Predictive and correlative techniques for the design, optimisation and manufacture of solid dosage forms

Abstract

There is much interest in predicting the properties of pharmaceutical dosage forms from the properties of the raw materials they contain. Achieving this with reasonable accuracy would aid the faster development and manufacture of dosage forms. A variety of approaches to prediction or correlation of properties are reviewed. These approaches have variable accuracy, with no single technique yet able to provide an accurate prediction of the overall properties of the dosage form. However, there have been some successes in predicting trends within a formulation series based on the physicochemical and mechanical properties of raw materials, predicting process scale-up through mechanical characterisation of materials and predicting product characteristics by process monitoring. Advances in information technology have increased predictive capability and accuracy by facilitating the analysis of complex multivariate data, mapping formulation characteristics and capturing past knowledge and experience.

A Particle Rearrangement Index Based on the Kawakita Powder Compression Equation

“…The testing of physical and mechanical properties of drugs and excipients represents an activity of increasing importance during the formulation of solid pharmaceutical preparations 1. Compared to the testing of mechanical properties of compacts formed from a powder, which has been a common approach in the literature,2, 3 the analysis of the compression process4, 5 has two main advantages: the amount of powder required for the test is low and poorly compactable powders can be analyzed.…”

“…Particle rearrangement without parallel particle fragmentation or deformation represents one type of powder flow. Various techniques to determine powder flowability have been developed 1, 12 among which the assessment of the degree to which a powder compresses as a function of applied pressure is common in pharmaceutical sciences. Compression is often accomplished by tapping and relationships between bulk and tapped densities are often used as indicators of powder flowability, such as the Hausner ratio13 and the Carr's compressibility index 14–16.…”

Compressibility of Binary Powder Formulations: Investigation and Evaluation with Compaction Equations

“…This need has initiated the development of predictive techniques that may have the benefit in reducing development time and research materials. 2 Even though some authors 3,4 investigated and evaluated in a detailed manner the microscopic interaction forces between particles and their influence on the mechanical properties of particulate systems, the behavior of interparticle forces is still far from being well understood and an underestimation of these forces can have tremendous effects in powder technology.…”

Multiscale Modelling Methodology for Virtual Prototyping of Effervescent Tablets

“…Rational formulation of tablets necessitates that the dependence of dissolution rate and mechanical properties on the composition and microstructure of the tablet be known 11–13. This relationship can be obtained either purely experimentally,14,15 with the help of mathematical models derived from theory, or from computer simulations of the dissolution process 16,17.…”