Direct Compaction Drug Product Process Modeling.

Most challenges during the development of solid dosage forms are related to the impact of any variations in raw material properties, batch size, or equipment scales on the product quality and the control of the manufacturing process. With the ever pertinent restrictions on time and resource availability versus heightened expectations to develop, optimize, and troubleshoot manufacturing processes, targeted and robust science-based process modeling platforms are essential. This review focuses on the modeling of unit operations and practices involved in batch manufacturing of solid dosage forms by direct compaction.

Predictive Approach to Understand and Eliminate Tablet Breakage During Film Coating.

Pharmaceutical tablets can be susceptible to damage such as edge chipping or erosion of the core during the tablet coating process. The intersection of certain process parameters, equipment design, and tablet properties may induce more significant tablet damage such as complete tablet fracture. In this work, a hybrid predictive approach was developed using discrete element method (DEM) modeling and lab-based tablet impact experiments to identify conditions that may lead to tablet breakage events.

Quantifying and reducing powder shear sensitivity when manufacturing capsules with lubricants.

The purpose of this work was to develop a methodology that quantifies the extent of shear induced during an encapsulation process and show how formulation composition and manufacturing process designs can be changed to reduce the negative impact on drug product quality attributes. The powder feed system used in a dosing disc type pharmaceutical capsule filling machine induced additional shear of the powder prior to slug formation. The shear occurred both in the hopper portion, via the rotation of the feed auger and impeller, and in the powder bowl via the tamping pin agitation and/or shear against the stationary surfaces such as the powder level scraper.

Discrete element method (DEM) simulations of stratified sampling during solid dosage form manufacturing.

Discrete element model (DEM) simulations of the discharge of powders from hoppers under gravity were analyzed to provide estimates of dosage form content uniformity during the manufacture of solid dosage forms (tablets and capsules). For a system that exhibits moderate segregation the effects of sample size, number, and location within the batch were determined. The various sampling approaches were compared to current best-practices for sampling described in the Product Quality Research Institute (PQRI) Blend Uniformity Working Group (BUWG) guidelines.

Modeling the motion and orientation of various pharmaceutical tablet shapes in a film coating pan using DEM.

Film coating uniformity is an important quality attribute of pharmaceutical tablets. Large variability in coating thickness can limit process efficiency or cause significant variation in the amount or delivery rate of the active pharmaceutical ingredient to the patient. In this work, the discrete element method (DEM) is used to computationally model the motion and orientation of several novel pharmaceutical tablet shapes in a film coating pan in order to predict coating uniformity.

The coefficient of rolling resistance (CoRR) of some pharmaceutical tablets.

Experiments have been conducted to measure the coefficient of rolling resistance (CoRR) of some pharmaceutical tablets and several common materials, such as glass beads and steel ball bearings. CoRR values are required as inputs for discrete element method (DEM) models which can be used to model particulate flows and solid dosage form manufacturing processes. Until now there have been no CoRR data reported for pharmaceutical materials, and thus these new data will help to facilitate more accurate modeling of pharmaceutical systems.

Process modeling in the pharmaceutical industry using the discrete element method.

The discrete element method (DEM) is widely used to model a range of processes across many industries. This paper reviews current DEM models for several common pharmaceutical processes including material transport and storage, blending, granulation, milling, compression, and film coating. The studies described in this review yielded interesting results that provided insight into the effects of various material properties and operating conditions on pharmaceutical processes.

Stress results from two-dimensional granular shear flow simulations using various collision models.

Collision resolution is one of the key elements in a discrete element method algorithm for modeling granular flows. Several collision models have been proposed for this process. The hard-particle collision approach is typically used for dilute systems, or for those in which the assumption of binary and instantaneous particle-particle contact remains valid.