Improvement of the Solubility and Dissolution Rate of the Steroidal Drug, Mesterolone, using Cyclodextrin Complexation

Samer Odeh, Hassan Muti, Ahmad Bani-Jaber

Abstract


Inclusion complexation between mesterolone (MN), a steroidal hormone, and β-cyclodextrin (βCD) or hydroxypropyl-β-cyclodextrin (HPβCD) was evaluated in aqueous environment and in solid state. Phase solubility profiles of MN with βCD or HPβCD were obtained and classified as AL-type and BL-type, respectively. An apparent stability constant was calculated from each phase solubility profile and was found to be higher for MN- βCD than for MN- HPβCD. Solid binary systems of MN-CD were obtained with both CDs by kneading and coevaporation at MN: CD molar ratios of 1: 1 and 1: 2. In comparison to the respective physical mixtures, the binary systems were characterized for % MN complex inclusion by chloroform extraction and for solid state by differential scanning calorimetry and X-ray diffractometry. MN inclusion was mostly dependent on MN: CD molar ratio and this dependence was higher with βCD than with HPβCD upon both kneading and coevaporation. The DSC results indicated MN inclusion and loss of MN crystallinity, which were higher at 1: 2 than at 1: 1 molar ratio for both CDs and for βCD than for HPβCD at each molar ratio. X-ray diffraction results confirmed the loss of drug crystallinity upon kneading and coevaporation particularly with βCD. The binary systems were subjected to dissolution studies in comparison to pure MN. An enhancement in MN dissolution was obtained and was explained based on local drug solubilization during dissolution, drug inclusion and loss of drug crystallinity. The enhancement in MN dissolution was found to strongly depend on MN: CD molar ratio with slight effect for CD type and preparation method.

Keywords


Cyclodextrins; Mesterolone; Inclusion complexation; Improvement of dissolution rate.

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