ABSTRACT
Sulindac is a poorly soluble nonsteroidal anti-inflammatory drug associated with gastrointestinal intolerance as its serious side effect. This work investigated the ability of Eudragit Ll00-55 (Eud L100-55), Cellulose acetate phthalate (CAP) and β-cyclodextrin (β-CD) to ameliorate its gastric ulcers induced in rats. Binary solid dispersions (SD) using solvent evaporation method were fabricated for the drug with different drug to polymer weight ratios of 1:1, 1:2 and 1:3. SD and physical mixture were characterized through in vitro dissolution, infrared spectroscopy, differential scanning calorimetry, X-ray diffraction and scanning electron microscopy. The best enteric SD and SD using β-CD was tested in vivo for their ulcerogenic activity. Sulindac was highly dispersed inside CAP system that efficiently limited its release inside the stomach while no occurrence of any physicochemical interactions with the drug. β-CD improved the drug aqueous solubility, however it couldn’t protect against gastric ulcers induced by sulindac. SD using CAP as enteric polymer at a ratio of 1:2 significantly suppressed gastric ulceration. Direct exposure of sulindac to the stomach wall had the major contribution to its ulcerogenic activity rather than its poor gastric solubility. The gastrointestinal intolerance of sulindac could be addressed by avoiding its acute local contact with the ulcer-prone areas.
ABSTRACT
The aim of this work was to enhance dissolution rate and oral bioavailability of repaglinide. This was achieved by development of liquisolid tablet with the liquid component being self emulsifying drug delivery system (SEDDS). Thus SEDDS was prepared using oleic acid as oil and Tween 20 or its mixture with propylene glycol surfactant/cosurfactant system. Formulations containing different oil concentrations were loaded with various amounts of drug and subjected to in vitro evaluation. Optimum formulations were prepared and evaluated as liquisoild tablets. This involved administration to diabetic rats and monitoring blood glucose level. Incorporation of repaglinide in the SEDDS enhanced the dissolution rate of the drug irrespective to the fraction of molecularly dispersed drug, compared to unprocessed drug. Formulation of the optimum system as liquisolid tablet did not change the dissolution pattern of the SEDDS indicating that the drug exists in solution or partially dissolved form. The in vivo study revealed enhancement of the rate and extent of drug absorption after incorporation into the SEDDS, this was evidenced by the rapid onset of action and higher area above the blood glucose versus time curve compared to the unprocessed drug. Overall, the developed system was able to increase the bioavailability of repaglinide.
ABSTRACT
Nisoldipine is used for treatment of hypertension and angina pectoris. However, it suffers from very low bioavailability due to its extensive pre-systemic metabolism. This together with its low dose made it excellent candidate for transdermal delivery. Accordingly, the aim of this study was to develop and evaluate transdermal delivery system for optimization of nisoldipine skin permeability. Proniosomes comprising cholesterol and span 60 with different ratios together with ethanol and minimal water were evaluated for such aim. The developed formulations were assessed with respect to drug entrapment efficiency, viscosity, in vitro drug release and transdermal permeability. All proniosomal formulations have significantly enhanced transdermal delivery of nisoldipine compared with saturated aqueous solution of the drug. Increasing cholesterol content resulted in reduced drug flux. The study was extended to compare the efficacy of such proniosomes to the corresponding niosomes. Proniosomes significantly optimized transdermal delivery of nisoldipine compared to their hydrated form. Such results contradict the hypothesis which claimed the necessity for niosome formation from proniosomes for efficient transdermal delivery with penetration enhancement being mainly responsible for improved delivery.