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BCS Class IV Drugs: Develop or Discard?
Thursday, November 15
8:30 am – 11:00 am
Symposium
ACPE #073-999-07-571-L04
Therapeutic molecules that are poorly soluble and moderately and/or poorly permeable under the Biopharmaceutics Classification System are designated as Class IV drugs. Class IV drugs present a major challenge for development of drug delivery system and the route of choice for administering such drugs is parenteral with the formulation containing solubility enhancers. Many Class IV molecules exhibit excellent in vitro pharmacological effect at very low concentrations however they typically have poor and variable absorption. This is not only due to dissolution rate/solubility and permeability-limited absorption, but also due to the various physicochemical, formulation, and in vivo variables that affect dissolution and permeation. Class IV drugs exhibit a lot of problems for effective oral administration. Fortunately, extreme examples of class IV compounds are the exception rather than the rule and are rarely developed and reach the market. Nevertheless a number of class IV drugs do exist. e.g. ritonavir, saquinavir, furosemide. A review of the literature reveals that these drugs often match the structure-activity relationship profile for high-affinity P-glycoprotein (Pgp) ligands, complicating the in vivo absorptive transport characteristics of these difficult-to develop compounds. However, because Pgp efflux is saturable and maintenance of high luminal drug concentrations by increasing the solubility and/or dissolution rate by using lipid delivery systems and/or solid dispersions are approaches for improving oral absorption of Class IV compounds. Since these molecules offer the dual challenge of solubility and permeability, it provokes an interesting dilemma of whether to develop these compounds or discard them. This symposium will discuss this interesting dilemma and provide insight into formulation and/or pharmacological approaches to develop these molecules and also discuss circumstances where it is reasonable to discard these molecules.
Moderators
Nagesh X. Bandi, Ph.D.
Sanofi Aventis Pharmaceuticals
Murti Vemuri, Ph.D.
Sanofi-Aventis Pharmaceuticals
Absorption Attributes Critical to Drug Product Performance
Srini Venkatesh, Ph.D.
Bausch and Lomb
Lipid Formulation Strategies for Enhancing Solubility and Permeability of BCS Class IV Drugs: In vitro/In vivo Case Studies
Panayiotis P. Constantinides, Ph.D.
Biopharmaceutical & Drug Delivery Consulting, LLC
Speech Title to be announced
Speaker to be announced
In Vitro and In Vivo Assessment of the Pharmacokinetic Behavior of BCS Class IV Drugs
Patrick Sinko, Ph.D.
Rutgers University