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The study aims to develop and optimize extended-release cinitapride matrix pellets using lipid wax glyceryl monostearate (GMS) and ethyl cellulose (EC) for treating functional dyspepsia and gastrointestinal reflux disease. Pellets were prepared using the extrusion spheronization technique by applying central composite design (CCD), keeping EC-7cps (matrix former), spheronization speed, and time as variables. The drug release, sphericity, and aspect ratio were quality parameters. The predicted optimized formulation was evaluated for chemical interaction, thermal stability, accelerated stability, and surface morphology. EC effectively controlled the overall Cinitapride release for up to 12 h, but burst release was reduced by sintering the matrix pellets. A direct relationship was observed between the sphericity and aspect ratio of the pellets with the spheronization speed and time. F pred followed the Korsmeyer-Peppas model, demonstrating a non-fickian diffusion at all pH levels. The bioavailability of F pred was compared with reference immediate release tablet by applying in silico PBPK modeling and comparable relative bioavailability. The PBPK predicted C max , T max , AUC 0-t , and AUC 0-∞ was 361.93 pg/ml, 6.88 h, 4567.8 pg/ml/h, and 5204.7 pg/ml/h, respectively. Lipid-cellulose-based extended-release Cinitapride matrix pellets were successfully prepared and can be effectively used as a single dose regimen for treating functional dyspepsia and gastrointestinal reflux disease., Competing Interests: Declaration of competing interest 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., (Copyright © 2025. Published by Elsevier B.V.)

Deferasirox (DFS) is an oral iron chelator that is employed in retinal ailments as a neuroprotectant against retinal injury and thus has utility in treating disorders such as excitoneurotoxicity and age-related macular degeneration (AMD). However, the conventional oral route of administration can present several disadvantages, e.g., the need for more frequent dosing and the first-pass effect. Microneedles (MNs) are minimally invasive systems that can be employed for intrascleral drug delivery without pain and can advantageously replace intravitreal injections therapy (IVT) as well as conventional oral routes of delivery for DFS. In this study, DFS was formulated into a nanosuspension (NS) through wet media milling employing PVA as a stabilizer, which was successfully loaded into polymeric dissolving MNs. DFS exhibited a 4-fold increase in solubility in DFS-NS compared to that of pure DFS. Moreover, the DFS-NSs exhibited excellent short-term stability and enhanced thermal stability, as confirmed through thermogravimetric analysis (TGA) studies. The mechanical characterization of the DFS-NS loaded ocular microneedles (DFS-NS-OcMNs), revealed that the system was sufficiently strong for effective scleral penetration. Optical coherence tomography (OCT) images confirmed the insertion of 81.23 ± 7.35 % of the total height of the MN arrays into full-thickness porcine sclera. Scleral deposition studies revealed 64 % drug deposition after just 5 min of insertion from DFS-NS-loaded ocular microneedles (OcMNs), which was almost 5 times greater than the deposition from pure DFS-OcMNs. Furthermore, both DFS and DFS-NS-OcMN exhibited remarkable cell viability when evaluated on human retinal pigment (ARPE) cells, suggesting their safety and appropriateness for use in the human eye. Therefore, loading DFS-NS into novel MN devices is a promising technique for effectively delivering DFS to the posterior segment of the eye in a minimally invasive manner., Competing Interests: Declaration of competing interest 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., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Microneedles are minimally invasive systems that can deliver drugs intradermally without pain and bleeding and can advantageously replace the hypodermal needles and oral routes of delivery. Deferasirox (DFS) is an iron chelator employed in several ailments where iron overload plays an important role in disease manifestation. In this study, DFS was formulated into a nanosuspension (NSs) through wet media milling employing PVA as a stabilizer and successfully loaded in polymeric dissolving microneedles (DMNs). The release studies for DFS-NS clearly showed a threefold increased dissolution rate compared to pure DFS. The mechanical characterization of DFS-NS-DMNs revealed that the system was sufficiently strong for efficacious skin penetration. Optical coherence tomography images confirmed an insertion of up to 378 µm into full-thickness porcine skin layers. The skin deposition studies showed 60% drug deposition from NS-DMN, which was much higher than from the DFS-NS transdermal patch (DFS-NS-TP) (without needles) or pure DFS-DMNs. Moreover, DFS-NS without DMNs did not deposit well inside the skin, indicating that DMNs played an important role in effectively delivering drugs inside the skin. Therefore, it is evident from the findings that loading DFS-NS into novel DMN devices can effectively deliver DFS transdermally.

