Dr. Andrew Parker, Dr. Sandeep Kumar, and John McDermott featured in Drug Development & Delivery's article, "PRECLINICAL SCREENING PLATFORM - From Preclinical Screening to Clinical Optimization: Accelerating Poorly Soluble Drug Development".
It’s well understood most drugs emerging from discovery pipelines possess poor aqueous solubility and/or low permeability, providing barriers to absorption and bioavailability. Enhancing absorption is therefore a cornerstone of formulation science, directly impacting oral bioavailability and therapeutic index.
When choosing a CDMO partner, finding one with experience in the development of enabled formulation systems, such as amorphous solid dispersions and lipidic systems, is critical to advancing molecules that have poor solubility. Additionally, an “end-to-end” integrated service philosophy, in which all elements of drug development can be procured through a single vendor with capabilities and experience to pivot to the respective needs of a drug’s biopharmaceutic properties, can further accelerate development at all stages.
In the preclinical phase, establishing formulations capable of achieving sufficient drug solubility to probe toxicology is key. Here, Quotient Sciences, applies a systematic, data-driven screening platform evaluating solubility-enhancement approaches to direct the toxicology formulation. As a drug approaches a first-in-human (FIH) trial, the Quotient Sciences Translational Pharmaceutics® platform enables development teams to minimize investment in GMP drug product manufacturing by making drug products on-demand. This allows the development team to reduce supply chain complexity and rapidly apply enabled formulations in the trial to ensure drug exposure. Finally, the Translational Pharmaceutics platform® can be applied to further optimize drug product formulations using clinical data following Phase 1 studies.
In one case, Quotient Sciences successfully developed an amorphous solid dispersion of a poorly soluble molecule using spray drying. The drug product was used in the first-in-human study of an oral therapy intended for the treatment of amyotrophic lateral sclerosis (ALS). The randomized, placebo- controlled Phase 1 trial evaluated safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and impact of food in healthy volunteers. Among the three formulations tested in this trial, the spray-dried version showed superior performance and was selected for further development. This study highlights how an integrated approach and adaptive design accelerates early phase development and de-risks formulation decisions using real-time clinical data.
Read the full article on Drug Development & Delivery's website here.