Abstract
The objective of this study was to increase the solubility of phenytoin by complexing it with varying concentrations of 2-hydroxypropyl-β- cyclodextrin (HPBCD) and create an entirely aqueous formulation with a pH significantly closer to physiologic pH (7.4). The phenytoin-HPBCD complexation was characterized using phase-solubility analysis at HPBCD concentrations ranging from 10 to 50% w/v over the pH range of 7.4-11.0. The two most promising formulations, i.e., a formulation consisting of 40% HPBCD at pH 10.4, and a second formulation consisting of 20% HPBCD at pH 11.0, were selected for further study. Both formulations were entirely aqueous and had a significantly decreased pH compared to the original commercial formulation (Parke-Davis, pH 12.0). These formulations also exhibited a significantly decreased tendency to precipitate in vitro. The tissue irritation potential of the 20% w/v HPBCD formulation at pH 11.0 was found to be reduced considerably compared to the commercial injection in a BALB/c mouse model.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 333-338 |
| Number of pages | 6 |
| Journal | Pharmaceutical Development and Technology |
| Volume | 5 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2000 |
| Externally published | Yes |
Keywords
- 2-Hydroxypropyl-β-cyclodextrin
- Complexation
- In vitro precipitation
- Phase solubility
- Phenytoin
- Skin toxicity
ASJC Scopus subject areas
- Pharmaceutical Science