Fabrication and evaluation of polymeric films for transdermal delivery of pinacidil.
The objective of the present work was to fabricate Eudragit RL 100-polyvinyl acetate films and evaluate their potential for transdermal drug delivery in a quest to develop a suitable transdermal therapeutic system for pinacidil. The polymeric films (composed of Eudragit RL100 and polyvinyl acetate in 2:8, 4:6, 6:4, 8:2 ratios in films P-1, P-2, P-3, P-4 respectively, together with 5% w/w of pinacidil and 5% w/w of dibutylphthalate in all the films) were cast on a glass substrate and evaluated for physicochemical parameters viz. thickness, weight, folding endurance (a measure of fragility), percent elongation at break (a measure of flexibility), drug content uniformity, water absorption capacity, moisture vapour transmission, drug-polymer interaction, in vitro drug release and skin permeation profiles. The films were also evaluated for appearance, smoothness and transparency. The film finally selected was assessed for its skin irritation potential, and its stability on storage under accelerated temperature and humidity conditions. The values of thickness, weight, folding endurance, percent elongation at break, percentage water absorbed, moisture vapour transmission, cumulative amount of drug released and permeated for different films were in the following order: P-1 < P-2 < P-3 < P-4. The results suggest that Eudragit RL 100, a freely permeable polymer, has a major influence on the physicochemical profile of the films. The higher the quantity of Eudragit RL100 in the film, the better its strength and flexibility as well as its higher drug release and skin permeation potential. The final optimized film (with a composition of Eudragit RL 100: polyvinyl acetate: pinacidil monohydrate: dibutylphthalate in 8.0:2.0:0.5:0.5 ratio) was found to be the best in terms of drug release (cumulative amount of drug released in 48 h was 96.09%) and skin permeation (permeability coefficient, 0.0164 cm/h). There was no apparent drug-polymer interaction in the films. The optimized film was seemingly free of potentially hazardous skin irritation. The film was found to be stable and intact at ambient temperature and humidity conditions. The films hold promise for the development of a matrix type transdermal therapeutic system for pinacidil.
Aqil
M
M
Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi, India. aqilmalik@yahoo.com
Ali
A
A
Sultana
Y
Y
Najmi
A K
AK
D000042:Absorption; D000279:Administration, Cutaneous; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D002855:Chromatography, Thin Layer; D016503:Drug Delivery Systems; D004355:Drug Stability; D004356:Drug Storage; D004487:Edema / Q000139:chemically induced / Q000473:pathology; D004890:Erythema / Q000139:chemically induced / Q000473:pathology; D005557:Formaldehyde; D066298:In Vitro Techniques; D007509:Irritants; D020110:Pinacidil / Q000008:administration & dosage* / Q000009:adverse effects; D010968:Plasticizers; D011108:Polymers; D011145:Polyvinyls; D011817:Rabbits; D051381:Rats
D000959:Antihypertensive Agents; D007509:Irritants; D010968:Plasticizers; D011108:Polymers; D011145:Polyvinyls; D005557:Formaldehyde; C013215:polyvinyl acetate; D020110:Pinacidil