Using Flory-Huggins phase diagrams as a pre-formulation tool for the production of amorphous solid dispersions; a comparison between hot-melt extrusion and spray drying

Yiwei Tian, Vincent Caron, David S. Jones, Anne-Marie Healy, Gavin P. Andrews

Research output: Contribution to journalArticlepeer-review

49 Citations (Scopus)

Abstract

Objectives: Amorphous drug forms provide a useful method of enhancing the dissolution performance of poorly water-soluble drugs; however, they are inherently unstable. In this article, we have used Flory–Huggins theory to predict drug solubility and miscibility in polymer candidates, and used this information to compare spray drying and melt extrusion as processes to manufacture solid dispersions.
Method:  Solid dispersions were characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry) and spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods. 
Key Findings: Spray drying permitted generation of amorphous solid dispersions to be produced across a wider drug concentration than melt extrusion. Melt extrusion provided sufficient energy for more intimate mixing to be achieved between drug and polymer, which may improve physical stability. It was also confirmed that stronger drug–polymer interactions might be generated through melt extrusion. Remixing and dissolution of recrystallised felodipine into the polymeric matrices did occur during the modulated differential scanning calorimetry analysis, but the complementary information provided from FTIR confirms that all freshly prepared spray-dried samples were amorphous with the existence of amorphous drug domains within high drug-loaded samples. 
Conclusion: Using temperature–composition phase diagrams to probe the relevance of temperature and drug composition in specific polymer candidates facilitates polymer screening for the purpose of formulating solid dispersions.
Original languageEnglish
Pages (from-to)256-274
Number of pages19
JournalJournal of Pharmacy and Pharmacology
Volume66
Issue number2
Early online date05 Nov 2013
DOIs
Publication statusPublished - Feb 2014

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