Abstract
Objective: To validate simple analytical method and its application in the determination of residual aripiprazole in production area equipment and to confirm the efficiency of cleaning procedure.Methods: The swab sampling and UV method for residual estimation of aripiprazole in swab samples from equipment surfaces after manufacturing of three consecutive batches of aripiprazole 10 mg uncoated tablets were developed and validated.Results: The swab sampling method was developed and validated in order to obtain the suitable recovery (>90%). The swabs were saturated with acetonitrile. The UV method was developed using UV-Vis spectrophotometer at 255 nm. The calibration curve was linear (r2 =1.0000) over a concentration range of 1-30 µg/ml. The LOD and LOQ were 0.43 µg/ml and 1.32µg/ml, respectively. No interference from swab solution was observed and samples were stable for 24h. The determined concentration varying from 1.00-5.687µg/swab was well below the calculated limit of contamination i.e., 24.2µg/swab or 24.2 µg/25 cm2.Conclusion: The results obtained from cleaning procedure confirmed that the proposed procedure was able to remove aripiprazole from equipment surfaces below the value of 10 ppm criteria. So the proposed validated UV method with appropriate swab wipe procedure could be applicable for cleaning validation on residues of aripiprazole.
Highlights
Cleaning validation is defined as providing a high degree of assurance that a cleaning process removes residues of the active pharmaceutical ingredients of the product manufactured in a piece of equipment, the cleaning aids utilized in the cleaning process and the microbial attributes [1, 2]
Establishment of cleaning level acceptance criteria for aripiprazole Swab sampling of area hardest to clean was done from equipment used in the manufacturing and residues were found in mg/ml. the smallest batch sized (SBS) subsequent products were selected for calculating the values of the maximal allowable carryover
Calculation of total carryover limits based on therapeutic dosage The formula used for the calculation of the lowest allowable residue value is shown: Where, acceptable residual limit (ARL) is the acceptance residual limit, STD is the smallest therapeutic dose of product A, SBS is the smallest batch size of any subsequent product to be manufactured in the small equipment train, SF is the safety factor i.e. 1/1000 or 0.001, MDD is the maximum daily dose of the product to be manufactured in the same equipment train, M is the surface area/swab (25 cm2), SSA is the shared equipment surface area
Summary
Cleaning validation is defined as providing a high degree of assurance that a cleaning process removes residues of the active pharmaceutical ingredients of the product manufactured in a piece of equipment, the cleaning aids utilized in the cleaning process and the microbial attributes [1, 2]. FDA requires firms to have written general procedures on how cleaning processes will be validated. The valuation of cleaning validation is regulated strictly, which usually mainly covers the aspects of equipment design, cleaning process written, analytical methods and sampling. Each of these processes has their related strict rules and requirements. Regarding the establishment of limits, FDA does not intend to set acceptance specifications or methods for determining whether a cleaning process is validated. Some limits that have been mentioned by industry include analytical detection levels such as 10 ppm, biological activity levels such as 1/1000 of the normal therapeutic dose and organoleptic levels [3,4,5]
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