited in vivo anti-inflammatory action with eleven being equal or better than indomethacin. Although, some of them had no or low inhibitory effect on COX-1/2 or LOX, certain compounds exhibited COX-1 inhibition much higher than naproxen and COX-2 inhibition, well explained by Docking analysis., Conclusions: A number of compounds with good anti-inflammatory action were obtained. Although, some exhibited remarkable COX inhibitory action this activity did not follow the anti-inflammatory results, indicating the implication of other mechanisms.

1,2,3-Triazole, a five-membered heterocyclic nucleus, is widely recognized as a key chromophore of great value in medicinal chemistry for delivering compounds possessing innumerable biological activities, including antimicrobial, antitubercular, antidiabetic, antiviral, antitumor, antioxidants, and anti-inflammatory activities. Mainly, in the past years, diverse conjugates carrying this biologically valuable core have been reported due to their attractive fungicidal potential and potent effects on various infective targets. Hence, hybridization of 1,2,3-triazole with other antimicrobial pharmacophores appears to be a judicious strategy to develop new effective anti-fungal candidates to combat the emergence of drug-sensitive and drug-resistant infectious diseases. Thus, the current review highlights the recent advances of this promising category of 1,2,3-triazole-containing hybrids incorporating diverse varieties of bioactive heterocycles such as conozole, coumarin, imidazole, benzimidazole, pyrazole, indole, oxindole, chromene, pyrane, quinazoline, chalcone, isoflavone, carbohydrates, and amides. It underlies their inhibition behavior against a wide array of infectious fungal species during 2015-2020., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Low aqueous solubility is one of the major reasons for the poor clinical efficacy of carvedilol in oral therapy. The aim of the present investigation was to evaluate the potential of liquisolid compact technique to enhance the dissolution rates of carvedilol and thereby the bioavailability. Liquisolid compacts were prepared using polyethylene glycol 400, Neusilin US2 and Aerosil 200. Experimental design and optimization was carried out by applying a 3 2 factorial design (batches D1-D9) to examine the effects of independent variables (amount of load factor and the excipient ratio) on dependent variables (angle of repose and % drug release). Differential scanning calorimetry and X-ray diffraction studies suggested transformation of carvedilol to amorphous in D6, a key factor responsible for dissolution rate improvement. This effect was evidenced in the dissolution data of D6 (>95% drug dissolved in 30 min) where the drug release kinetics followed Weibull model. It was observed that the amount of load factor influenced angle of repose and excipient ratio affected drug dissolution of liquisolid compacts. Pharmacokinetic profile of D6 was prominent, demonstrating greater carvedilol absorption than the control in rats. The observed increase in systemic bioavailability of carvedilol AUC 0-∞ (p < 0.005) by liquisolid compact is likely due to the improvement in drug solubility. The data observed in the current study demonstrated that the liquisolid compact technique could be a promising strategy to enhance the bioavailability of carvedilol and could be used in oral therapy. Graphical abstract.

A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2- a ]quinoline-3-carboxylates 4a - f and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2- a ]quinoline-2,3-dicarboxylates 4g - k have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8-128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2- a ]quinoline-2,3-dicarboxylate 4j emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of Mycobacterium tuberculosis at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.

Administration of almotriptan as an oral therapy is largely limited because of poor aqueous solubility and rather low bioavailability. The aim of present investigation was to formulate oral mucoadhesive film of almotriptan to improve the drug delivery and desired therapeutic effects. Placebo films (F1-F8) were prepared by varying the concentrations of Proloc 15 (7.5-15% w/v) and Eudragit RL 100/RS 100 (15-30% w/v) polymers. Physicomechanical and pharmaceutical characteristics of drug loaded films (FA1-FA4) were examined. Selected FA4 film was evaluated in vivo by assessing the pharmacokinetic profile and compared with oral therapy in rabbits. FA1-FA4 films exhibited excellent physicomechanical properties and rapid hydration. A biphasic and considerably greater drug release (p < 0.05) was observed in FA3 and FA4 films contain higher amount of hydrophilic polymer. The rate of permeation of almotriptan was found to be significantly higher in FA4 than FA3 film (p < 0.005). Fourier transform infrared spectral scan indicates no incompatibility exists between the drug and polymers used. Differential scanning calorimetry thermogram represents the evidence of almotriptan amorphization and molecular dispersion of it in the film. Scanning electron microscopy images shows that FA4 possess good morphological features and hence suitable for use in the buccal application. In vivo data demonstrated rapid and efficient absorption (p < 0.005) of almotriptan with greater AUC 0-12 (>2 folds, p < 0.0001) by FA4 film as compared to oral (control). In general, the data established the potential of FA4 film to improve the therapeutic delivery of almotriptan and offers a promising option in migraine therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2019 The Author(s).)

