Preparation, Characterization and Transdermal Permeation of Losartan-Amlodipine Molecular Salt

Abstract

Drug molecular salt composed of the antihypertensive compound losartan (LOS) as the anion and the antihypertensive drug amlodipine (AMLO) was prepared. The prepared salt (LOS-AMLO) was characterized by measurement of purity, water content, solubility, partition coefficient, and melting behavior in addition to common spectroscopic techniques (UV, FTIR and NMR). NMR spectral shifts of particular protons of LOS in particular were quite useful in explaining the points of interaction and association between the two ionic species so that a 3D structure could be proposed. LOS-AMLO exhibited a significantly lower melting point than its parent compounds (65 oC) which places the salt within the ionic liquids category, in a broad sense of the definition. LOS-AMLO was found to have much lower solubility than LOS with a substantially higher apparent partition coefficient. The high partition coefficient together with lower melting temperature is favorable properties for the transdermal permeation of pharmaceuticals. However, diffusion studies through the human stratum corneum, from an aqueous solution based on propylene glycol revealed a vast decrease in the permeation of both drugs from the molecular (ionic liquid) salt form. Interestingly the experiment demonstrated that the salt structure might be maintained during permeation but with indications of strong chemical interaction between the salt and the constituents of the barrier.