Abstract
The present study was an attempt to develop a powder dosage form of insulin for nasal mucosal administration, and to investigate the effect of various excipients on the bioauail-ability of insulin in powder form in comparison with liquid dosage forms. The absorption of insulin in dogs in powder form was better than that in liquid form. The preparations were administered to the nasal cavity of beagle dogs, and the changes in plasma glucose level and in plasma immunoreactive insulin were determined. An effect of solution pH on the absorption of insulin in the powder form was not clear in this study. Different types of enhancement and time curves for absorption were observed with several excipients such as lactose, crystalline cellulose (MCC), hydroxypropyl cetlulose-H (HPQ and neutralized Carbopol 934 (CP-Na), which were added to freeze-dried insulin powder. The absorption of insulin from nasal mucosa was fastest in the preparation with MCC, and was sustained in the preparation with CP-Na. In addition, it was found that a high enhancement of absorption was brought about by the new powder dosage form when that consisted of insulin and Carbopol 934 (CP) freeze-dried together. This final powder dosage form successfully produced hypoglycemia of one-third the extent of that reached by intravenous injection, assuming that the same dose of insulin was administered.
Published Version
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