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Quotient Sciences SME comments on solubility & bioavailability challenges in Drug Development & Delivery feature article

John McDermott, Quotient Sciences' Executive Drug Development Consultant, discusses Integrated Development Strategies Overcome Solubility Challenges, in Drug Development & Delivery's Special Feature in Drug Development & Delivery's Special Feature entitled: "Solubility & Bioavailability: Utilizing Enabling Technologies."

There is no one-size-fits-all solu­tion for improving bioavailability and solubility, and what is correct for one molecule could be over-engineering, or worse, limiting the potential of an­other drug. It is therefore crucial for development teams to understand the drivers of a given molecule’s solubility and its permeability properties to se­lect the correct technologies for as­sessment, and then back up that selection with data. “One of the biggest challenges we see is the expectation of an in vitro/in vivo cor­relation in developing these technolo­gies, which is not realized when clinical data is obtained,” says John McDermott, Executive Drug Develop­ment Consultant, Quotient Sciences. “Having access to human data to as­sess formulation technologies for poorly soluble drugs is therefore cru­cial in guiding formulation selection and optimization.”

Quotient Sciences has had the opportunity to work on several programs that have assessed the clinical performance of some of these novel and emerging technologies to enhance drug bioavailability. “We have seen some great successes for some drugs, and we have also had experiences where performance observed in preclinical and in vitro studies have not translated into humans,” he says.

Quotient Sciences delivers fully in­tegrated programs incorporating for­mulation development with clinical manufacturing, regulatory support, and clinical testing. This platform, termed Translational Pharmaceutics™, can be applied to accelerate the pro­gression of prototype formulations to clinical assessment and onward, to ef­ficiently and accurately assess candi­date formulations, and to improve the likelihood of clinical and commercial success, explains Mr. McDermott.

In one recent case study, a cus­tomer with a BCS II molecule had completed its first-in-human study, which demonstrated inadequate ex­posure and a significant food effect. These issues were stalling the project from advancing into proof-of-concept patient studies. To respond to this, the client needed to rapidly evaluate sol­ubility enhancement technologies and demonstrate its utility to enable effi­cacy assessments in order to proceed to the next project milestone.

In this program, Quotient Sci­ences developed three different solu­bility-enhancing formulations: a micronized form of API; a self-emulsi­fied lipid delivery system; and a spray-dried dispersion. A Translational Pharmaceutics study was performed to achieve a quick proof-of-concept as­sessment, removing the need to con­duct larger scale, cost-prohibitive process development and lengthy sta­bility programs for multiple technolo­gies. The human pharmacokinetic (PK) study used a 5 period cross-over de­sign in 16 healthy volunteers with the micronized formulation delivering the best outcome.

“By applying our Translational Pharmaceutics approach, the overall timeline – from initiating formulation lab work to having clinical PK data to select the optimal formulation – was just six months,” says Mr. McDermott. “While it’s exciting to be involved at the forefront of research in drug deliv­ery technologies, it’s important to re­main focused on the patient – and the best model for assessing humans is a human.”

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