ArticlePDF Available

Abstract and Figures

This review focuses on the design, synthesis and pharmacological effects of non-steroidal anti-inflammatory (NSAIDs) mefenamic acid which is an anthranilic acid derivative. Mefenamic acid is a non-steroidal anti-inflammatory drug used to treat pain, including menstrual pain. Exploitation of the prodrug approach has the potential to achieve a reduction of mefenamic acid GI (gastrointestinal) intolerance, enhance its bioavailability, mask its unpleasant sensation and prolong its duration of action. Mefenamic acid, an effective NSAID has always been used as an anti-inflammatory and analgesic agent. A brief note on various marketed formulations of mefenamic acid provides an insight of the potential capability of this drug and its future scope.
GSC Biological and Pharmaceutical Sciences, 2019, 07(02), 052059
Available online at GSC Online Press Directory
GSC Biological and Pharmaceutical Sciences
e-ISSN: 2581-3250, CODEN (USA): GBPSC2
Journal homepage: https://www.gsconlinepress.com/journals/gscbps
Corresponding author
E-mail address:
Copyright © 2019 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution Liscense 4.0
(REVIEW ART I C L E )
An insight of non-steroidal anti-inflammatory drug mefenamic acid: A review
Srivastava Rajat 1, *, Mishra Manoj Kumar 1, Patel Amit Kumar 1, Singh Abhishek 1 and Kushwaha
Krishna 2
1 Shambhunath Institute of Pharmacy, Jhalwa, Prayagraj, Uttar Pradesh, India-211012.
2 Lutawan Institute of Pharmacy, Sakara Jaitpura, Ghazipur, Uttar Pradesh, India-233001.
Publication history: Received on 14 April 2019; revised on 11 May 2019; accepted on 14 May 2019
Article DOI: https://doi.org/10.30574/gscbps.2019.7.2.0066
Abstract
This review focuses on the design, synthesis and pharmacological effects of non-steroidal anti-inflammatory (NSAIDs)
mefenamic acid which is an anthranilic acid derivative. Mefenamic acid is a non-steroidal anti-inflammatory drug used
to treat pain, including menstrual pain. Exploitation of the prodrug approach has the potential to achieve a reduction of
mefenamic acid GI (gastrointestinal) intolerance, enhance its bioavailability, mask its unpleasant sensation and prolong
its duration of action. Mefenamic acid, an effective NSAID has always been used as an anti-inflammatory and analgesic
agent. A brief note on various marketed formulations of mefenamic acid provides an insight of the potential capability
of this drug and its future scope.
Keywords: Anti-inflammatory drugs; Mefenamic acid; Rheumatoid arthritis; Dosage formulations
1. Introduction
Mefenamic acid (MA) is an anthranilic acid derivative. In particular, it is structured as N-(2,3-xylyl) anthranilic acid. This
drug shares relatedness to 3-hydroxyanthranilic acid, a naturally occurring metabolite of tryptophan [1].
Its physicochemical properties, especially the extremely low solubility in water (<< 1 mg mL1) and distinct adhesive
properties give rise to major challenges during dosage form development and manufacturing. Hence, serious effort was
made to increase dissolution characteristics of MA to improve its biopharmaceutical performance [2].
The short biological half- life of Mefenamic acid is 2h. Conventionally it is available as tablets, capsules and suspensions.
Because of short half-life oral dose required to frequent administration of drug to maintain the desired steady state
level. The available dose for this drug is 250mg thrice a day. MA is classified as class II on the basis of biopharmaceutical
classification system, because of its poor solubility over the pH range 1.2-7.5. It is inherently highly permeable through
biological membranes, but exhibits low aqueous solubility. Due to its low solubility, various researches were done to
improve the low solubility or bioavailability such as solid dispersion and micronization. Mefenamic acid is widely used
in mild to moderate pain including headache, dental pain, dysmenorrhea, rheumatoid arthritis, osteoarthritis and other
joint disorders also leads to side effects such as gastrointestinal disorders, like gastrointestinal bleeding and gastric
upset.
