title: Near InfraRed Spectroscopy homogeneity evaluation of complex powder blends in a small-scale pharmaceutical preformulation process, a real-life application.
abstract: Near InfraRed Spectroscopy (NIRS) is a potentially powerful tool for assessing the homogeneity of industrial powder blends. In the particular context of hospital manufacturing, we considered the introduction of the technique at a small pharmaceutical process scale, with the objective of following blend homogeneity in mixtures of seven components. This article investigates the performance of various NIRS-based methodologies to assess powder blending. The formulation studied is prescribed in haematology unit, as part of the treatment for digestive decontamination in children receiving stem-cell transplantation. It is composed of the active pharmaceutical ingredients (APIs) colimycin and tobramycin and five excipients. We evaluated 39 different blends composing 14 different formulations, with uncorrelated proportions of constituents between these 14 formulations. The reference methods used to establish the NIRS models were gravimetry and a High Performance Liquid Chromatography method coupled to an Evaporative Light Scattering Detection. Unsupervised and supervised qualitative and quantitative chemometric methods were performed to assess powder blend homogeneity using a bench top instrument equipped with an optical fibre. For qualitative evaluations, unsupervised Moving Block Standard Deviation, autocorrelation functions and Partial Least Square Discriminant Analysis (PLS-DA) were used. For quantitative evaluations, Partial Least Square Cross-Validated models were chosen. Results are expressed as API, and major excipient percentages of theoretical values as a function of blending time. The 14 different formulations were only satisfactorily discriminated by supervised algorithms, such as an optimised PLS-DA model. The homogeneity state was demonstrated after 16 min of blending, quantifying three components with a precision between 1.2% and 1.4% w/w. This study demonstrates, for the first time, the effective implementation of NIRS for blend homogeneity evaluation, as early as the preformulation step in a small hospital manufacturing unit. It shows how NIRS involving sampling with an optic fibre can be useful to characterise, optimise and control a small-scale mixing processes on the basis of the distribution of APIs and excipients during blending.
authors.affiliation: Groupe de Chimie Analytique de Paris-Sud, EA 4041, IFR 141, School of Pharmacy, Univ Paris-Sud, Châtenay-Malabry, France.
authors.forename: I
authors.initials: I
authors.lastname: Storme-Paris
authors.forename: I
authors.initials: I
authors.lastname: Clarot
authors.forename: S
authors.initials: S
authors.lastname: Esposito
authors.forename: J C
authors.initials: JC
authors.lastname: Chaumeil
authors.forename: A
authors.initials: A
authors.lastname: Nicolas
authors.forename: F
authors.initials: F
authors.lastname: Brion
authors.forename: A
authors.initials: A
authors.lastname: Rieutord
authors.forename: P
authors.initials: P
authors.lastname: Chaminade
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D003091:Colistin / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods*; D004867:Equipment Design; D008027:Light; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011208:Powders / Q000737:chemistry; D012542:Scattering, Radiation; D012984:Software; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000379:methods; D014031:Tobramycin / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D011208:Powders; D014031:Tobramycin; D003091:Colistin