Transdermal therapeutic system of enalapril maleate using piperidine as penetration enhancer.
The aim of this work was to formulate transdermal therapeutic system (TTS) of an antihypertensive drug, enalapril maleate (EM) using a new penetration enhancer, piperidine hydrochloride (PH), belonging to the class of Dihydropyridines. The TTS of EM was prepared by solvent evaporation technique using polymers Eudragit E100 and polyvinyl pyrrolidone K-30 in varying ratios, 5% w/w dibutylphthalate as plasticizer and 10% w/w PH as penetration enhancer. The TTS was evaluated for in-vitro drug release using paddle over disc method and ex-vivo skin permeation using modified Keshary and Chein diffusion cell. The interaction studies were carried out by comparing the results of assay, UV and TLC analysis for pure drug and medicated and TTS formulation. Skin irritation potential of TTS was assessed by visual examination of treated rat skin. Stability studies were conducted according to ICH guidelines at a temperature of 40+/-0.5 degrees C and 75+/-5% RH. The optimized formulation was evaluated for preclinical bioavailability and antihypertensive efficacy using albino rat model. The optimized formulation provided 87.3% drug release in-vitro and a flux of 380 microg/cm(2)/hr over a period of 48 hours. No chemical interaction was found between the drug and excipients and there were no signs of skin irritation on application of patch. The optimized formulation was stable with a tentative shelf life of two years. Significant fall in BP (p<0.001) was observed in experimental hypertensive rats which was maintained for 2 days. There was 3 fold improvement in bioavailability with TTS vis-à-vis marketed tablet (AUC(0 to t) : 1253.9 ng.h/ml vs. 422.88 ng.h/ml). These preclinicial studies indicate the feasibility of matrix-type TTS of EM for 2 day management of hypertension. Further studies on human beings are warranted to establish clinical utility of the above TTS.
Aqil
M
M
Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi, India. aqilmalik@yahoo.com
Bhavna
Chowdhary
I
I
Sultana
Y
Y
Talegaonkar
S
S
Ahmad
F J
FJ
Ali
M M
MM
D000179:Acrylates / Q000737:chemistry; D000279:Administration, Cutaneous; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001682:Biological Availability; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004355:Drug Stability; D004356:Drug Storage; D004656:Enalapril / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D005079:Excipients / Q000737:chemistry*; D005260:Female; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D010539:Permeability; D010880:Piperidines / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry; D051381:Rats; D012869:Skin Absorption
D000179:Acrylates; D000959:Antihypertensive Agents; C477020:Eudragit E100; D005079:Excipients; D010880:Piperidines; D011108:Polymers; C032727:piperidine; D004656:Enalapril; D011205:Povidone