Development of enteric submicron particles formulation of alpha-amylase for oral delivery

作者：Sharma Manu; Sharma Vinay; Panda Amulya K; Majumdar Dipak K^*

来源：Pharmaceutical Development and Technology, 2013, 18(3): 560-569.

DOI：10.3109/10837450.2011.604782

• Enzyme
• HPMCP
• Eudragit L 100
• pH sensitive polymer
• zeta potential
• stability

Enteric submicron particles (SPs) formulations of alpha-amylase were prepared by w/o/w emulsion solvent evaporation using hydroxypropyl methylcellulose phthalate (HPMCP) and Eudragit L 100, to avoid gastric inactivation of alpha-amylase. Smaller internal and external aqueous phase volume provided maximum encapsulation efficiency (71.92-73.40%), least particle size (546.4-595.4 nm) and 23-26% loss of enzyme activity. Release studies in 0.1 N HCl confirmed the gastro-resistance of formulations. The anionic SPs aggregated in 0.1 N HCl (i.e. gastric pH 1.2), due to protonation of carboxylic groups of enteric polymer. The aggregates being <500 mu m size would not impede gastric emptying. However, at pH >5.0 (duodenal pH), SPs showed de-aggregation due to restoration of surface charge. HPMCP and Eudragit L 100 SPs facilitated almost complete release of alpha-amylase within 30 min at pH 6.0 and 6.8, respectively, following Higuchi kinetics. PXRD and DSC indicated amorphous character and scanning electron microscope showed spherical shape of SPs. In simulated gastro-intestinal pH condition, HPMCP and Eudragit L 100 SPs showed good digestion of cooked rice and could serve as potential carrier for oral enzyme delivery. Stability studies indicated the formulations as quite stable to ensure 2 years shelf life at room temperature.

• 出版日期2013-6