β-Cyclodextrin as an excipient in solid oral dosage forms: In vitro and in vivo evaluation of spray-dried diazepam-β-cyclodextrin products

Abstract Diazepam-β-cyclodextrin and diazepam-lactose products were prepared by spray-drying. Complex formation could be demonstrated by differential scanning calorimetry and by application of a so-called “ether-wash” method, for diazepam-β-cyclodextrin but not for diazepam-lactose. Intrinsic dissolution rates were measured using a rotating disc method. The results indicated that, for the drug tested, complexation played only a minor role in dissolution rate enhancement. Both the processing of the drug and the excipient as well as the solubility and amount of the excipient used seemed to be rate-determining factors. Release rates from tablets and capsules were measured using the USP paddle method. For the capsules an enhancement of the dissolution rate by complex formation of the drug with β-cyclodextrin, was only found when low stirring rates were used (20 rpm). The difference in dissolution rate, as obtained at 50 and 20 rpm, can be explained by the presence of an aggregate at the bottom of the beaker at low stirring rates. In the microenvironment around the aggregate the solubility of the drug is enhanced by complex formation. Absorption experiments in human volunteers showed also an increased absorption of diazepam by β-cyclodextrin complexation.