The development of a meaningful dissolution procedure for drug products with limited water solubility has been a challenge to both the pharmaceutical industry and the agencies that regulate them. Enhancement of dissolution and absorption of mefenamic acid. Super disintegrants alone or in combination with polyvinyl pyrrolidine could be used to enhance the dissolution rate of mefenamic acid. Index terms solubility enhancement, complexation, cosolvency, solid dispersion, dispersible tablet, mefenamic acid. Mefenamic acid is a nonsteroidal antiinflammatory drug belongs to the biopharmaceutics classification system bcs class ii drug. Mf1, mf2 batches were formulated by direct compression. Each bluebanded, ivory capsule contains 250 mg of mefenamic acid for oral administration.
It is a member of fenamate group of nonsteroidal antiinflammatory drugs. Mefenamic acid is considered as a competitive inhibitor of cox1 and cox2. Mefenamic acid is a nonsteroidal antiinflammatory agent, acting as a competitive inhibitor of hcox1, with ic50s of 40 nm and 3. In vitro dissolution studies on solid dispersions of mefenamic acid.
Mefenamic acid medicinal forms bnf content published by nice. Peak plasma levels are attained in 24 h and the elimination halflife approximates 2 h. Stabilization of a supersaturated solution of mefenamic. Preparation and investigation of mefenamic acid polyethylene glycol sucrose ester solid dispersions mefenamic acid ma is a widely used nonsteroidal antiinflammatory nsaid drug. The term solid dispersion refers to the dispersion of one or more active ingredient in an inert carrier or matrix at solid state prepared by melting fusion, solvent, or the melting solvent method. Mefenamic acid 50mg5ml oral suspension ennogen healthcare ltd active ingredients size unit nhs indicative price drug tariff drug tariff price. Approximately fiftytwo percent of a mefenamic acid dose is excreted into the urine primarily as glucuronides of mefenamic acid 6%, 3hydroxymefenamic acid 25% and 3carboxymefenamic acid 21%. Jun 01, 2015 the mechanism of solubility enhancement was investigated using multiple methodologies, including tga, dsc, pxrd, sem and ftir. Comparative dissolution studies for mefenamic acid polyethylene glycol solid dispersion systems and tablets. Mefenamic acid is a white to greyishwhite, odorless, microcrystalline powder with a melting point of 230231c and water solubility of. Mefenamic acid tastemasked oral disintegrating tablets with.
A new selfemulsifying formulation of mefenamic acid with. Pdf mefenamic acid ma solid dispersions were prepared employing methanol as a common solvent using peg4000 as a drug carrier with two different. The solid dispersions sds were prepared by hot melting metho d at 1. Influence of the microwave technology on solid dispersions of. The results showed that the dissolution rate of mefenamic acid, and also the release of drug from witepsol h15 suppositories, were significantly increased by using egg albumin. Amaravathi vikram international journal of pharmaceutical.
Enhancement of dissolution and absorption of mefenamic acid by egg albumin teruko imai, katsuhiko nohdomi, fa. Arch nano op acc j volume 2 ssue 1 c oprig rishna sailaa et al. Dissolution rate, mefenamic acid, polyvinyl pyrrolidone. The adverse effects typical of nsaids are also present in the case of ma, partly due to its low water solubility. Formation and characterization of mefenamic acidnicotinamide. Solidstate characterization of mefenamic acid panchagnula.
Suggested that the drug was present in a eutectic mixture in a microcrystalline. Aug 27, 2014 the development of a meaningful dissolution procedure for drug products with limited water solubility has been a challenge to both the pharmaceutical industry and the agencies that regulate them. Characterisation of the thermal, spectroscopic and drug. Dissolution rate is the rate determining step in the bioavailability of the mefenamic acid. Preparation of mefenamic acid tablets mefenamic acid tablets were prepared by using pure drug and solid dispersions 1. Pdf in vitro dissolution studies on solid dispersions of. A solid dispersion generally composed of two components the drug and the polymer matrix.
