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Published on: July 4, 2017
In vitro/in vivo correlation of fast release mephenamic acid microspheres in humans
Mohamed A Etman1, Ragwa M Farid, Aly H Nada
1Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt.
Objectives:
The objectives of this study were to assess the bioavailability of an optimized mephenamic acid (MFA) microspheres (test) against a Ponstan® capsule (reference) in healthy volunteers, and to establish a correlation with in vitro parameters.
Subjects And Methods:
Four subjects received the test and reference (250 mg MFA each) in a randomized crossover design, separated by a 1-week washout period. The drug was analyzed in plasma by a specific high-performance liquid chromatographic method. The relevant pharmacokinetic parameters [maximum plasma concentration (C(max)), time of peak concentration (T(max)), area under plasma concentration-time curves from 0 to 12 h (AUC(0-12)) and area under plasma concentration-time curves from zero to ∞ (AUC(0-)∞)] were calculated from the plasma drug concentration-time data.
Results:
The test product exhibited faster absorption (T(max) of 1.87 ± 0.482 vs. 2.14 ± 0.20 h; C(max) of 5.91 ± 0.604 vs. 3.58 ± 0.671 μg/ml) when compared to the reference. The relative bioavailability of the test compared to the reference capsule was 172%. Good correlations were established between the in vitro 90% dissolution (T90) and each of the AUC(0-12) and T(max), as well as between the percentage of drug released and plasma concentrations.
Conclusion:
The formulation of MFA microsphere with polyethylene glycol improved the dissolution rate and bioavailability of MFA, as evidenced by a higher C(max), AUC(0-12) and AUC(0-)∞, and shorter T(max) values. Good correlations between T90 and both AUC(0-12) and T(max) as well as between the percentage of drug released and plasma concentrations were achieved.
Insights
Optimized mephenamic acid (MFA) microspheres showed significantly faster absorption and 172% higher bioavailability than standard capsules. In vitro dissolution correlated well with in vivo pharmacokinetic parameters.
Area of Science:
- Pharmacokinetics
- Drug Delivery Systems
- Formulation Science
Background:
- Mephenamic acid (MFA) is a nonsteroidal anti-inflammatory drug (NSAID).
- Optimizing drug delivery systems can enhance therapeutic efficacy.
- Microsphere formulations offer potential for improved drug absorption.
Purpose of the Study:
- To compare the bioavailability of optimized MFA microspheres against a reference capsule.
- To establish correlations between in vitro dissolution and in vivo pharmacokinetic parameters.
- To evaluate the impact of polyethylene glycol on MFA microsphere performance.
Main Methods:
- A randomized crossover study in four healthy volunteers.
- Administration of 250 mg MFA (test and reference) with a 1-week washout.
- Plasma drug analysis using high-performance liquid chromatography (HPLC).
- Calculation of pharmacokinetic parameters: C(max), T(max), AUC(0-12), and AUC(0-∞).
Main Results:
- MFA microspheres demonstrated faster absorption (T(max) 1.87h vs 2.14h) and higher peak plasma concentration (C(max) 5.91 μg/ml vs 3.58 μg/ml).
- Relative bioavailability of MFA microspheres was 172% compared to the reference capsule.
- Significant correlations were found between in vitro T90 dissolution and AUC(0-12), T(max), and plasma concentrations.
Conclusions:
- Polyethylene glycol-modified MFA microspheres significantly enhance dissolution rate and bioavailability.
- The optimized formulation leads to improved pharmacokinetic profiles, including higher C(max) and AUC values.
- Strong in vitro-in vivo correlations support the predictive value of dissolution testing for MFA microspheres.
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