Rapid advancement in drug discovery process is leading to a number of potential new drug candidates having excellent drug efficacy but limited aqueous solubility. By virtue of the submicron particle size and distinct physicochemical properties, nanosuspension has the potential ability to tackle many formulation and drug delivery issues typically associated with poorly water and lipid soluble drugs. Conventional size reduction equipment such as media mill and high-pressure homogenizers and formulation approaches such as precipitation, emulsion-solvent evaporation, solvent diffusion and microemulsion techniques can be successfully implemented to prepare and scale-up nanosuspensions. Maintaining the stability in solution as well as in solid state, resuspendability without aggregation are the key factors to be considered for the successful production and scale-up of nanosuspensions. Due to the considerable enhancement of bioavailability, adaptability for surface modification and mucoadhesion for drug targeting have significantly expanded the scope of this novel formulation strategy. The application of nanosuspensions in different drug delivery systems such as oral, ocular, brain, topical, buccal, nasal and transdermal routes are currently undergoing extensive research. Oral drug delivery of nanosuspension with receptor mediated endocytosis has the promising ability to resolve most permeability limited absorption and hepatic first-pass metabolism related issues adversely affecting bioavailability. Advancement of enabling technologies such as nanosuspension can solve many formulation challenges currently faced among protein and peptide-based pharmaceuticals., Competing Interests: Competing interestThe authors declare that they have no competing interests., (© The Author(s). 2020.)

Objective: Clinical utility of lornoxicam in oral therapy is primarily restricted by the low solubility and gastric adverse effects. This study evaluated the prospective of optimized proniosomal gel to improve the clinical efficacy of lornoxicam and compare with oral therapy., Methods: Proniosomes were formulated by coacervation phase separation technique using span 60, lecithin and cholesterol. A four-factor three-level Box-Behnken design was used to evaluate the effect of amount of four independent variables; span 60 (X 1 ), cholesterol (X 2 ), lecithin (X 3 ) and lornoxicam (X 4 ) on response variables; vesicle size (Y 1 ), entrapment efficiency (Y 2 ) and transdermal flux (Y 3 ). The selected proniosomal gel (F19) was characterized, and evaluated for the transdermal efficacy by ex vivo and in vivo experiments., Results: Optimization study signifies that amount of formulation components (span 60, cholesterol, lecithin and lornoxicam) influence the vesicle size, entrapment efficiency and/or transdermal flux. Optimized formulation F19 exhibited nano size with high entrapment efficiency, adequate zeta potential, greater transdermal flux and better stability (at refrigerated conditions). The entrapment of lornoxicam in the bilayers of proniosome vesicles was confirmed by differential scanning calorimeter. Release profile of F19 was distinct (p < 0.001) from gel prepared using hydroxypropyl methylcellulose (control) and displayed steady lornoxicam release by Fickian diffusion. Transdermal administration of F19 significantly inhibited the carrageenan induced hind-paw edema in rats as compared to oral lornoxicam group., Conclusions: The data observed in this study demonstrated that the developed proniosomal gel (F19) improved the clinical efficacy of lornoxicam as compared to oral therapy. Graphical Abstract Proniosomal gel for transdermal delivery of lornoxicam: optimization using factorial design and in vivo evaluation in rats.

Given the distinctive characteristics of both epilepsy and antiepileptic drugs (AEDs), therapeutic drug monitoring (TDM) can make a significant contribution to the field of epilepsy. The measurement and interpretation of serum drug concentrations can be of benefit in the treatment of uncontrollable seizures and in cases of clinical toxicity; it can aid in the individualization of therapy and in adjusting for variable or nonlinear pharmacokinetics; and can be useful in special populations such as pregnancy. This review examines the potential for TDM of newer AEDs such as eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, perampanel, pregabalin, rufinamide, retigabine, stiripentol, tiagabine, topiramate, vigabatrin, and zonisamide. We describe the relationships between serum drug concentration, clinical effect, and adverse drug reactions for each AED as well as the different analytical methods used for serum drug quantification. We discuss retrospective studies and prospective data on the serum drug concentration-efficacy of these drugs and present the pharmacokinetic parameters, oral bioavailability, reference concentration range, and active metabolites of newer AEDs. Limited data are available for recent AEDs, and we discuss the connection between drug concentrations in terms of clinical efficacy and nonresponse. Although we do not propose routine TDM, serum drug measurement can play a beneficial role in patient management and treatment individualization. Standardized studies designed to assess, in particular, concentration-efficacy-toxicity relationships for recent AEDs are urgently required., Competing Interests: Compliance with Ethical Standards Shery Jacob and Anroop Nair have no conflicts of interest that are directly related to the content of this work. Funding No sources of funding were used to conduct this study or prepare this manuscript.

