Physical Stability and Crystallization Inhibition

Abstract

In order to successfully utilize amorphous solid dispersions (ASDs) to enhance drug delivery, it is essential to maintain the amorphous form of the drug during the manufacturing process and the shelf life of the formulated product. It is essential to evaluate the crystallization tendency of the drug exposed to different environmental conditions and to develop strategies to modify crystallization kinetics through the addition of crystallization inhibitors. This chapter initially discusses crystallization in the solid state, including a consideration of the role of temperature, residual water, and additives. Subsequently, phase behavior during dissolution of an amorphous formulation is explored. The chapter presents an overview of the factors that need to be understood and controlled for successful formulation of an amorphous solid dispersion. It discusses different methods for physical stability assessment. Solid‐state nuclear magnetic resonance spectroscopy (SSNMR) is used to investigate a number of aspects of amorphous solid dispersions.

Use of a Polymer Additive To Enhance Impurity Rejection in the Crystallization of a Pharmaceutical Compound

“…The influence of nonadsorbing polymers on the phase behavior of compounds is of great interest to scientists from a variety of disciplines and is a focus of several research groups. , However, the insights gained from these academic studies are not typically leveraged in pharmaceutical process design. Our study is unique in that aspect.…”

“…Our study is unique in that aspect. While the influence of additives on solubilization of pharmaceutical compounds and on nucleation suppression of crystals is recognized in general, these concepts are often based on empirical observations. − This paper attempts to bridge the gap in understanding by providing a methodology on relating the driving force and energy barrier of nucleation to solubility, thus enabling one to carry out a systematic investigation of crystallization process development. The study described herein relates specifically to the substances used in this study; this crystallization protocol is not claimed to be broadly applicable, and therefore, each substance must be individually tested to understand whether the crystallization protocol and theory described above would be applicable.…”

Crystallisation properties of amorphous cyclodextrin powders and their complexation with fish oil

“…Crystalline materials with anisotropic properties under polarized light showed a birefringent phenomenon which appeared colourful and bright with regions of different contrasts depending on their orientation. On the other hand, amorphous powders with isotropic properties appeared in a similar colour to the background which results in a dark colour (Taylor 2015). There were other differences observed in the polarized light images of amorphous and crystalline CD powders.…”

Support Tools in Formulation Development for Poorly Soluble Drugs

“…Therefore, the stability of amorphous drugs has been the subject of many studies. [34][35][36][37][38][39] If the amorphous stability of an API could be predicted early on in the formulation development, it would be possible to conclude if amorphization were a viable route for an API. Nurzynska et al 40 recently developed a predictive model of the amorphous stability of neutral poorly soluble drugs.…”