INTRODUCTION:

Cefpodoxime proxetil (CP) (Fig. 1) is a third-generation cephalosporin antibiotic used in the treatment of various bacterial infections, including gonorrhea, community acquired pneumonia, and sinusitis. CP is a prodrug which is absorbed and de-esterified by the intestinal mucosa to Cefpodoxime.

Fig.1: Chemical Structure of Cefpodoxime proxetil

The effect CP is dependent on its binding to penicillin-binding proteins (PBPs) located in the bacterial cytoplasmic membrane. Binding results in the inhibition of the transpeptidase enzymes, thereby preventing cross-linking of the pentaglycine bridge with the fourth residue of the pentapeptide and interrupting consequent synthesis of peptidoglycan chains. As a result, cefpodoxime inhibits bacterial septum and cell wall synthesis formation¹.

The clinical and therapeutic effectiveness of oral dosage forms depends on the amount of drug released in to the body and its bioavailability. The main role of oral tablets is to deliver the drug in to the body at certain amount through the gastrointestinal system for absorption and to produce therapeutic effect. So, the formulation of the drug product can have a significant effect on the quality control parameters such as weight variation, hardness, friability, disintegration time, dissolution profile etc. Also, these parameters are essential tools for maintaining batch to batch consistency during manufacturing process.

Hence, Pharmaceutical manufacturers must satisfy certain standards to assess the quality of drug products. To ensure the quality of medicine, the manufacturer should evaluate the drug product during and after manufacturing at frequent interval up to its shelf-life. The main objective of this work was to perform the in-vitro quality evaluation of four brands of CP 200 mg tablets commercially available in the market of Dindigul district and compare the values of quality parameters with Pharmacopeial specifications^2,3,4.

MATERIALS AND METHODS:

Chemicals:

Four brands of CP tablets of different manufacturers with labeled contents of 200 mg were obtained from various retail pharmacies of Dindigul district in Tamilnadu. All the samples were properly checked for their physical appearance, manufacturer’s name, batch number, manufacturing date, expiration date, manufacturing license number, and the maximum retail price at the time of purchase. The samples were properly coded with CP1, CP2, CP3 and CP4.

Equipments:

Equipments used in this work were mortar, pestle, Electronic Balance (Wensar), Hardness Tester (Vinsyst), Disintegration Test Apparatus (Rolex India), Dissolution Test Apparatus USP (Ceyone) and UV Visible Spectrophotometer (Sytronics).

Table 1: Brands of Cefpodoxime proxetil Tablets

S. No	Brand Name	Maufacturers	Sample Code	Batch Number
1.	Monotax- O-200	Zydus Healthcare Limited	CP 1	BPB220668
2.	Gudcef-200	Relax Pharmaceuticals Pvt Ltd	CP2	B5AKV124
3.	Doxcef-200	Lupin Ltd	CP3	F100885
4.	Monocef-O -200	Aristo Pharmaceuticals Pvt Ltd	CP4	A22063MSA

In-vitro Quality Control Tests^5-15:

Weight variation test:

Weight of each tablet may mainly affected by such factors like type of compression machine, head pressure, machine speed and flow properties of the powder. Uniformity of weight is an in process test parameter which ensures consistency of dosage units during compression.

The test for weight variation for each brand of CP tablets was carried out by weighing the twenty tablets individually using analytical balance. The mean tablet weight and the standard deviation were calculated.

Hardness test:

Hardness may be defined as the resistance of tablets to capping, abrasion or breakage under conditions of storage, transportation and handling. It is the property of a tablet that is measured to assess its resistance to permanent deformation. The tablet hardness tester was used to check tablet hardness. The hardness of each branded tablet was measured in unit kg/cm2. Each sample was analyzed in a triplicate.

Disintegration Test:

Disintegration is the breakdown of the tablets into smaller particles or granules when it comes in contact with a solution. For a drug to be absorbed from a solid dosage form after oral administration, it must first be in solution, and the first important step toward this condition is usually the break-up of the tablet, and also if the disintegration time is not uniform in a set of samples being analysed, it indicates batch inconsistency and lack of batch uniformity. DT of tablets was carried out by filling the beaker with 900mL of simulated gastric fluid without enzymes at pH 1.2 under a temperature of 37°C ±1°C. Each tablet was placed into the basket-rack assembly individually and the time required for each tablet to disintegrate was recorded.

Dissolution studies^16-19

Preparation of dissolution medium glycine buffer pH 3.0:

In a 1 litre standard flask, 54.5g of glycine and 42.6g of sodium chloride were dissolved in 500mL of water and 14.2mL of hydrochloric acid was added with swirling. The content was allowed to cool, further diluted with water (stock solution) and mixed well. About 50 mL of the stock solution was transferred to a volumetric flask and diluted with 900mL of water to obtain a medium glycine buffer pH 3.0. A pH of 3.0±0.1 of the stock solution was adjusted with 10 N NaOH^20,21.

