Design and evaluation of chitosan films for transdermal delivery of glimepiride.
Glimepiride is a third generation oral antidiabetic sulphonylurea drug frequently prescribed to patients of type 2 diabetes. However, its oral therapy is encountered with bioavailability problems due to its poor solubility leading to irreproducible clinical response, in addition to adverse effects like dizziness and gastric disturbances. As a potential for convenient, safe and effective antidiabetic therapy, the rationale of this study was to develop a transdermal delivery system for glimepiride. Chitosan polymer was utilized in developing transdermal films for glimepiride. Chitosan has film forming ability, bioadhesive and absorption enhancing properties. Aiming at optimizing the drug delivery and circumventing the skin barrier function, inclusion complexation of glimepiride with beta-cyclodextrin (beta-CyD) as well as the use of several conventional penetration enhancers were monitored for augmenting the drug flux. The physical and mechanical properties of the prepared films were investigated using tensile testing, IR spectroscopy and X-ray diffractometry. Release studies revealed adequate release rates from chitosan films. Permeation studies through full thickness rat abdominal skin were conducted. High flux values were obtained from films comprising a combination of the drug with limonene and ethanol as well as from films containing glimepiride-beta-CyD complex. In vivo studies on diabetic rats for selected formulae revealed a marked therapeutic efficacy sustained for about 48 hours. The above-mentioned results shed light on feasibility of utilizing chitosan as an effective, safe transdermal delivery system for glimepiride characterized by increased patient compliance and better control of the disease.
Department of Pharmaceutical Technology, National Research Centre, Cairo, Egypt. husseinammar@hotmail.com
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Ammar
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Salama
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El-Nahhas
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Elmotasem
D000279:Administration, Cutaneous; D000818:Animals; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000378:metabolism*; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013453:Sulfonylurea Compounds / Q000008:administration & dosage* / Q000737:chemistry; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000008:administration & dosage
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D047392:beta-Cyclodextrins; C057619:glimepiride; D048271:Chitosan; C031215:betadex