INTRODUCTION:

Alverine citrate (ALV) belongs to a class of anti-spasmodic agents that can reduce the motility and sensitivity of smooth muscle. These drugs are more effective in treating irritable bowel syndrome (IBS). By restraining Ca²⁺ from penetrating smooth muscle of intestine, they induce smooth muscle relaxation. Both digestive motility and sensitivity are positively impacted by this medication^1-4.

Received on 28.01.2024 Revised on 16.09.2024

Accepted on 12.02.2025 Published on 02.05.2025

Available online from May 07, 2025

Research J. Pharmacy and Technology. 2025;18(5):2075-2080.

DOI: 10.52711/0974-360X.2025.00297

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.

Generic medications are chemically and bio-pharmaceutically comparable to the original medicines. The healthcare sector of developing countries is greatly benefited from the use of these generic medicines^5,6. However, in poor and industrialized nations, the quality of generic drugs is in doubt^7-9. Counterfeit medicines may include products containing no claimed active drug, an incorrect quantity of drug, a substandard drug, inappropriate, contaminants, or repackaged perished products¹⁰. According to WHO reports, roughly 10 percent of pharmaceutical enterprises worldwide are producing counterfeit medications, of which 14% of incidents involve industrialized areas. A prior report showed that the incidence of inferior or bogus medicines is approximately 45 percent in several countries^11-13. In Bangladesh, 25 toddlers died from the toxicity of pediatric paracetamol accompanied by noxious diethylene glycol¹⁴. Anti-cancer and heart disease pharmaceuticals are among the many that counterfeiters are increasingly targeting since they are commercially valuable and in high demand¹⁵. WHO also published that 28 percent of antibiotics and nearly 90 percent of antimalarial medications are ineffective in meeting the specifications¹⁶. Counterfeit medicines are dangerous because every faked medicine has the potential for massacre. To be high-quality products, they must meet exact pharmaceutical, pharmacological, and regulatory conformity¹⁷. To ensure the safety and efficiency of medicines, product standards need to be consistent and repeatable from batch to batch¹⁸. Therefore, drug makers must test their products at various stages from the starting of raw materials to post-production to guarantee necessary quality of pharmaceuticals¹⁹. Moreover, as WHO buttresses the prescription of generic names, pharmacopoeial specifications of Available generic medicines must be equivalent. Numerous research showed that switching from one brand to other causes changes in the biopharmaceutical natures, which results in therapeutic failure and/or adverse drug reactions^20-22. Therefore, bioequivalence studies for generic products are crucial since the impoverished in developing nations like Bangladesh are constantly looking for less expensive options^23,24. Furthermore, the in-vitro physicochemical and pharmaceutical properties are key indicators for in-vivo bioavailability^25-28. Therefore, as every brand in the market must pass the quality control tests, and the parameters should be within limits, we took this study to appraise the in-vitro quality of ALV 60 mg products obtainable in Bangladesh.

MATERIALS AND METHODS:

Study design:

This project was carried out by using several test parameters to evaluate the standard of ALV 60mg tablet dosage form. Comparative evaluation among commercially Available ALV 60mg Tablets was studied by checking diameter and thickness, hardness, disintegration time, friability, assay, weight variation, and dissolution test.

Sample collection and identification:

In order to carry out this study, ALV Tablets of four different commercially Available brands were bought from a model pharmacy in Kushtia, Bangladesh. All the Tablets’ brands were labeled to contain 60mg of ALV per tablet. After collection, Tablets were checked properly for physical appearance, manufacturer identification, manufacturing, and expiry date. The samples were then perfectly marked as A, B, C, and D for evaluation.

Instruments:

Instruments used in this study were slide calipers (Mitutoyo, Japan), analytical balance (Unilab, USA), digital friability test apparatus (Electronics, India), Monsanto hardness tester (Harrison Pharma machinery private limited, India), tablet disintegration test apparatus (Electronics, India), tablet dissolution test apparatus (Electronics, India), and ultraviolet (UV) spectrophotometer (Apel, Japan).

