Quality-by-Design III: Application of Near-Infrared Spectroscopy to Monitor Roller Compaction In-process and Product Quality Attributes of Immediate Release Tablets

Abstract

The objective of this study is to use near-infrared spectroscopy (NIRS) coupled with multivariate chemometric models to monitor granule and tablet quality attributes in the formulation development and manufacturing of ciprofloxacin hydrochloride (CIP) immediate release tablets. Critical roller compaction process parameters, compression force (CFt), and formulation variables identified from our earlier studies were evaluated in more detail. Multivariate principal component analysis (PCA) and partial least square (PLS) models were developed during the development stage and used as a control tool to predict the quality of granules and tablets. Validated models were used to monitor and control batches manufactured at different sites to assess their robustness to change. The results showed that roll pressure (RP) and CFt played a critical role in the quality of the granules and the finished product within the range tested. Replacing binder source did not statistically influence the quality attributes of the granules and tablets. However, lubricant type has significantly impacted the granule size. Blend uniformity, crushing force, disintegration time during the manufacturing was predicted using validated PLS regression models with acceptable standard error of prediction (SEP) values, whereas the models resulted in higher SEP for batches obtained from different manufacturing site. From this study, we were able to identify critical factors which could impact the quality attributes of the CIP IR tablets. In summary, we demonstrated the ability of near-infrared spectroscopy coupled with chemometrics as a powerful tool to monitor critical quality attributes (CQA) identified during formulation development.

Quality-by-Design II: Application of Quantitative Risk Analysis to the Formulation of Ciprofloxacin Tablets

“…However, we will not include mixing parameters in the design space because for high-dose drugs like ciprofloxacin (50% w/w in this study), generally, blending is considered a low to moderate risk processing step, and we have implemented a near infrared (NIR) monitoring system to ensure blend homogeneity. The development and application of this system are described in Kona et al (39).…”

Process analytical technology tools for process control of roller compaction in solid pharmaceuticals manufacturing

“…The research articles listed above demonstrate that NIR can be successfully utilized for monitoring single- (24,28,35) or multi-component (12,36,37) placebo blends. Moreover, studies have also included mixtures containing API (24,(38)(39)(40)(41)(42), offering better insight into potential monitoring of the roller compaction process of real formulation.…”

“…In the use of NIR spectroscopy in evaluating subsequent granules and tablets, the acquisition of spectra is less complex; on the other hand, on-line monitoring can be more technically challenging. Kona et al (41) investigated tablets and granules by analyzing powder blends in glass scintillation vials, whereas the tablets were analyzed directly. The authors achieved good predictive values of the models for both granules and tablets.…”

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“…The QTPP is an essential element of a QbD approach and forms the basis of design of the generic product 16,17 [20][21][22][23] . While hardness is considered as process variable and risk assessment had been discussed.…”