Drug delivery at specific site is affected by carriers used. Carrier used should be biocompatible and immunogenic in
nature. Also, suitable for route administration and desired release profile of drug. Eudragit RL 100 and Ethyl cellulose
have been used as drug carriers to achieve sustained and controlled drug delivery for the past few decades [3].
Srivastava et al. / GSC Biological and Pharmaceutical Sciences 2019, 07(02), 052059
53
Figure 1 Structure of mefenamic acid
Table 1Characteristic feature of mefenamic acid
Characteristic feature
Description
Molecular formula
C15H15NO2
Molecular weight
241.28
Chemical name
2-[(2,3-dimethylphenyl)amino]benzoic acid
Volume of distribution
1.06 L/kg
Protein binding
90%
Half life
2 h
LD50
740 mg/kg
Solubility
0.0137 mg/mL
log P
5.4
pKa
3.89
Refractive index
71.88 m3.mol-1
Melting point
230-231
Color
White to off-white, crystalline powder
Boiling point
398.8
Density
1.2gm/cm
Molar volume
200.6 cm
1.1. Mode of action
MA binds the prostaglandin synthetase receptors COX-1 and COX-2, inhibiting the action of prostaglandin synthetase.
As these receptors have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-
dependent plasticity, the symptoms of pain are temporarily reduced.
Cox-1: Cyclooxygenase-1, an enzyme that acts to speed up the production of certain chemical messengers, called
prostaglandins, in a variety of areas of the body such as the stomach, kidneys, and sites of inflammation. In the stomach,
prostaglandins promote the production of a protective natural mucus lining. They also interact within certain cells that
are responsible for inflammation and other functions.
Cox-2: Cyclooxygenase-2, an enzyme that acts to speed up the production of certain chemical messengers, called
prostaglandins that play a key role in promoting inflammation. When cox-2 activity is blocked, inflammation is reduced.
Unlike cox-1, cox-2 is active only at the site of inflammation, not in the stomach.
1.2. Pharmcokinetics
1.2.1. Absorption
Mefenamic acid is rapidly absorbed after oral administration. Mean extent of absorption was 30.5 mcg/h/mL.
Srivastava et al. / GSC Biological and Pharmaceutical Sciences 2019, 07(02), 052059
54
1.2.2. Distribution
Apparent volume of distribution was found to be 1.06 L/Kg for 500 mg tablet.
1.2.3. Metabolism
Mefenamic acid is metabolized by cytochrome P450 enzyme CYP2C9 to 3-hydroxylmethylmefenamic acid (Metabolite
I). Further oxidation to a 3- carboxymefenamic acid (Metabolite II) may occur.
1.2.4. Excretion
Approximately 52% of a mefenamic acid dose is excreted into urine primarily as glucuronides of mefenamic acid (6%),
3- hydroxymefenamic acid (25%) and 3- carboxymefenamic acid (21%). The fecal route of elimination accounts for up
to 20% of the dose. The elimination half-life of mefenamic acid is approximately 2 h [4].
1.3. Drug interaction
(R)-warfarin: the risk or severity of gastrointestinal bleeding can be increased.
(S)-Warfarin:The risk or severity of gastrointestinal bleeding can be increased.
2, 5-Dimethoxy-4-ethylamphetamine: The risk or severity of hypertension can be increased.
4-Bromo-2, 5-dimethoxyamphetamine: The risk or severity of hypertension can be increased.
4-hydroxycoumarin: The risk or severity of gastrointestinal bleeding can be increased.
1.3.1. Side effect
Cardiovascular thrombotic
GI Bleeding, Ulceration
Hepatotoxicity
Hypertension
Renal toxicity and Hyperkalemia
Serious skin reaction
Hematologic toxicity
1.3.2. Contraindication
Methotrexate- Neutopenia, Renal dysfunction,
Aspirin- GI bleeding, Ulceration
Cyclosporine- Increase cyclosporine’s nephrotoxicity
Other NSAIDs- GI bleeding, Ulceration
2. Formulations of mefenamic acid
The suitable formulation for the synthesized drugs is always a challenge for the researchers. The compatibility of all the
components including pharmaceutical active ingredients plays significant role in designing the formulation so always it
is taken into consideration. The developed formulation should be cost effective, stable and physiologically the active
ingredients should be available on release [5].
