Quotient featured in Drug Development & Delivery's Solubility Special Feature Report

Quotient's Vice President of Drug Development Sciences, Dr Sarah Stevens, discusses our integrated approach to accelerating the development of poorly soluble compounds in Drug Development & Delivery's Special Feature article entitled: "Improving Bioavailability & Solubility: Each Molecule Is Unique"

Quotient Sciences: Integrated Approach Accelerates Drug Development

Solving bioavailability and solubil­ity challenges to support successful drug delivery is an ever-enduring challenge (and opportunity) for phar­maceutical formulation scientists. Along with well-established ap­proaches to improving each, there are many emerging platform technolo­gies, providing options in the toolbox. In many ways, though, availability of such formulation and process technol­ogy approaches does not present the primary barrier to improving universal solubility and bioavailability chal­lenges. Instead, a key challenge is the continued lack of predictive, clinically relevant models to guide formulation selection early enough in the develop­ment process – such that money and time are not unnecessarily expended, and avoidable risks not taken.

“With many examples of mislead­ing nonclinical and in vitro predictabil­ity out there, robust predictive models would afford the ability to understand and adapt for successful clinical out­comes from the outset,” says Dr. Sarah Stevens, Vice President of Drug Development Sciences at Quotient Sciences. “Quotient Sciences embod­ies science-led decision making, therefore not relying simply on poten­tially unreliable predictive models. A combination of unique development approaches provides the most expedi­tious means to improve potential bioavailability and solubility chal­lenges.”

Quotient, she says, deploys technologies such as particle size reduction, lipid-based formulation mechanisms, HME, SDD, etc., but more pertinently, drives early formula­tion selection by cutting through in­dustry silos and integrating across a range of capabilities to accelerate the drug development process. One ex­ample is Quotient’s Translational Pharmaceutics® platform, which inte­grates drug product manufacturing and clinical testing and ensures a con­tinuum among lead compound selec­tion, formulation development, and clinical assessments. “This reduces formulation development timelines and money, and mitigates risk in the development pathway by utilizing real-time clinical data to improve bioavailability and solubility,” says Dr. Stevens.

This integrated approach requires finely tuned project management and processes to ensure the most expedi­tious path to evaluate new molecules and formulations in the clinic. Prior to any clinical assessment, Quotient de­ploys a number of approaches based around the Developability Classifica­tion System (DCS) to deeply under­stand molecule properties – physico­chemical characterization, the use of biorelevant methods and physiologi­cally-based modelling/simulation to best position the formulation strategy for success. Quotient uses real-time product manufacturing and clinical testing to make, dose, and test new dosage forms within a 14-day cycle time, using arising clinical PK data to adjust formulation compositions.

As an example, she explains how Quotient rapidly screened a range of formulation types, including a mi­cronized API, spray-dried dispersions, and a lipid-based formulation using both biorelevant media and the inte­grated clinical manufacturing and testing platform.

“Nonclinical data was unable to provide clarity on which formulation strategy would be optimal to address PK issues seen with a simple first-in-human suspension system,” says Dr. Stevens. “Our ability to make decisions based on human PK data al­lowed identification of a powder-in-capsule formulation containing micronized drug, which demonstrated improved exposure, linear PK, and a reduced food effect, saving time and money for our client. This example supports my assertion that the lack of predictive, non-clinical or biorelevant models is the real barrier to success in the development of bioavailability/sol­ubility enhancing formulations.”

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