Drug substances have to reach their place of action within the body at the appropriate concentration for a defined time span in order to be effective and safe.
The delivery of drug substances via the oral route is often much more challenging than other routes of administration as, for example, the direct delivery into the body via injection or infusion. The complexity of oral drug absorption is reflected by the fact that, despite numerous attempts until today, a reliable prediction of the rate and extent of the absorption of drug substances from the human gastrointestinal tract is neither provided by in silico and in vitro methods nor animal models.
Physico-chemical properties of the drug substance are also critical for drug absorption. Most of all the often extremely limited water solubility of drugs and drug candidates has become a very serious issue. In order to overcome these hurdles that are limiting oral drug absorption drug delivery technologies are essential.
However, the successful design and development of an appropriate drug delivery technology requires a profound knowledge of the interplay of the drug substance interaction at cellular level and the enzymatic first-pass metabolism, as well as the interplay between the drug delivery system and the physiology of the gastrointestinal tract.
Whilst the interplay at the cellular level is substance (or substance class) specific, the interplay with the physiology of gastrointestinal transport, fluid balance, media composition can be hugely modulated by the delivery system..
The availability of in vitro methods is vital to rationalize and simulate what may happen in vivo.
The final target of the dissolution test should be the reflection of in vivo behavior. One intended use for the dissolution test is to reproduce in vitro the key determining factors that influence the in vivo behavior of the product, with the ambitious final target of mimicking the in vivo performance of the dosage form. Thus, dissolution release profiling can be fruitfully applied to the selection of the API with the most suitable developability properties as well as of the most appropriate formulation/s to be dosed in toxicological and human Phase I studies. Dissolution methods that use a medium that mimics human GI fluids (a.k.a. simulated physiological fluids) should be investigated and challenged to probe in vivo–in vitro correlations and relationships.
Therefore, the dissolution testing is largely used in drug development not only as a powerful quality control tool, but definitely to guide formulation design. Dissolution is instrumental in characterizing an API; developing, selecting, and optimizing formulations; studying drug-release mechanisms; ensuring batch-to-batch consistency; monitoring stability; and demonstrating bioequivalence between formulations as related to their equivalent release of API for absorption. As an overall statement, dissolution testing can support the “qualification” of a dosage form in line with a “Quality by Design” paradigm.
Benefits to the Participants
Acquaintance and the different elements that play a role in drug absorption: GI tract, physical-chemical properties of the API, in vitro biorelevant tools such as dissolution release testing as a pre-requisite for an effective drug delivery .
- A science-based discussion of the values of dissolution testing used in the drug-development continuum for the characterization of in vitro drug liberation from oral dosage forms.
- Case Studies will be presented to show how absorption issues have been tackled and solved all along the drug development process.
Issues to be covered
Drug delivery and Drug absorption
- The GI Tract
- Biopharmaceutical classification System
- Understanding the in vivo behavior of dosage form
- Misconception in GI physiology
- The physico–chemical profile
- The solid state characterization
- Solubility and solubility profiles
- Characterization techniques
- Case studies
- Dissolution process and bio-relevant dissolution tools
- Dissolution as a Quality Control & Formulation Tool
- Approaches to Formulation Screening and Selection
- Dissolution throughout the development phases of a drug
- Case Studies
- Active Pharmaceutical ingredients and choice of the formulation
- Absorption of an oral dosage form
- Getting the drug to its absorption site
- Getting the drug into dissolution
- Solubilisation strategy
Who should attend
|Anyone involved in the development of pharmaceutical products. This would include those involved in research & development, phys prop and analytical characterisation, formulation development and drug delivery.
About the Speaker
Dr. Dionigio Franchi
Up to December 2010 Director, Pharmaceutical Development, GlaxoSmithKline R&D – Verona, Italy.
with more than 25 years experience in the Pharmaceutical Industry.
Proven technical leader in the pharmaceutical industry through development, registration and commercialization of medicines. Experience across a wide range of pharmaceutical dosage forms (tablets, suspensions, injectables). Doctorate in Chemistry with in-depth knowledge of GMP, GLP, USP, FDA, and ICH requirements. Experience building capable, teamwork-oriented organizations and leading multidisciplinary teams to achieve challenging goals.
Technical expertise and management:
Academic and international involvement:
- Partner within Discovery to an efficient screening and evaluation of the compounds selection and ensuring that the developability criteria are met;
- Characterization of physical, chemical and biopharmaceutical aspects of chemical entities and product dosage forms;
- Development of high quality formulations (enhanced bioavailability, developability, robustness, stability) and analytical characterization for pre-clinical/clinical studies and market;
- Definition of specifications and assessment of stability of active ingredient and product dosage forms;
- Scale up and timely transfer of process and analytical technology to manufacture site;
- Preparation of the documentation for regulatory submissions.
- Visiting professor at University of Siena, Bologna and Padova
- Active member of the EUFEPS Committee for Industrial Relationship (CIRR) since 2001