Gefitinib-cyclodextrin inclusion complexes: physico-chemical characterization and dissolution studies.

BACKGROUND: Gefitinib, an anticancer drug, has an extremely low aqueous solubility, and its oral absorption is limited by its dissolution rate. The solubility and dissolution of gefitinib can be improved by complexation with cyclodextrins (CDs). METHODS: Phase solubility studies of gefitinib with hydroxypropyl betaCD (HPbetaCD) and randomly methylated betaCD (RMbetaCD) in n various aqueous systems was conducted to characterize the complexes in the liquid state. The inclusion complexes in the solid state were prepared by freeze-drying method and characterized by X-ray diffractometry (X-RD) and differential scanning calorimetry (DSC). RESULTS: Gefitinib formed stable complexes with HPbetaCD and RMbetaCD in distilled water as indicated by the association rate constants (Ks) of 458.9 and 1096.2 M(-1) for HPbetaCD and RMbetaCD, respectively. The complexation of gefitinib with CDs in pH 4.5 acetate buffer indicated an A(N) type of phase-solubility diagrams, whereas gefitinib and HPbetaCD in distilled water in the presence of polymers such as polyvinyl pyrrolidone K-30 (PVP) or hydroxypropyl methylcellulose E3 (HPMC) resulted in A(P)-type phase-solubility diagrams. The solid-state amorphous complexes (as described by DSC and X-RD) showed substantial increases in the solubility and dissolution rate of gefitinib with both CDs. Further increases in the solubility and dissolution rate of the gefitinib-HPbetaCD freeze-dried complex were obtained by physically mixing the complex with PVP and HPMC. CONCLUSION: Gefitinib formed stable inclusion complexes with HPbetaCD and RMbetaCD, and the solubility and dissolution rate of the drug was significantly increased.

Enhancement of transdermal delivery of phenylbutazone from liposomal gel formulations through deer skin.

Phenylbutazone (PBZ) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain and arthritis. Topical and transdermal administration of PBZ would be beneficial in large animals in terms of minimizing gastro-intestinal ulcerations and other side effects, easy administration to legs and joints and minimizing the dose to reduce systemic toxicity of the drug. A topical liposomal preparation with different concentrations of a mono-substituted alkyl amide (MSA) and PBZ was formulated. The formulations were evaluated by in vitro skin-permeation kinetics through deer skin using Franz diffusion cells. By increasing drug loading from 1% to 5% w/w, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Similarly, by increasing the MSA concentration from 0% to 4%, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Overall, by increasing the drug load and the use of an appropriate amount of the penetration enhancer, the steady-state flux of PBZ through skin was increased fourfold (P < 0.001). MSA at both 2% and 4% w/w concentrations significantly increased the skin levels of PBZ as compared with control (P < 0.05). In conclusion, MSA served as an effective skin-penetration enhancer in the liposomal gel of PBZ for deer.