Monitoring Magnesium Stearate Blending in a V-Blender Through Passive Vibration Measurements.

Process analytical technologies are implemented within the pharmaceutical manufacturing process to rectify issues associated with current sampling methods. These include inline monitoring methods such as passive vibration measurements which are non-intrusive and less costly to other methods. In the final mixing stage of the tablet manufacturing process, a lubricant is added to ensure the mixture is ejected from the tablet die cleanly.

An Investigation of Magnesium Stearate Mixing Performance in a V-Blender Through Passive Vibration Measurements.

Prior to compression in tablet manufacturing, a lubricant is added and mixed in a V-blender to ensure the mixture is ejected from the tablet die smoothly. Mixing is conducted batch-wise and must be analyzed offline afterwards to ensure the mixture is uniform and will produce desired tablet properties, thereby a costly and time-consuming step within the manufacturing process. To improve process efficiency, inline monitoring methods using passive acoustic emissions or vibration measurements could be implemented.

Methods to Assess Mixing of Pharmaceutical Powders.

The pharmaceutical manufacturing process consists of several steps, each of which must be monitored and controlled to ensure quality standards are met. The level of blending has an impact on the final product quality; therefore, it is important to be able to monitor blending progress and identify an end-point. Currently, the pharmaceutical industry assesses blend content and uniformity through the extraction of samples using thief probes followed by analytical methods, such as spectroscopy, to determine the sample composition.

An application of deep learning to detect process upset during pharmaceutical manufacturing using passive acoustic emissions.

The multivariate nature of a fluidized bed system creates process complexity that increases the risk of production upset. This research explores the use of passive acoustic emissions monitoring paired with an artificial neural network to detect fluidized bed distributor plate blockage. In many cases, early process failure detection can allow for immediate intervention, thus lowering operation costs.

Inline acoustic monitoring to determine fluidized bed performance during pharmaceutical coating.

Fluidized beds are used by pharmaceutical manufacturers for multi-particulate drug coating. They provide effective mass and heat transfer; however, unit optimization can be difficult due to the multivariate nature of a fluidized bed system. This research explores the use of passive acoustic emissions monitoring as a method to improve temperature management during pellet coating.

Passive acoustic emissions from particulates in a V-blender.

Context: Regulatory agencies are recommending the development of process analytical technologies (PAT) to improve the efficiency and product quality during pharmaceutical manufacturing.

Objective: The objective of the research was to investigate the potential application of passive acoustic emission monitoring of a V-blender.

Materials And Methods: Trials were conducted with sugar spheres, lactose or MCC in a V-blender.

A comparison of granules produced by high-shear and fluidized-bed granulation methods.

Placebo granules were manufactured by both wet high-shear and fluidized-bed techniques. The granules were compared based on size, shape, surface morphology, and a variety of different flowability measurements. This comparison showed that granule formation and growth were different, with induction growth for high-shear granulation and steady growth for fluidized-bed granulation.

The effect of moisture on the flowability of pharmaceutical excipients.

The effect of moisture content on flowability of six pharmaceutical powders (microcrystalline cellulose (MCC), hydroxypropyl methylcellulose (HPMC), carboxymethyl cellulose (CMC), polyvinylpyrrolidone (PVP), corn starch, and potato starch) was investigated. Powder flowability was measured using established static techniques and emerging dynamic avalanche behavior measurements. Static techniques did not provide enough resolution to clearly identify changes in flowability due to increasing powder moisture content.

The effect of lubricants on powder flowability for pharmaceutical application.

Pharmaceutical tablets are manufactured through a series of batch steps finishing with compression into a form using a tablet press. Lubricants are added to the powder mixture prior to the tabletting step to ensure that the tablet is ejected properly from the press. The addition of lubricants also affects tablet properties and can affect the behavior of the powder mixture.

The effect of process parameters on audible acoustic emissions from high-shear granulation.

Product quality in high-shear granulation is easily compromised by minor changes in raw material properties or process conditions. It is desired to develop a process analytical technology (PAT) that can monitor the process in real-time and provide feedback for quality control. In this work, the application of audible acoustic emissions (AAEs) as a PAT tool was investigated.

The effect of the chopper on granules from wet high-shear granulation using a PMA-1 granulator.

Chopper presence and then chopper speed was varied during wet high shear granulation of a placebo formulation using a PMA-1 granulator while also varying the impeller speed. The granules were extensively analyzed for differences due to the chopper. The effect of the chopper on the granules varied with impeller speed from no effect at a low impeller speed of 300 rpm to flow interruptions at an impeller speed of 700 rpm to minimal impact at very high impeller speeds as caking at the bowl perimeter obscured the effect of the chopper on the flow pattern.

Monitoring fluidized bed drying of pharmaceutical granules.

Placebo granules consisting of lactose monohydrate, corn starch, and polyvinylpyrrolidone were prepared using de-ionized water in a high-shear mixer and dried in a conical fluidized bed dryer at various superficial gas velocities. Acoustic, vibration, and pressure data obtained over the course of drying was analyzed using various statistical, frequency, fractal, and chaos techniques. Traditional monitoring methods were also used for reference.

Audible acoustics in high-shear wet granulation: application of frequency filtering.

Previous work has shown analysis of audible acoustic emissions from high-shear wet granulation has potential as a technique for end-point detection. In this research, audible acoustic emissions (AEs) from three different formulations were studied to further develop this technique as a process analytical technology. Condenser microphones were attached to three different locations on a PMA-10 high-shear granulator (air exhaust, bowl and motor) to target different sound sources.

Detection of the breakage of pharmaceutical tablets in pneumatic transport.

Pneumatic transport of pharmaceutical tablets is very convenient, compact and greatly reduces contamination. A potential problem, however, is the breakage of a significant fraction of the transported tablets, causing serious product quality problems. Since the flowrate of tablets transported through a given pneumatic transport line increases with gas velocity, lines are often operated at gas velocities slightly below the velocity at which tablets break.