There has been a noticeable shift from pharmaceutical batch processing towards a more continuous mode of manufacture for solid oral dosage forms. Continuous solid oral dose processes would not be possible in the absence of a highly accurate feeding system. The performance of feeders defines the content of formulations and is therefore a critical operation in continuous manufacturing of solid dosage forms. It was the purpose of this review to review the role of the initial powder feeding step in a continuous manufacturing process. Different feeding mechanisms are discussed with a particular emphasis on screw controlled loss in weight (LIW) feeding. The importance of understanding the physical properties of the raw materials and its impact on the feeding process is reviewed. Prior knowledge of materials provides an initial indication of how the powders will behave through processing and facilitates in the selection of the most suitable (i) feeder (capacity), (ii) feeding mechanism, and (iii) in the case of screw feeder - screw type. The studies identified in this review focus on the impact of material on powder feeding performance.

Real-time process monitoring using process analytical technology (PAT) tools can augment process understanding, enable improved process control, and hence facilitate the production of high-quality pharmaceutical products. While beneficial for batch processes, the availability of PAT tools to monitor continuous processes in real time is required to ensure product quality. This paper presents the application of novel process analytical technology (PAT) tools in combination with off-line analytical techniques for the study of a laboratory-scale roller compaction dry granulation process. An experiment whereby roll pressure was linearly increased and the effects thereof on roller compacted ribbon and granule properties of a placebo formulation is described. Analysis of the ribbons and granules was performed using both in-line and off-line techniques. Ribbon envelope density was measured using the GeoPyc, and the results were compared to off-line near-infrared (NIR) measurements and a novel in-line NIR tool, the Multieye. Particle size analysis of roller compacted granules was assessed with traditional sieve analysis, Camsizer and a novel technique, the Eyecon. Both Camsizer and Eyecon have the potential of being used as PAT tools in-line. Additionally the compressibility of the granules was determined using in-die Heckle analysis and the hardness of the resultant compacts was assessed. The compacts were subsequently analysed using off-line Raman spectroscopy to investigate the surface smoothness which was shown to indicate crushing strength for compacts prepared. The results of this initial study demonstrate a good relationship between in-line and off-line measurement of key in-process material attributes. The findings thus support the further exploitation of these new in-line PAT methods in monitoring of continuous unit operations at a commercial scale.

The ability of broadband acoustic resonance dissolution spectroscopy (BARDS) to assess the wettability of powder blends is investigated. BARDS is a novel analytical technology developed on the basis of the change in acoustic phenomena observed when material is added into a solvent under resonance. Addition of solid material to the solvent results in the introduction of gas (air) into the solvent, changing the compressibility of the solvent system, and reducing the velocity of sound in the solvent. As a material is wetted and dissolved, the gas is released from the solvent and resonance frequency is altered. The main purpose of this work is to demonstrate the ability of BARDS to assess differences in the wetting behavior of tablet excipients (microcrystalline cellulose (MCC) and magnesium stearate (MgSt)) and a model drug (metoclopramide hydrochloride) as single component powders and multicomponent powder blends. BARDS acoustic responses showed a prolonged release of gas for the powdered blends with lubricant compared to unlubricated blends. As the elimination of gas from the solvent was assumed to follow first order elimination kinetics, a compressible gas elimination rate constant was calculated from the log plots of the gas volume profiles. The gas elimination rate constant was used as a parameter to compare the release of gas from the powder introduced to the solvent and hence the powder wetting behavior. A lower gas elimination rate constant was measured for lubricated blends compared to nonlubricated blends, suggesting the prolonged hydration of lubricated blends. Standard wetting techniques such as contact angle measurements and wetting time analysis were also used to analyze the blends and confirmed differences in wetting behavior determined by BARDS. The study results demonstrate the capability of BARDS as a rapid, analytical tool to determine the wetting behavior of the pharmaceutical powder blends and the potential of BARDS as a process analytical technology (PAT) tool.