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Evaluation of Physiochemical Characteristics of Mefenamic Acid CR tablets containing - Methocel K100M Premium EP as Drug Release Controlling Polymer

Muhammad Usman1, Muhammad Tariq Khalil1, Hafsa Bibi2, Irshad Ali2, Javeid Iqbal3, Altaf Hussain4
  1. 1Mohi-Ud-Din Islamic Institute of Pharmaceutical Sciences, Mirpur, AJ&K
  2. Department of Chemistry, Gomal University, Dera Ismail Khan, KPK, Pakistan
  3. Faculty of Pharamcy, Hamdard University, Karachi
  4. Pakistan Institute of medical sciences, Islamabad
Corresponding Author: Muhammad Tariq Khalil Mohi-Ud-Din Islamic Instituteof Pharmaceutical Scienecs, Mirpur, AJ&K e-mail: star82_hmtk@hotmail.com
Received:05 October 2012 Accepted: 14 October 2012
Citation: Muhammad Usman, Muhammad Tariq Khalil, Hafsa Bibi, Irshad Ali, Javeid Iqbal, Altaf Hussain “Evaluation of Physiochemical Characteristics of Mefenamic Acid CR tablets containing - Methocel K100M Premium EP as Drug Release Controlling Polymer” Int. J. Drug Dev. & Res., October-December 2012, 4(4):279-283. doi: doi number
Copyright: © 2010 IJDDR, Muhammad Usman et al. This is an open access paper distributed under the copyright agreement with Serials Publication, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Abstract

The controlled release dosage form is now a days getting more attraction than the conventional dosage form. In the recent study, our aim was to develop the CR tablets of Mefenamic Acid (NSAID). In this study Methocel K100 M Premium EP was used as polymer to control the release of drug from the tablets. Three different formulations were designed by changing the ratio of the drug to polymer ratio. The dissolution profiles and the release kinetic studies reveal that the designed formulations fulfill the requirements for the controlled release dosage form. Hence, the designed formulations can successfully be used for the commercial production of the controlled release tablets of the Mefenamic Acid.

Keywords

Controlled Dosage Form, Release Kinetics, tablets, Dissolution Study, Polymer, Methocel

Introduction

Mefenamic acid belongs to NSAIDs group of drug. Chemically it is a derivative of benzoic acid. Its IUPAC name is 2-(2,3-dimethylphenyl)aminobenzoic acid. Orally, its bioavailability is 90% with a protein binding of 90%. It is mainly metabolized in the liver with CYP2C9 enzyme system and excreted via renal and fecal route (1). It is mainly indicated for to overcome the inflammation, however, it is also prescribed for the prophylaxis of perimenstrual migraine headache (2).
The conventional immediate release tablets have some limitation as dosage form such as frequent side effects and noncompliance of the patients towards dosage regimen. In order to overcome such problems, the Mefenamic acid is now-a-days available as controlled release dosage form (3). Controlled drug delivery is one which delivers the drug at a predetermined rate, for locally or systemically, for a specified period of time. Thus the controlled release drug dosage form provides Continuous oral delivery of drugs at predictable and reproducible kinetics for predetermined period throughout the course of GIT (4, 5, 6).
The aim and focal point of this study is to design and formulate the controlled release tablets of Mefenamic acid tablets by using Methocel K100M premium EP (Methyl Cellulose) as polymer to control the release of active from the tablets. During this work, there was evaluation of dissolution kinetics of the CR Mefenamic acid tablets along with checking the effects of various excipients over release kinetics.

Material & Methods

Chemicals & Instrumentation

The Chemical materials used in the research work included Sodium Hydroxide (Merck, Germany), Mono basic potassium phosphate (Merck, Germany), Carboxy Methyl Cellulose (Dow Chemical Co., Midland USA), Starch (Dow Chemical Co., Midland USA), Mefenamic Acid (Gift sample from Bio Labs Pharma Islamabad, Pakistan), Lactose and Magnesium stearate (BDH Chemical Ltd., Pool England), and Methocel K100M Premium EP (Dow Chemical Co., Midland USA).
The instruments used during the manufacturing and evaluations of tablet were Dissolution Apparatus (Pharma Test), Electronic Balance Model No, AX- 200 (Shimadzu, Japan) Single Punch Tablet machine (Erweka AR 400, Germany), UV-Visible spectrophotometer (UVIDEC-1601 Shimadzu, Japan), Friability Tester (Erweka TA3R, Germany) and Hardness Tester (Erweka Apparatus TB24, Germany).

