The aim of this study was to prepare and evaluate a solid dosage form of insulin (INS) for oral administration capable to protect insulin from acid and enzymatic degradation in stomach. Insulin was formulated in granules by wet granulation method and microencapsulated with Eudragit L100, an entric coating polymer, using Wurster method. Sodium cholate (SC), aprotinin (AP) and carbopol 934 (CP) were also incorporated into granules as penetration enhancer, protease inhibitor and mucoadhesive respectively. INS content of microcapsules (MC) and the release rate of INS from MC were determined by radioimmunoassay (RIA). The effects of SC, AP and CP on the release of INS were also investigated. The results showed that the present method would be appropriate for preparation of small batches of MC to which active ingredient and excipeints could be easily incorporated. Secondly, formulation conditions could provide insulin stability in the stomach. Eudragit was found to be able to prevent release of insulin in artificial stomach medium. The formulation prepared by the aforementioned method released all its insulin content after 30 mins in a buffer with pH 7.4. It was also shown that CP could delay the release of insulin while AP and SC had no significant effect on the release of INS from coated granules.
Finally the formulation marked as ACSF which contained AP, CP and SC was chosen as the most appropriate formulation. It was found that ACSF was able to protect INS from degradation by the stomach medium and release more than 75% of its insulin content into small intestine where INS should be released and absorbed.