Process validation of prasugrel hydrochloride tablet USP

Process validation is an essential part for the safety and quality of the drug products. Validation act as guidance that is intended to assist manufacturers in understanding quality management system requirements concerning process validation. It is a fundamental component for assuring the quality system used by pharmaceutical industries. Process validation is the key element to ensure the identity, purity, safety, and efficacy of drug products. The process validation of Prasugrel Hydrochloride Tablet USP precisely focused on the aim and method of analysis. The emphasis will be on the practical inspectional requirement, rather than on a theoretical approach that does not reflect the practicalities encountered when validating actual production operations. The Process validation reduces product recalls and troubleshooting assignments which results in more economical manufacturing process and quality products. In this paper an overview is given on process validation with special reference to solid dosage form of Prasugrel Hydrochloride Tablet USP containing dose of 10 mg. © 2020 Published by Innovative Publication. This is an open access article under the CC BY-NC license (https://creativecommons.org/licenses/by-nc/4.0/)


Introduction 1-17
Process validation establishes the flexibility and constraints in the manufacturing process controls to attain the desirable attributes in the drug product while preventing undesirable properties.
This is an important concept, because of support and define the validation, which is a systematic approach to identifying, measuring, evaluating, documenting, and reevaluating a series of critical steps in the manufacturing process that require control to ensure a reproducible final product. Validation therefore challenges the adequacy and reliability of a system or process to meet predetermined criteria on a consistent basis from batch to batch.
The primary objective of process validation is; to provide a high degree of assurance of quality, to ensure the consistency of the manufacturing operation and reproducibility, to demonstrate the robustness of the process and to ensure the existence of all necessary quality 3. Molecular Weight-373 44100g/mol g mol-1.

Selection of Formulation Selection of formulation and preparation of drug/excipient profile
Prasugrel Hydrochloride tablets USP 10 mg were selected for the process validation. Drug profile was prepared for formulation and it included the chemical data, pharmacokinetic data and therapeutic consideration. Each excipients used in the formulation was described for their physical properties, solubility, pH, storage and also their functional category.

Selection of type of process validation and preparation of validation protocol
Process validation was selected for that three consecutive batches were taken or selected.

Analysis of sample as per specification
Various tests were carried out as per specification mentioned in protocol after collecting the sample. Results of the entire test were prepared.

Review and compilation of results
Review and compilation of all three batches had done. Submission of final discussion and reports, deviation, summary and conclusion of any observation was included.

Material and Methods
All the equipment's and instruments must be calibrated before use.

Experimental Work
Evaluation parameters of tablet are as follows:

Content uniformity
After the compression method the content uniformity of tablets was tested. The assay method was followed to check the content uniformity.

Weight variation
Twenty tablets were randomly selected from each batch and individually weighed. The average weight and standard deviation of 20 tablets was calculated.

Hardness
The crushing strength Kg/cm2 of prepared tablets was determined for 10 tablets of each batch by using Monsanto tablet hardness tester. The average hardness and standard deviation was determined.

Thickness
Twenty tablets were randomly selected from each batch and thickness was measured by using Digital Vernier Caliper.

Friability
Twenty tablets were weighed and placed in the Roche friability testing apparatus and apparatus was rotated at 100 rpm. After revolutions the tablets were deducted and weighed again. Difference in initial and final weight determines friability.

Dissolution test
Dissolution test were carried out to determine the amount of drug released during a specific period of time using USP apparatus-I. 5ml of sample was withdrawn after specified time interval, and was replaced by an equal volume of fresh dissolution medium to maintain the sink condition. Collected samples were analyzed spectrophotometrically.

Disintegration test
Six tablets from each batch were utilized for disintegration studies in distilled water at 37 • C using a Disintegration Apparatus USP STD. The disintegration time was taken to be the time no granule of any tablet was left on the mesh of the apparatus.

Sampling location
Samples were taken from the packing belt.

Sampling interval
Samples were taken at initial, middle and end of packing.

Number of samples, sampling quantity and testing
2 packs of 10's was taken at initial, middle and end from the packing belt. Tests were performed on composite sample: Description of pack, Sealing quality, Number of tablets in pack (count), Leak test (For 10's only).

Results and Discussion
Process validation of Prasugrel hydrochloride tablets Batch-1, Batch-2, and Batch-3 (Batch size: 10, 00, 000 tablets) had been carried out as per approved validation protocol and sampling plan. All the procedures carried out as per specifications for blend, core tablet and coated tablet along with critical step of manufacturing such as milling, blending, lubrication, compression and packing.

Packing Process
After the inspection, the coated tablets were packed in the blisters on blister packing machine as per the BPR. The tablets were packed in 10's blister pack. The packing operation was monitored by sampling and testing the packs at initial, middle and end of packing operation. The results are summarized in below Table 5.

Summary & Conclusion
On evaluation of results from three batches of "Prasugrel hydrochloride tablet 10 mg", there was no significant variation between batch to batch and all the process variables were studied and therefore it can be concluded that the process of Prasugrel hydrochloride tablets for three batches stands validated. The results of all critical stage were found within the standard specification and acceptance criteria mentioned in the process validation protocol and finished product specification. Hence manufacturing process of "Prasugrel hydrochloride tablet 10 mg" is considered validated and approved for routine production.

Conflict of Interest
None