2.1. Mefenamic acid suspension
Drugs dispensed as suspensions because of poor aqueous solubility (BCS class II). Drug formulated as suspensions are
more bioavailable than solid dosage form [6]. Possible modification of the drug’s bioavailability can be another
advantage of this dosage form, The prodrugs were already reported as chemically stable and bio-labile so for the
suspension first there is preparation of prodrug of mefenamic acid which results in delayed drug release, provides
clinically useful plasma concentration of the drug [7].
Srivastava et al. / GSC Biological and Pharmaceutical Sciences 2019, 07(02), 052059
55
2.1.1. Material
Mefenamic acid, Tween-80, Potassium chloride, Methyl cellulose, Sodium CMC, Sodium citrate, Sodium benzoate,
Glycerine, etc.
2.1.2. Preparation of suspensions of prodrugs
The weighed quantities of prodrugs were wetted by trituration with aqueous solution of wetting agent. Glycerin was
added by trituration to form smooth paste. Now water soluble ingredients (sodium citrate, sodium benzoate) were
dissolved in water and added slowly and triturated. Potassium chloride dissolved in water added with trituration.
Thereafter aqueous solution of suspending agent and syrup was added to above mixture with trituration. Then flavor
was added and mixed. The suspension so formed transferred to a measuring cylinder and volume was made to 100 mL.
Table 2List of marketed products of Mefenamic acid suspension
Sr. No.
Marketed product (Brand name)
Manufacturing company
1
Meftal-P
Blue I Cross Laboratories
2
Paramol-M
Parkinson Pharma
3
Panston
Pfizer
4
Meftagesic
Blue Cross Laboratories
5
Alide P
Altar Life Sciences
6
Nimucet MF
Intas laboratories Pvt. Ltd.
7
Zuesic Forte
Zodak Health Care Ltd.
8
M Gesic
Cure Quick Remedies
9
Pyritec M DS
Innovative Pharmaceuticals
10
Parafit M
Medlab Pharmaceuticals Pvt. Ltd.
2.2. Controlled release tablets containing mefenamic acid
Oral drug delivery system have the advantages that these are easy to administer, ease of manufacturing and higher
patient compliance. In oral drug delivery systems the most profound objective was to maintain constant drug plasma
concentrations for a certain period of time to reduce the dosage frequency and this goal achieved by the development
of controlled drug delivery system [8].
Oral sustain/controlled release drug delivery systems is dominating the market and have an increased safety and
patient compliance. These dosage forms can deliver the drug in a predetermined manner to the site of action following
drug release from matrices occurs by diffusion or degradation mechanism.
Polymers, Polyurethanes for elasticity.
Polysiloxanes or silicones for insulating ability.
Polymethyl methacrylate for physical strength and transparency.
Polyvinyl alcohol for hydrophilicity and strength.
Polyethylene for toughness and lack of swelling.
Polyvinyl pyrrolidone for suspension capabilities.
To be successfully used in controlled drug delivery formulations, a material must be chemically inert and free of
leachable impurities, controls release of drug in a slow and nearly constant manner to obtain nearly constant peak
plasma level [9, 10].
Srivastava et al. / GSC Biological and Pharmaceutical Sciences 2019, 07(02), 052059
56
2.2.1. Material
Mefenamic acid, sodium hydroxide, mono basic potassium phosphate, caboxy methyl cellulose, starch, lactose and
magnesium stearate.
2.2.2. Formulation of tablets
Mefenamic acid 200 mg controlled release matrix tablets were prepared using 100 mg drug and weighing
concentrations of polymer and excipients. Starch was used as filler and magnesium stearate was used a lubricant.
2.2.3. Preparation of tablets
Drug and polymer was taken in mortar and was grind to fine powder than all other excipients were added except
lubricant. This mixture was passed through 20 sieve size mesh for three times and then lubricant was added and again
passed through the same sieve. The prepared powder was compressed to tablets using single punch tabletting machine
at an average hardness of 7 kg/cm2.
