Pharmacological evaluation of membrane-moderated transdermal system of glipizide.
1. Membrane-moderated transdermal systems of glipizide were prepared using drug-containing carbopol gel (drug reservoir) and ethyl cellulose, as well as Eudragit RS-100, Eudragit RL-100 (Rohm Pharma, Darmstadt, Germany) and ethylene vinyl acetate (EVA; 2, 9 and 19% vinyl acetate content) rate-controlling membranes, and were subsequently evaluated in vitro (drug content and drug permeation studies) and in vivo (acute and long-term hypoglycaemic activity, effect on glucose tolerance, biochemical and histopathological studies, skin irritation test and pharmacokinetic studies in mice). 2. The drug content of the systems was found to be more than 99%. Variations in drug permeation patterns were observed among the formulations containing different rate-controlling membranes. 3. The system with the EVA (19% vinyl acetate) rate-controlling membrane was selected for in vivo experiments. This transdermal system produced better improvement with respect to hypoglycaemic activity, glucose tolerance and tested biochemical, histopathological and pharmacokinetic parameters all compared with oral administration and exhibited negligible skin irritation. 4. The transdermal system successfully prevented severe hypoglycaemia in the initial hours and it was also effective for chronic application.
Mutalik
Srinivas
S
Manipal College of Pharmaceutical Sciences, Manipal 576 104, Karnataka State, India. ssmutalik@yahoo.com
Udupa
Nayanabhirama
N
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D019540:Area Under Curve; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D005260:Female; D005913:Glipizide / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D005951:Glucose Tolerance Test; D005905:Glyburide / Q000008:administration & dosage / Q000493:pharmacokinetics; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011506:Proteins / Q000378:metabolism; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D012882:Skin Tests
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D011506:Proteins; D006003:Glycogen; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005905:Glyburide; D005913:Glipizide