Passive and iontophoretic permeation of glipizide gel: an in vitro and in vivo study.
The purpose of the present work was to formulate and evaluate skin permeability of a glipizide gel to assess its suitability for transdermal delivery. A polymer gel was prepared by soaking hydroxypropyl methyl cellulose (5 g) overnight in phosphate buffer: ethanol (50:50, v/v) and mixing it with separately prepared glipizide solution in the same vehicle to bring the concentration to 2 mg /ml. In vitro skin permeability was assessed in full thickness skin of rabbits and pigs. For in vivo studies New Zealand rabbits were used. In vitro passive permeation was carried out in Franz diffusion cell but for iontophoresis, diffusion cell was modified according to Glikfield design. Iontophoresis was performed at a current density of 0.5 mA/cm2 via silver/silver chloride electrodes with the passive controls but for in vivo study current density was reduced to 0.125 mA/cm2. Blood samples were analyzed for drug content by HPLC and blood sugar levels were also recorded periodically during in vivo permeation. Results of the in vitro study indicated that iontophoresis considerably increased the permeation rate of glipizide compared to passive controls in both the skin types (P<0.05). For in vivo studies current densities and drug concentration had to be lowered to 0.125 mA/cm2 as excessive permeation resulting in hypoglycemic shocks were noted when study was carried out at a current density of 0.5 mA/cm2. The low intensity current was well tolerated. The plasma concentration of glipizide was significantly higher (P<0.05) than that obtained in the passive controls. The study indicated even at very low current density, iontophoresis could enhance the permeation of glipizide significantly.
Ghosh
Bijaya
B
Department of Pharmaceutical Technology, K.L.E. Society's College of Pharmacy, Rajajinagar II Block, Bangalore, Karnataka-560010, India. bijayadd@yahoo.co.in
Jain
Ashish
A
Ashok
Purnima
P
Patel
Bhavik
B
Tarafdar
Kushal
K
D000279:Administration, Cutaneous; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002626:Chemistry, Pharmaceutical; D004058:Diffusion; D005260:Female; D005782:Gels; D005913:Glipizide / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D065347:Hypromellose Derivatives; D066298:In Vitro Techniques; D007478:Iontophoresis / Q000379:methods; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives; D010539:Permeability; D011817:Rabbits; D012867:Skin; D013552:Swine; D013997:Time Factors
D001786:Blood Glucose; D005782:Gels; D007004:Hypoglycemic Agents; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D005913:Glipizide