Table 3List of marketed products of Mefenamic acid tablet
Sr.
No.
Marketed products
(Brand name)
Manufacturing company
1
Abdrot Plus
CaptabBiotec
2
Alide-P
Altar Pharma
3
MefProxyvon
Wockhardt
4
Meflup
Lupin
5
Meflup Forte
Lupin
6
Ponstan
Pfizer
7
Meftal 500
Blue Cross Laboratories
8
Biospas Forte
Biochem
9
Mictal 250
Biochem
10
Meff P
Bastochem
2.3. Mefenamic acid emulgel for topical delivery
Gels are a relatively newer class of dosage form created by entrapment of large amounts of aqueous or hydroalcoholic
liquid in a network of colloidal solid particles, which may consist of inorganic substances, such as aluminum salts or
organic polymers of natural or synthetic origin. They have a higher aqueous component that permits greater dissolution
of drugs, and also permit easy migration of the drug through a vehicle that is essentially a liquid, compared with the
ointment or cream base. In spite of many advantages of gels a major limitation is in the delivery of hydrophobic drugs
[11].
So to overcome this limitation, emulgels are prepared and used so that even a hydrophobic therapeutic moiety can enjoy
the unique properties of gels [12]. When gels and emulsions are used in combined form the dosage forms are referred
as EMULGELS [13].
In recent years, there has been great interest in the use of novel polymers with complex functions as emulsifiers and
thickeners because the gelling capacity of these compounds allows the formulation of stable emulsions and creams by
decreasing surface and interfacial tension and at the same time increasing the viscosity of the aqueous phase [14].
Emulgels for dermatological use have several favorable properties such as being thixotropic, greaseless, easily
spreadable, easily removable, emollient, non-staining, long shelf life, bio-friendly, transparent and pleasing appearance
[15].
2.3.1. Material
Mefenamicacid, carbopal 940, liquid paraffin, tween 20, span20, propylene glycol, methyl paraben, ethyl paraben,
mentha oil, clove oil, water.
Srivastava et al. / GSC Biological and Pharmaceutical Sciences 2019, 07(02), 052059
57
2.3.2. Preparation of emulgel
The gel phase in the formulations was prepared by dispersing Carbopol 940 in purified water with constant stirring at
a moderate speed using mechanical shaker, then the pH was adjusted to 66.5 using tri ethanol amine (TEA). The oil
phase of the emulsion was prepared by dissolving span 20 in light liquid paraffin while the aqueous phase was prepared
by dissolving tween 20 in purified water. Methyl and ethyl parabens were dissolved in propylene glycol whereas
mefenamic acid was dissolved in ethanol, and both solutions were mixed with the aqueous phase. Clove oil and mentha
oil were mixed in oil phase. Both the oily and aqueous phases were separately heated to 7080ºC, then the oily phase
was added to the aqueous phase with continuous stirring until it got cooled to room temperature. The obtained
emulsion was mixed with the gel in 1:1 ratio with gentle stirring to obtain the emulgel [16].
Table 4 List of marketed products of NSAIDS emulgel
Sr. No.
Marketed products (Brand name)
Manufacturing company
1
Volini GEL
Ranbaxy Laboratories
2
DiclonEmulgel
Med Pharma
3
Voltaren
Novartis Pharma
4
Voltarol Emulgel P
Glaxo Smith Kline Pharma
5
Isofen Emulgel
Beitjala Pharma
2.4. Topical gel containing microsponges of mefenamic acid
The microsponge delivery system is patented polymeric system consisting of porous microsphere. They are tiny sponge
like spherical particles that consist of myriad of inter connecting void within a non-collapsible structure through which
active ingredient are released in a controlled manner. Microsphere surrounded by the vehicle acts like microscopic
sponges, storing the active ingredient until its release is triggered by skin application. Release of drug into the skin is
triggered by a variety of stimuli, including rubbing and higher skin temperature than ambient one. Their high degree of
cross linking results in particles that are insoluble, inert and of sufficiently strong strength to withstand the high shear
commonly used in creams, lotions, and powders [17, 18].
