title: Enteric microsphere formulations of papain for oral delivery.
abstract: Enteric microspheres formulations of papain were prepared by w/o/w emulsion solvent evaporation using hydroxypropyl methylcellulose phthalate (HPMCP), Eudragit L 100 and Eudragit S 100, to avoid gastric inactivation of papain. Smaller internal and external aqueous phase volume provided maximum encapsulation efficiency (74.49-79.76%), least particle size (52.4-60.2 µm) and 21-26% loss of enzyme activity. Release studies in 0.1 N HCl confirmed the gastro-resistance of formulations. The anionic microspheres, zeta potential between -18.21 and -20.06 mV, aggregated in 0.1 N HCl (i.e., gastric pH 1.2), due to protonation of carboxylic groups of enteric polymer and loss of surface charge with subsequent change in zeta potential. The aggregates being <500 µm size would not impede gastric emptying. However, at pH>5.0 (duodenal pH) the microspheres showed de-aggregation due to restoration of surface charge. HPMCP and Eudragit L 100 microspheres facilitated almost complete release of papain within an hour at pH 6.0 and 6.8, respectively while Eudragit S 100 microspheres released 84.56% papain at pH 7.4, following Higuchi kinetics. FTIR spectroscopy revealed entrapment of enzyme; PXRD & DSC indicated amorphous character and SEM showed spherical shape of microspheres. In simulated gastro-intestinal pH condition, HPMCP, Eudragit L 100 and Eudragit S 100 microspheres showed good digestion of paneer and milk protein. Thus, enteric microspheres formulations could serve as potential carrier for oral enzyme delivery. Stability studies indicated the formulations with around 5% overage would ensure 2 years shelf life at room temperature.
authors.affiliation: Department of Pharmacy, Banasthali Vidhyapith, Banasthali, India.
authors.forename: Manu
authors.initials: M
authors.lastname: Sharma
authors.forename: Vinay
authors.initials: V
authors.lastname: Sharma
authors.forename: Amulya K
authors.initials: AK
authors.lastname: Panda
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Majumdar
mesh_terms: D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D004355:Drug Stability; D004655:Emulsions; D006863:Hydrogen-Ion Concentration; D008747:Methylcellulose / Q000031:analogs & derivatives; D008863:Microspheres; D010206:Papain; D010316:Particle Size; D011109:Polymethacrylic Acids; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water
chemical_list: D004655:Emulsions; D011109:Polymethacrylic Acids; D012997:Solvents; D014867:Water; C038300:methylmethacrylate-methacrylic acid copolymer; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate; D010206:Papain