Drug-cyclodextrin complexation in the presence of water-soluble polymers: Enhanced solubility and percutaneous transport

For variety of reasons, including production capabilities, toxicology and cost, the amount of cyclodextrin that can be used in drug and cosmetic formulations will be limited. In order to use less cyclodextrin the complexation efficacy (K_c[S_o] or [D•CD]/[CD]) must be increased. We have shown that the complexation efficacy of various lipophilic drugs can be significantly increased by heating cyclodextrin drug solution up to 120-130°C for 20-40 minutes in the presence of small amount of water soluble polymers. At least 30% enhancement in complexation efficacy is common and in some cases over 200% increase is observed. Phase-solubility studies revealed that this was due to an apparent increase in the complexation stability constant (K_c). The percutaneous transport through hairless mouse skin in-vitro from drug-cyclodextrin solutions was increased up to 200% by addition polymer and in-vivo studies showed that the bioavailability of for example dexamethasone from eye-drop solutions could be increased about four fold. Formulation of drugs with cyclodextrins and polymers can thus enhance the attractive properties of cyclodextrins as pharmaceutical excipients.