Solid dispersions of mefenamic acid were prepared by common solvent method employing methanol as solvent. In vitro dissolution studies on solid dispersions of. Masaki otagiri, x faculty of pharmaceutical sciences, kumamoto university, 51 oehonmachi, kumamoto 862, japan faculty of pharmaceutical sciences, kumamoto university 51 oehonmachi kumamoto 862 japan a. Preparation and investigation of mefenamic acidpolyethylene. Solid dispersions of mefenamic acid showed a marked enhancement in dissolution rate and dissolution efficiency. Preparation and evaluation of mefenamic acid nanoparticles by nanoprecipitation technique. Powder xray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid and solution. Therefore, various methods to improve the dissolution of poorly soluble drugs have been reported and. May 25, 2016 approximately fiftytwo percent of a mefenamic acid dose is excreted into the urine primarily as glucuronides of mefenamic acid 6%, 3hydroxymefenamic acid 25% and 3carboxymefenamic acid 21%. Solid dispersions of mefenamic acid ma, with a water soluble polymer pvp and a super disintegrant namely, primojel pj, were prepared by common solvent. Mefenamic acid undergoes metabolism by cyp2c9 to 3hydroxymethyl mefenamic acid, and further oxidation to a 3carboxymefenamic acid may occur 3. The stable supersaturated solution with a high mfa concentration of 3.
Mefenamic acid is rapidly absorbed after oral administration. Introduction mefenamic acid, an anthranilic acid derivative, is a non. In patients with renal or hepatic impairment, clearance of metabolites may be decreased. Dissolution profile of the mefenamic acid was improved by solid dispersion technique. Mefenamic acid tastemasked oral disintegrating tablets. Mefenamic acid is used for the shortterm treatment of mild to moderate pain from various conditions. Nsaids like mefenamic acid may affect egg release ovulation in women.
Mefenamic acid ma is a highdose, antiinflammatory, analgesic agent that is widely indicated for pain related to menstrual disorders. Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid article pdf available in plos one 127. It is used in mild to moderate pain including headache. Mefenamic acid drug showed a peak in the region 1242, and capryol with mefenamic acid showed a peak in region 1262, mefenamic acid with span 80 showed a peak in the region 1247, mefenamic acid with propylene glycol showed a peak in the region 1214 which all indicate the presence of cn functional group in them. The aim of this study was to increase the water solubility of ma in order to influence its absorption and bioavailability. Mefenamic acid is a problematic drug in granulation, tableting, and dissolution due to its poor solubility, hydrophobicity, and tendency to stick to surfaces. Comparative dissolution studies for mefenamic acidpolyethylene glycol solid dispersion systems and tablets. The order of increasing dissolution rate was observed with increase in primojel ratio. The solid dispersions were prepared by cryogenic grinding method. Physicochemical and crystallographic characterization of mefenamic acid complexes with alkanolamines. The intermolecular interaction between mefenamic acid mfa, a poorly watersoluble nonsteroidal antiinflammatory drug, and eudragit epo epo, a watersoluble polymer, is investigated in their supersaturated solution using highresolution magicangle spinning hrmas nuclear magnetic resonance nmr spectroscopy. Mefenamic acid is typically prescribed for oral administration. The present studies were undertaken to develop solventfree solid dispersions sds for poorly soluble antiinflammatory drugs mefenamic acid.
Mefenamic acid ma using solid dispersion technique with hydrophilic polymers such as poly ethylene glycol peg, polyvinyl pyrrolidone pvp, hydroxyl. M has cytotoxic effects on kb, saos2, and 21n cells, however, u87mg cells are resistant to mefenamic acid2. In vitro and in vivo evaluation of mefenamic acid and its complexes. Comparative study on solubility enhancement methods for.
Estimation and analysis of mefenamic acid suspension. Enhancement in aqueous solubility of mefenamic acid using. Dsc thermogram of a mefenamic acid, b tromethamine, and c multicomponent crystal of mefenamic acidtromethamine. Following a single 1g oral dose, mean peak plasma levels ranging from 10 to 20 mgml have been reported. The aim of this study was to investigate the solubility of mefenamic acid ma, a highly cohesive, poorly water. Andrews gp, zhai h, tipping s, jones ds 2009 characterisation of the thermal, spectroscopic and drug dissolution properties of mefenamic acid and polyoxyethylenepolyoxypropylene solid dispersions. Ponstel mefenamic acid is a member of the fenamate group of nonsteroidal antiinflammatory drugs nsaids. Mefenamic acid ingestion, usually in excess and over prolonged period is known to produce interstitial nephritis, or less commonly papillary necrosis, with acute renal failure 1. Therefore, various methods to improve the dissolution of poorly. Multicomponent crystals of mefenamic acid with improved. Stabilization of a supersaturated solution of mefenamic acid. The aim of this study was to prepare and cha racterize solid dispersions of water insoluble non steroidal anti inflammatory drug, mefenamic acid ma, with polyethylene glycol 4000 peg4000 for enhancing the dissolution rate of the drug. The sds of ma and ffa were prepared using microwaves irradiation mw technique. Halflife 5 times longer in preterm infants compared with adults.
