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