Preparation and Physicochemical Characterization of Atorvastatin Choline Salt and its Potential for Transdermal Permeation

Ruba T. Tarawneh, Randa SH. Mansour, Dina El-Sabawi, Imad I Hamdan

Abstract


Atorvastatin calcium (ATV) is an anti-hyperlipidemic agent with poor bioavailability. Several approaches were reported to improve the solubility of ATV. In this study ATV was prepared as a choline salt (ATV-C) and a complex of the prepared salt with hydroxy-propyl-beta-cyclodextrin (HPβCD) (ATV-C-CD) hoping to enhance ATV solubility, decrease the partition coefficient and improve its transdermal permeability. The pharmaceutical properties of the products were investigated. The prepared salts were characterized by FTIR, NMR and DSC, UV and HPLC. 2D NMR was successfully employed to unequivocally assign the protons of ATV, which was essential for better understanding of the structure of the formed salt. ATV-C showed higher solubility in phosphate buffer than ATV. Its log Po/phosphate buffer was found to be 1.1 while that for ATV 1.78. This change had an effect on the transdermal permeation where the ATV-C compound achieved a 4 times greater diffusion compared to ATV. Interestingly, ATV-C seemed to cause a tighter fitting of the drug into the HPβCD cavity leading to higher binding constant. However, the ATV-C-CD complex showed a negative effect on transdermal permeation.

Keywords


atorvastatin, bioavailability, transdermal, Log P

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