Micelles entrapped microparticles technology: a novel approach to resolve dissolution and bioavailability problems of poorly water soluble drugs.

Aim: Aim of this study was to design a solid oral delivery system for a weakly basic drug such as dasatinib (DAS), so as to achieve pH-independent dissolution and improved oral bioavailability.Methods: DAS was solubilised using sodium lauryl sulphate as an aqueous micellar system and such a system containing lactose monohydrate as carrier was spray-dried to obtain a solid mass. Subsequently, the DAS-solid was converted into a tablet using conventional tableting methods.Results: The dissolution study revealed pH-independent dissolution over a wide range of pH conditions. An in vivo bioavailability testing on rats revealed an improved Cmax and AUC0-24. Similarly, viability assay showed a better inhibitory effect of spray-dried dasatinib over the DAS.Conclusions: Micellar solubilisation and spray-drying technology can be approached to resolve poor dissolution and bioavailability of drugs belonging to biopharmaceutical classification system II and III. This technology is amenable to scale-up and has commercial potential.

Microparticles-entrapped micelles: a novel delivery system to improve solubility and dissolution rate of poorly water-soluble valsartan.

Surfactants are routinely included in tablets during wet or dry granulations or along with directly compressible vehicles to improve wetting, disintegration and dissolution. Besides this micellar solubilization can improve permeability of poorly soluble drugs via gastrointestinal tract membranes thereby enhancing oral bioavailability. Microparticle-entrapped micelles (MEM) technology is a novel method of incorporating surfactants in tablets for improving in vitro and in vivo performance of poorly water-soluble drugs. Valsartan (VAL) was solubilized in cremophor EL micelles at cloud point temperature; lactose was dissolved in micellar dispersion and the dispersion was directly spray-dried to obtain solid product, which was subsequently converted into tablets using suitable excipients. VAL tablets produced by applying MEM technology improved dissolution performance of valsartan tablets. These tablets exhibited superior dissolution rate over controls and marketed tablets in all media employed irrespective of pH conditions and composition.

Biodistribution of ascorbyl palmitate loaded doxorubicin pegylated liposomes in solid tumor bearing mice.

The aim of this study is to develop ascorbyl palmitate (ASP) loaded doxorubicin (DOX) pegylated liposomes and to evaluate their targeting potential to tumor. We have prepared conventional (DL), pegylated DOX liposomes with (SDL) and without ascorbyl palmitate (SDL-A). The vesicle size in all the formulations was within the range 105-120 nm and in vitro release studies in serum confirmed the stability of the liposomes. Biodistribution studies carried out in Ehrlich ascites tumor bearing mice indicate higher area under the curve for SDL and SDL-A liposomes compared to DL and plain drug solution. Drug targeting index assessed from tumor-to-serum concentration ratio and therapeutic availability of DOX in tumor tissue was also significantly higher for pegylated liposomes. In conclusion, biodistribution study reveals that the presence of ascorbyl palmitate alters the distribution pattern of liposomes and paves way for better drug targeting.