title: Applications of NIR in early stage formulation development. Part I. Semi-quantitative blend uniformity and content uniformity analyses by reflectance NIR without calibration models.
abstract: This article describes a semi-quantitative reflectance near infrared (SQ-NIR) method for blend uniformity (BU) and content uniformity (CU) analyses in early stage formulation development. Applicability of the method depends upon three factors: separation of NIR signals of the active pharmaceutical ingredient (API) from placebo; strength of the signal; and a quantitative relationship between API concentration and NIR signal. Based on these three criteria, suitable NIR signals of the API, separated from those of placebo through suitable pretreatment of the spectra, can be used for BU and CU calculations without calibration models. The method was applied to an early stage formulation development project. Multiple batches of tablets were prepared and analyzed using the SQ-NIR method and a validated UV-VIS reference method. The SQ-NIR method was able to distinguish between batches that had satisfactory and unsatisfactory content uniformity and potency. In addition, effects of compression force and API particle size on the SQ-NIR results are discussed. It is proposed that the SQ-NIR method may be used as an independent test in early stage formulation development. The advantages and limitations of the method compared with traditional HPLC or UV-VIS methods are also discussed.
authors.affiliation: Analytical Development, Johnson & Johnson Pharmaceutical Research & Development, LLC, Welsh & McKean Roads, Spring House, PA 19477, USA. wli1@prdus.jnj.com
authors.forename: Weiyong
authors.initials: W
authors.lastname: Li
authors.forename: Abraham
authors.initials: A
authors.lastname: Bashai-Woldu
authors.forename: John
authors.initials: J
authors.lastname: Ballard
authors.forename: Mark
authors.initials: M
authors.lastname: Johnson
authors.forename: Maria
authors.initials: M
authors.lastname: Agresta
authors.forename: Henrik
authors.initials: H
authors.lastname: Rasmussen
authors.forename: Steven
authors.initials: S
authors.lastname: Hu
authors.forename: John
authors.initials: J
authors.lastname: Cunningham
authors.forename: Denita
authors.initials: D
authors.lastname: Winstead
mesh_terms: D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D019245:Compressive Strength; D003692:Delayed-Action Preparations; D005240:Feasibility Studies; D008956:Models, Chemical; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000592:standards; D011786:Quality Control; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D019265:Spectroscopy, Near-Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D013607:Tablets