Monitoring of high-load dose formulations based on co-processed and non co-processed excipients.

This work presents the evaluation of a co-processed material for high-load dose formulations and its real-time monitoring by near-infrared (NIR) spectroscopy at the tablet press feed frame. The powder and tableting properties of co-processed material blends were evaluated and compared to the blend of the individual excipients. The formulations with the co-processed material showed excellent flow properties and were superior to the physical blend of individual excipients. Two NIR spectroscopic methods were developed to monitor ibuprofen concentration between 40.0 and 60.0% w/w, one method using a co-processed material as the main excipient and the other using the blend of the individual excipients. The NIR spectra were obtained while the powder blends flowed within a three-chamber feed frame from a Fette 3090 tablet press. The NIR spectroscopic method with the co-processed material presented better performance with significantly lower prediction error. Variographic analysis demonstrated that using the co-processed material considerably reduces the sampling and analytical errors in the in-line determination of ibuprofen. The authors understand that this is the first study where the sampling errors are evaluated as a function of the excipients used in the pharmaceutical formulation. This study demonstrated that selecting a suitable excipient for the formulation helps optimize the manufacturing process, reducing the magnitude of the total measurement error.

Isoniazid-loaded orodispersible strips: Methodical design, optimization and in vitro-in silico characterization.

Drug treatment remains the most effective global approach to managing and preventing tuberculosis. This work focuses on formulating and evaluating an optimized polyvinyl alcohol-polyethylene glycol based orodispersible strip containing isoniazid, a first-line anti-tubercular agent. A solvent casting method guided through a Taguchi experimental design was employed in the fabrication, optimization and characterization of the orodispersible strip. The optimized strip was physically amalgamated with a monolayer, uniformly distributed surface geometry. It was 159.2 ±â€¯3.0 µm thick, weighed 36.9 ±â€¯0.3 mg, had an isoniazid load of 99.5 ±â€¯0.8%w/w, disintegration and dissolution times of 17.6 ±â€¯0.9 s and 5.5 ±â€¯0.1 min respectively. In vitro crystallinity, thermal measurements and in silico thermodynamic predictions confirmed the strip's intrinsic miscibility, thermodynamic stability and amorphous nature. A Korsmeyer-Peppas (r = 0.99; n > 1 = 1.07) fitted kinetics typified by an initial burst release of 49.4 ±â€¯1.9% at 4 min and a total of 99.8 ±â€¯3.3% at 30 min was noted. Ex vivo isoniazid permeation through porcine buccal mucosa was bi-phasic and characterized by a 50.4 ±â€¯3.8% surge and 95.6 ±â€¯2.9% at 5 and 120 min respectively. The strip was physicomechanically robust, environmentally stable and non-cytotoxic.

Generic Raman-based calibration models enabling real-time monitoring of cell culture bioreactors.

Raman-based multivariate calibration models have been developed for real-time in situ monitoring of multiple process parameters within cell culture bioreactors. Developed models are generic, in the sense that they are applicable to various products, media, and cell lines based on Chinese Hamster Ovarian (CHO) host cells, and are scalable to large pilot and manufacturing scales. Several batches using different CHO-based cell lines and corresponding proprietary media and process conditions have been used to generate calibration datasets, and models have been validated using independent datasets from separate batch runs. All models have been validated to be generic and capable of predicting process parameters with acceptable accuracy. The developed models allow monitoring multiple key bioprocess metabolic variables, and hence can be utilized as an important enabling tool for Quality by Design approaches which are strongly supported by the U.S. Food and Drug Administration.

Implementation of an advanced hybrid MPC-PID control system using PAT tools into a direct compaction continuous pharmaceutical tablet manufacturing pilot plant.

It is desirable for a pharmaceutical final dosage form to be manufactured through a quality by design (QbD)-based approach rather than a quality by testing (QbT) approach. An automatic feedback control system coupled with PAT tools that is part of the QbD paradigm shift, has the potential to ensure that the pre-defined end product quality attributes are met in a time and cost efficient manner. In this work, an advanced hybrid MPC-PID control architecture coupled with real time inline/online monitoring tools and principal components analysis (PCA) based additional supervisory control layer has been proposed for a continuous direct compaction tablet manufacturing process. The advantages of both MPC and PID have been utilized in a hybrid scheme. The control hardware and software integration and implementation of the control system has been demonstrated using feeders and blending unit operation of a continuous tablet manufacturing pilot plant and an NIR based PAT tool. The advanced hybrid MPC-PID control scheme leads to enhanced control loop performance of the critical quality attributes in comparison to a regulatory (e.g. PID) control scheme indicating its potential to improve pharmaceutical product quality.