The microsponges were prepared by free radical suspension method or quassi emulsion solvent diffusion method. It was
shown that the drug: polymer ratio, stirring rate, volume of dispersed phase influenced the particle size and drug release
behavior of the formed microsponges and that the presence of emulsifier was essential for microsponge formation [19].
2.4.1. Material
Mefenamicacid, eudragit RS100, eudragit RL 100, ethyl cellulose, polyvinyl alcohol, ethanol, carbopol 934P,
triethaolamine, distilled water
2.4.2. Formulation of mefenamic acid loaded microsponges
Microsponge were prepared by quasi-emulsion solvent diffusion method using an external phase of distilled water and
polyvinyl alcohol (PVA), and internal phase consisting of drug, ethyl alcohol, polymer(ethyl cellulose, eudragit RS100 &
eudragit RL 100) and glycerol (which was added at an amount of 20% of the polymer in order to facilitate the plasticity).
For preparing microsponge, the internal phase was prepared and added to the external phase at room temperature.
After emulsification process is completed, the mixture was continuously stirred for 2 h at 500 rpm. Then the
microsponges were separated by filtration. The product was washed and dried under vacuum oven at 40°C for 12 h [20,
21].
2.4.3. Mefenamic acid microsponge gel
Accurately weighed amount of carbopol 934 P was taken and dissolved in water using propeller. Microsponge
formulations containing mefenamic acid was added to the above solution with constant stirring. This final solution was
neutralized slowly adding triethanolamine with constant stirring until the gel is formed [22].
Srivastava et al. / GSC Biological and Pharmaceutical Sciences 2019, 07(02), 052059
58
Table 5List of other marketed products of Mefenamic acid
Sr. No.
Marketed products (Brand name)
Manufacturing company
1
Mefpra (Syrup)
Immune Life Sciences
2
Ladex P (Syrup)
Allenge India
3
Migesic (Syrup)
Hauz Pharma Pvt. Ltd.
4
Nimley P (Syrup)
Zodley Pharmaceutical Pvt. Ltd.
5
Zuesic P (Syrup)
Zodak Health Care
6
Nukind M (Syrup)
Ambic Aayurchem
7
Mifucet (Suppository)
Intas Pharmaceuticals Ltd.
8
Armef Forte (Capsule)
Ardor Drugs Pvt. Ltd.
3. Conclusion
Mefenamic acid, a BCS class II drug gives a reason to improve its solubility and by studying about its formulations it
gives major goal for formulation development of modified drug delivery system such as Nanocrystals, Nanostructured
lipid carriers etc. for improved bioavailability of the drug at desired site of action.
Compliance with ethical standards
Acknowledgments
All authors are highly grateful to their respective management for encouraging this work.
Disclosure of conflict of interest
The review article bears no conflict of interest.
References
[1] Winder CV. (1966). Experimental observations on flufenamic, mefenamic, and meclofenamic acids. I.
Pharmacology. Annals of Physical and Rehabilitation Medicine, Suppl. 7-16.
[2] Sriamomsak P, Limmatvapirat S, Piriyaprasarth S, Mansukmanee P and Huang Z. (2015). A new emulsifying
formulation of mefenamic acid with enhanced drug dissolution. Asian Journal of Pharmaceutical Sciences, 10(2),
121-127.
[3] Patel KC and Pramanik S. (2014). Formulation and characterization of Mefenamic acid loaded polymeric
nanoparticles. World Journal of Pharmacy and Pharmaceutical Sciences, 3(6), 1391-1405.
[4] Shah K, Shrivastava SK and Mishra P. (2014). Formulation and evaluation of suspensions: Mefenamic acid
prodrugs. Pakistan Journal of Pharmaceutical Sciences, 27(4), 917-923.
[5] Ansel HC and Popovish NK (1995). Pharmaceutical dosage forms and drug delivery system, sixth edition. BI
Waverly Pvt. Ltd., New Delhi, India, 253-254.
[6] Shah K, Shrivastava SK and Mishra P. (2013). Evaluation of mefenamic acid mutual prodrugs. Medicinal Chemical
Research, 22(1), 70-77.
