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Improvements in solubility and stability of thalidomide upon complexation with hydroxypropyl-beta-cyclodextrin
M Krenn1, M P Gamcsik, G B Vogelsang
1Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218.
Journal of Pharmaceutical Sciences
|July 1, 1992
Summary
Hydroxypropyl-beta-cyclodextrin enhances thalidomide solubility and stability, enabling an intravenous formulation. This improved drug delivery shows potential for better graft-versus-host disease treatment in leukemia patients.
Area of Science:
- Pharmacology
- Drug Delivery Systems
- Biochemistry
Background:
- Thalidomide is used for graft-versus-host disease (GVHD) post-bone marrow transplant.
- Oral thalidomide exhibits low plasma levels, necessitating an intravenous formulation.
- Thalidomide's poor aqueous solubility and instability limit its therapeutic potential.
Purpose of the Study:
- To enhance the aqueous solubility and stability of thalidomide.
- To develop an intravenous formulation of thalidomide for improved GVHD therapy.
Main Methods:
- Complexation of thalidomide with hydroxypropyl-beta-cyclodextrin.
- High-performance liquid chromatography (HPLC) for solubility assessment.
- Proton nuclear magnetic resonance (1H NMR) spectrometry for stability analysis.
Main Results:
- Aqueous solubility of thalidomide increased from 50 µg/mL to 1.7 mg/mL.
- Half-life of a diluted thalidomide solution extended from 2.1 to 4.1 hours.
- Demonstrated significant improvement in thalidomide's solubility and stability.
Conclusions:
- Hydroxypropyl-beta-cyclodextrin complexation effectively improves thalidomide's aqueous solubility and stability.
- An intravenous thalidomide-hydroxypropyl-beta-cyclodextrin formulation is feasible.
- This formulation could enhance GVHD treatment by ensuring sustained high plasma drug levels.