Comparative analysis of novel modified drug delivery systems for improving the oral bioavailability of water-insoluble tadalafil using copovidone, TPGS and hydroxypropyl-β-cyclodextrin

초록

This study aims to develop novel modified drug delivery systems (MDDS) including solid dispersions, solid self-nanoemulsifying drug delivery system (S-SNEDDS) and inclusion compound (IC) of poorly water-soluble tadalafil using various biological macromolecules and compare their ability to improve solubility, dissolution and bioavailability. Ingredients of MDDS were extensively screened using SEM, DSC, and XRD. The MDDS were testified for improved solubilization, dissolution, and bioavailability and were compared with tadalafil powder and commercial product (Cialis tablets 20 mg). All MDDS demonstrated excellent physicochemical properties, improved solubility and dissolution of tadalafil. The sequence of highest solubilization and dissolution was found to be SE-solid dispersion, S-SNEDDS, SA-solid dispersion, and IC. SE-solid dispersion and IC showed spherical morphology and comparatively small particle size. In SA-solid dispersion, the hydrophilic carriers were found attached with the drug surface. Similarly, S-SNEDDS demonstrated the absorbance of L-SNEDDS inside the pores and surface of calcium silicate. All MDDS showed improved oral bioavailability (P < 0.05) in the order of SE-solid dispersion ≥ S-SNEDDS > SA-solid dispersion > commercial product > IC, when compared with tadalafil powder in rats. Thus, the SE-solid dispersion with highest solubility (660-folds) and oral bioavailability (10-folds) of tadalafil may be recommended as the most suitable candidate for the development of oral pharmaceutical products.

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