Module 3: Advanced biopharmacy

Abstract

Develop an integrated view on computational, in vitro, in situ and in vivo tools and their role in the drug and dosage form development and evaluation process.

Objective

Biopharmacy is an interdisciplinary field whose basic principles are well integrated into the drug discovery and development process. Examples include compound selection and lead optimization with respect to biopharmaceutic and pharmacokinetic drug properties, including biological, physicochemical and computational strategies. The properties include e.g. gastrointestinal absorption, protein binding, brain permeation and metabolic profiling. Furthermore, basic biopharmaceutic and pharmacokinetic concepts are applied in the evaluation of the biopharmaceutic quality of dosage forms, the design and optimization of controlled-release dosage forms and the drug product registration process. This course is an extension of the Biopharmazie 1 and 2 basic course. Students understand the principles in the biopharmaceutic characterization and evaluation of candidate drugs and dosage forms. Students develop an integrated view on computational, in vitro, in situ and in vivo tools and their role in the drug and dosage form development and evaluation process.

Content

- Advanced Biopharmacy and Pharmacokinetics in Drug Discovery and Development - An Overview - Physiological barriers to drug input, distribution and excretion and exploitation of administration routes (Biological membranes, membrane transport mechanisms, pharmaceutically relevant membrane transporters, pharmacokinetic relevant membrane barriers (including blood-brain-barrier); Models for investigating transport processes; Transport in the GI tract, skin, nose, rectum, vagina, eye, ear, liver, kidney. - Drug delivery via active transport: Relevance of membrane transporters oral drug delivery, examples (e.g., Pept1, P-gp), use of pro-drugs to target transporters, chemo-sensitivity and -resistance, use of genomics approaches to identify new potential drug carriers - Classification of transporters - Classifying two or three relevant transporters: Use of GO system, Pfam database, TC by M. Saier via web. - Extracting gene expression profiles for relevant transporters: GEO by NCBI, CleanEX, SNP database by UCSF etc. - Computer Demonstration: Modern Biopharmaceutics CD - Simulation and Modelling in Drug Discovery and Development Non-compartmental evaluation of pharmacokinetic data; Compartmental pharmacokinetic models, data fitting and predictions; Physiological-based pharmacokinetic modelling and tools (PBPK); Allometric scaling: From animals to man; Pharmacokinetics as a predictor of drug effect: PK/PD relationships and models - QA session on topics of Day 1 (industrial outlook) - Computer demonstrations and exercises (WinNonlin®) on topics of Day 2 - Biopharmaceutic properties and molecular structure optimization including prodrugs. In silico predictions of biopharmaceutic properties from molecular structure (e.g. clogP, ADMET predictor), BCS, Rule of five, BDDCS - Bioavailability and bioequivalence - Biorelevant in vitro dissolution methods - In vitro / In vivo correlation - Biowaivers - Computer demonstrations and exercises (GastroPlus®, Deconvolution, Wagner-Nelson, Loo-Riegelman, Mean time analysis, DDDPlus®, IVIVC tool by WinNonlin). Analysis of given problem sets - Computer demonstrations (ADMET predictor®, clogP and Modern Biopharmaceutics CD)

Resources