No abstract

Taken together, our novel thermosensitive and biadhesive nanomicelles demonstrated the ability to improve the bioavailability and chemotherapeutic potential of DCT in vivo. To the best of our knowledge, this is the first report describing the rectal delivery of DCT-loaded nanomicelles.

The main purpose of this work was to optimize the rheological properties of docetaxel (DCT)-loaded thermosensitive liquid suppositories for rectal administration. DCT-loaded liquid suppositories were prepared by a cold method and characterized in terms of physicochemical and viscoelastic properties. Major formulation parameters including poloxamer (P407) and Tween 80 were optimized to adjust the thermogelling and mucoadhesive properties for rectal administration. Notably, the gel strength and mucoadhesive force significantly increased with the increase in these variables. Furthermore, DCT incorporation did not alter the viscoelastic behavior, and the mean particle size of nanomicelles in it was approximately 16 nm with a distinct spherical shape. The formulation existed as liquid at room temperature and transformed into gel at physiological temperature through the reverse gelation phenomenon. Thus, DCT-loaded thermosensitive liquid suppositories [DCT/P407/P188/Tween 80 (0.25/11/15/10 %)] with optimal gel properties were easy to prepare and administer rectally, and might enable the gel to stay in the rectum without getting out from rectum.

To develop a novel itraconazole-loaded solid dispersion without crystalline change with improved bioavailability, various itraconazole-loaded solid dispersions were prepared with water, polyvinylpyrroline, poloxamer and citric acid. The effect of carriers on aqueous solubility of itraconazole was investigated. Their physicochemical properties were investigated using SEM, DSC, and powder X-ray diffraction. The dissolution, bioavailability in rats and stability of solid dispersions were evaluated. Unlike conventional solid dispersion system, the itraconazole-loaded solid dispersion with relatively rough surface did not change crystalline form of drug. Our DSC and powder X-ray diffraction results suggested that this solid dispersion was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting in conversion of the hydrophobic drug to hydrophilic form. The itraconazole-loaded solid dispersion at the weight ratio of itraconazole/polyvinylpyrroline/poloxamer of 10/2/0.5 gave maximum drug solubility of about 20 microg/mL. It did not change the crystalline form of drug for at least 6 months, indicating that it was physically stable. It gave higher AUC, C(max) and T(max) compared to itraconazole powder and similar values to the commercial product, suggesting that it was bioequivalent to commercial product in rats. Thus, it would be useful to deliver a poorly water-soluble itraconazole without crystalline change with improved bioavailability.

The itraconazole-loaded gelatin microcapsule without ethanol developed using a spray-drying technique at half the dose of the commercial product can deliver itraconazole in a pattern that allows fast absorption in the initial phase, making it bioequivalent to the commercial product.