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Triamterene-beta-cyclodextrin systems: preparation, characterization and in vivo evaluation
Alka Pravin Mukne1, M S Nagarsenker
1Bombay College of Pharmacy, Kalina, Santacruz (East), Mumbai-400098, Maharashtra, India.
AAPS Pharmscitech
|June 17, 2004
Summary
This study improved triamterene solubility using beta-cyclodextrin complexation. The resulting solid dispersions significantly enhanced drug release and in vivo performance, offering better bioavailability.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Physical Chemistry
Background:
- Triamterene, a diuretic, exhibits poor water solubility, leading to low oral bioavailability and high intersubject variability.
- Beta-cyclodextrin (β-CD) is a cyclic oligosaccharide known for its ability to form inclusion complexes with poorly soluble drugs.
- Complexation with β-CD is a potential strategy to enhance the dissolution and bioavailability of triamterene.
Purpose of the Study:
- To improve the solubility, dissolution, and bioavailability of triamterene through complexation with beta-cyclodextrin.
- To formulate and characterize solid dispersions of triamterene-β-CD using various methods.
- To evaluate the in vitro and in vivo performance of the developed triamterene-β-CD systems.
Main Methods:
- Phase solubility studies were conducted to determine complex stoichiometry and stability.
- Solid dispersions were prepared using cogrinding, kneading, and coevaporation techniques under low pH conditions.
- Characterization involved Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC).
- In vitro dissolution studies were performed in 0.1N HCl and pH 6.8 phosphate buffer.
- In vivo studies in rats measured net sodium ion excretion to assess bioavailability.
Main Results:
- Phase solubility studies indicated a 1:1 stoichiometry complex with a stability constant of 167.67 M⁻¹.
- Characterization confirmed the inclusion of triamterene's phenyl ring within the β-CD cavity, particularly in the coevaporate.
- All solid dispersions showed significant improvement in in vitro drug release profiles, with the coevaporate exhibiting the most remarkable enhancement.
- Oral administration of the coevaporate in rats resulted in improved in vivo activity compared to pure triamterene powder.
Conclusions:
- Coevaporation of triamterene and beta-cyclodextrin under acidified alcohol conditions is an optimal method for forming inclusion complexes.
- The resulting binary system demonstrates significantly improved in vitro drug release and in vivo performance.
- This approach offers a promising strategy for enhancing the therapeutic efficacy of poorly water-soluble drugs like triamterene.