In-vitro quality control parameter:

Diameter and thickness:

The consistency of the tablet manufacturing process, like granulation, size distribution, particle size, and mixing of powder, is determined by measuring thickness. A slide caliper was used to estimate the thickness and diameter of the Tablets. Five Tablets of each manufacturer were used to measure diameter and thickness. Then the average value was determined²⁹.

Weight variation test:

The weight variation study was carried out by weighing twenty Tablets from each brand individually with an electrical balance. The equation stated below was used to compute weight variation^30,31.

Weight variation = (I_w− A_w)/A_w× 100%

Where, I_w = Individual weight of each tablet.

A_w = Average weight of twenty tablet.

Hardness test:

The hardness of ALV Tablets was determined by using a hardness tester. Ten samples of each were used for this. This measures the force needed to crush Tablets using pressure with a moving jaw^32,33.

Friability test:

For this test, we used a digital friability test apparatus. Ten Tablets were weighed from each brand and placed in friabilator, which operated for four minutes at twenty-five rpm. The Tablets were wiped with tissue paper and weighed again. We calculated the friability value using the following equation^34,35.

Percent friability = [(W₁-W₂) / W₁] x 100

Where, W₁= Initial weight.

W₂ = Final weight.

Disintegration test:

It was done by using a tablet disintegration test apparatus. Six Tablets from each company were used. During this test, Tablets were placed into the basket of the test apparatus containing 900 ml demineralized H₂O (DW). The disintegration medium was kept at 37± 0.2˚C. Perforated plastic lid was used to avoid the sample floating. Time was recorded after the complete breakdown of Tablets³⁶.

Dissolution test:

For this, we used the modified paddle method. DW was used as a dissolution medium. At the beginning of this test, the tablet was immersed in the dissolution medium while the paddle speed and temperature were fixed at 75 rpm and 37±0.2˚C, respectively. After the specified time interval, aliquot 10ml sample was withdrawn and substituted with equal fresh DW to maintain a constant dissolution medium volume. It was continued for 2hr when the sink condition was complied with. Then, the sample was filtered by using a filter paper. Finally, the absorbance of sample was determined with UV spectrometer at 253nm^37-39.

Assay test:

One ALV tablet from each brand was taken and powdered. ALV equivalent to 60mg was accurately weighed and placed in DW and methanol solution to make the volume 120µg/ml. The solution was agitated and filtered. One ml of this solution was taken into a test tube to make the volume 10ml. A different working standard solution was prepared by appropriate dilution (10, 20, 30, 40, 50, 60, 70, 100, 120µg/ml), then absorbance was measured at λ_max 253nm. To get a more accurate result, we repeated the experiment three times. Absorbance was recorded at 253nm by using a UV spectrometer³⁹.

Statistical analysis:

Results are presented as average ±standard deviation (S.D.). Microsoft Office Excel 2013 was used to construct the graph. We considered data as statistically significant if p<0.001.

RESULTS AND DISCUSSION:

Diameter and thickness:

As illustrated in Figure 1, the average diameter of studied brands is determined in ascending order: Brand A < Brand D < Brand B < Brand C. Likewise, as shown in Figure 2, the average thickness of the four distinct brands found is Brand A < Brand B, Brand C < Brand D. Since these characteristics relate to patient convenience and administration, they must be managed even when they have no direct impact on treatment efficacy. The die and punches used to make the Tablets determine their thickness and diameter, and different thicknesses and sizes of Tablets can be produced without affecting their weight. Moreover, these are related to general appearance, identification, controlling lot-to-lot, and tablet-t- tablet uniformity⁴⁰.

Figure 1. Diameter of different ALV 60mg Tablets. Results are presented as average ±S.D.

Figure 2. Thickness test of different ALV 60 mg Tablets. Results are presented as average ± S.D.

Figure 3. Weight variation of different ALV 60 mg Tablets. Results are presented as average ± S.D.

Figure 4. Hardness of different ALV 60 mg Tablets. Results are presented as average ± S.D.

