Category: Formulation and Quality
Purpose: The main purpose of this study is to investigate an alkaline grade Neusilin® S2 (NEUS2) to improve the solubility of a poorly soluble drug Indomethacin (IND) via a one-step twin screw process.
Methods: In the present study, NEUS2, an alkaline grade neusilin, was investigated as a solubilizing carrier in preparation of solid dispersions (SDs) of Indomethacin (IND), a poorly soluble drug, via a one-step twin screw process. Differential scanning calorimetry (TA Instruments DSC 25) was used to determine the melting temperature of IND. Physical mixtures were mixed at three different weight ratios 20, 40 and 60% (w/w) of IND and blended using a V-blender (GlobePharma, MaxiblendTM) for 15 minutes. The SDs of IND were prepared using twin screw process in a 16mm (ThermoScientific® Prism Eurolab) extruder with screw speed of 100 rpm and at a temperature of 170°C. The obtained SDs were milled and sifted through ASTM #25 and those that passed the sieve were collected and used for further studies. The obtained formulations were further characterized using DSC to determine the nature of the drug. In vitro drug release studies were performed in 750 mL of pH 7.2 phosphate buffer for 2 h using USP apparatus II (SR8-plus, Hanson) at an agitation speed of 50 rpm. The samples were collected at predetermined time intervals, diluted suitably and analyzed for drug content
Results: Thermal analysis revealed that IND has a melting point of about 161°C, thus a process temperature (170°C) above the melting point of IND was used. The product obtained from the twin screw process was a free-flowing powder at 20% and 40% drug loads of IND, while at 60% IND was granules. A 60% drug load of IND produced higher torque values in comparison to 20% and 40% drug loads. Solid state characterizations of all prepared IND formulations revealed the amorphous form of IND was present. In vitro dissolution studies revealed faster drug release from all formulations compared to pure IND. However, the rate of dissolution was higher at lower drug loads, the percent drug release was about 98.18, 86.8 and 54.3, for the 20%, 40% and 60% loads respectively, at 30 min time point
Conclusion: For the first time, NEUS2 was successfully utilized to improve the solubility of pH dependent poorly soluble drug (IND) via a one-step twin screw process. The prepared formulations showed significant improvement in dissolution rate. The obtained product is suitable either for a tablet or capsule dosage form.
Bahl, D., & Bogner, R. H. (2006). Amorphization of indomethacin by co-grinding with Neusilin US2: amorphization kinetics, physical stability and mechanism. Pharmaceutical research, 23(10), 2317-2325.
Maniruzzaman, M., Nair, A., Scoutaris, N., Bradley, M. S., Snowden, M. J., & Douroumis, D. (2015). One-step continuous extrusion process for the manufacturing of solid dispersions. International journal of pharmaceutics, 496(1), 42-51.
Venkata Raman Kallakunta– PhD student, University of Mississippi, Ocford, Mississippi
Suresh Bandari– Post-doc, University of Mississippi, Oxford, Mississippi
Michael Repka– Professor, University of Mississippi, Oxford, Mississippi