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Inclusion complex effect on the bioavailability of clotrimazole from poloxamer-based solid suppository
Prabagar Balakrishnan1, Chung Kil Song, Hyun-Jong Cho
1College of Pharmacy, Yeungnam University, Gyongsan 712-749, Korea.
Archives of Pharmacal Research
|August 7, 2012
Summary
Low molar ratios of clotrimazole-β-cyclodextrin (βCD) inclusion complexes in poloxamer suppositories significantly enhanced drug bioavailability in rats. This formulation strategy offers a promising approach for improving the delivery of hydrophobic drugs like clotrimazole.
Area of Science:
- Pharmaceutical Sciences
- Drug Delivery Systems
- Physical Chemistry
Background:
- Clotrimazole is a hydrophobic antifungal agent with poor aqueous solubility, limiting its bioavailability.
- Poloxamer-based suppositories offer a potential delivery route for localized or systemic drug administration.
- β-cyclodextrin (βCD) is a cyclodextrin capable of forming inclusion complexes to enhance the solubility and bioavailability of hydrophobic drugs.
Purpose of the Study:
- To investigate the effect of β-cyclodextrin (βCD) inclusion complex on the bioavailability of clotrimazole.
- To develop and characterize poloxamer-based suppository formulations containing clotrimazole-βCD inclusion complexes.
- To evaluate the in vitro release profile and in vivo bioavailability of clotrimazole from these novel formulations.
Main Methods:
- Clotrimazole-βCD inclusion complexes were prepared at various molar ratios (1:0.25, 1:0.5, 1:1, 1:2).
- Complexation was characterized using differential scanning calorimetry (DSC), X-ray diffraction (XRD), and phase solubility studies.
- Poloxamer-based suppositories (P188, propylene glycol) were formulated with the inclusion complexes.
- In vitro release studies and in vivo pharmacokinetic studies in rats were conducted.
Main Results:
- Complexation with βCD, especially at higher molar ratios (1:1, 1:2), significantly reduced clotrimazole release.
- Suppositories with low molar ratio inclusion complexes (1:0.25, 1:0.5) exhibited excellent in vitro release profiles.
- In vivo studies in rats demonstrated that formulations with low molar ratio inclusion complexes (F1, F2) significantly increased the area under the curve (AUC) compared to control and high molar ratio formulations.
Conclusions:
- Poloxamer-based suppositories incorporating clotrimazole-βCD inclusion complexes at low molar ratios can enhance the bioavailability of hydrophobic drugs.
- The F1 formulation (1:0.25 drug to βCD molar ratio) shows significant potential for improving clotrimazole bioavailability.
- This approach offers a viable strategy for developing effective suppository formulations for poorly soluble drugs.
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