Transdermal drug delivery systems of a beta blocker: design, in vitro, and in vivo characterization.
The matrix type transdermal drug delivery systems (TDDS) of metoprolol were prepared by film casting technique using a fabricated stainless steel film casting apparatus and characterized in vitro by drug release, skin permeation, skin irritation, and in vivo pharmacodynamic and stability studies. Four formulations were prepared that differed in the ratio of matrix forming polymers. Formulations M-1, M-2, M-3, and M-4 were composed of Eudragit RL-100 and polyvinyl acetate with the following ratios: 2:8, 4:6, 6:4, and 8:2, respectively. All the four formulations carried 10% (w/w) of metoprolol tartrate, 5% (w/w) of dibutylphthalate, and 5% (w/w) of (+/-) menthol in dichloromethane:isopropyl alcohol (80:20 v/v). Cumulative amount of drug released in 48 hr from the four formulations was 79.16%, 81.17%, 85.98%, and 95.04%. The corresponding values for cumulative amount of drug permeated for the said formulations were 59.72%, 66.52%, 77.36%, and 90.38%. On the basis of in vitro drug release and skin permeation performance, formulation M-4 was found to be better than the other three formulations and it was selected as the optimized formulation. The formulation appeared to be stable when stored at 40 degrees C and 75% RH with negligible degradation of the drug. The TDDS was found to be free of any skin irritation as suggested by skin irritation score of 1.16 (<2.00) under Draize score test. Statistically significant reduction in mean blood pressure (p < .01) was achieved in methyl prednisolone-induced hypertensive rats on treatment with the TDDS.
Aqil
M
M
Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi, India. aqilmalik@yahoo.com
Sultana
Yasmin
Y
Ali
Asgar
A
Dubey
Kiran
K
Najmi
A K
AK
Pillai
K K
KK
D019840:2-Propanol / Q000737:chemistry / Q000493:pharmacokinetics; D000180:Acrylic Resins / Q000008:administration & dosage / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D003993:Dibutyl Phthalate / Q000737:chemistry / Q000493:pharmacokinetics; D004338:Drug Combinations; D004339:Drug Compounding / Q000379:methods; D016503:Drug Delivery Systems / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D004867:Equipment Design / Q000295:instrumentation; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy; D007279:Injections, Subcutaneous; D008297:Male; D008610:Menthol / Q000737:chemistry / Q000493:pharmacokinetics; D008752:Methylene Chloride / Q000737:chemistry / Q000493:pharmacokinetics; D008775:Methylprednisolone / Q000008:administration & dosage / Q000493:pharmacokinetics; D008790:Metoprolol / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology; D023422:Skin Irritancy Tests / Q000379:methods; D012995:Solubility
D000180:Acrylic Resins; D000319:Adrenergic beta-Antagonists; D004338:Drug Combinations; D008610:Menthol; D003993:Dibutyl Phthalate; C050528:Eudragit RS; D008752:Methylene Chloride; D008790:Metoprolol; D019840:2-Propanol; D008775:Methylprednisolone