Development of valsartan-loaded gelatin microcapsule without crystal change using hydroxypropylmethylcellulose as a stabilizer

Abstract

To develop a valsartan-loaded gelatin microcapsule using hydroxypropylmethylcellulose (HPMC) as a stabilizer, which could improve the physical stability and bioavailability of valsartan, the gelatin microcapsules were prepared with various ratios of gelatin and HPMC using a spray-drying technique. Their solubility, dissolution, thermal characteristics, crystallinity, and physical stability were investigated. The bioavailability of drug in valsartan-loaded microcapsule was then evaluated compared to drug powder and commercial product in rats. The microcapsule with gelatin and/or HPMC enhanced the solubility and dissolution of drug compared to valsartan powder. Among the formulations tested, the valsartan-loaded gelatin microcapsule at the weight ratio of valsartan/gelatin/HPMC of 1/2/1 gave excellent drug solubility of approximately 2 microg/ml and dissolution of 70% at 1 h. The crystal state of valsartan in this microcapsule was changed from crystalline to amorphous form during the spray-drying process and maintained as an amorphous form at 40 degrees C for at least 3 months, indicating that it was physically stable. HPMC in this microcapsule could inhibit the recrystallization, resulting in stabilizing the amorphous form of valsartan. Furthermore, it improved the oral bioavailability of valsartan compared to valsartan powder and gave the similar AUC, C(max), and T(max) values to commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, the gelatin microcapsule with HPMC would be a more effective and stable oral delivery system of poorly water-soluble valsartan.

Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan

“…To solve these drawbacks, several oral formulations have been developed for VST delivery. 14 – 16 Although SD formulations using VST have already been reported, 17 the application of HME technique to their preparation has not been investigated.…”

A Comparison between Use of Spray and Freeze Drying Techniques for Preparation of Solid Self-Microemulsifying Formulation of Valsartan andIn VitroandIn VivoEvaluation

“…The drug in plasma samples was quantified by HPLC methods as reported by Li et al [37]. Plasma (200  μ L) was mixed with 300  μ L of methanol.…”

Excipients That Facilitate Amorphous Drug Stabilization

“…No crystal growth was observed even after a period of 3 months storage at 40 °C, and the oral bioavailability of the water insoluble valsartan had been enhanced in rats (Li et al 2010). In another study by Deng et al (2013) among various polymers tested PVP 17PF and amino methacrylate copolymer Eudragit ® EPO exhibited a significant inhibitory effect on fenofibrate recrystallization in the hot-melt extrudates (Deng et al 2013).…”