Preparation of stock solution:

Accurately weighed 100mg of CP was transferred in a 100mL volumetric flask and dissolved in methanol. The final volume of this stock solution (A) was made up to 100mL with methanol to make 1000 µg/mL concentration.

Preparation of standard curve of CP:

From the above stock solution (A), 10ml of the solution was taken and further diluted to 100mL with dissolution medium glycine buffer pH 3.0 to make 100µg/mL concentrations (stock solution B). Then, the dilutions were made from the stock solution B to get the concentration of 10 - 50µg/mL, where the UV absorbance were measured on UV-Visible spectroscopy at 257nm for the preparation of standard curve of CP¹⁰.

Percentage drug release determination:

The release rate of CP film-coated tablets was determined by using USP dissolution testing apparatusII (Paddle type). The dissolution test was performed using 900 mL of glycine buffer pH 3.0 at a temperature of 37°C±0.5°C with rotation of 75rpm. An aliquot (20 mL) of the solution was withdrawn from the dissolution vessel, filtered through a 0.45µm Whatman filter paper, and 10mL of the filtered content was diluted with same dissolution medium at time interval of 10min, 20min, and 30min. Each aliquot was replaced with a fresh dissolution medium to maintain the sink conditions. The absorbance of diluted solutions was measured at 257nm.

Drug content determination:

For drug content analysis, tablets from each brand were crushed into fine powder and sufficient amount of powder was weighed which is equivalent to 100mg of active drug and dissolved in 100ml glycine buffer pH 3.0. Further dilution was made to obtain 10µg/ml for each brand and the absorbance of was measured at 257 nm against the glycine buffer pH 3.0 as blank.

RESULTS AND DISCUSSION:

Weight variation test:

Weight variation test is essential to ensure that the drug content in each unit dose is distributed in a narrow range around the label claim. The %RSD results for weight variation for four brands obtained were in the following order: Brand CP 1 (0.4219 %) < Brand CP 2 (0.8980 %) < Brand CP 4 (0.9659 %) < Brand CP 3 (1.0165 %) and the results were graphically shown Fig. 2 which indicates that all the brands were complied with the Pharmacopeial specification. As per IP specification, the percentage deviation should be within 5 % for tablets having average weight more than 250 mg.

Hardness test^22,23:

Hardness test for tablets is indicative of its strength. In this study, the hardness of different brands of CP tablet was measured by hardness tester. The acceptable limit of hardness of a tablet is 4 to 7kgf (kilogram of force). Besides, a force between 4 – 10kgf is also considered to be satisfactory. The hardness for all the brands was determined and the observed results are graphically shown on Fig. 3.

Fig. 2: Weight variation for different brands of CP

Fig. 3: Hardness for different brands of CP

Disintegration time:

Disintegration is first step towards dissolution; it could be directly related to dissolution and subsequent bioavailability of a drug. The disintegration times of four brands of CP tablets was determined and mean disintegration time was calculated, the observed results are graphically shown in Fig. 4.

Fig. 4: Disintegration time for different brands of CP

Dissolution study:

Comparison of in vitro dissolution profiles of the four brands of CP tablets are illustrated in Figure 5. After 30 minutes, the release rate of different brands of CP tablets was satisfactory and ranged from 93.15% to 94.95%. According to BP (2004), the amount of cefpodoxime proxetil released within 30 min should not be less than 80% of the stated amount. From the dissolution test results, all the brands of CP tablets showed more than 80% of drug release within 30 min. Hence, all the products complied with the BP and USP dissolution tolerance limits.

Fig. 5: Percentage drug release for different brands of CP after 30 minutes

Drug content determination:

The assay results of all brands are between 92.20% and 101.40%. The results for the mean percentage label claim of the different brands of CP tablets included in this study are presented in Fig.6. Hence, all the brands studied passed as per the pharmacopeial specification and statistical comparison for drug content indicates that with 95% confidence interval, there is no significant difference in the drug content among the different brands (P>0.05).

Fig. 6: Percentage drug content for CP

Statistical analysis:

All the results were expressed as mean±SD. Statistical analysis and graphical representation of result of all the marketed brands was done using graph pad prism 7.0 software and Microsoft office excel work sheet. Applying, one way ANOVA, it was found that there is no significant difference in all four brands using p-test showed that there was no significant difference. Thus, above studies indicate that all the brands having an almost similar profile, and has good bioavailability as indicated by its dissolution rate.

CONCLUSION:

From the present study it was demonstrated that all of the brands of CP tablet met the criteria laid in the official monographs for in-vitro quality control tests. Highest percentage drug release on dissolution criteria made the product therapeutically effective. The data reported in this study can help the health care professionals. So the healthcare professionals should focus on quality to ensure good health of people. It will ultimately force the pharmaceutical industry to invest more for quality control to provide better pharmaceutical formulations. The standard of the products are based upon their analytical results which achieve therapeutic and quality goals.

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Received on 20.07.2023 Modified on 06.11.2023

Asian J. Pharm. Res. 2024; 14(1):10-14.

DOI: 10.52711/2231-5691.2024.00002