Weight variation:

Figure 3 presents the findings from the weight variation investigation. Brand B had the highest (314.5mg) mean value among the brands, while Brand A had the lowest (202.5mg). It was shown that, although the average weight of these products varies markedly, all the brands met IP and USP requirements, which permit a weight fluctuation of ±7.5% for Tablets weighing 80-250mg and 130-324mg, respectively^41,42.

Hardness:

According to Figure 4, which presents the results of the hardness investigation, the average values for Brands A, B, C, and D are 2.6kg/cm², 4.6kg/cm², 4kg/cm², and 3 kg/cm², respectively. The tablet brands also satisfy the acceptability criteria of hardness, 2.5 to 10kg/cm² for regular Tablets⁴³.

Friability:

The average friability values for the four distinct ALV tablet brands are displayed in Table 1. Brand C had the highest friability, while Brand B had the lowest. The likelihood of Brand C losing particles during handling is higher than that of Brand B. All tablet brands met the compendium requirements since their friability was less than 1%^44,45.

Disintegration study:

We performed this test to measure the time required for a tablet to disintegrate into smaller particles in the solution. The disintegration times obtained for four brands were in the following order: Brand C < Brand A < Brand B < Brand D (Table 1), and all the Tablets’ brands complied with the compendium specifications^45,46.

Table 1. Summary of friability, disintegration and assay results of different ALV 60 mg Tablets

Brands	Studied parameters
Brands	Friability (%)	Disintegration time (second)	Drug content (%)
A	0.06	43.2±3.6	98.7±1.5
B	0.04	51±5.4	100.3±1.5
C	0.19	32.4±1.2	103.7±1.5
D	0.05	186±3.6	105.7±1.5

Figure 5. In-vitro drug release profile of different ALV 60mg Tablets.

In-vitro dissolution study:

The percentages of drug release for four brands of ALV are presented in Figure 5. According to the findings, all the tested brands release over 90% of the ALV in less than five minutes. By the end of the study, Brand D had released the highest 98.5% of its content. According to BP requirements, our investigation corresponded with the disintegration criterion and agreed with other findings. Therefore, while being made by different companies, each brand met the BP standards⁴⁷.

Drug content:

To ascertain the presence, absence, or amount of one or more components in the dosage form, an assay test is crucial. Table 1 shows the percentages of the drug content of the Tablets. In contrast to Brand A, which had the lowest amount of drug content, Brand D had the highest percentage. The correlation coefficient value (r²) was used to identify the model that best fits the data. The proportion of drug release is determined using the developed regression equation, y = 0.002x+0.3, where y is the absorbance and x is the correlation. For every brand, the average percentage of medication release was further computed. The correlation coefficient r² = 0.08 (Figure 6) indicates a linear relationship between concentration and absorbance of sample. Every brand has fulfilled with the USP-NF and BP assay test requirements^47,48.

Figure 6. Calibration curve of Alverine citrate.

CONCLUSION:

All of the brands of ALV Tablets that were examined in this study were found to satisfy the requirements outlined in the official monographs for the in-vitro quality control test. It is not only important for the ALV brands but also essential to meet the standard specification for all other generic drug formulations to be therapeutically effective. In a developing country like Bangladesh, the quality of drugs is at greater risk. The quality control test is required to verify the safety profiles of pharmaceuticals, allowing medical practitioners to concentrate on the drug's quality rather than promotional offerings. It contributes to the patients' safety also. Therefore, this study’s results may help the regulatory body for getting an idea regarding the quality marketed medicines. As a result, this kind of research is regularly required to raise public knowledge regarding the quality of medications and is crucial for the advancement of the pharmaceutical industry.

CONFLICT OF INTEREST:

The authors declare no conflicts of interest regarding this experimental work.

ACKNOWLEDGMENTS:

The authors would like to acknowledge the Department of Pharmacy, Islamic University, Kushtia-7003, Bangladesh, for providing all sorts of instrumental support to conduct the research as a part of the B. Pharm. (Hons.) degree.

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Received on 17.04.2024 Revised on 14.08.2024

Accepted on 28.11.2024 Published on 02.05.2025

Available online from May 07, 2025

Research J. Pharmacy and Technology. 2025;18(5):2070-2074.

DOI: 10.52711/0974-360X.2025.00296

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.