title: Near infrared spectroscopic calibration models for real time monitoring of powder density.
abstract: Near infrared spectroscopic (NIRS) calibration models for real time prediction of powder density (tap, bulk and consolidated) were developed for a pharmaceutical formulation. Powder density is a critical property in the manufacturing of solid oral dosages, related to critical quality attributes such as tablet mass, hardness and dissolution. The establishment of calibration techniques for powder density is highly desired towards the development of control strategies. Three techniques were evaluated to obtain the required variation in powder density for calibration sets: 1) different tap density levels (for a single component), 2) generating different strain levels in powders blends (and as consequence powder density), through a modified shear Couette Cell, and 3) applying normal forces during a compressibility test with a powder rheometer to a pharmaceutical blend. For each variation in powder density, near infrared spectra were acquired to develop partial least squares (PLS) calibration models. Test samples were predicted with a relative standard error of prediction of 0.38%, 7.65% and 0.93% for tap density (single component), shear and rheometer respectively. Spectra obtained in real time in a continuous manufacturing (CM) plant were compared to the spectra from the three approaches used to vary powder density. The calibration based on the application of different strain levels showed the greatest similarity with the blends produced in the CM plant.
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemistry, University of Puerto Rico, Mayaguez Campus, Mayaguez, PR 00681, USA.
authors.forename: Andrés D
authors.initials: AD
authors.lastname: Román-Ospino
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Ravendra
authors.initials: R
authors.lastname: Singh
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Marianthi
authors.initials: M
authors.lastname: Ierapetritou
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Rohit
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemical Engineering, University of Puerto Rico, Mayaguez Campus, Mayaguez, PR 00681, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Méndez
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemistry, University of Puerto Rico, Mayaguez Campus, Mayaguez, PR 00681, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ortega-Zuñiga
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemical and Biochemical Engineering, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Muzzio
authors.affiliation: Engineering Research Center for Structured Organic Particulate Systems (C-SOPS), Department of Chemistry, University of Puerto Rico, Mayaguez Campus, Mayaguez, PR 00681, USA. Electronic address: rodolfoj.romanach@upr.edu.
authors.forename: Rodolfo J
authors.initials: RJ
authors.lastname: Romañach
mesh_terms: D002138:Calibration; D004339:Drug Compounding; D015233:Models, Statistical; D011208:Powders / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D011208:Powders
keywords: Monitoring; Near infrared spectroscopy (NIRS); Powder density; Powder rheometer; Process analytical technology (PAT); Quality by design (QbD).