CONCURRENT PROCESS VALIDATION OF GLIBENCLAMIDE 2.5 MG TABLET

CONCURRENT PROCESS VALIDATION OF GLIBENCLAMIDE 2.5 MG TABLET

Prashant B. Patil, Vilas L. Badgujar, Rajendra D. Wagh and Kundan H. Deore *

NES’s Gangamai College of Pharmacy, Nagaon, Dhule - 424005, Maharashtra, India.

ABSTRACT: The present study of concurrent process validation delivers an extraordinary degree of quality assurance that a specific process for manufacturing of Glibenclamide Tablets will consistently manufacture a product that meets its predetermined quality attributes and specifications. Glibenclamide is generally suggested for the treatment of type II diabetes mellitus and it is mainly a sulfonylurea derivative.  It mainly comprises the stages to be followed to evaluate and qualify the acceptability of the manufacturing process of Glibenclamide 2.5 mg tablets. The process is limited to the three batches H, I, and J manufactured of specific batch size with the help of specified equipment’s and different quality control parameters for tablets. It involves all parameters related to each step were evaluated by the respective standard test involved in the manufacturing. All analytical results of each stage were found to be within the acceptable limit and criteria. Other tests related to compression such as hardness, thickness, disintegration and dissolution for all three batches were also found within the acceptable limit.

Keywords: Glibenclamide, Assay, Concurrent, Tablets

INTRODUCTION: Validation is defined as the process of founding through a documented database program, which provides a high degree of assurance that a specific process will constantly produce a product meeting its pre-determined specifications and critical quality attributes. The word validation simply means ‘assessment of validity’ or ‘action of proving effectiveness’ a validated manufacturing process is one, which has been proved to do what it purports to or is represented to do.

Validation essentially contains process qualification (the qualification of materials, equipment, system, buildings and personnel, i.e., Design Qualification, Installation Qualification, Operation Qualification, Performance Qualification).

Process Validation is defined as the collection and evolution of data from the process design stage throughout production, which establishes scientific evidence that a process can consistently deliver quality products. It assures Quality, Safety and efficacy. The process validation is the analysis of data collected throughout the design and manufacturing of a product to endorse that the process gives consistent production of products with a given standard. The main aim of process validation of Glibenclamide is to ensure various inputs lead to consistent and great quality productions and its continuing process that must be regularly improved as manufacturing feedback is gathered. Glibenclamide, also known as glyburide, is an anti-diabetic drug in the class of medications known as sulfonylurea and thoroughly related to sulfonamide antibiotics. Glibenclamide, it’s a second-generation sulfonylurea commonly used to treat type II diabetes mellitus. Glibenclamide was firstly granted FDA approval on May 01, 1984 and formulation with metformin was granted FDA approval on July 31, 2000. Glibenclamide is a sulfonylurea derivative and is recommended for the treatment of type II diabetes mellitus. Glibenclamide goes through the hepatic first-pass effect in its oral administration, such that only 45% of the drug is absorbed and considering its short half-life, the persistent has to take the drug in several divided doses to maintain the desired therapeutic effect. Gastrointestinal adverse effects of Glibenclamide have been reported for the drug, which decreases the patients’ compliance.

Process Validation Should Proceed in the following Condition

• Processes remained finished products tests are poor
• When implementing new processes for manufacturing of the product
• When new equipment’s are installed or used in the manufacturing process
• Process and equipment which are having altered suit changing the priority

MATERIALS AND METHODS: Concurrent process validation was performed on the three batches of Glibenclamide 2.5 mg Tablets. The three consecutive batches were labeled as (Batch E, Batch F and Batch G) ^3-9. List of Equipment and Stages indicate a list of equipment used in the manufacturing process of Glibenclamide 2.5 mg tablets and listed the involved equipment in which manufacturing stage details are mentioned in Table 1.

Details of input material indicate material or ingredients used in manufacturing Glibenclamide 2.5 mg tablets with their category, which is shown in Table 2. Sampling and Testing Plan indicates the planning for sampling and testing with their manufacturing stage, procedure, quantity to be sampled, and acceptance criteria for sampling to manufacture Glibenclamide 2.5 mg tablets described in Table 3. The manufacturing process flow chart indicates the manufacturing stages of the manufacturing process of Glibenclamide 2.5 mg tablets depicted in Fig. 1.

TABLE 1: LIST OF EQUIPMENT’S

FIG. 1: MANUFACTURING PROCESS FLOW CHART OF GLIBENCLAMIDE 2.5 mg TABLET

TABLE 2: LIST OF INGREDIENTS

RESULTS AND DISCUSSION: These results and discussion are limited to evaluating three consecutive batches of Glibenclamide 2.5 mg tablets for concurrent process validation. Three manufacturing batches are validated in concurrent process validation; the batches are labeled as Batch E, Batch F, Batch G at blend stage, compression stage and packing stage.

TABLE 3: SAMPLING AND TESTING PLAN

Product Details-Product Name: Glibenclamide Tablets 2.5 mg.

Dry Mixing: Dry mixing was carried out in Rapid Mixer Granulator for 10 minutes, and samples were collected from eleven different six locations for Blend Uniformity. The blend uniformity test was performed and the acceptance criteria for it is individual values should be between 90.0% to 110.0% of the labeled amount of Glibenclamide with RSD not more than 5%; the results are described in Table 4. The RSD of Glibenclamide Tablets for all three validation batches were within found within the specification. Based on % RSD data of Glibenclamide Tablets for three validation batches, it was evident that the dry mixing throughout the sampling locations and all their results are found within acceptable limit.

