Solid State Properties

Module 7 : Pharmaceutical Preformulation : Basics and Industrial Applications

Levels of solid state properties

A vast majority of APIs and excipients are used in the solid form and their solid sate properties have an impact on their stability and performance. Solid state properties can be envisaged at three levels – molecular, particle and bulk.

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Solid State Properties

Molecular level of solid state

Molecular level deals with the arrangement of the individual molecules in the solid form and involves phenomenon like crystalline, polymorphism, solvated state, amorphous form and co-crystals. Molecular level has direct forbearance on solubility, dissolution kinetics, chemical reactivity and compaction behavior. It can be characterized using various analytical tools like – microscopy (polarized light), thermal (Differential Scanning Calorimetry, Thermal Gravimetric Analysis and Hot Stage Microscopy), spectroscopic (solid state NMR, FTIR, raman and near IR) and crystallographic (Powder X Ray Diffraction and Single Crystal X Ray Diffraction).

Particle level of solid state

Particle level deals with properties of individual particles and includes properties like crystal habit, particle size, particle shape and surface area. They have forbearance on dissolution, flow properties, compaction and hygroscopicity. Particle properties can be characterized using optical / scanning electron microscopy, laser diffraction technique and other suitable analytical tools.

Bulk level of solid state

Bulk level properties encompass an ensemble of particles and includes properties like flow behavior and compaction behavior. They primarily affect the processability of powders. Bulk level properties can be studied using tools for characterizing flow and compaction behavior. Unit process of granulation during processing of solid dosage forms is aimed at modifying the bulk level properties.

Significance of solid state properties

Solid state properties during drug discovery and development have critical implications on solubility, dissolution kinetic and oral absorption. Most stable solid form has the lowest solubility and reactivity. As a rule of thumb drug product is developed using most stable form, to avoid possibility of phase transformation of meta-stable form to stable form, during shelf life and dissolution. Solid form also provides a unique opportunity for patent life extension, as new solid forms can be protected with patents.


Solid state properties are a very important ‘material property’ that affects stability, processability and performance. Solid state properties also play a crucial role in achieving objectives of ‘quality by design (QbD)’, wherein a comprehensive understanding of impact of material properties of process and performance is developed.

Dr. Arvind Bansal

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