Improve The Weight Uniformity Of Ranitidine Hydrochloride Capsules

According to the validation and qualification of Good Manufacturing Practice,process validation should be throughout the product lifecycle;Continuous process verification should be performed during routine manufacture;Statistical methods should be applied to evaluate process robustness in continues process verification;Amelioration is made to continuously improve product quality when necessary.Process capability analysis is a normal statistical method to assess the process robustness.Process capability index Cpk value is calculated,when Cpk ≥1.0,the process capability is considered as normal and acceptable,only appropriate monitoring during production is required;when Cpk ≥1.33,the process is considered as adequate,the frequency of monitoring during production can be reduced;when Cpk<1.0,process capacity is considered as insufficient,actions need to be taken to improve the process.Statistically analyzed the weight data of capsule filling process of ranitidine hydrochloride capsules in continuous process verification,calculated process capability index Cpk value is 0.80,meaning the process control ability is insufficient,actions need to be taken to improve the process capacity of weight control in capsule filling step.The purpose of this article is to improve the process capability(Cpk value)of ranitidine hydrochloride capsules filling,which means to improve the weight uniformity of ranitidine hydrochloride capsules.Analyzed and confirmed the strategy by Boston matrix and four quadrant classifications,the strategy is to improve the physical properties of raw materials to achieve the purpose of improving the process capability of capsule filling.Ranitidine hydrochloride raw material of different density is compared in trials to determine the impact of density on weight uniformity,the result shows that the weight uniformity had significantly improvement by using the density of 0.50-0.70g/ml than below 0.50g/ml.Using 3 different batches of ranitidine hydrochloride raw material whose density are within 0.50-0.70g/ml to perform 3 pilot batches ranitidine hydrochloride capsules,further confirms the trial result.Cpk value of capsule weight in filling process are 1.12,1.10 and 1.05,all comply with the expectation(≥1.0).Performed quality study by using 3 pilot batches sample,the results showed that the change has no impact on the product quality.Ranitidine hydrochloride raw material with new density is purchased from new supplier,who is qualified as per good manufacture practice.Supplemental application of changed supplier is submitted to authority as per registration regulatory.Process qualification for commercial production is performed after the approval of raw material supplier change.Process qualification is successfully performed.Cpk values of capsule weight in filling process are 1.00,1.17 and 1.24,all comply with the requirement(≥1.0),and the data are consistent with pilot batches.The final results showed that the process capability Cpk value of ranitidine hydrochloride capsule filling was significantly improved;purpose of continuous improvement product quality is achieved.