Amorphous solid solutions using hot melt extrusion

Author

Ashish Sarode, University of Rhode Island

Date of Award

2010

Degree Type

Dissertation

First Advisor

Hossein Zia

Abstract

Poorly water soluble drugs--Indomethacin (IND), Itraconazloe (ITZ), and Griseofulvin (GSF) and hydrophilic polymers--Eudragit EPO, Eudragit L-100-55, Eudragit L-100, HPMCAS-LF, HPMCAS-MF, Pharmacoat-603, and Kollidon VA-64 were mixed in different ratios to prepare physical mixtures (PMs). The processing parameters of HME were estimated using solubility parameter calculations, thermal analysis, and rheological evaluation to manufacture hot melt extrudates (HMEs) by Haake MiniLab Microcompounder. The HMEs were characterized using powder X-ray diffraction (PXRD), polarized light microscopy (PLM), fourier transformed infrared (FTIR) spectroscopy, and dissolution study to assess the performance aspect. Further, HMEs were manufactured by Leistritz Twin Screw Extruder using few selected PMs and their stability was investigated using moisture analysis, thermal analysis, PXRD, and dissolution study. The solubility parameter calculations could predict the immiscibility of ITZ with Eudragit EPO that was confirmed by thermal analysis. Based on the softening temperatures and zero rate viscosity, it was possible to estimate the HME processing conditions and produce transparent glassy HMEs from most of the PMs. The PXRD and PLM indicated that HME transformed crystalline drugs into their amorphous forms that were relatively stable in the dissolution medium. Although FTIR analysis could determine the drug-polymer interactions that occurred during HME, it could not differentiate the stronger counter-ionic interactions. The improvement in dissolution of weakly acidic IND and weakly basic ITZ was variable in SGF and SIF and found to be dependent on their pH dependent ionization properties and interactions with the polymers rather than merely amorphous transformation. Conversely, the dissolution improvement of GSF was similar in SGF and SIF due to its neutral property and was found to be dependent on both amorphous transformation and interactions with the polymers. Amorphous ITZ was found to be physically unstable at very high temperature and humidity levels and its crystallization was observed. Where as, chemical degradation of IND was identified in stability samples of HMEs with Eudragit EPO stored at 50°C. Interestingly, the supersaturation of weakly acidic IND and weakly basic ITZ were improved for stability samples of HMEs manufactured using counter-ionic polymers to these drugs due to probable increase in drug-polymer interactions.

Recommended Citation

Sarode, Ashish, "Amorphous solid solutions using hot melt extrusion" (2010). Open Access Dissertations. Paper 2361.
https://digitalcommons.uri.edu/oa_diss/2361