[7] Usman M, Ali I, Bibi H, Iqbal J and Iqbal K. (2012) Preparation and evaluation of controlled release tablets
containing Mefenamic acid. Journal of Clinical and Experimental Pharmacolology, 2(1), 107.
[8] Kumar L and Verma R. (2010). In vitro evaluation of topical gel prepared using natural polymer. International
Journal of Drug Delivery 2, 58-63.
Srivastava et al. / GSC Biological and Pharmaceutical Sciences 2019, 07(02), 052059
59
[9] Shah SU, Shah KU, Rehman A and Khan GM. (2011). Investigating the in vitro drug release kinetics from controlled
release diclofenac potassium-ethocel matrix tablets and the influence of co-excipients on drug release patterns.
Pakistan Journal of Pharmaceutical Sciences, 24(2), 183-192.
[10] Khullar R, Kumar D, Seth N and Saini S. (2012). Formulation and evaluation of mefenamic acid emulgel for topical
delivery. Saudi Pharmaceutical Journal, 20(1), 63-67.
[11] Steiger M. (2004).Topical emulsion, gel composition comprising diclofenac sodium. European Patent
Specification no. WO/2004/017998).
[12] Mohamed MI. (2004). Optimization of chlorphenesinemulgel formulation. AAPS Journal, 6 (3), 81-87.
[13] Gupta A, Mishra AK, Singh AK, Gupta V and Bansal P. (2010). Formulation and evaluation of topical gel of
diclofenac sodium using different polymers. Drug Invention Today, 2(5), 250-253.
[14] Stanos, SP. (2007). Topical agents for the management of musculoskeletal pain. Journal of Pain Symptom
Management, 33(3), 342-355.
[15] Jain A, Deveda P, Vyas N, Chauhan J, Khambete H and Jain S. (2011). Development of antifungal emulsion based
gel for topical fungal infection(s). International Journal of Pharmaceutical Research and Development, 2 (12), 18-
25.
[16] Shuhaib B and Suja C. (2019).Studies on formulation and characterization of topical emulgel containing
microsponges of mefenamic acid. European Journal of Pharmaceutical and Medical Research, 6(1), 314-326.
[17] Embil K and Nacht S. (1996). The microsponge delivery system (MDS): a topical delivery system with reduced
irritancy in-cooperating multiple triggering mechanism for the release of actives. Journal of Microencapsulation,
13(5): 575-588.
[18] Comoglo T, Gonul N and Baykara T. (2003). Preparation and in vitro evaluation of modified release ketoprofen
microsponges. Farmaco, 58(2), 101-106.
[19] Ali N, Mitra J, Mohammad-Reza S and Siavoosh D. (2005). The effect of formulation type on the release of benzoyl
peroxide from microsponges. Iranian Journal of Pharmaceutical Sciences, 1(3), 131-142.
[20] Mahaparale PR, Nikam SA and Chavan MS. (2018). Development and evaluation of terbinafine hydrochloride
polymeric microsponges for topical drug delivery. Indian Journal of Pharmaceutical Sciences, 80(6), 1086-1092.
[21] Mandava SS and Thavva V. (2014). Novel approach: microsponge drug delivery system. International Journal of
Pharmaceutical Sciences and Research, 3(4), 967-980.
[22] Swetha A, Rao GM, Ramana VK, Niyaz BB and Reddy KV. (2011). Formulation and in vitro evaluation of etodolac
entrapped in microsponge based drug delivery system. International Journal of Pharmacy, 1(2) 73-80.
How to cite this article
Srivastava R, Mishra MK, Patel AK, Singh A and Kushwaha K. (2019). An insight of non-steroidal anti-inflammatory drug
mefenamic acid: A review. GSC Biological and Pharmaceutical Sciences, 7(2), 52-59.
... Mefenamic acid is widely used in mild to moderate pain including headache, toothache, dysmenorrhea, rheumatoid arthritis, osteoarthritis and others [10]. Based on research ...
