scholarly journals Process Control of Drug Product Continuous Manufacturing Operations—a Study in Operational Simplification and Continuous Improvement

2020 ◽  
Author(s):  
Joseph Medendorp ◽  
Sreedhar Shapally ◽  
Derek Vrieze ◽  
Kelly Tolton
Keyword(s):  
Process Control ◽  
Near Infrared ◽  
Drug Product ◽  
Measurement Techniques ◽  
Fixed Dose ◽  
Continuous Manufacturing ◽  
Monitoring And Control ◽  
Spectroscopic Measurements ◽  
Gravimetric Measurements ◽  
Drug Concentrations

Abstract Purpose The purpose of this manuscript is to demonstrate that implementation of gravimetric measurements provides the same assurance of product quality and process control as spectroscopic measurements (1) for control of drug content in a fixed-dose combination (FDC) tablet and (2) for identification of non-conforming material. Methods A wet granulation continuous tableting line was used to make the FDC drug product batches. Comparative data was generated for ten batches using near-infrared (NIR) spectroscopy for core tablets, and gravimetric in-process control measurements (IPCs) applied to the ratio control of intra- and extra-granular blend (IG and EG). HPLC reference data were collected to further demonstrate uniformity at each stage of the production process, including IG, final blend, and core tablets. All possible sources of variation not directly detectable by the gravimetric measurements were considered and quantified. Results The two IPC measurement techniques showed excellent agreement where both were within 2% of the target drug concentrations and within 2% of each other for the ten comparative batches. The NIR was more sensitive to material and process variations than the gravimetric IPCs; thus, it was more variable within and across batches. Gravimetric IPCs were demonstrated as an effective replacement for spectroscopic measurements for continuous tableting operations, capable of ensuring on target manufacturing and detection of non-conforming material. Conclusions As pharmaceutical companies continue to push toward operational simplicity and sustainable manufacturing processes, soft-sensor and gravimetric controls as alternatives to their spectroscopic counterparts will be applied more broadly for process monitoring and control.

scholarly journals Application of near-infrared spectroscopy for monitoring and control of cell culture and fermentation

2009 ◽  
pp. NA-NA ◽  
Author(s):  
Albert E. Cervera ◽  
Nanna Petersen ◽  
Anna Eliasson Lantz ◽  
Anders Larsen ◽  
Krist V. Gernaey
Keyword(s):  
Cell Culture ◽  
Infrared Spectroscopy ◽  
Near Infrared Spectroscopy ◽  
Near Infrared ◽  
Monitoring And Control ◽  
And Control

scholarly journals Vibrations of Air-Coupled Web Systems

2020 ◽  
Vol 143 (1) ◽  
Author(s):  
Dan Feng ◽  
Jie Wang ◽  
George T.-C. Chiu ◽  
Arvind Raman
Keyword(s):  
Closed Form ◽  
Process Monitoring ◽  
Low Frequency ◽  
Stretchable Electronics ◽  
Continuous Manufacturing ◽  
Monitoring And Control ◽  
Roll To Roll ◽  
Aspect Ratios ◽  
Manufacturing Technologies ◽  
Web Systems

Abstract The prediction and measurement of vibrations of the low-frequency transverse modes of tensioned webs are of increasing interest for process monitoring, quality control, and process stability in roll-to-roll flexible hybrid and stretchable electronics manufacturing, nanomanufacturing, coated layer patterning, and other continuous manufacturing technologies. Acting as distributed added mass, the surrounding air significantly affects the frequency responses of taut thin webs in ambient roll-to-roll processes in comparison with those in vacuo. In this paper, we present closed-form, semi-analytical, universal hydrodynamic functions used to accurately predict the lowest symmetric and anti-symmetric transverse frequency response for any uniaxially tensioned web of arbitrary material and aspect ratio used in roll-to-roll processes. Experimental validation is carried out by using pointwise laser measurements of acoustically excited webs with different pre-tensions, web materials, and aspect ratios. These closed-form hydrodynamic functions provide roll-to-roll process designers a convenient way to predict the lowest frequencies of such web systems without the need to resort to computationally intensive methods; alternately, these functions allow for the quick identification of conditions when air-coupling is important to determine the web’s vibration response. The results presented herein are expected to help ongoing efforts to improve process monitoring and control in a variety of roll-to-roll continuous manufacturing technologies.

scholarly journals DERIVATIVES OF THE RATIO SPECTRA FOR DETERMINATION OF ACETYLSALICYLIC ACID, ACETAMINOPHEN, AND CAFFEINE IN FIXED-DOSE COMBINATION FORMULATIONS: APPLICATION TO DISSOLUTION STUDIES

2020 ◽  
pp. 253-257
Author(s):  
JOSE RAUL MEDINA-LÓPEZ ◽  
JOSUE GIOVANI PACHECO PINEDA ◽  
PEDRO ALBERTO ROJAS GARFIAS ◽  
NICASIO CASTRO CHÁVEZ
Keyword(s):  
Drug Product ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Reference Drug ◽  
Zero Crossing ◽  
Dissolution Studies ◽  
Derivative Method ◽  
Dose Combination ◽  
Derivatives Of

Objective: To develop a ratio-derivative spectrophotometric method for the simultaneous quantification of acetilsalycilic acid (ASA), acetaminophen (ACE), and caffeine (CAF) in fixed-dose combination formulations. The proposed method was applied to the reference drug product Excedrin® in dissolution studies. Methods: The method is based on the use of the first-and second-derivatives of the ratio spectra and measurements at zero-crossing wavelengths. The dissolution profiles of ASA, ACE, and CAF were obtained following pharmacopeial conditions, USP Apparatus 2 at 100 rpm and 900 ml of water. Dissolution samples were treated with the proposed UV-derivative method and the results were compared with those obtained with a validated HPLC procedure. The dissolution efficiency was used to compare dissolution profiles (HPLC vs. UV-derivative method). Results: The method was linear in the range of 5-25 µg/ml of ASA, 2.5-20 µg/ml of ACE, and 1-8 µg/ml of CAF (R2>0.999, *P<0.05). The precision and accuracy of synthetic mixtures were within acceptable criteria (2.11-3.43% and 96.78-104.15%, respectively). Nitrocellulose filters were the best option to filter samples and stability of all drugs was adequate when standard solutions were stored at 4 °C during 24 h. No significant differences were found between dissolution profiles (*P>0.05). Conclusion: The proposed UV-derivative method allows the simultaneous determination of ASA, ACE, and CAF in commercial formulations. The method is simple, accurate, and precise and can be used in dissolution studies. Spectrophotometric methods are of low cost and harmless to the environment and, therefore, a better alternative than chromatographic methods.

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