Statistical Process Control Implementation in Inspection of Active Medicinal Compound Quality: A Model of First-Generation Antihistaminics

Özet

This study is part of a large project that includes surveying and screening medicinal compounds manufactured by chemical and pharmaceutical plants, notably in Asian countries and exported to developing countries. The current investigation focused on the active pharmaceutical ingredients (API) of one of the first-generation antihistamines of ethanolamine class known as 2-(diphenylmethoxy)-N,N-dimethylethanamine hydrochloride according to the International Union of Pure and Applied Chemistry (IUPAC) nomenclature. Harmonization of the specifications and analysis criteria were harmonized and all raw materials were claimed to be complying with the British Pharmacopoeia (BP) according to the manufacturers. Accordingly, all testing procedures were done according to the official standard methods detailed in the monograph of the chemical molecule. The selected tests were acidity or alkalinity, related substances, loss on drying (LOD), sulfated ash and assay (based on dried substance). Datasets were gathered and processed using Statistical Process Control (SPC) software. Preliminary data examination was done using box plots and distribution identification for screening the best-fitting one. With the exception of the assay, all results showed a failure to follow specific dispersion. All raw data failed normality tests (Anderson-Darling test, P < 0.05). Accordingly, the output of the tests was adjusted to fit the application of the attribute charts. Laney modification was used to correct data dispersion. The correction factor acidity/alkalinity, impurity A, any other impurities, total impurities, LOD and sulphated ash were 1.003, 1,18568, 1.21158, 1.71165, 1.44613 and 0.883609, respectively. Control chart for normal data was used after Johnson transformation following equation 0.558 + 1.211 x Ln ((X – 98.929)/(101.13 – x)). It should be noted that even when there was no out-of-specification there were several out-of-control points that highlight the necessity for appropriate investigation and correction for assignable causes of variations between batches. There should be governmental enforcement of industrial SPC rules for the quality and safety of the supplied medicinal substances from the chemical manufacturing companies.