Polymethyacrylate based microparticulates of insulin for oral delivery: Preparation and in vitro dissolution stability in the presence of enzyme inhibitors

The purpose of this investigation was to (a) evaluate the coprecipitation t echnique for preparing micro particulates of insulin, (b) study the effect of variables such as addition of salts in the precipitating medium and rati o of polymeric solution to volume of precipitating medium on the dissolutio n and encapsulation efficiency of insulin microparticulates, and (c) evalua te the in-vitro enzymatic dissolution stability of insulin microparticulate s in the presence of chicken ovomucoid (CkOVM) and duck ovomucoid (DkOVM) a s inhibitors, Insulin dissolved in 0.01 N HCl was mixed with alcohol USP to get a final concentration of 32% v/v. Eudragit L100, a representative poly methyacrylate polymer, was then dissolved in this solution which was transf erred to a beaker containing cold water with homogenization to obtain micro particulates. Dissolution studies were carried out in pH 6.8 phosphate buff er using a 100-ml conversion kit in a standard dissolution assembly. Dissol ution stability of microparticulates was evaluated in the presence of 0.5 m uM trypsin and 0.1 muM chymotrypsin at various ratios of CkOVM and DkOVM. T he results indicated that insulin microparticulates could be prepared using the coprecipitation technique with high encapsulation efficiency by proper selection of experimental conditions and amount of polymer. Presence of sa lts in the precipitating medium decreased the dissolution of insulin from t he microparticulates. As the ratio of precipitating medium with respect to the polymeric solution was increased, the encapsulation efficiency increase d. In dissolution stability experiments, insulin was not detected in the pr esence of enzymes alone. When CkOVM and DkOVM were incorporated, the stabil ity of insulin increased significantly in a concentration dependent fashion . (C) 2001 Elsevier Science BN. All rights reserved.