Characterization of beta-cyclodextrin for direct compression tableting.

Abstract

A physically modified beta-cyclodextrin sample (BCD-DC) was characterized as a filler-binder for direct compression tableting by comparing it to a commercially available beta-cyclodextrin product (Kleptose{dollar}\sp\circler{dollar}) and commonly used direct compression filler-binders such as microcrystalline cellulose (MCC), spray dried lactose (SDL) and dicalcium phosphate (DCP). Aspects examined included the compactibility of beta-cyclodextrin, deformation mechanism of beta-cyclodextrin, the role of moisture in the compactibility of beta-cyclodextrin and the effect of beta-cyclodextrin on the dissolution of poorly soluble actives. The physical modification of beta-cyclodextrin resulted in a considerable improvement in its properties as a direct compression filler-binder. The compactibility of the BCD-DC sample was comparable to that of MCC and significantly better than Kleptose{dollar}\sp\circler{dollar}, SDL and DCP. BCD-DC possessed adequate flow for direct compression using a rotary press. The primary deformation mechanism of BCD was found to be plastic flow. Scanning electron photomicrographs of BCD-DC showed the presence of cracks and laminations which result in the higher surface area of BCD-DC relative to Kleptose{dollar}\sp\circler{dollar}. These differences in the external particle characteristics are primarily responsible for the greater compactibility of BCD-DC. Moisture plays a critical role in the compactibility of beta-cyclodextrin. The moisture sorption-desorption isotherms revealed considerable hysteresis. The complete removal of water results in a loss of the compactibility of beta-cyclodextrin. There appears to be an optimal level of moisture for maximum compactibility. The dissolution studies using direct compression formulations of spironolactone revealed that dissolution rate of the drug was significantly faster from a formulation containing beta-cyclodextrin as a filler than from those containing MCC, SDL, or DCP as the fillers. This can be attributed to the increased solubility of spironolactone due to complexation with beta-cyclodextrin. The beta-cyclodextrin formulation was more compactible than the SDL and DCP formulations but less than the MCC formulation. For the medroxyprogesterone acetate formulations, dissolution rate was fastest from the formulation containing SDL as the filler followed by the beta-cyclodextrin formulation. This was attributed to the higher solubility of SDL and lack of interaction with beta-cyclodextrin. beta-Cyclodextrin has been characterized more than any other modern tablet excipient prior to commercialization and has considerable promise as a direct compression filler-binder.