Conference Paper
Full-text available
Self-medication refers to the use of medications without consulting a doctor. This study aimed to determine the effect of education on students’ knowledge about self-medication of mefenamic acid using Powerpoint slides at the Luhur Islamic Boarding School in Malang City. This was quantitative research with a pre-experimental method and a one-group pretest-posttest design. The number of samples needed was determined using the Slovin formula, and 70 respondents participated. Data were collected using a questionnaire. Respondents filled out the pretest questionnaire to determine the knowledge related to self-medication of the drug mefenamic acid, then the researcher delivered the education by using Powerpoint slides and after that the posttest questionnaire was distributed. The data were analyzed using the Wilcoxon test. The pretest and posttest values were significantly different (p < 0.05). Therefore, we can conclude that education about self-medication of mefenamic acid using Powerpoint slides had an effect on the knowledge of students at the Luhur Islamic Boarding School in Malang. Keywords: self-medication, mefenamic acid, education, Powerpoint slides, knowledge level
Article
Background During the development of the new formulations, the hydrophobic drugs face many problems leading to poor water solubility and problems related to bioavailability. Topical drug delivery is a popular and unique process that directs the action of various drugs on the skin for the treatment and diagnosis of various diseases and disorders such as urticaria, inflammation, rheumatism, etc. This topical release system is usually used to escape the first-pass metabolism. An emulgel is a superior formulation with combined advantages of both an emulsion and agel. Gel preparations normally offer earlier drug release than other predictable ointments and creams. Objective The main aim of this review is to deal with the problems associated with the delivery of hydrophobic drugs and to tackle these problems using an emulgel formulation. Emulgel mainly provides better stability, prolonged local contact, controlled release of drugs with short half-life, and better loading capacity. Methods The review was extracted from the searches performed in PubMed, Google Patents, Medline, and Google Scholars, etc. Data from these searches were collected and evaluated to get information about the available literature on the emulgel formulation. The literature obtained was studied thoroughly as per the requirement of the objective of this review. Results The details of the emulgel formulation, the advantages and disadvantages associated with it, and the methods for characterization of the formulation are compiled here in this review. Along with this, some reported patents have also been included in this review to conclude the future of emulgel formulation in topical drug delivery. Conclusion Emulgel is becoming very popular as a drug delivery system to deliver many antifungal, analgesics, anti-acne, anti-inflammatory drugs, and a number of cosmetics with a wide scope to be explored further. This review article is motivated by the formulation, characterization, patents, and biological activities of emulgel formulation.
Article
A cocrystal of mefenamic acid (MA) - nicotinamide (NA) has been reported to increase the solubility of MA, but it still does not exceed the solubility of sodium mefenamate (SM). Accordingly, this research dealt with a new salt cocrystal arrangement of SM – NA. Cocrystal screening was performed, followed by powder and single-crystal preparation. Solvent drop grinding and slow evaporation at cold and ambient temperatures were employed to produce the multicomponent crystal. Two new salt cocrystals were found as hemihydrates and monohydrates, named SMN-HH and SMN-MH, respectively. SMN-MH single crystals were successfully isolated and analyzed using a single crystal X-ray diffractometer. Pharmaceutical properties were investigated, including hydrate stability, solubility, and intrinsic dissolution. The experiments showed that the hemihydrate was stable under ambient humidity and temperature, and that the monohydrate rapidly changed to hemihydrate. Both hydrates improved the solubility and intrinsic dissolution of SM, but SMN-HH was superior. The data showed that SMN salt cocrystals combine the advantages of salt and cocrystals and show potential for dosage form development.
Article
A series of d‐glucose derived N‐glycopeptides containing mefenamic acid have been synthesised and in vitro evaluation of all these molecules have been performed as COX‐2 (human) enzyme inhibitor using Enzymes Immuno Assay kit. These studies were further supported by docking experiments on human COX‐2 enzyme (PDB ID: 5IKR). All the compounds exhibited a fair amount of COX‐2 enzyme inhibition during both the modes of study and tryptophan derivative showed the best activity. Acute toxicity (LD50) in rat has also been evaluated using General Unrestricted Structure‐Activity Relationships (GUSAR) software, where acute oral toxicity for most of the molecules was found to be less than the pure mefenamic acid. Eight new N‐glycoconjugates containing amino acids with hydrophobic side chain and mefenamic acid have been synthesized and their COX‐2 inhibition potential has been explored. Both, in vitro and in silico studies on inhibition are found to be complementary, where best result was obtained for tryptophan derivative. Acute toxicity (LD50) in rat has also been evaluated using GUSAR software, where acute oral toxicity for most of the glycoconjugates was found to be less than the pure mefenamic acid.
