Identification of Challenges for ‘Drugability’
Preformulation studies play a critical role during drug discovery and development process. It is customary to generate a document called preformulation report, on culmination of experimental protocols. Pre formulation report during drug discovery presents an assessment of impact of solubility, permeability and stability on ‘drugability’ of the molecule. In case any parameter poses a risk to drugability, strategies to mitigate that risk are discussed in the preformulation report. For example if solubility poses a risk to ‘drugability’, then various solubilization approaches relevant to that molecule arediscussed. A comparison of required solubility improvement and solubility enhancement possible from a particular approach, can help in taking informed decision regarding ‘drugability’. Similarly decision regarding developing a particular salt form or drug analogues is based on the findings of preformulation studies. A careful paper exercise on ‘drugability’, based on preformulation findings, helps in reducing the later stage failures.
Preformulation Guides the Formulation Development
Similarly a preformulation report is generated before initiating formulations for various stages of clinical trials. This report discussed the physic-chemical properties of the molecule, in specific to the intended dosage form. The objective of this report is to identify possible challenges during formulation development and strategies to overcome these challenges. As we are aware, findings of the compatibility studies help in identifying the excipients for formulation development. And derived preformulation properties like bulk density, flow properties and compaction profile, help in understanding challenges during processing. Findings of hygroscopicity and solid-state stability dictate choice of environmental conditions and primary packaging compaction. Need for appropriate particle size is also revealed during this phase. Such findings on solid state properties and particle size distribution lay the foundation for drug substance and drug product specifications.
Hence it can be concluded that a carefully executed preformulation protocol helps assessing the ‘drugability’ of a NCE. In the later stages it lays a strong foundation for development of a robust formulation. Preformulation report is like the resume of the molecule and provides scientific basis for drug discovery and development.
Dr. Arvind Bansal
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