Correlation between dissolution rate and bioavailability of different commercial mefenamic acid capsules

Shinkuma, Denji; Hamaguchi, Tsuneo; Yamanaka, You; Mizuno, Nobuyasu

doi:10.1016/0378-5173(84)90093-0

Cited by 24 publications

(12 citation statements)

References 20 publications

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“…The objective of this study was to formulate the drug in such a way to attain peak plasma levels with a smaller dose and fewer side effects. The observed C max for the proposed formula O of this study after a single 250-mg oral dose was 5.90 µg/ml ± 0.60, which is more than half the value reported in another study after a single 1-gram dose [16]. Therefore, it could be suggested that a 500-mg dose of our proposed formula could probably provide therapeutic plasma levels comparable to those obtained after a 1-gram dose of the untreated drug.…”

Section: Discussionsupporting

confidence: 63%

“…The reported peak plasma level after a 1-gram oral dose was found to be 10 µg/ml [16]. However, after oral administration of 250 mg 3 times daily for 4 days to 10 subjects, C max of 0.3–2.4 µg/ml were attained [17].…”

Section: Discussionmentioning

confidence: 99%

“…This higher bioavailability could be due to the improvement of the dissolution of formula O. Finholt [18] has stated that the rate of the dissolution of drugs from capsules is a complex function of the rates of different processes, such as the solution of the gelatin shell, the penetration of water into the powder mass, the deaggregation of the powder mass and the dissolution of the drug particles. However, despite these complex processes, the drug from a well-formulated product may be released within 5–10 min after oral administration of a capsule [16]. The deaggregation rate and solubility of the drug released into digestive fluids after the disintegration of a capsule have been reported to exert an influence on the absorption of the drug concerned [19,20].…”

Section: Discussionmentioning

confidence: 99%

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In vitro/in vivo Correlation of Fast Release Mephenamic Acid Microspheres in Humans

et al. 2011

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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 andMethods: 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.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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In vitro/in vivo Correlation of Fast Release Mephenamic Acid Microspheres in Humans

et al. 2011

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“…2) should be good candidates for the development of in vitro / in vivo relationships using dissolution rate as a predictor for in vivo performance. Indeed, the possibility of such an approach has been investigated in the literature 74, 75. One additional interesting aspect of the study by Shinkuma et al74 provides further evidence that dissolution rate is the primary barrier to oral bioavailability.…”

Section: Results‐selected Example Drugsmentioning

confidence: 99%

The Developability Classification System: Application of Biopharmaceutics Concepts to Formulation Development

Butler

Dressman

2010

Journal of Pharmaceutical Sciences

343

194

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“…Mefenamic acid solubility in water is 0.04 mg mL -1 (14). Mefenamic acid is rapidly absorbed after oral administration.…”

mentioning

confidence: 97%

Formulation and evaluation of mefenamic acid sustained release matrix pellets

Ibrahim

2013

Acta Pharmaceutica

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Interest in pellets as dosage forms has been increasing continuously. Several therapeutic advantages could be achieved by using pellets as a drug delivery system, over the single-unit regimen, such as less irritation of the gastrointestinal tract and a lowered risk of side effects due to dose dumping (1 The objective of the study was to prepare mefenamic acid (MA) sustained release matrix pellets and investigate the formulation parameters affecting pellet attributes and drug release in vitro. A mixer torque rheometer (MTR) was used to characterize the rheological properties of wet mass used in pellet formulation. Mefenamic acid pellets were prepared by extrusion/spheronization techniques using microcrystalline cellulose (MCC) in combination with lactose as pellet forming agents and water as the binding liquid. Also, the prepared pellets were characterized for their particle size and in vitro drug dissolution. The results revealed that the increase in lactose weight ratio to MCC resulted in a significant reduction of both maximum torque and binder ratios, while the addition of 2 % (m/m) polyvinyl pyrolidone (PVP) to MCC-lactose influenced only the mean torque rather than the wetting liquid (water). Particle size ranged from 945 to 1089 mm and had small span values (0.56-0.67). Furthermore, an inverse relation was observed between the rheological character of pellet wet masses (expressed by peak torque) and in vitro release rate. Increasing MA loading from 2.5 to 5 and 10 % was accompanied by a decrease in dissolution rates. In conclusion, properties of MA matrix pellets could be successfully monitored by controlling the wet mass characteristics by measuring torque.

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Correlation between dissolution rate and bioavailability of different commercial mefenamic acid capsules

Cited by 24 publications

References 20 publications

In vitro/in vivo Correlation of Fast Release Mephenamic Acid Microspheres in Humans

In vitro/in vivo Correlation of Fast Release Mephenamic Acid Microspheres in Humans

The Developability Classification System: Application of Biopharmaceutics Concepts to Formulation Development

Formulation and evaluation of mefenamic acid sustained release matrix pellets

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