Modified Roller Compaction Model to Account for Roll Speed Effect on Powder Compaction in Dry Granulation Process.

This study introduces a modification to the roller compaction model proposed by Sousa et al.1 to account for the effect of roll speed on powder compaction in the dry granulation process. The proposed model enhances the prediction accuracy, particularly at higher roll speeds, which are often overlooked in existing models. The modified model is validated using literature data, demonstrating improved performance compared to the original model. Additionally, the model is applied to a pharmaceutical formulation, showing its applicability in an industrial context. The integration of the model into gPROMS allows for global sensitivity analysis and design space exploration, providing valuable insights for process optimization and scale-up. The study contributes to the understanding of roller compaction dynamics and offers a practical tool for decision-making in pharmaceutical manufacturing.

A Hybrid Model to Predict Formulation Dependent Granule Growth in a Bi-Component Wet Granulation Process.

In this study, a hybrid modeling framework was developed for predicting size distribution and content uniformity of granules in a bi-component wet granulation system with components of differing hydrophobicities. Two bi-component formulations, (1) ibuprofen-USP and micro-crystalline cellulose and (2) micronized acetaminophen and micro-crystalline cellulose, were used in this study. First, a random forest method was used for predicting the probability of nucleation mechanism (immersion and solid spread), depending upon the formulation hydrophobicity. The predicted nucleation mechanism probability is used to determine the aggregation rate as well as the initial particle distribution in the population balance model. The aggregation process was modeled as Type-I: Sticking aggregation and Type-II: Deformation driven aggregation. In Type-I, the capillary force dominant aggregation mechanism is represented by the particles sticking together without deformation. In the case of Type-II, the particle deformation causes an increase in the contact area, representing a viscous force dominant aggregation mechanism. The choice between Type-I and II aggregation is determined based on the difference in nucleation mechanism that is predicted using the random forest method. The model was optimized and validated using the granule content uniformity data and size distribution data obtained from the experimental studies. The proposed framework predicted content non-uniform behavior for formulations that favored immersion nucleation and uniform behavior for formulations that favored solid-spreading nucleation.

A moving-boundary model of dissolution from binary drug-excipient granules incorporating microstructure.

Accurate mechanistic in vitro dissolution models can deliver insight into drug release behaviour and guide formulation development. Drug release profiles from drug-excipient granules can be impacted by variation of porosity and drug load within granules, which may arise from inherent variability in granulation processes. Here, we analyse and validate a recent model of drug release from a single spherical granule with a matrix of insoluble excipient, incorporating radial variation of porosity and drug load. The model is presented and specialised to the case where the initial drug load is large compared to the capacity of the granule's pores at solubility. In this limit, the model reduces to a single ordinary differential equation describing depletion of a shrinking, drug-saturated core. Model validation is performed using drug release data from the literature for a granule system consisting of acetaminophen and microcrystalline cellulose. A new extended model to describe dissolution from a polydisperse collection of granules is derived. The performance is compared to single particle models using equivalent spherical diameters. The developed model provides a new tool to explore the dissolution parameter space for these systems and for considering the impact of radial variation of granule porosity and drug load arising from manufacturing processes.