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INTRODUCTION: Chronic kidney disease (CKD) is becoming increasingly prevalent worldwide, particularly among the elderly, along with an increase in the incidence of hypertension and cardiovascular disorders. Developing lipid-based oral dosage forms with a higher expected bioavailability of antihypertensive drugs with nephroprotective effects poses a challenge. Lercanidipine hydrochloride (LRCH) is a newer type of third-generation dihydropyridine calcium channel blocker that functions as an antihypertensive and has significant nephroprotective effects. Due to its extensive first-pass metabolism, its bioavailability is about 10% and increases to 3-4 times when taken with a high-fat meal. Targeting this drug to the lymphatic system using the solid self-nano-emulsifying drug delivery system (SSNEDDS) is a promising approach for improving LRCH's bioavailability and dispersion rate. SSNEDDS combines the benefits of both liquid self-emulsifying and solid dosage forms, improving drug stability and extending storage time. MATERIALS AND METHODS: In this study, liquid SNEDDS composed of 10% peppermint oil, 67% Tween 20, and 22.5% propylene glycol was solidified using two adsorbent agent mixtures (SSNEDDS1: Avicel PH 101 and Aerosil 200) and (SSNEDDS2: Avicel PH 102 and Aerosil 200) separately. The prepared formulations were evaluated for powder flow, drug content, and an in-vitro dispersion test in comparison to the brand-marketed tablet as a standard or pure drug. DSC and X-ray diffraction analysis were also used. RESULTS: The SSNEDDS2 shows excellent flowability, a higher drug content (99.761%), and a significantly higher and faster dispersion rate of 100% within 10 minutes compared to 92% of the marketed LRCH tablet and 18.1% of the pure drug for 60 minutes. The solid-state characterization of the formulation composed of SSNEDDS2 confirmed that the LRCH was in an amorphous form inside the solidified nano system without interacting with the excipient. CONCLUSION: This study successfully prepared LRCH using the promising strategy of SSNEDDS as a hard gelatin capsule with a higher dispersion rate. It improved its stability and expected bioavailability compared to the brand-marketed tablet as the standard.

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Introduction The research aimed to develop a robust, high-performance liquid chromatography (HPLC) analytical method for the quantitative assessment of rebamipide encapsulated in ethosomes. Rebamipide, a quinolinone derivative, holds promise as a therapeutic agent for dry eye, but challenges such as low bioavailability and vision clouding post-installation have prompted innovative approaches. Encapsulation in ethosomes, lipid-based nanovesicles, offers a potential solution to enhance ocular bioavailability. Materials and methods The study focused on creating a specific, linear, accurate, precise, and robust HPLC method, addressing entrapment efficiency (%EE), drug content, and drug release of rebamipide in prepared ethosomes. Statistical validation followed International Conference of Harmonization (ICH) specifications. The method's parameters were evaluated within a concentration range of 4-24 µg/ml, with recovery rates indicating accuracy and low % relative standard deviation (RSD) values confirming precision. Limits of detection (LOD) and quantification (LOQ) for rebamipide were determined. Results After preparing the ethosome dosage form by film hydrating method for rebamipide, the rebamipide entrapment efficiency in ethosomes was established at 76% ± 7, while the drug content was found to be 93% ± 6. The drug release process demonstrated zero-order kinetics and five different models of kinetics were applied for a comprehensive analysis. The method exhibited excellent system suitability, specificity, and linearity. Recovery rates for rebamipide ranged from 90% to 100%, and repeatability was confirmed by low %RSD values. The LOD and LOQ for rebamipide were determined to be 1.04 µg/mL and 3.16 µg/mL, respectively. Conclusion The developed HPLC method proved suitable for the quantitative determination of rebamipide in ethosomes, offering rapid and accurate analysis. The results underscore the method's specificity, accuracy, and precision within the specified concentration range. Overall, the validated method contributes to the advancement of ocular drug delivery systems, providing a reliable analytical tool for pharmaceutical research.