Pre-formulation Study:

Tablet Formulations:e

In this study, the average theoretical weight of compressed tablets was 200mg. This weight include 100mg of the API i.e. Mefenamic acid and the rest of the weight was polymer (Methocel K100M Premium EP) and that of various excipients used. The formulations were altered by using different ratios of polymer and excipients. The table 1 shows the diverse formulations intended in this study.

Physical Analysis of Mixed Powder:

For physical analysis, the mixed powder of drug and polymer was evaluated using numerous QC tests. The angle of repose was determined using funnel method. And the compressibility index was calculated by cylindrical method. All these tests were performed as per USP guidelines.

Tablet Processing:

The active drug and polymer was grind to fine powder with the help of pestle and mortar, then all other excipients except lubricant were added. 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 tableting machine at an average hardness of 7 kg/cm2.

Physical Analysis of Tablets:

During physical analysis procedure, the hardness of the tablets was determined by hardness tester (Erweka Apparatus TB24, Germany) and dimensional tests were performed using Vernier calliper. The friability of the tablets was determined using Friability tester (Erweka TA3R, Germany).

Study of Drug Release Kinetics:

PharmaTest dissolution apparatus was used to check the in- vitro drug release studies of prepared Mefenamic acid CR tablets. This was done by USP apparatus I; at 100 rpm by using phosphate buffer pH 7.2 as dissolution medium in each station (900 ml). The Samples (5ml) were withdrawn from the each station at specific time intervals for the analysis of drug concentration. Then, each sample was analyzed for drug concentration by using UV visible spectrophotometer at 350 nm wavelength.
The data of dissolution profiles were fitted in several kinetic models and drug release mechanism from tablets were calculated. These kinetic models include:
(i) Zero-order Kinetics W = k1 t
(ii) First-order Kinetics ln (100 - W) = ln100 - k2 t
(iii) Hixon Crowel’s Equation (erosion model) (100 –W) 1/3 = 100 1/3 - k3t
(iv) Higuchi’s Square of Time Equation (diffusion model)
W = k4 t 1/2
(v) Power Law Equation (diffusion/relaxation model) Mt / M = k5 t n
Where
W = Percent release of drug at a time t,
K1-k4 = Release rates constants
Mt/M = Fractional release of the drug into the dissolution medium
k5 = Constant which incorporates geometric and structural characteristic of tablets
n = Diffusion exponent that characterizes the release of the drug transport mechanism (7).

Results and Discussion

Physical Tests of Powder

The physical parameters such as hardness, dimensional, and friability tests related to CR tablets of Mefenamic acid containing Methocel K100M Premium EP as polymer are given in table 2. The Hardness of the tablets was in the range from 6.4-7.2 ± 0.168 kg/cm2 which were within the acceptable range. The thickness of tablets was less than 2.6 ± 0.05mm which. The diameter of the tablets was found 8 ± 0.007mm, which were within the USP range i.e. (4-13mm). The friability test was performed and the loss of weight of the tablets was from less than 0.28±0.01 % which was in the USP acceptable friability range (< 0.8%).

Dissolution study:

The release profiles of the test formulations of Mefenamic acid and Methocel K100M Premium EP (i.e. F1, F2, F3) as compared to that of the reference standard formulation are shown in figure 1, 2, and 3. As shown in figure Mefenamic acid formulations prepared by this method with Methocel K100 M Premium extends the release of drug.
The Kinetic Parameters were also applied to CR tablets of Mefenamic acid-Methocel K100M Premium EP (table 3). In this case also, the value of (n) from equation, for all the formulations of Mefenamic acid-Methocel K100M Premium EP were larger than 0.5 indicating that the formulations exhibited anomalous, non Fickian drug diffusion (8, 9).

Conclusion:

The results achieved from special parameters illustrate that Methocel can be used productively in order to process directly compressed prolonged release tablets of slightly soluble drugs such as Mefenamic acid. Particle size of polymer is a influential factor in controlling the release of Mefenamic acid from tablets. Methocel could more proficiently extend the release of the drugs as compared to the reference conventional dosage form. The f2 resemblance and f1 dissimilarity procedures used for dissolution equivalency exposed that f2 values of all the formulations were less than 50 and f1 values were all greater than 15, representing that the release rates from the designed formulations were significantly different from those of the reference formulations.

Tables at a glance

Table icon Table icon Table icon
Table 1 Table 2 Table 3
 

Figures at a glance

Figure 1 Figure 2 Figure 3
Figure 1 Figure 2 Figure 3
 

References










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