Dissolution Profile of Mefenamic Acid Solid Dosage Forms in Two Compendial and Biorelevant (FaSSIF) Media

Abstract

Mefenamic acid is a non-steroidal anti-inflammatory drug (NSAID) that is widely used for the treatment of mild-to-moderate pain. Mefenamic acid belongs to the Biopharmaceutical Classification System (BCS) class II drug which has lower water solubility but high permeability. There are two different compendial methods available for dissolution tests of mefenamic acid solid dosage forms, i.e. methods of United States Pharmacopeia 37 (USP) and Pharmacopoeia of the People’s Republic of China 2010 (PPRC). Indonesian Pharmacopeia V ed. (FI) adopted the USP method. On the other hand, many researches focused on the use of a ‘biorelevant’ medium to develop the dissolution test method. The aim of this research was to study the dissolution profile of mefenamic acid from its solid dosage forms (caplet and capsule) available in the Indonesian market with three different dissolution medium: USP, PPRC, and biorelevant fasted simulated small intestinal fluid (FaSSIF) media. The tested products consisted of the innovator’s product (available only in caplet dosage form, FN caplet) and generic products (available as caplet and capsule). The dissolution test of the drug products in all dissolution media was performed in 900 mL of medium using apparatus II (paddle) at a temperature of 37°C and rotation speed of 75 rpm, except for the capsule product and for USP medium, both of which tests were done using apparatus I (basket) with rotation speed of 100 rpm. The solubility test of mefenamic acid was carried out in all media at temperature of 37°C. The result obtained from the solubility test showed that the the highest solubility of mefenamic acid was obtained in USP medium (approximately 2 mg/mL), followed by PPRC medium (about 0.5 mg/mL), and FaSSIF medium (approximately 0.06 mg/ml). In the dissolution test, percentage of drug dissolved in in the USP and PPRC media after 45 min for all products reached more than 75%, except for the PN caplet in USP medium which reached only about 44%. Meanwhile, in the biorelevant medium, the percentage of drug dissolved for all products did not exceed 16%. In all dissolution media, the capsule dosage form achieved the highest dissolution rate.

Nanoplatforms of Manganese Ferrite Nanoparticles Functionalized with Anti‐Inflammatory Drugs

“…The mixture of the two forms existing at the pH region of 2–5 seems to be the key of balanced dissolution and absorption rate . As far as mefenamic acid concerned the dissolution rate increases with pH reaching its maximum at pH = 9 . In case of NAP, the solubility is low at the pH region 2.2 to 5.8 due to unionization of drug, while an intermediate dissolution rate is recorded at pH = 6.4.…”

Modeling of Disintegration and Dissolution Behavior of Mefenamic Acid Formulation Using Numeric Solution of Noyes-Whitney Equation with Cellular Automata on Microtomographic and Algorithmically Generated Surfaces

“…The necessity to use such a large value for an unstirred diffusion layer thickness is dictated by the experimental data [22] and a tendency to produce a cone of powder at the bottom of the dissolution vessel, where mass migration processes are solely diffusion-driven. Unlike the suggested paddle rotation speed [22], the dissolution test was carried out at 75 rpm to reduce the cone effect impact on the release rate [40]. Despite this change, the cone was still clearly observable, and a further increase in the rotation rate would introduce a significant deviation from the literature reference profiles.…”

From structure to crystallisation and pharmaceutical manufacturing: the CSD in CMAC workflows

“…Fenamic acid derivatives are a class of NSAIDs that are known to display challenging properties for industrial recrystallisation, including diverse conformational polymorphism, 17,18 high hydrophobicity and particle adhesion, 19 and low aqueous solubility leading to reduced bioavailability. 20 MC crystallisation offers a route to modify the crystal form, targeting improved physical properties and processability.…”