title: The critical role of NIR spectroscopy and statistical process control (SPC) strategy towards captopril tablets (25 mg) manufacturing process understanding: a case study.
abstract: In this work, near-infrared spectroscopy (NIRS) method was used to evaluate the uniformity of dosage units of three captopril 25 mg tablets commercial batches. The performance of the calibration method was assessed by determination of Q value (0.9986), standard error of estimation (C-set SEE = 1.956), standard error of prediction (V-set SEP = 2.076) as well as the consistency (106.1%). These results indicated the adequacy of the selected model. The method validation revealed the agreement of the reference high pressure liquid chromatography (HPLC) and NIRS methods. The process evaluation using the NIRS method showed that the variability was due to common causes and delivered predictable results consistently. Cp and Cpk values were, respectively, 2.05 and 1.80. These results revealed a non-centered process in relation to the average target (100% w/w), in the specified range (85-115%). The probability of failure was 21:100 million tablets of captopril. The NIRS in combination with the method of multivariate calibration, partial least squares (PLS) regression, allowed the development of methodology for the uniformity of dosage units evaluation of captopril tablets 25 mg. The statistical process control strategy associated with NIRS method as PAT played a critical role in understanding of the sources and degree of variation and its impact on the process. This approach led towards a better process understanding and provided the sound scientific basis for its continuous improvement.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of Sao Paulo , Sao Paulo , Brazil .
authors.forename: Cátia Panizzon Dal
authors.initials: CP
authors.lastname: Curtivo
authors.forename: Nathália Bitencourt
authors.initials: NB
authors.lastname: Funghi
authors.forename: Guilherme Diniz
authors.initials: GD
authors.lastname: Tavares
authors.forename: Sávio Fujita
authors.initials: SF
authors.lastname: Barbosa
authors.forename: Raimar
authors.initials: R
authors.lastname: Löbenberg
authors.forename: Nádia Araci
authors.initials: NA
authors.lastname: Bou-Chacra
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry*; D002138:Calibration; D002216:Captopril / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016018:Least-Squares Analysis; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013607:Tablets
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D013607:Tablets; D002216:Captopril
keywords: Capability indices; multivariate analysis; process analytical technology; quality by design pharmaceutical processes