If you are 65 or older, use mefenamic acid with care. Stabilization of a supersaturated solution of mefenamic acid from a solid dispersion with eudragit epo article pdf available in pharmaceutical research 2910. Insights into atomiclevel interaction between mefenamic acid. Powder xray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid and solutionstate nmr spectroscopies were used to. The solid dispersions in combined carriers gave much higher rates of dissolution than super. Mefenamic acid medicinal forms bnf content published. Sep 23, 2015 mefenamic acid ponstel is an oral drug used shortterm to treat pain, including menstrual cramps. The mechanism of solubility enhancement was investigated using multiple methodologies, including tga, dsc, pxrd, sem and ftir. In most cases, the specifications of a drug by the pharmacopoeia include identification and purity, but they do not describe the physicochemical drug properties precisely. Numerous methods are existing to prepare the solid dispersions such as melting method, solvent evaporation method, fusion method, kneading method. Preparation and evaluation of mefenamic acid nanoparticles. Extreme high moderate low section 1 chemical product and company identification product name mefenamic acid statement of hazardous nature considered a hazardous substance according to osha 29 cfr 1910.
Preparation and evaluation of mefenamic acid nanoparticles by. Solidstate characterization of mefenamic acid sciencedirect. Preparation and investigation of mefenamic acid polyethylene glycol. The stabilization mechanism of a supersaturated solution of mefenamic acid mfa from a solid dispersion with eudragit epo epo was investigated. Mar 03, 2020 if you are 65 or older, use mefenamic acid with care. This goes back to normal when mefenamic acid is stopped. Introduction mefenamic acid mfa is a wellknown as nonsteroidal antiinflammatory drug figure 1 has low aqueous solubility, so its absorption in gastrointestinal tract git is limited by its dissolution, therefore has a low bioavailability after oral administration merck index, 1996. Various techniques used for characterization included microscopy. Peg4000 can be used in order to raise the dissolution rates of poorly soluble drugs such as mefenamic acid. In general, there are two approaches to enhance the solubility and dissolution rate of poorly soluble drugs. Habib comparative dissolution studies for mefenamic acidpolyethylene glycol solid dispersion systems and tablets pharm.
Pdf in vitro dissolution studies on solid dispersions of mefenamic. The solid dispersions in combined carriers gave much higher. Mefenamic acid decreases inflammation and uterine contractions by a stillunknown mechanism. Mefenamic acid ponstel is an oral drug used shortterm to treat pain, including menstrual cramps. Influence of the microwave technology on solid dispersions. Mefenamic acid ma is an active pharmaceutical ingredient that has antiinflammatory and analgesic.
Comparative dissolution studies for mefenamic acid. Mefenamic acid has been reported as being greater than 90% bound to albumin. Preparation and investigation of mefenamic acid polyethylene glycol sucrose ester solid dispersions ibolya fulop 1, arpad gyeresi 1, lorand kiss 2, maria a. Insights into atomiclevel interaction between mefenamic. It is used in the treatment of primary dysmenorrhea, soft tissue and dental pain and also has analgesic, antiinflammatory, antirheumatic and antipyretic. It is used to treat moderate pain and menstrual pain. The solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrants alone.
On the other hand, poorly soluble drugs present a big problem in pharmaceutical formulations. Pdf solid dispersions of mefanamic acid with a watersoluble polymer polyvinyl pyrrolidine and a super disintegrant, primojel were prepared. Enhancement of dissolution and absorption of mefenamic. Finally, mefenamic acid odts were successfully produced using hme solid dispersion techniques demonstrating short disintegration times, sufficient taste masking and high drug release profiles. The fecal route of elimination accounts for up to 20% of the dose, mainly in the form of unconjugated 3carboxymefenamic acid. The present studies were undertaken to develop solventfree solid dispersions sds for poorly soluble antiinflammatory drugs mefenamic acid ma and flufenamic acid ffa in order to enhance their in vitro dissolution rate and in vivo antiinflammatory effects. Mefenamic acid ma is a widely used nonsteroidal antiinflammatory nsaid drug.
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