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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.
J Pharm Pharmacol. 2014 Feb; 66(2):256-74.JP

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 prepared using two different techniques (hot-melt extrusion and spray drying), and characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry), spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods.

KEY FINDINGS

Spray drying permitted generation of amorphous solid dispersions 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.

Authors+Show Affiliations

The Drug Delivery and Biomaterials Group, School of Pharmacy, Medical Biology Centre, Queen's University, Belfast, UK.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

24192445

Citation

Tian, Yiwei, et al. "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." The Journal of Pharmacy and Pharmacology, vol. 66, no. 2, 2014, pp. 256-74.
Tian Y, Caron V, Jones DS, et al. 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. J Pharm Pharmacol. 2014;66(2):256-74.
Tian, Y., Caron, V., Jones, D. S., Healy, A. M., & Andrews, G. P. (2014). 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. The Journal of Pharmacy and Pharmacology, 66(2), 256-74. https://doi.org/10.1111/jphp.12141
Tian Y, et al. 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. J Pharm Pharmacol. 2014;66(2):256-74. PubMed PMID: 24192445.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Tian,Yiwei, AU - Caron,Vincent, AU - Jones,David S, AU - Healy,Anne-Marie, AU - Andrews,Gavin P, Y1 - 2013/11/05/ PY - 2013/05/24/received PY - 2013/08/06/accepted PY - 2013/11/7/entrez PY - 2013/11/7/pubmed PY - 2014/9/11/medline KW - Flory-Huggins phase diagram KW - amorphous solid dispersion KW - hot-melt extrusion KW - physical stability KW - spray drying SP - 256 EP - 74 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 66 IS - 2 N2 - 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 prepared using two different techniques (hot-melt extrusion and spray drying), and characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry), spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods. KEY FINDINGS: Spray drying permitted generation of amorphous solid dispersions 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. SN - 2042-7158 UR - https://www.unboundmedicine.com/medline/citation/24192445/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_ L2 - https://doi.org/10.1111/jphp.12141 DB - PRIME DP - Unbound Medicine ER -