Electronic Theses and Dissertations

Date of Award


Document Type


Degree Name

M.S. in Pharmaceutical Science

First Advisor

Michael A. Repka

Second Advisor

Eman A. Ashour

Third Advisor

Walter G. Chamblis

Relational Format



The present study is intended to increase the solubility and dissolution rate of atorvastatin calcium trihydrate by converting it into an amorphous solid dispersions using the hot melt extrusion (HME) technique. The solubility of the drug is a significant aspect to be considered while developing pharmaceutical products. Poor solubility of drugs can lead to poor oral bioavailability. In this regard, several techniques are available for enhancing drug solubility or dissolution. HME is one such technique that has been widely used in the pharmaceutical industry. It is a single-step, continuous manufacturing, and scalable method that has proved successful in improving the solubility of poorly soluble drugs. In this study, ATH amorphous solid dispersions were prepared with HPMC K100 LV and PEG 3350 (plasticizer) via hot-melt extrusion (Minilab extruder). Formed extrudates were milled and compressed into tablets. An in vitro drug release study was carried out using a pH 6.8 buffer for all the formulations. Saturation solubility of all formulations and pure drug was performed in water for 48 hrs. The lead formulation with different drug loads was extruded on minilab evaluate the effect of drug loads on the solubility and drug release. As a scale-up process, the lead formulation F4 was extruded on the process 11mm HME at different temperatures to observe the effect of temperature. DSC study was carried out to confirm the amorphous conversion of crystalline ATH. FTIR was used to investigate interactions between API and polymers over the 900-4000cm-1 range. The F4 formulation showed the highest drug release when compared to all other formulations. It is worth mentioning the dissolution profile rate of the physical mixture of lead formulation shows less drug release than that of the HME formulation, revealing that the amorphous conversion of ATH gave a superior effect in terms of solubility and dissolution. The lead formulation showed no apparent changes after accelerated stability testing for 1 month.

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