Physicochemical Interactions in Solid Dosage Forms

Abstract

Complete characterization and mechanistic understanding of physicochemical interactions in solid dosage forms are not only important for consistent manufacturability, stability, and bioavailability of the drug product, but are also expected under the quality-by-design paradigm of drug development. Lack of this understanding can impact successful and timely development, scale-up, and commercial manufacture of dosage forms. This article highlights the stability and bioavailability implications of physicochemical interactions in dosage forms citing a couple of examples where such interactions necessitated the recall of commercial drug products.

The crystallinity of cellulose controls the physical distribution of sorbed water and the capacity to present water for chemical degradation of a solid drug

“…More on, it is argued (Narang et al, 2012) that better understanding of physico-chemical interactions in solid dosage forms is needed under the quality by design paradigm of product development. Cellulose, especially in the form referred to as microcrystalline cellulose (MCC), is one of the most commonly used excipients in solid dosage forms (Kachrimanis et al, 2006) due to suitable technical properties, such as compactability (Michaut et al, 2010) and pelletizing ability (Mascia and Wilson, 2007).…”

Real-Time Assessment of Granule Densification in High Shear Wet Granulation and Application to Scale-up of a Placebo and a Brivanib Alaninate Formulation

“…Drug release or dissolution of drug from a tablet is defined as a critical drug product quality attribute (CQA) that can affect drug absorption . Dependence of tablet dissolution on the in‐process material attributes of granules was investigated by studying the porosity and dissolution of granules prepared under different process conditions.…”

Pharmaceutical Development and Regulatory Considerations for Nanoparticles and Nanoparticulate Drug Delivery Systems

“…In terms of physical instability, the particles tend to exhibit higher surface interactions and aggregation. In terms of chemical instability, the rates of degradation reactions of drugs are typically higher for smaller sized APIs . Cryomilling is a process platform for particle size reduction under low temperature conditions that may mitigate chemical drug instability and improve physical processability of material during the high impact milling process.…”