A novel enteric positioning osmotic pump capsule-based controlled release system of sinomenine hydrochloride: In vitro and in vivo evaluation

Abstract

A novel enteric positioning osmotic pump capsule of sinomenine hydrochloride (SH) was developed to promote the efficacy of the drug by enteric positioning and zero-order release. The capsule shell was prepared by dipping method using cellulose acetate (CA) as a semipermeable membrane, containing hydroxypropyl methylcellulose phthalate HP50 (HPMCP-HP50) for enteric positioning, polyethylene glycol (PEG) 6000 for flexibility and permeability, then filled with SH, osmotic agents and permeation promoting polymer. In vitro effects of different formulation factors on the drug release was evaluated. The optimal formulation showed complete drug release with a zero-order kinetics. The dyeing test and osmotic pressure test demonstrated that drug release mechanism was regulated mainly by osmotic pressure. The in vivo test was performed in beagle dogs. Compared with commercially formulation, the developed formulation provided a prolonged Tmax and MRT and the plasma concentration was more stable. The results indicated that the novel enteric osmotic pump capsule successfully controlled the release of SH thereby drug plasma concentration. Consequently, the novel controlled delivery system with combination of enteric positioning and osmotic pump system is a promising strategy to avoid medication for stomach irritation and an effective way to reduce dosing frequency, minimize the drug fluctuation in plasma.