Evaluation of polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions prepared by hot-melt extrusion

Objective: The aim of this study was to evaluate several polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions (SD) prepared by hot-melt extrusion (HME) and select the most appropriate polymer carrier. Methods: Solid dispersions containing bifendate in different polymers, including Plasdone® S-630, Eudragit® EPO and Kollidon® VA 64 were prepared by hot-melt extrusion. Differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD) and dissolution testing were used to characterize the systems. Then, the thermal degradation during the HME process and the storage stability of tablets consisting of bifendate-Kollidon® VA 64 SD were investigated. Finally, the oral bioavailability of bifendate dosage forms with bifendate-Plasdone® S-630 (1/9), bifendate-Eudragit® EPO (1/4) and bifendate-Kollidon® VA 64 (1/9) SD in beagle dogs was compared with that of commercially available benfidate pills. Results: DSC and XDR analysis showed the dispersion of the drug in the polymer on a molecular basis or in the amorphous state. The drug release from both bifendate-Plasdone® S-630 SD and bifendate-Eudragit® EPO SD was up to more than 90% with the pH 1.2 simulated gastric fluid as the dissolution medium, while the relative bioavailability was just 87.8 ± 51.8% and 110 ± 62% compared with commercial pills, respectively. The directly compressed tablets with bifendate-Kollidon® VA 64 SD were found to dissolve rapidly over 95% within 30 min and the relative bioavailability was 145.0 ± 35.2%. Conclusion: The bioavailability of water-insoluble bifendate was markedly enhanced by dispersing the drug in the polymer carrier Kollidon® VA 64 employing HME technology.

[1]  Xing Tang,et al.  In vitro and in vivo evaluation of fenofibrate solid dispersion prepared by hot-melt extrusion , 2010, Drug development and industrial pharmacy.

[2]  Wagh Vinod Tukaram.  Solid Dispersions as Strategy to Improve Oral Bioavailability of Poor Water Soluble Drugs , 2013 .

[3]  Yatindra Joshi,et al.  Phase Behavior of Amorphous Molecular Dispersions II: Role of Hydrogen Bonding in Solid Solubility and Phase Separation Kinetics , 2005, Pharmaceutical Research.

[4]  Xing Tang,et al.  Part II: Bioavailability in Beagle Dogs of Nimodipine Solid Dispersions Prepared by Hot-Melt Extrusion , 2007, Drug development and industrial pharmacy.

[5]  Peng Wang,et al.  Effects of extrusion process parameters on the dissolution behavior of indomethacin in Eudragit E PO solid dispersions. , 2010, International journal of pharmaceutics.

[6]  W. Brostow,et al.  Glass transitions in binary drug+polymer systems , 2009 .

[7]  B. Perissutti,et al.  Studies in dissolution enhancement of atenolol. Part I , 1998 .

[8]  J Dressman,et al.  Improving drug solubility for oral delivery using solid dispersions. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[9]  Yatindra Joshi,et al.  Phase Behavior of Amorphous Molecular Dispersions I: Determination of the Degree and Mechanism of Solid Solubility , 2004, Pharmaceutical Research.

[10]  S. Schulte,et al.  Carcinogenicity and chronic toxicity of copovidone (Kollidon VA 64) in Wistar rats and Beagle dogs. , 2004, Food and Chemical Toxicology.

[11]  Deliang Zhou,et al.  A calorimetric investigation of thermodynamic and molecular mobility contributions to the physical stability of two pharmaceutical glasses. , 2007, Journal of pharmaceutical sciences.

[12]  Z. Lili,et al.  Stable nimodipine tablets with high bioavailability containing NM-SD prepared by hot-melt extrusion , 2010 .

[13]  G. Van den Mooter,et al.  Solid state characteristics of ternary solid dispersions composed of PVP VA64, Myrj 52 and itraconazole. , 2005, International journal of pharmaceutics.

[14]  E. Pavlidou,et al.  Physicochemical studies on solid dispersions of poorly water-soluble drugs: Evaluation of capabilities and limitations of thermal analysis techniques , 2005 .

[15]  P. Schmidt.  Encyclopedia of Pharmaceutical Technology. Vol. 1; Eds. J. Swarbrick and J. C. Boylan, M. Dekker, Inc. New York 1988, 494 p. hardcov. Price: see review text , 1990 .

[16]  A. Xenakis,et al.  Effect of hydrogen bonding interactions on the release mechanism of felodipine from nanodispersions with polyvinylpyrrolidone. , 2006, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.