Poorly soluble compounds create uncertainty for CMC and clinical
The first challenge to address is whether a formulation will achieve the required clinical exposure in humans, and the second is which formulation and manufacturing / CMC pathway should be advanced. Rather than assuming that greater formulation complexity is always the answer, an evidence-led approach focuses on making the formulation decision only when sufficient data are available.
A sound framework for development often begins with understanding the molecule and identifying the factors most likely to constrain clinical exposure. From there, development teams can preserve credible formulation options using API-sparing, fit-for-phase approaches that avoid premature commitments while key questions remain unanswered. Human pharmacokinetic (PK) data then provide the most direct evidence of whether additional formulation complexity delivers meaningful clinical benefit.
Different programs can always lead to different outcomes. The goal doesn't always have to be the most sophisticated or complex formulation possible if desired clinical performance can be achieved, while remaining viable through later development and commercial manufacture. In some cases, enabling technologies such as spray-dried dispersions may be justified by substantial improvements in exposure.
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Our experts examine a full technical discussion about solubility enhancement, with case studies and evidence-led formulation selection for poorly soluble compounds.
Download now: How to Address Poor Solubility: A Data-Driven Path to Success (Infographic)
Watch our latest webinar on-demand
Quotient Sciences' speakers, joined by Dr. Mark A. Krook, CMC & Early Drug Development at NGT Biopharma Consultants, recently discussed how a connected development strategy can help address drug solubility challenges from formulation selection through scale-up. They explored approaches including hot melt extrusion, spray-dried dispersions, lipid-based formulations and particle size reduction, highlighting how early formulation decisions can reduce downstream development and manufacturing risks.
Watch now: "Improve Drug Solubility from Formulation to Scale-Up"