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Nanoemulsions (NE) are isotropic, dispersions of oil, water, surfactant(s) and cosurfactant(s). A range of components (11 surfactants, nine cosurfactants, and five oils) were investigated as potential excipients for preparation of ketorolac tromethamine (KT) ocular nanoemulsion. Diol cosurfactants were investigated for the effect of their carbon chain length and dielectric constant (DEC), Log P, and HLB on saturation solubility of KT. Hen's Egg Test-ChorioAllantoic Membrane (HET-CAM) assay was used to evaluate conjunctival irritation of selected excipients. Of the investigated surfactants, Tween 60 achieved the highest KT solubility (9.89 ± 0.17 mg/mL), followed by Cremophor RH 40 (9.00 ± 0.21 mg/mL); amongst cosurfactants of interest ethylene glycol yielded the highest KT solubility (36.84 ± 0.40 mg/mL), followed by propylene glycol (26.23 ± 0.82 mg/mL). The solubility of KT in cosurfactants was affected by four molecular descriptors: carbon chain length, DEC, log P and HLB. KT solubility was directly proportional to DEC and the HLB yet, inversely proportional to carbon chain length and log P. All surfactants, except Labrasol ALF, were non-irritant. The majority of cosurfactants were slightly irritant, butylene glycol was a moderate irritant, pentylene and hexylene glycols were strong irritants. These findings will inform experiments aimed at developing NE formulations for ocular administration of KT.

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Diazepam is one of the most prescribed benzodiazepines. The purpose of the present research was to optimize the formulation of orodispersible tablets of diazepam. Orodispersible tablets of diazepam were prepared using different types of superdisintegrants (Ac-Di-Sol, sodium starch glycolate, and crospovidone (CP)) and different types of subliming agents (camphor and ammonium bicarbonate (AB)) at different concentrations and two methods of tablets preparations (wet granulation and direct compression methods). The formulations were evaluated for flow properties, wetting time, hardness, friability, content uniformity, in vivo disintegration time (DT), release profiles, and buccal absorption tests. All formulations showed satisfactory mechanical strength except formula F5 which contains camphor and formula F9 which is prepared by direct compression method. The results revealed that the tablets containing CP as a superdisintegrant have good dissolution profile with shortest DT. The optimized formula F7 is prepared using 10% CP as a superdisintegrant and 20% AB as a subliming agent by wet granulation method which shows the shortest DT and good dissolution profile with acceptable stability. This study helps in revealing the effect of formulation processing variables on tablet properties. It can be concluded that the orodispersible tablets of diazepam with better biopharmaceutical properties than conventional tablets could be obtained using formula F7.

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The aim of the present study was to enhance the dissolution rate of meloxicam (MLX), a practically water-insoluble drug by preparation of solid dispersion using a hydrophilic polymer, poloxamer 188 (PXM). The kneading technique was used to prepare solid dispersions. A 3(2) full factorial design approach was used for optimization wherein the drug, polymer ratio (X1), and the kneading time (X2) were selected as independent variables and the dissolution efficiency at 60 min (%DE60) and yield percent were selected as the dependent variable. Multiple linear regression analysis revealed that for obtaining higher dissolution of MLX from PXM solid dispersions, a high level of X1 and a high level of X2 were suitable. The use of a factorial design approach helped in optimization of the preparation and formulation of solid dispersion. The optimized formula was characterized by solubility studies, angle of repose, and contact angle; Fourier transform infrared spectroscopy, differential scanning calorimetry, x-ray diffraction studies, and scanning electron microscopy demonstrated that enhanced dissolution of MLX from solid dispersion might be due to a decrease in the crystallinity of MLX and PXM. Analysis of dissolution data of optimized formula indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics as Fickian diffusion. In conclusion, dissolution enhancement of MLX was obtained by preparing its solid dispersion with PXM using kneading technique.

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