Abstract
The objective of the present study was to formulate insulin gel for intranasal administration and to evaluate with respect to in vitro release studies and hypoglycemic activity in animal model and healthy human volunteers. The insulin gel was formulated using the combination of carbopol and hydroxypropyl methylcellulose as gelling agent. The in vivo efficacy of insulin gel administered intranasally was assessed by measuring the blood glucose levels and serum insulin levels at specified time intervals in rats and humans. The use of bioadhesive nasal gel containing insulin not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity but also facilitated direct absorption of medicament through the nasal mucosa. Absorption of the drug through the nasal mucosa was high in the first 0.5 to 1.5 hours of the study with a sharp decline in blood sugar and rise in insulin values corresponding to that decline in blood sugar. This study further demonstrates that administration of insulin intranasally in gel form is a pleasant and painless alternative to injectable insulin.
KeyWords: nasal, diabetes mellitus, insulin, gel, carbopol, preclinical, clinical
Full Text
The Full Text of this article is available as a PDF (92.2 KB).
References
- 1.Pillai O, Panchagnula R. Insulin therapies—past, present and future. Drug Discov Today. 2001;6:1056–1061. doi: 10.1016/S1359-6446(01)01962-6. [DOI] [PubMed] [Google Scholar]
- 2.Davis SN, Granner DK. Insulin, oral hypoglycemic agents, and the pharmacotherapy of the endocrine pancreas. In: Hardman JG, Limbird LE, editors. The Pharmacological Basis of Therapeutics. 9th ed. New York, NY: McGraw-Hill; 1996. pp. 1487–1517. [Google Scholar]
- 3.Arunachalam S, Gunasekaran S. Diabetic research in India, and China today: from literature-based mapping to health-care policy. Curr Sci. 2002;9–10:1086–1097. [Google Scholar]
- 4.Ugwoke MI, Verbeke N, Kinget R. The biopharmaceutical aspects of nasal mucoadhesive drug delivery. J Pharm Pharmacol. 2001;53:3–22. doi: 10.1211/0022357011775145. [DOI] [PubMed] [Google Scholar]
- 5.Jiang G, Qiu W, DeLuca PP. Preparation and in vitro/in vivo evaluation of insulin-loaded poly(acryloyl-hydroxyethyl starch)-PLGA composite microspheres. Pharm Res. 2003;20:452–459. doi: 10.1023/A:1022668507748. [DOI] [PubMed] [Google Scholar]
- 6.Khan Ghilzai NM. New developments in insulin delivery. Drug Dev Ind Pharm. 2003;29:253–265. doi: 10.1081/DDC-120018199. [DOI] [PubMed] [Google Scholar]
- 7.Shahiwala A, Misra A. Pulmonary absorption of liposomal levonorgestrel. AAPS PharmSciTech. 2004;5:E13–E13. doi: 10.1208/pt050113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Sanna V, Kirschvink N, Gustin P, et al. Preparation and in vivo toxicity study of solid lipid microparticles as carrier for pulmonary administration. AAPS PharmSciTech. 2004;5:E27–E27. doi: 10.1208/pt050227. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Grover JK, Rathi SS, Vats V. Amelioration of experimental diabetic neuropathy and gastropathy in rats following oral administration of plant (Eugenia jambolana, Mucurna pruriens andTinospora cordifolia) extracts. Indian J Exp Biol. 2002;40:273–276. [PubMed] [Google Scholar]
- 10.Illum L, Davis SS. Microspheres for nasal administration. In: Duchene D, editor. Buccal and Nasal Administration as an Alternative for Parenteral Administration. Paris, France: Edition de Sante; 1992. pp. 125–137. [Google Scholar]
- 11.Moses AC, Gordon GS, Carey MC, Flier JS. Insulin administered as an insulin-bile salt aerosol: effectiveness and reproductibility in normal and diabetic subjects. Diabetes. 1983;32:1040–1047. doi: 10.2337/diabetes.32.11.1040. [DOI] [PubMed] [Google Scholar]
- 12.Gizurarson S. The relevance of nasal physiology to the design of drug absorption studies. Adv Drug Deliv Res. 1993;11:329–347. doi: 10.1016/0169-409X(93)90015-V. [DOI] [Google Scholar]
- 13.Singh S. Drug stability testing and shelf life determination according to international guidelines. Pharm Tech. 1999;7:69–79. [Google Scholar]