Engineering APIs to improve bioavailability

Using the science of SSRD and PreForm to drive API development and improvement of drug product performance

by Boris Gorin, Ph.D., R&D, Senior Scientific Advisor, Eurofins Alphora; Kevin Rosenthal, Business Head, Formulations & Finished Product Operations, Eurofins Alphora

Therapeutic effectiveness of a drug depends upon its bioavailability - the fraction of an administered dose of an active pharmaceutical ingredient (API) that reaches the systemic circulation. Physicochemical characterisation of an API is a critical tool of an Investigational New Drug (IND), enabling development and the selection of the optimum drug candidate.

Solubility, dissolution and GI permeability are fundamental parameters that control rate and extent of drug absorption and its bioavailability. Optimising the parameters of the API through the selection and design of physical forms (polymorphs, salts, solvates, co-crystals, etc.) provides an opportunity to enhance drug bioavailability early in the development process. A systematic and extensive screening is recommended to discover and develop stable and formulation-suitable solid forms. Eurofins Alphora Solid State R&D and Drug Product Operations teams work together to provide scientifically sound development services from API solid form discovery through pre-formulation and a final dosage form.

Eurofins Alphora’s high throughput screening (HTS) programmes for polymorph, solvate, salt, and co-crystal discovery allow experimentations using only minimum (mg) quantities of API, resulting in a significant reduction in cost, manpower and time. Integration of the HTS with an automated multi-sampler PXRD system provides rapid experimentation, exploring different crystallisation methods and conditions.

With the introduction of Pion μFlux and μDissolution technologies, Eurofins Alphora’s Preformulation scientists can help to assess and rank order the solubility and drug absorption potential of APIs and finished products, thus optimising candidates far earlier in the development process. Furthermore, Eurofins Alphora Formulation Scientists have various techniques available to enhance the solubility and ultimately the bioavailability of the API through particle size reduction and amorphous dispersions. Collaboration between Eurofins Alphora’s development teams help our clients achieve early clinical success in a more rapid and cost-effective way.

For more information visit: www.eurofins.com/cdmo