Tablets manufacturing – Direct Scale-up from Lab to Manufacturing Facilities

• Autor(a) principal: Saramago, Artur Rafael Servo Nunes Duarte
• Data de Publicação: 2020
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/113511
• topic: Roller Compaction; Dry Granulation scale-up; Tableting; Amorphous Solid Dispersions; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

Nowadays, oral dosage forms are the preferred drug delivery route. Concerning tablets as drug delivery systems, some solubility and flowability problems often arise, which can be fixed by manufacturing amorphous solid dispersions (ASD) and/or tablets via granulation (wet or dry) techniques. In this work, HPMCAS and PVPVA, typically selected polymers for ASD production, were incorporated in a standard formulation suitable for a dry granulation process. Generally, the process consists of ASD manufacturing via spray drying (SD), intragranular blending, roller compaction (RC) (includes compaction and milling) or slugging and milling (laboratory), extragranular blend, and tableting. An RC model, based on Johanson’s rolling theory, for predicting the intragranular material solid fraction (SF) at the rolls minimum gap and calibrated from in-die data from compaction simulator, was validated by comparing with experimental data from SF estimation via throughput. Using different toolings and dwell time, the Lab slugging was not able to mimic the manufacturing facilities (MF) ribbons produced via RC. Even when comparing ribbons and tablets from a case-study project with low SD dispersion percentage incorporated, the same difference was observed. It was evaluated how RC parameters, namely compaction force, gap between the rolls, and milling step (lab or MF), affected the granules size distribution and flowability. In terms of flowability, both formulations yielded results within typical dry granulation categories. Also, the MF milling step was successfully simulated at the lab, by selecting the same milling tip speed. Compactability-Tabletability-Compressibility (CTC) profiles were generated to compare the impact of the different processing routes, lab or MF, on tablets’ properties. Regardless of the manufacturing parameters, PVPVA tablets, showed better tableting characteristics and plastic deformation, comparing to HPMCAS formulation. A scale-up methodology was proposed based on out-of-die compressibility profiles. This approach aims to eliminate, whenever possible, non-GMP tests, decreasing costs and expanding MF’s availability.