Article
Full-text available
In this study, we tried to formulate and evaluate the Mefenamic acid (MA) nanoparticles. Mefenamic acid loaded nanoparticles made up of polymers Eudragit RL 100 and Ethyl cellulose were prepared by nanoprecipitation and solvent evaporation method, using Pluronic F68 as stabilizer. Drug and polymer compatibility study was carried out with FTIR and DSC study and results indicated that there were no interaction between drug and polymers. The nanoparticles were characterized in terms of nanoparticle size, surface morphology, encapsulation efficiency, in vitro drug release profile, release kinetics and stability study. Results indicated that the particle size, drug entrapment efficiencyand drug release rate was influenced by verifying polymer ratio. The release rate of nanoparticles could be controlled by adjusting the combination of polymers in different ratios. The particle size analysis data revealed that the average particle size of the optimized formulation was 278.88 nm and the entrapment efficiency was 91.04% and drug release of about 95% at 12 th hour. The in-vitro release profiles from nanoparticles were fitted into various kinetic models and the best fit with the highest correlation coefficient was observed in zero order plot, indicating that the predominant release mechanism was controlled release. The release profiles of MA nanoparticles stored at temperature of 3-5°C was stable during three months of storage condition. These results indicate that prepared MA nanoparticles could be prepared providing a sustained release in the intestine region and increase the solubility of MA.
Article
Gastrosparing novel prodrugs (MAM and MAT) synthesized consisted of mefenamic acid (MA) with menthol (M) and thymol (T). Structural characterizations of synthesized esters were done by Infra red spectroscopy (IR), proton nuclear magnetic resonance (1HNMR), mass spectroscopy. After evaluation of pharmacological i.e. anti-inflammatory, analgesic and ulcerogenic activities, the preformulation studies were undertaken. Based on these a few formulation (suspensions) were designed and prepared. The formulated suspensions were evaluated for content uniformity, sedimentation volume, recovery studies, redispersibility, viscosity, pH, particle size, zeta potential, effect of temperature and in-vitro dissolution rate. All the above parameters were found to be within the limit these indicated that the synthesized esters are good candidate for liquid dosage form. Thus it can be concluded synthesized prodrugs can be formulated in suspension form.
Article
A wide choice of vehicles ranging from solids to semisolids form has been used for skin care and topical treatment of dermatological disease, High molecular weight water soluble polymers of Hydroxypropyl methylcellulose (HPMC), Carbapol 934P, Sodium alginate that possess very high viscosity, transparency, film forming properties at low concentration, are reported to useful in formation of gel. In the present investigation Diclofenac sodium gels were prepared for topical drug delivery by using different concentration of HPMC, Sodium alginate, Carbapol 934P, with an objective to increase transparency and spreadability. From the study it was concluded that HPMC gel containing Diclofenac sodium showed good consistency, homogeneity, spreadability and stability and has wider prospect for topical preparations as compared to Sodium alginate, Carbapol 934P gel containing Diclofenac sodium.
Article
Mutual prodrugs consisting of mefenamic acid with menthol and thymol have been synthesized as a gastrosparing NSAIDs, devoid of ulcerogenic side effects. The structures of synthesized esters were confirmed by IR, 1H NMR, and mass spectroscopy. The kinetics of ester hydrolysis was studied in nonenzymatic buffer solutions, at pH 2 and 7.4 as well as in human plasma by HPLC. Its anti-inflammatory, analgesic, and ulcerogenic activities were evaluated. Then biochemical parameters (GWM and Hexosamine), oxidative parameters (LPO, GSH, CAT, and SOD), and protein estimation was also done. The results indicated that synthesized prodrugs are chemically stable, biolabile, and posses optimum lipophilicity. The synthesized prodrugs are characterized by better ulcer index than the parent drug.