Understanding the concept of extrapolation of dose between species is important for pharmaceutical researchers when initiating new animal or human experiments. Interspecies allometric scaling for dose conversion from animal to human studies is one of the most controversial areas in clinical pharmacology. Allometric approach considers the differences in body surface area, which is associated with animal weight while extrapolating the doses of therapeutic agents among the species. This review provides basic information about translation of doses between species and estimation of starting dose for clinical trials using allometric scaling. The method of calculation of injection volume for parenteral formulation based on human equivalent dose is also briefed.

Oral bioavailability of acyclovir is limited, primarily because of low permeability across the gastrointestinal membrane. The purpose of this study is the prospective evaluation of buccal films impregnated with acyclovir loaded nanospheres as a drug delivery system to improve systemic bioavailability. Acyclovir polymeric nanospheres were prepared by double emulsion solvent evaporation technique. Nanospheres were embedded into buccoadhesive films (A1-A4) comprising of different concentrations of polymers (Eudragit RL 100, HPMC K15 and carbopol 974P). Films were characterized for physico-mechanical properties, mucoadhesive strength, hydration, drug release and ex vivo permeation. In vivo studies were carried out on rabbits to assess the pharmacokinetic profile of buccal film (A3) as compared to oral therapy. The prepared films demonstrated excellent physical properties, adequate hydration and buccoadhesive strength. In vitro drug release data inferred that the drug release was dependent on the composition of film. Ex vivo permeation studies indicated greater flux in film A3. In vivo studies revealed a significant enhancement in absorption of acyclovir (P<0.0001) with Cmax (~3 folds) and AUC0-α (~8 folds, P<0.0001) when compared to oral dosing. Moreover, the extended Tmax value (6h) signifies the potential of the prepared film to prolong acyclovir delivery. Given the promising results, the study concludes that the developed buccal film (A3) impregnated with acyclovir loaded nanospheres could be a promising approach for effective delivery of acyclovir., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Purpose: Transdermal reverse iontophoresis offers a noninvasive tool for clinical and therapeutic monitoring of drugs and endogenous molecules. This study investigated the viability of reverse iontophoresis as an alternative technique to blood sampling for the monitoring of gabapentin., Methods: Ex vivo studies assessed the influence of polarity, applied current (0.064-0.32 mA) and subdermal concentration (0.5-20 μg/mL) on the recovery of gabapentin. These experiments were carried out in vertical Franz diffusion cell for a period of 3 h using rat skin. In vivo experiments examined the versatility of this method to extract gabapentin from the subdermal region following intravenous administration of gabapentin (30 mg/kg) in rat model., Results: Preliminary studies demonstrate that greater amount of gabapentin was extracted in the cathodal chamber due to the contribution of electroosmosis. Increasing the current intensity significantly enhances the extraction flux (P < 0.005) and shown linear relation (r(2) = 0.84) between the applied electrical dose (mA*h) and the amount of gabapentin recovered (μg). Indeed, transdermal iontophoresis of gabapentin was found to be concentration dependent in the range studied (0.5-20 μg/mL), which includes clinically relevant level. Further, a linear relationship was established between the iontophoretically recovered gabapentin 3 h flux values and the subdermal concentrations studied. The linear correlation with good regression value (r(2) = 0.92) observed in the in vivo studies infers that the drug in the plasma is proportionally extracted through the skin and potentially represents the subdermal drug concentrations., Conclusions: Given the promising results, this study concludes that the transdermal reverse iontophoresis technique could be a promising alternative for the noninvasive monitoring of gabapentin.

For cancer therapy, microspheres can be used to increase effectiveness while decreasing side effects of treatments. We prepared gelatin microspheres containing carboplatin (GCPtM) for treating lung cancer. We prepared gelatin microspheres of carboplatin (GCPtM) for use in treating lung cancer. Microspheres were prepared using a Buchi B-90 nano spray-drier. Surface morphology was found to be shriveled to nearly spherical, with an average size of 14.7 μm. Drug loading and percentage yield were found to be 72 ± 0.4 and 88 ± 0.2 %, respectively. In vitro release studies indicated that diffusion followed the Peppas model, with 99.3 % of total carboplatin released from GCPtM after 12 h, while for the pure drug this value was 92.4 % in 0.5 h. Liquification was observed during stability studies at 37 °C with an relative humidity of 75 %. Plasma concentration profile was described using a two-compartment model after intravenous injection of GCPtM. Carboplatin containing microspheres distributed in the lung, spleen, liver, and blood were found to be primarily distributed in the lungs. We used a powder technology (spray-dryer) method in this study to significantly reduce the overall production time and desired particle size, without using organic solvents; additionally, this method is economically feasible. Thus, microsphere may be an effective method for successfully delivering carboplatin to the lungs.