The development of dissolving microneedles (DMN) is one of the advanced technologies in transdermal drug delivery systems, which precisely deliver the drugs through a rapid dissolution of polymers after insertion into the skin. In this study, we fabricated nanoemulsion-loaded dissolving microneedle (DMN) arrays for intradermal and transdermal drug delivery. For this task, model drug (amphotericin B, AmB)-loaded nanoemulsion (NE) were prepared by the probe-sonication method. AmB-loaded-NE was prepared using Capmul MCM C-8 EP/NF, Tween ® 80, poly(vinyl alcohol) (PVA-10 kDa), and poly (vinyl pyrrolidone) (PVP-360 kDa or K29/32) by using SpeedMixer™, followed by probe-sonication and evaluated for particle size and polydispersity index (PDI). Transmission electron microscopy (TEM) was also used to assess the particle size before and after DMN casting. AmB-NE embedded DMN arrays were found to be strong enough, revealed efficient skin insertion, and penetrated down to the fourth layer (depth ≈ 508 μm) of Parafilm M ® (validated skin model). Ex vivo skin deposition experiments in full-thickness neonatal porcine demonstrated that after 24 h, AmB-NE-DMN arrays were able to deposit 111.05 ± 48.4 µg/patch AmB into the skin. At the same time, transdermal porcine skin permeation studies showed significantly higher permeability of AmB (29.60 ± 8.23 μg/patch) from AmB-NE-DMN compared to MN-free AmB-NE patches (5.0 ± 6.15 μg/patch) over 24 h. Antifungal studies of optimized AmB-NE-DMN, AmB-loaded discs and drug-free DMN against Candida albicans, confirmed the synergistic activity of Campul-MCM C-8, used in the nanoemulsion formulation. This study establishes that nanoemulsion based dissolving microneedle may serve as an efficient system for intradermal as well as transdermal drug delivery., (© 2021. The Author(s).)

Daclatasvir dihydrochloride is an antiviral drug used in the treatment of Hepatitis C and for its estimation in drug product, no Pharmacopeial method is available. Therefore, a simple, rapid, precise and accurate isocratic RP-HPLC method was developed and validated for quantification of daclatasvir dihydrochloride in pharmaceutical dosage form. The quantification was carried out using Hypersil ODS - C18 Column (250mm, 4.6mm, 5μm), Shimadzu LC-2030 Prominence-I Series. The mobile phase composed of phosphate buffer (pH 3.5, adjusted with ortho phosphoric acid) and acetonitrile (60:40 v/v). The flow rate was 1.0ml/min with UV detection at 308 nm. The validation of developed method was conducted for specificity, linearity, accuracy, precision, LOD and LOQ. A linearity was established in the concentration range of 0.5-150% with coefficient of correlation 0.9993. The limit of detection (LOD) was 0.005μg/ml and the limit of quantification (LOQ) was 0.01μg/ml. The method was successfully applied to the assay and in-vitro dissolution studies of daclatasvir dihydrochloride in tablet dosage form. It can be concluded that this method can be very helpful in the quality control estimation of daclatasvir dihydrochloride in different pharmaceutical products intended for hepatitis C infections.

This study is based on the QbD development of extended-release (ER) extruded-spheronized pellets of Meclizine HCl and its comparative pharmacokinetic evaluation with immediate-release (IR) pellets. HPLC-fluorescence method was developed and validated for plasma drug analysis. IR drug cores were prepared from lactose, MCC, and PVP using water as granulating fluid. Three-level, three-factor CCRD was applied for modeling and optimization to study the influence of Eudragit (RL100-RS100), TEC, and talc on drug release and sphericity of coated pellets. HPLC-fluorescence method was sensitive with LLOQ 1 ng/ml and linearity between 10 and 200 ng/ml with R 2  > 0.999. Pharmacokinetic parameters were obtained by non-compartmental analysis and results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with a 90% CI limit of 0.8-1.25. The AUC 0-t and AUC 0-∞ of ER pellets were not significantly different with geometric mean ratio 1.0096 and 1.0093, respectively. The C max of IR pellets (98.051 ng/ml) was higher than the ER pellets (84.052 ng/ml) and the T max of ER pellets (5.116 h) was higher than the IR pellets (3.029 h). No significant food effect was observed on key pharmacokinetic parameters of ER pellets. Eudragit RL100 (6%) coated Meclizine HCl pellets have a potential therapeutic effect for an extended time period.

To evaluate and compare the pharmacokinetic (PK) characteristics of a newly developed oral osmotically controlled drug delivery system of Eperisone 150 mg tablets with Eperisone immediate release (IR) marketed tablet brand as a reference formulation. It was a single dose, two treatment, two sequence, randomized, crossover study, involving 12 healthy human subjects. A modified, sensitive LC-ESI-MS/MS method was developed and validated as per FDA guidelines for estimation of Eperisone in plasma using a simple extraction and quick protein precipitation method. Non-compartmental pharmacokinetic model was used for PK analysis. Results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25. The bio-analytical method used for estimating drug plasma concentration was found to be simple, selective, linear, accurate and precise with 0.01 ng/ml as limit of detection. The comparative PK analysis revealed an insignificant difference in AUC 0-∞, AUC 0-t, V z /F, Cl/F and t 1/2λz , whereas a significant difference in C max , T max and MTTs were found. The relative bioavailability of Eperisone osmotic tablet was 109.7%. The osmotic controlled release drug formulation was found to release Eperisone for an extended period with less inter individual fluctuation in pharmacokinetic variables.

