Discriminative Disintegration Techniques For Various Brands of NimesulideTablets Available in the Market

Introduction

Owing to its anti-inflammatory effectiveness and therapeutic safety profile, Nimesulide (N- (4-Nitro-2- phenoxyphenyl) methane sulphonamide is categorised as an alkyl sulphonamide and is a non-steroidal anti-inflammatory selective inhibitor of the enzyme cyclooxygenase (COX) type 2. It is a weak acid that is almost insoluble in water and appears as a pale-yellow powder, crystalline, somewhat unctuous to the touch, odourless, and non-hygroscopic. Oral Solid Dosage Forms (OSDF) are most commonly utilised by the population and most commonly prescribed by health experts, and they have various advantages over other pharmaceutical forms, including low production costs and good stability. When compared to liquid forms, certain active principles have better physicochemical and microbiological qualities, as well as a lesser sense of disagreeable taste and odour.^1-2

OSDFs present as a unit dosage form with greater dose precision and less variability in content. They are also lighter and more compact than other oral dosage forms making them easier to carry. They can be manufactured on a larger scale, are easy to administer eliminating the need for specialised technical people.³

Oral tablets are used to deliver a specific and specified dose of medicine to the human body via the gastrointestinal tract. Studies on medication bioavailability from various dosage forms indicated that, in many cases, tablets containing the same drug and drug content did not have the same therapeutic benefit. The tablet formulation ingredients, physical form of the drug employed in the tablet, and tablet manufacturing method vary from manufacturer to manufacturer, and can be responsible for variations in observed dissolution profiles and therapeutic effects.⁴

Pharmaceutical availability, often known as in vitro availability, is one component of medication bioavailability. The dissolve test is done on tablets and is thought to be sensitive, reliable, and reasonable for predicting in vivo drug availability behaviour.⁵

In the Indian market, a wide range of Nimesulide formulations are available. Because there are several brands of Nimesulide available in our medication market today, doctors and pharmacists encounter a tough challenge of selecting an appropriate brand or considering alternate uses. Furthermore, there are emerging worries that different Nimesulide formulations may have varying bioavailability and that resistance development would be accelerated if suboptimal doses are utilised. Despite the fact that Nimesulide tablets are used in a variety of ways in India, there no studies reported on their bioavailability and bioequivalence.^6-10

As a result, the current study was designed to evaluate various in vitro quality control characteristics of six commercially available Nimesulide tablets, with a focus on dissolution rate investigations.

Methods and Materials

Six different brands of Nimesulide pills of 100 mg potency were acquired from a local market in Tirupati, Andhra Pradesh, India. The products were labelled with the letters A, B, C, D, E and F. At the time of the study, all the selected products were manufactured within the previous six months. All brands of tablets had a shelf life of 36 months from the date of manufacture. According to Indian Pharmacopoeia (IP) procedures, all brands of tablets were examined for weight uniformity, hardness, friability, content, disintegration time, and dissolving profile. Vernier calipers were used to determine the size and shape of the tablets. The tablet hardness was determined using a Monsanto tablet hardness tester. Tablet friability was determined using a Roche friability tester. All trials were repeated three times, and the averages were given on the table.^11-14

Size and shape

The diameter and thickness of the Nimesulide tablet were measured with a Vernier caliper. The determinations were made in triplicates, and the averages were reported.

Hardness test

Monsanto hardness tester was used to measure the hardness of Nimesulide tablets. This tester works on the same premise as a pair of pliers. The power required to break the tablet is measured in kilograms, and most oral pills have a hardness of 4 to 10 kg/cm² . The average tablet hardness was computed and reported.

Friability test

The Roche Friability testing was used to determine the friability of Nimesulide tablets. The tablets were subjected to the combined effects of abrasions and stress using a plastic chamber that revolves at 25 rpm for 100 revolutions. In addition, the percent friability

Weight variation

By individually weighing 20 pieces at random on an electronic balance, the average weight and maximum % variance was calculated.^15-18

Drug content

The drug content was determined using the procedure given in I.P. The solution was passed through a 0.45 nylon disc filter and tested for drug content using a UVvisible spectrophotometer at 397 nm.

Disintegration test

The average disintegration time was calculated after performing the I.P method on six tablets using the Disintegration test apparatus with disc in distilled water medium at 37^oC.

Dissolution test

In vitro dissolution experiments of tablet formulations were carried out in 900 mL of dissolving medium, pH 7.4 phosphate buffer IP using a USP XXI type 2 dissolution rate test instrument at a speed of 50 rpm and a temperature of 37 ± 1°C. At different time intervals, a 5 mL aliquot was removed and filtered through a 0.45 m nylon disc filter, each sample was replaced with 5 mL of fresh dissolving medium. The filtered samples were diluted as needed and Nimesulide absorbance was measured at 397 nm.^19-25

Results

According to Indian Pharmacopoeia (IP) rules, the in vitro dissolving investigation was performed on six brands of Nimesulide tablets using the paddle method. Other quality control tests like hardness and disintegration time were also performed and all of these different brands of Nimesulide pills met compendial standards. All of the brands tested met the disintegration time criteria.

Discussion

The general appearance of tablets of all brands was as follows: colour-sunset yellow for brands B, C and F, and quinoline yellow for brands A, D, and E. All brands had a round, slightly curved, biconvex form. All of the brands had high hardness strength, which is necessary for safe handling and shipping. The hardness was determined to be between 3.8 and 4.4 kg. All brands had less than 1% friability, with brand E having the lowest friability of 0.31% and brand A having the highest friability of 0.68%. All brands had acceptable friability and hardness limitations, demonstrating adequate mechanical strengths. Nimesulide content in each tablet brand was consistent with I.P.

The weight variation test, as required by I.P., was cleared by all tablet brands. All pill brands passed the I.P disintegration time, indicating that they will breakdown fast in gastrointestinal tract fluid after oral administration. However, the disintegration time varied greatly between brands. Formulation F had a disintegration time of only 1 minutes and 29 seconds, but formulation E had a disintegration time of 5 minutes and 52 seconds. Except for brand C and E, brands A, B, D, and F passed the I.P dissolving test.

Conclusion

Our in vitro dissolution results revealed that the bioavailability of Nimesulide varied significantly between the several brands of Nimesulide tablets. Almost all of the brands cleared all of the official I.P. testing. The formulation ingredients in the tablet, the physical shape of the medicine in the tablet form, and the manufacturing process differed from manufacturer to manufacturer, accounting for the diversity in reported dissolving profiles. In conclusion, our findings demonstrate that, with the exception of C and E, all the Nimesulide tablet brands studied appeared to have a high dissolution rate and thus have extremely good bioavailability. >45 percent of Nimesulide was released within 30 minutes thus clearing the Indian Pharmacopoeia criterion for uncoated tablet dissolution. Samples A, B, D and F were bioequivalent and interchangeable. However, in vivo research is required to further validate the in vitro predictions. This study emphasises the importance of continuous monitoring of new products launched into our medicine market in order to ensure bioequivalence and compliance with pharmacopoeia requirements.

Conflict of interest

None