Clinical benefits, industry interest, regulatory precedence, and strong market potential have made transdermal research the fastest growth area in drug delivery. As most drugs permeate poorly through skin, a major challenge is achieving the therapeutic level by enhancement of permeation rate. Iontophoresis, utilizing a minimal amount of current, is found to affect the skin permeation process drastically. Ideally suited for protein drugs, attempts have been made to utilize the technology for accelerating the low-molecular-weight drugs for chronic administration. However, because of the difficulty associated with the energy supply, commercialization was not feasible until recent times. Fortunately, the unprecedented growth of microelectronics has bridged this lacuna and brought the technology right into limelight. This article analyses the advantages of electrically assisted drug delivery in relation to passive permeation, with special reference to some cardiovascular drugs, for which there is already a demand in the market.

Therapeutic molecules possessing distinct pharmacokinetic variation, narrow therapeutic index and concentration dependent therapeutic/adverse effects demand constant monitoring. The current methods for blood sampling are invasive and possess low patient compliance. Human skin, selective and effective membrane to chemical permeation, offers an alternative route for the extraction of endogenous molecules in the body. Significant attention has been received in the application of reverse iontophoresis in extracting drugs/biomaterials from the subdermal region. This technique involves transiting of a low electric current across the skin usually with couple of skin electrodes to extract charged as well as neutral molecules. Electromigration and electroosmosis are the two basic mechanisms involved in transport of molecules. Several in vitro and in vivo experiments demonstrated the potential of reverse iontophoresis as a noninvasive tool in clinical chemistry and therapeutic drug monitoring. This technology is currently being used in device such as Glucowatch Biogrpaher which allows blood glucose detection across skin layers. Advances in technology and rapid progress in research has widely improved the opportunity of this system, and the recent trend indicates that several products are likely to be developed very soon. This review provides an overview about the recent developments in reverse iontophoresis for therapeutic drug monitoring.

Topical nail drug delivery could be improved by identifying potent chemical penetration enhancers. The purpose of this study was to assess the effect of polyethylene glycols (PEGs) on the trans-ungual delivery of terbinafine. In vitro permeation studies were carried out by passive and iontophoresis (0.5 mA/cm2) processes for a period of 1 h using gel formulations containing different molecular weight PEGs (30%w/w). The release of drug from the loaded nail plates and the possible mechanisms for the enhanced delivery was studied. Passive delivery using formulation with low molecular weight PEGs (200 and 400 MW) indicated moderate enhancement in the permeation and drug load in the nail plate, compared to the control formulation. However, the effect of low molecular weight PEGs was predominant during iontophoresis process with greater amount of terbinafine being permeated (≈35 µg/cm2) and loaded into the nail plate (≈2.7 µg/mg). However, little or no effect on drug delivery was observed with high molecular weight PEGs (1000- 3350 MW) in passive and iontophoresis processes. Release of drug from the nail plates loaded by iontophoresis using low molecular weight PEG (400 MW) exhibited sustain effect which continued over a period of 72 days. The enhancement in drug permeation by low molecular weight PEGs is likely due to their ability to lead to greater water uptake and swelling of nail. This study concluded that the low molecular weight PEGs are indeed a promising trans-ungual permeation enhancer.

An inert hydrophobic buoyant coated-core was developed as floating drug delivery system (FDDS) for sustained release of cisapride using direct compression technology. Core contained low density, porous ethyl cellulose, which was coated with an impermeable, insoluble hydrophobic coating polymer such as rosin. It was further seal coated with low viscosity hydroxypropyl methyl cellulose (HPMC E15) to minimize moisture permeation and better adhesion with an outer drug layer. It was found that stable buoyant core was sufficient to float the tablet more than 8 h without the aid of sodium bicarbonate and citric acid. Sustained release of cisapride was achieved with HPMC K4M in the outer drug layer. The floating lag time required for these novel FDDS was found to be zero, however it is likely that the porosity or density of the core is critical for floatability of these tablets. The in vitro release pattern of these tablets in simulated gastric fluid showed the constant and controlled release for prolonged time. It can be concluded that the hydrophobic coated buoyant core could be used as FDDS for gastroretentive delivery system of cisapride or other suitable drugs.