Using a Material Library to Understand the Impacts of Raw Material Properties on Ribbon Quality in Roll Compaction

Abstract

The purpose of this study is to use a material library to investigate the effect of raw material properties on ribbon tensile strength (TS) and solid fraction (SF) in the roll compaction (RC) process. A total of 81 pharmaceutical materials, including 53 excipients and 28 natural product powders (NPPs), were characterized by 22 material descriptors and were compacted under five different hydraulic pressures. The transversal and longitudinal splitting behaviors of the ribbons were summarized. The TS-porosity and TS-pressure relationships were used to explain the roll compaction behavior of powdered materials. Through defining the target ribbon quality (i.e., 0.6 ≤ SF ≤ 0.8 and TS ≥ 1 MPa), the roll compaction behavior classification system (RCBCS) was built and 81 materials were classified into three categories. A total of 24 excipients and five NPPs were classified as Category I materials, which fulfilled the target ribbon quality and had less occurrence of transversal splitting. Moreover, the multivariate relationships between raw material descriptors, the hydraulic pressure and ribbon quality attributes were obtained by PLS regression. Four density-related material descriptors and the cohesion index were identified as critical material attributes (CMAs). The multi-objective design space summarizing the feasible material properties and operational region for the RC process were visualized. The RCBCS presented in this paper enables a formulator to perform the initial risk assessment of any new materials, and the data modeling method helps to predict the impact of formulation ingredients on strength and porosity of compacts.

Pharmaceutical application of multivariate modelling techniques: a review on the manufacturing of tablets

“…Therefore, several mathematical models were established, including one-dimensional (1D), 2D, and 3D models to study the roller compaction process. 70–73 However, due to the diversity of pharmaceutical powders and the complexity of manufacturing solid dosage forms, these mathematical models are only suitable for particular powders and roller compactors, 74 making it challenging to build a “one size fits all” model. 75 …”

“…In many studies, the MVA model was developed to study the complex roller compaction process. 79–81 For example, Yu et al 74 developed a PLS model to explore the effect of raw material properties on ribbon properties using 81 pharmaceutical powders. Next, the CMAs and CPPs of roller compaction were identified based on the VIP of the PLS model.…”

“… 285 Furthermore, control engineering theories for pharmaceutical continuous manufacturing process have not yet achieved a common understanding or wider application in the pharmaceutical process. The material library, which was proposed to gain sufficient knowledge about raw material attributes, 74,311,312 has not been studied for the CM process in solid oral dosages. In the future, based on the material library, multivariate modeling techniques or hybrid models should be established to study the relationship between critical equipment settings (CEEs), CMAs, CPPs and CQAs.…”

Sample Size Requirements of a Pharmaceutical Material Library: A Case in Predicting Direct Compression Tablet Tensile Strength by Latent Variable Modeling

“…The material library method aims to develop a standard material characterization framework to collect and store the physiochemical properties and related information of pharmaceutical materials [ 1 ]. By using a material library, both new and generic drug development activities could be enhanced in different ways, such as by understanding the relationship among different material quality attributes and simplifying the material characterization workload, finding the surrogate or equivalent materials for costly APIs during initial process development, and supporting the development of process models by linking the materials’ physical properties to unit operations [ 2 , 3 , 4 , 5 , 6 , 7 ].…”

Downstream processing of spray-dried ASD with hypromellose acetate succinate – Roller compaction and subsequent compression into high ASD load tablets

“…Recently, L-HPC was included in a systematic study with 81 excipients in roller compaction. L-HPC was, among others, categorized as category 1 material providing ribbon tensile strength >1 MPa with 0.6 ≤ SF ≤ 0.8 at low hydraulic pressure (30–70 bar) ( Yu et al, 2019 ). However, there is no report on the application of L-HPC in spray-dried dispersion downstream processing.…”