Glipizide matrix transdermal systems for diabetes mellitus: preparation, in vitro and preclinical studies.
The aim of the present investigation was to prepare glipizide matrix transdermal systems using the combinations of ethyl cellulose/polyvinylpyrrolidone and Eudragit RL-100/Eudragit RS-100. The systems were evaluated for various in vitro (drug content, drug permeation, scanning electron microscopy and drug-polymer interactions) and in vivo (acute and long-term hypoglycemic activity, biochemical and histopathological studies, skin irritation and pharmacokinetic studies in mice) parameters. Drug content of the patches was found to be more than 98%. Variations in drug permeation profiles were observed among various formulations. The scanning electron microscopy of the patches showed the formation of pores on the surface after in vitro permeation studies. The drug-polymer interaction results suggested no interaction between drug and polymers. The in vivo results revealed that the patches successfully prevented the severe hypoglycemia in the initial hours and they were also effective on chronic application. The transdermal route exhibited negligible skin irritation and produced better improvement with all the tested in vivo parameters compared to oral administration.
Mutalik
Srinivas
S
Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal-576 104, Karnataka, India. srinivas.mutalik@manipal.edu <srinivas.mutalik@manipal.edu>
Udupa
Nayanabhirama
N
Kumar
Sharath
S
Agarwal
Sunil
S
Subramanian
Ganesh
G
Ranjith
Averineni K
AK
D000180:Acrylic Resins / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000473:pathology; D016503:Drug Delivery Systems; D005913:Glipizide / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D008099:Liver / Q000473:pathology; D008112:Liver Glycogen / Q000032:analysis; D051379:Mice; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D011205:Povidone / Q000031:analogs & derivatives / Q000737:chemistry; D012867:Skin / Q000648:ultrastructure
D000180:Acrylic Resins; D007004:Hypoglycemic Agents; D008112:Liver Glycogen; C077842:polyvinylpolypyrrolidone; C050528:Eudragit RS; C013517:ethyl cellulose; D002482:Cellulose; D011205:Povidone; D005913:Glipizide