The influence of water-soluble polymers and pH on hydroxypropyl-beta-cyclodextrin complexation of drugs

The effect of water-soluble polymers and ionization of the drug molecules on the cyclodextrin, mainly 2-hydroxypropyl-beta-cyclodextrin (HP beta CD), solubilization of drugs was investigated. HP beta CD has significant solubilizing effect on acetazolamide, prazepam, and sulfamethoxazole in aqueous solutions. All three polymers tested-i.e., hydroxypropyl methylcellulose (HPMC), polyvinylpyrrolidone (PVP), and carboxymethylcellulose-in crease the solubilizing effect of HP beta CD. The polymers increase the solubilization by increasing the apparent stability constant (K-c) of the drug-HP beta CD complex. Thus, addition of 0.10% (w/v) HPMC to the aqueous complexation medium results in a 56% increase in K-c for the acetazolamide-HP beta CD complex and a 200% increase in K-c for the prazepam-HP beta CD complex. Addition of 0.25% (w/v) PVP to the complexation medium results in a 138% increase in K-c for the sulfamethoxazole-HP beta CD complex. The HP beta CD solubilization of the drugs can also be improved by ionization of the drug molecule through pH adjustments. However, larger improvements of the HP beta CD solubilization are obtained when both methods are used simultaneously compared to when either method is used separately.