Jessie Sofia Pamudji

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

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.

PVA-Ketoprofen Nanofibers Manufacturing Using Electrospinning Method for Dissolution Improvement of Ketoprofen

Background and purpose: Ketoprofen is an NSAIDs agent which has analgesic and anti inflammation effects. Ketoprofen is classified into class II in the biopharmaceutical classification system that has a high permeability but low solubility. Hence, the absorption rate of this substance is governed by its dissolution rate. Electrospinning is a method that combine solid dispersion technology and nanotechnology. This method can be selected to enhance the dissolution rate of active substances. The aim of this research is to improve the dissolution rate of ketoprofen through the preparation of polymeric nanofiber polivinyl alcohol (PVA) containing ketoprofen using electrospinning process. Methods: Preparation of nanofibers with various of PVA-ketoprofen ratio, flow rate, and PVA concentration in the solution were accomplished using electrospinning instrument. Casting solid dispersion film were also prepared by solvent evaporation method and used as a reference. The rates of dissolution of ketoprofen from each of nanofibers, casting films, and pure ketoprofen were conducted in HCl pH 1.2 medium at 37oC. Characterization of nanofibers was carried out using Scanning Electron Microscope (SEM) and X-ray Diffraction (XRD). Results: Nanofibers which contained of PVA-ketoprofen 1:1 in ratio w/w showed a significant improvement in dissolution (p<0.05) compared to the pure ketoprofen. Meanwhile, nanofibers obtained from a solution containing 7.5 % PVA (w/v) and 4 ml/h in flow rate showed the best dissolution rate improvement and significantly different (p<0.05) with either the casting film or the pure ketoprofen. The improvement of ketoprofen dissolution was due to the increasing of surface area of nanofiber and the change of ketoprofen from crystalline into amorphous form. Conclusion: Electrospinning technique can be used to improve the dissolution rate of ketoprofen through the PVA-ketoprofen nanofiber formation by choosing the appropriate polymer concentration and manufacturing process.