Abstract
The effect of product design parameters on the formation and properties of an injection molded solid dosage form consisting of poly(ethylene oxide)s (PEO) and two different active pharmaceutical ingredients (APIs) was studied. The product design parameters explored were melting temperature and the duration of melting, API loading degree and the molecular weight (Mw) of PEO. The solid form composition of the model APIs, theophylline and carbamazepine, was of specific interest, and its possible impact on the in vitro drug release behavior. Mw of PEO had the greatest impact on the release rate of both APIs. High Mw resulted in slower API release rate. Process temperature had two-fold effect with PEO 300,000g/mol. Firstly, higher process temperature transformed the crystalline part of the polymer into metastable folded form (more folded crystalline regions) and less into the more stable extended form (more extended crystalline regions), which lead to enhanced theophylline release rate. Secondly, the higher process temperature seemed to induce carbamazepine polymorphic transformation from p-monoclinic form III (carbamazepine (M)) into trigonal form II (carbamazepine (T)). The results indicated that the actual content of carbamazepine (T) affected drug release behavior more than the magnitude of transformation.
| Original language | English |
|---|---|
| Journal | International Journal of Pharmaceutics |
| Volume | 518 |
| Issue number | 1-2 |
| Pages (from-to) | 203-212 |
| Number of pages | 10 |
| ISSN | 0378-5173 |
| DOIs | |
| Publication status | Published - 25 Feb 2017 |
Keywords
- Calorimetry, Differential Scanning
- Carbamazepine
- Chromatography, Gel
- Drug Compounding
- Drug Liberation
- Polyethylene Glycols
- Powder Diffraction
- Spectroscopy, Fourier Transform Infrared
- Theophylline
- X-Ray Diffraction
- Journal Article