Development and Evaluation of Olmesartan Medoxomil-Loaded Medicated Jellies Using Β-Cyclodextrin Inclusion Complexes for Pediatric Hypertension

Resumen

Background: Pediatric hypertension is a new global health challenge, and the prevalence of the condition is increasing with childhood obesity, with the prevalence of the condition ranging between 3-6% of children across the world. It predisposes to the adult cardiovascular disease, stroke and renal failure. Olmesartan medoxomil (OLM), a BCS Class II angiotensin II receptor blocker (ARB), has poor aqueous solubility (0.00742 mg/mL) and low oral bioavailability (26%), which limits its use in children due to its limitations in aqueous solubility, bitter taste, and swallowing difficulties. Methods: Physical mixing, kneading, solvent evaporation, spray drying and freeze-drying were used to prepare OLM-2 -cyclodextrin (BCD) and polyvinylpyrrolidone K30 (PVP K30) inclusion complexes at 1:1 and 1:2 drugs polymer ratios. The optimized complex (BCD 1:2, spray-dried) was added to medicated jellies by heat-congealing. The formulations (J1-J10) were different concentrations of gelatin (8-14% w/w) and sugar syrup (40-70% w/w) and were optimized by central composite design (CCD) using viscosity and drug release (percent drug released at 60 minutes) as responses. Physicochemical analyses involved pH, viscosity, syneresis, FTIR, DSC, SEM and in vitro dissolution in pH 6.8 phosphate buffer (USP Type II). Results: BCD 1:2 complex was most easily dissolved (93.27% at 60 min) when spray-dried. Optimized jelly J8 (8% gelatin, 70% sugar syrup) exhibited pH 7.10, viscosity 10,500 cPs, uniform weight (5.01±0.11 g), no syneresis, and 96.36% DR at 60 min, surpassing marketed tablet (87.80%). FTIR/DSC compatibility and amorphization; SEM porous, spherical particles. Discussion: Interaction of BCD complexation by spray drying improved OLM solubility/dissolution by amorphizing and increasing the surface area. J8 jelly, optimized to address CCD challenges, such as poor solubility, taste, swallowability, and so on, was developed to meet the needs of the pediatric population, offering a stable, palatable dosage form that is more effective than tablets in the antihypertensive treatment of the pediatric population.