Multivariate methods in tablet formulation suitable for early drug development: Predictive models from a screening design of several linked responses

Application of Multivariate Tools in Pharmaceutical Product Development to Bridge Risk Assessment to Continuous Verification in a Quality by Design Environment

“…2) to detect the possible emergence of patterns in this subset. The application of MVA, particularly principal components analysis (PCA) and related methods for the exploration and optimisation of pharmaceutical products and processes, is reported in various articles [4,[18][19][20][21][22]. Whilst the strategy for the CQV approach may evolve over time as further data and knowledge are gathered in the commercial environment, for new drug products, the outcome from RA, i.e.…”

The Future of Pharmaceutical Manufacturing Sciences

“…The number of experiments can be reduced systematically by implementing fractional factorial design, with the experimental load calculated as 2 k ‐ p , where 1/ p is the size of fraction. For example, Andersson et al aimed to optimize early drug development tablet formulation by creating a model with a high predictive power and performing as few experiments as possible. The authors highlighted the importance of considering the number of experimental points when the availability of a drug substance is a limitation and utilized a fractional factorial design to minimize the number of experimental runs in their study.…”

Towards Better Process Understanding: Chemometrics and Multivariate Measurements in Manufacturing of Solid Dosage Forms

“…In general, very few of these processes in the tablet compression phase—some of which take place in very short time, for example the compression phase in few milliseconds—cannot be handled by chemometrics. However, compression profile and tableting are usually based on pre‐formulation stage trials or more sophisticated models and planned experiments such as chemometric‐based feed‐forward process modelling, which may connect compaction force and time with material and process conditions and pre‐defined quality attributes49,55,65 and designing of experiments (DoE) 167, 179,180,181. The tablets themselves can also be characterised with the aid of chemometrics as will be described later.…”

“…The pre‐formulation phase is the foundation for every drug production strategy covering studies of selection of the formulation type (i.e. the quality target product profile), components to be included (API and excipients) and their interactions 179,180. The optimisation of tablet manufacturing is also incorporated in formulation studies including the choice of manufacturing method, target dissolution, strength and disintegration time as well as amounts and types of different fillers and inactive excipients 179,180.…”

“…the quality target product profile), components to be included (API and excipients) and their interactions 179,180. The optimisation of tablet manufacturing is also incorporated in formulation studies including the choice of manufacturing method, target dissolution, strength and disintegration time as well as amounts and types of different fillers and inactive excipients 179,180. Compaction profiles, compaction force, punch velocity and diameter of the die are examined at this phase because all these modify the tablet properties 167.…”