Alvarado-Hernández, Bárbara B.

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    Development of Blend Uniformity Determination Methodologies in Continuous Pharmaceutical Manufacturing Processes using Near- Infrared Spectroscopy
    (2020-04-17) Alvarado-Hernández, Bárbara B.; Romañach, Rodolfo J.; College of Arts and Sciences - Art; Méndez, Rafael; Alcalá, Manel; Torres, Jessica; Department of Chemistry; Acevedo, Aldo
    Pharmaceutical companies are responsible for the development of their own blend uniformity specifications and guidelines to assure uniformity and homogeneity. Blend uniformity is a critical in the manufacturing of solid oral dosages due to patient safety. It is crucial that a patient receive the correct amount of drug needed for therapeutic effect. Drug product below or above the intended dosage can have deadly consequences to public safety. The establishment of process analytical technology resulted in new control strategies to control the amount of active pharmaceutical ingredient and ensure product quality through timely measurements. These studies will serve as a starting point for a guideline for blend uniformity method development in the pharmaceutical industry. The studies focused on the evaluation blend uniformity using near infrared spectroscopy: 1) the evaluation of the effect of high excipient content on the development of low drug content NIR calibration models. The physical properties of the blends had a more significant effect on the NIR spectra obtained, by affecting the baseline shift and band intensity of the spectra. 2)A blending method transfer from a research laboratory setting to a continuous manufacturing plant. The study showed the model was able to identify flow issues, identified as baseline shifts, that could be used to alert to problems in the powder bed that may warrant diversion from a production line. And finally, 3) the testing of an innovative sampling system based on the theory of sampling for flowing powder was successfully tested, as well as the sampling analytical errors for the material characteristics used were defined using variographic analysis. The three studies help determine possible specifications needed for the transfer of a blending method to a continuous manufacturing setting, provides innovative sampling method which can help in the estimation of the sampling and analytical errors involved in a process as well as characterize the intrinsic heterogeneity of the blends used and the challenges faced when determining blend uniformity at lower drug concentrations in pharmaceutical powders.