A Molecular Design Approach for Drug Tablet Formulation and Impact On Personalized Medicine

A molecular design approach for drug tablet formulation and impact on personalized medicine

Naresh Pavurala, Luke E.K Achenie

Department of Chemical Engineering, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24060

One of the major challenges faced by the pharmaceutical industry is to accelerate the drug innovation process and reduce the time-to-market for new drug developments. This involves billions of dollars of investment due to the large amount of experimentation and validation processes involved. A computational modeling approach, which could rapidly explore the design space, reduce uncertainty and make better, faster and safer decisions, fits into the overall goal and complements the drug development process.

In the drug discovery and development process, the tablet formulation (oral drug delivery) is an important step. The tablet consists of active pharmaceutical ingredient (API), excipients and polymer. A controlled release of drug from this tablet usually involves swelling of the polymer, forming a gel layer and diffusion of drug through the gel layer into the body. The polymer is mainly responsible for controlling the release rate (of the drug from the tablet), which would lead to a desired therapeutic effect on the body.

In this presentation we propose a molecular design strategy for generating molecular structures of polymer candidates with desired properties estimated through structure-property models. Our work is expected to aid in generating the most favorable polymers based on the biopharmaceutical and pharmacokinetic properties. This could help in precipitating development failures in the early stages of drug discovery as well as reduce the very expensive late-stage failures.

In greater detail, we utilized group contribution models to estimate several desired polymer properties such as grass transition temperature (T_g), density (ρ) and linear expansion coefficient (α). We subsequently solved an optimization model, which generated molecular structures of polymers with desired property values. Some of the polymer repeat-units are already available in the literature; these include polyvinyl alcohol (PVA) and polyvinyl chloride (PVC) repeat-units. Examples of new repeat units are –CH=CH-COO–, –CHCl–CH₂–CHCl–. These repeat-units could potentially lead to novel polymers with interesting characteristics; a polymer chemist could further investigate these. We recognize the need to develop group contribution models for other polymer properties such as porosity of the polymer and diffusion coefficients of water and drug in the polymer, which are not currently available in literature. We expect our modeling approach to aid in the drug development process and contribute to the development of personalized medicine.