Effects of beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin on minoxidil solutions

Abstract

The effects of beta-cyclodextrin (β-CD) and hydroxypropyl-beta-cyclodextrin (HP-β- CD) on solubility, stability and membrane permeation of minoxidil were investigated. From the solubility diagrams showed that β-CD increased minoxidil solubility by Bs- type complex formation while HP-β-CD gave AL-type complex formation. The existence of complexes was confirmed by differential scanning calorimetry (DSC) and IR spectroscopy. The stoichiometric ratio of the complexes with both β-CD and HP-β-CD was 1:1. The formation constants (Kc) between minoxidil and β-CD and HP-β-CD were 953.83 and 207.91 1/mol, respectively. Minoxidil 2% solutions containing 0, 0.1, 0.4 and 0.7 %w/v of β-CD and 0, 5.0, 10.0, 15.0 and 20.0 %w/v of HP-β-CD were formulated with appropriate volumes of alcohol and propylene glycol. After storage at room temperature and 70°c, the degradation kinetic was determined by first-order approach. The degradation rate constants (k) at room temperature and at 70°c of all solutions were negligible, but the yellow coloration occured in the solutions at 70°c after 2 weeks. This suggested that cyclodextrin in concentration range studied could not prevent the color change of minoxidil solutions. The in vitro permeation through newborn pig skin using Modified Franz diffusion cell apparatus of all formulations and the commercial solution, Regaine® was evaluated. The results indicated that both cyclodextrins decreased the flux and percent cumulative amounts of minoxidil permeated at 12 and 24 hours.