Objective: In this study, pharmacokinetics (PKs) and bioavailability of newly developed extended release (ER) Itopride HCl 150 mg encapsulated ER pellets (test) and 150 mg Ganaton ER once-daily (OD) tablets (reference) were compared and evaluated under fasted and fed conditions., Methods: Twelve healthy human subjects were enrolled in a single dose, randomized; two treatments, two sequences, four period crossover study. A modified and validated liquid chromatographic method was used for the estimation of Itopride HCl in plasma samples. The data were analyzed through non-compartmental model using PK software Phoenix Winnonlin version 7. The outcome was measured on logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25., Results: The C max , AUC 0- t , and AUC 0-∞ values of Itopride HCl 150 mg ER pellets versus that of OD 150 mg tablets, in fed and fasted states, were within the limits specified by FDA to establish bioequivalence. The relative bioavailability of Itopride HCl 150 mg ER pellets were 1.019 (fed) and 1.081(fasted). The 90% CIs of AUC values for Itopride HCl 150 mg ER pellets and OD 150 mg tablets in fed versus fast were significantly greater and were not within 80-125% limit., Conclusion: The test and reference formulations had similar pharmacokinetic parameters in each condition studied. However, an increase in the amount of drug was observed in the fed state.

The objective of study was to develop Aceclofenac fast dispersible compacted pellets with improved taste and fast drug release. Pellets were prepared by extrusion spheronization technique followed by direct compression to make compacted pellets. Formulations were comprised of sucrose, mannitol, ac-di-sol, aspartame, pine apple flavor and magnesium stearate. A mixture of distilled water and isopropyl alcohol (1:1) was used for wet massing. The effect of ac-di-sol on the drug release pattern was examined and dissolution profile comparison was established. All formulations followed First order and Weibull models and f2 values indicated dissimilarity with the marketed immediate release product. Taste of compacted pellets was evaluated by a panel of 12 human volunteers. Formulation P5 was found to be an optimized formulation due to satisfactory quality attributes.

Background: Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated., Methods: Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found., Results: Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R  = 0.891-0.997), Precirol ® (e R  = 0.611-0.743), Compritol ® (e R  = 0.665-0.729) and Carnauba wax (e R  = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2  = 0.978-0.993) indicated non-Fickian diffusion (n = 0.519-0.597). Combinations of (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax pellets followed Zero-order (R 2  = 0.991-0.995). Similarity test was performed using combination of Geleol ® and Compritol ® (i) as a reference., Conclusions: Matrices for the extended release of Meclizine HCl from extruded-spheronized pellets were successfully formed by using three lipids (Geleol ® , Compritol ® and Carnauba wax) in different combinations. The encapsulated pellets of Meclizine HCl can be effectively used for treatment of motion sickness, nausea and vertigo for extended period of time.

A high-pressure liquid chromatography (HPLC-UV) based simple and specific method for simultaneous quantitative determination of aspirin, amlodipine besylate and simvastatin in a capsule formulation has been developed and validated according to ICH guidelines. Chromatographic separation of the three drugs was carried out by aSpherisorbODS2 reverse phase column (4.6 x 250 mm; 5 μm) using amobile phase, which consisted of 70: 30 (v/v) mixture of acetonitrile and triethylamine phosphate buffer (pH 3; 0.015 M) with final pH adjusted to 2.5 using dilute ortho-phosphoric acid, at a flow rate of 1mL/min. The eluents were detected at UV wavelength of 237 nm and the retention times for aspirin, amlodipine besylate and simvastatin were ~2.7 mins, ~6.1 mins and ~10.5mins, respectively. This method is suitable and specific for the three drugs and was found to be linear (R2>0.995), accurate, specific, reproducible and robust in the concentration range of 375 to 1125mcg/ml for aspirin, 25 to 75mcg/ml for amlodipine besylate and 50 to 150mcg/ml for simvastatin. This simple and convenient method could be easily utilized for the characterization and quantitation of the three drugs in a single formulation for combination therapy of cardiovascular diseases.

The aim of this study is to evaluate the susceptibility and resistance pattern of clinical isolates causing different types of infections and to compare the efficacy of antibiotics namely levofloxacin and cefepime. The in-vitro antibacterial activity and resistance patterns of these two well known antibiotics were studied and compared using disk diffusion method. For this, one hundred clinical isolates comprising of Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa were collected from different local pathological laboratories and hospitals. Escherichia coli (17.95% against cefepime and 30.77% against levofloxacin), Staphylococcus aureus (30% against cefepime and 46.66% against levofloxacin) and Pseudomonas aeruginosa (23.53% against cefepime and 35.29% against levofloxacin) were found resistant against the studied antibiotics which show that cefepime is more effective than levofloxacin. In case of Klebsiella pneumoniae, resistance was 42.85% against cefepime and 35.71% against levofloxacin thereby showing that levofloxacin is more effective than cefepime. Concluded that the clinical isolates collected were susceptible to both the antibiotics but the microbial resistance against these antibiotics is increasing in our population which is alarming. Therefore, it is recommended the physicians may prescribe these antibiotics unless no other substitute is available in clinical practice.