Amorphous solid dispersions of ritonavir by melt-quenching
A quality by design approach
Keywords:
ritonavir, melt-quenching, amorphous solid dispersions, quality by design, statistical optimizationAbstract
Ritonavir is crystalline solid which is very slightly soluble in water yet having high dose. This condition necessitates enhancement of solubility before developing into dosage forms. Melt-quenching is recently exploring technique for developing amorphous solid dispersions (ASDs) for crystalline drugs to with a hydrophilic carrier to enhance solubility. ASDs have a drawback of poor thermodynamic stability which needs to be considered. The current work was aimed to develop ASDs for Ritonavir with improved solubility yet thermodynamically stable. Quality by design (QbD) was employed to elucidate the effects of the carrier, plasticizer and cooling temperature on the solubility and stability of the prepared ASDs. Differential scanning calorimetry (DSC) and X-ray diffraction (X-RD) analysis were performed to investigate the physical state of Ritonavir and the stability of the ASDs upon storage. These results illustrated the effects of the factors on the solubility and stability were significant at p< 0.05. Statistical optimization was performed to identify the best combination of the factors to obtain ASDs with maximum solubility and stability. ASDs prepared with Soluplus as carrier at 50% w/w, Poloxamer 188 as plasticizer 15% w/w at6.81oC temperature were found to have desired solubility and stability.
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