TABLE 4: DRY MIXING STAGE BLEND UNIFORMITY RESULTS

T: Top, B: Bottom

Drying Analysis: The drying analysis carried for the % LOD of dried granules of Glibenclamide analysis with the help of or air oven. The samples were collected from the fluidized bed dryer bowl from the top, middle and bottom side and their results are shown in Table 5. % loss of drying of dried granules of Glibenclamide was within the range 7.32 to 7.81 w/w at 120 °C for 20 min respectively for all three validation batches, which were within the acceptable limit.

TABLE 5: RESULTS OF DRYING HOMOGENEITY ANALYSIS

Analytical Data for Lubricated Blend: Blending was carried out in the Octagonal Blender for 13 minutes, and samples were collected from 12 different locations (12-points) for test Blend Uniformity such as upper site, middle site, lower side, and bottom. The results are as follows in Table 6. % RSD of Glibenclamide for all three validation batches were within the range 1.08 to 1.16, which were found within the acceptance criteria. % RSD of Glibenclamide for all three validation batches. It was evident that no segregation occurs in the blender and mixing is homogeneous throughout the sampling locations and their points are depicted in Fig. 2.

FIG. 2: SAMPLING LOCATION IN DOUBLE CONE BLENDER

TABLE 6: RESULT OF BLEND UNIFORMITY OF LUBRICATED BLEND

Analysis of Lubricated Blend: Lubricated blend analysis is done by different parameters like blend, assay, loss on drying, bulk density, tapped density, and sieve test parameters; their results are described in Table 7. Description, Assay, loss on drying, bulked density, tapped density sieve test of the lubricated blend of Glibenclamide for three validation batches were within the acceptable specification and criteria.

TABLE 7: RESULTS OF ASSAY OF LUBRICATED BLEND

Physical Characteristics of Lubricated Blend: Physical characteristics of the lubricated blend were done by a description of the lubricated blend, bulk density, tapped density, loss on drying, angle of repose, and particle size distribution parameters, and their results are shown in Table 8. The physical parameter of a lubricated blend, such as description, bulk density, tapped density, loss on drying, and particle size distribution for three validation batches was satisfactory and found consistent within the acceptable limit. No significant observation related to the flow of the blend was observed throughout the compression activity.

TABLE 8: PHYSICAL CHARACTERISTIC OF LUBRICATED BLEND

Compression Stage Physical Parameters: During compression, samples from the compression machine at minimum speed and maximum speed were collected from three consecutive batches for performing physical parameters. The physical parameters checks as description, average weight, uniformity of weights, thickness, hardness, friability, disintegration, assay, dissolution test performed. The results are as follows in Table 9. The physical parameter of Glibenclamide tablet at Minimum Speed (2200 Tabs/min) and Maximum Speed (2750 Tabs/ Min) of compression for three validation batches X, Y, Z were found in the range within the acceptance criteria and specification.

TABLE 9: COMPRESSION STAGE PHYSICAL PARAMETERS BACH X, BATCH Y, AND BATCH Z

Compression Stage Analytical Results: Compression stage analysis in their content uniformity, assay by HPLC and dissolution were checked at minimum speed and maximum speed as same as to physical parameters and results described in Table 10. % dissolution of Glibenclamide at Optimum speed of compression for three validation batches E, F & G were found in the range within the acceptance criteria.

TABLE 10: COMPRESSION STAGE ANALYTICAL RESULTS

Analysis of Compressed Tablet: The analysis of compressed tables is done by assay, content uniformity and dissolution rate of Glibenclamide compressed tablets results are shown in Table 11. Assay, content uniformity, and dissolution rate of Glibenclamide at initial, middle, end and composite stage of compression at optimum were found within the acceptable limit of Glibenclamide 2.38 to 2.63 mg/tablets.

TABLE 11: RESULTS OF ANALYSIS OF COMPRESSED TABLET

*Min: Minimum, Max: Maximum, Avg: Average

CONCLUSION: The concurrent process validation of Glibenclamide 2.5 mg tablet has been performed for three batches X, Y, and Z. All the parameters and results were found within the acceptance limit at all stages, such as dry mixing, wet granulation, drying, milling, lubrication and compression. Based on the results of the validation data for three batches X, Y and Z, it was concluded that the manufacturing process used for the formulation of Glibenclamide 2.5 mg tablet will consistently produce the stable product meeting its predetermined specifications and quality attributes. Hence, it can be concluded that the method employed in the manufacture of the given Glibenclamide 2.5 mg tablet is considered to be validated and can be routinely followed.

ACKNOWLEDGEMENT: The authors are thankful to Wockhardt Ltd., Aurangabad.

CONFLICTS OF INTEREST: The authors declare that there is no conflict of interest regarding the publication of this paper.

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   How to cite this article:

   Patil PB, Badgujar VL, Wagh RD and Deore KH: Concurrent process validation of glibenclamide 2.5 mg tablet. Int J Pharm Sci & Res 2021; 12(10): 5407-13. doi: 10.13040/IJPSR.0975-8232.12(10).5407-13.

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