Abstract
Solid dispersion technologies such as hot-melt extrusion and spray drying are often used to enhance the solubility of poorly soluble drugs. The biggest challenge associated with solid dispersion systems is that amorphous drugs may phase-separate from the polymeric matrix and recrystallize during storage. A more fundamental understanding of drug-polymer mixtures is needed for the industry to embrace the solid dispersion technologies. In this study, a theoretical model based on Flory-Huggins lattice theory was utilized to predict the solubility of a model drug acetaminophen (APAP) in a semi-crystalline polymer poly(ethylene oxide) (PEO) at 300 K. The interaction parameter χ was calculated to be -1.65 from the depression of drug's melting temperature determined from rheological and differential scanning calorimetry analysis. The equilibrium solubility in amorphous PEO was estimated to be 11.7% at 300 K. Assuming no APAP molecules dissolve in the crystalline part of PEO, the adjusted theoretical solubility is around 2.3% considering PEO being 80% crystalline. The solubility of APAP in PEG 400 was calculated to be 14.6% by using the same χ value, close to the experimental measurement 17.1%. The drug's solubility could be altered noticeably by the change of both χ and polymer molecular weight. The study also suggests that the depression of drug's melting point is a good indicator for preliminary polymer screening. The polymer that reduces the melting point the most is likely to be most miscible with the drug.
Original language | English (US) |
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Pages (from-to) | 102-108 |
Number of pages | 7 |
Journal | Drug Development and Industrial Pharmacy |
Volume | 39 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2013 |
All Science Journal Classification (ASJC) codes
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry
Keywords
- Acetaminophen/paracetamol
- Flory-Huggins interaction parameter χ
- Hot-melt extrusion
- Poly(ethylene oxide)
- Solid dispersion
- Solubility