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Abstract:  Nisoldipine is used for the treatment of hypertension and angina pectoris. However, it has very low bioavailability, which is attributed to extensive pre-systemic metabolism. In addition, nisoldipine is highly potent (used at a low dose). Taking into consideration the fact that transdermal delivery avoids the pre-systemic metabolism and is only suitable for potent drugs, nisoldipine can be considered as an excellent candidate for transdermal delivery. Accordingly, the purpose of this study was to optimize nisoldipine transdermal delivery. That was achieved initially by investigating the effect of vehicles on skin penetration. The tested vehicles were ranked with respect to transdermal flux of nisoldipine as isopropyl myristate > oleic acid > propylene glycol > water > polyethylene glycol 400. A combination of oleic acid with propylene glycol was synergistic with a ratio of 1:2 w/w being the best. These results were taken further to develop microemulsion systems using either oleic acid or isopropyl myristate as the oil phase. Both cases employed polyoxyethylene sorbitan monooleate as a surfactant with propylene glycol being utilized as a cosurfactant in the case of oleic acid and ethanol in the case of isopropyl myristate. The developed microemulsions produced significant enhancement in nisoldipine transdermal delivery with the flux being even greater than that obtained from the corresponding pure vehicles. This achievement was recorded in optimum microemulsion formulations which contained a cosurfactant. The study provided stepwise optimization of a vehicle for transdermal delivery of nisoldipine.

Related Keywords: Gamal M. El Maghraby, PhD, Amal A. Ahmed, MS, Mohamed A. Osman, PhD, nisoldipine, second generation dihydropyridine calcium channel blocker, hypertension, antihypertensive, high blood pressure, angina pectoris, cardiac chest pain, transdermal delivery, pure vehicles, microemulsions, oleic acid, isopropyl myristate, polyoxyethylene sorbitan monooleate, surfactant, cosurfactant, skin permeation, permeability studies, transdermal penetration, binary vehicle mixtures, pseudoternary phase diagrams

Related Categories: EXCIPIENTS, PEER-REVIEWED, CARDIOLOGY, DOSAGE FORMS/DRUG CARRIERS

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