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ANANBIOANAL - 2010
Pharmaceutical R & D Summit
doi:10.4172/2155-9872.1000100
Preformulation Challenges and Advices to Obtain the
Bioavailability and Bioequivalence Studies of Pharmaceuticals
Josélia Larger Manfio
Biocinese – Biopharmaceutical Studies Center, Toledo, Brazil
A
ctually the approval at a Bioavailability/Bioequivalence Studies is a great
challenge after a development of Pharmaceuticals. In many instances, the
reproach in these studies were correlated successfully to dissimilar drug blood levels
caused mainly by impaired absorption. A biopharmaceutical assessment of drug
substance is crucial in generic drug product development. An extensive formulation
screening has gained increasing attention during the last years after it became
evident that decrease the failure bioequivalence risk. Bonding, binding, isomerism
and polymorphism (dissolution behavior) are important processes that influence
that activity and elimination of many drugs. The identification, characterization
and quantification of crystal forms are becoming increasingly important within the
pharmaceutical industry. A combination of different physical analytical techniques
(as differencial scanning calorimetry, for instance) is usually necessary for this
task. Herein a drug categorization according to the biopharmaceutical classification
system (BCS) is helpful. The drug solubility in indifferent systems and the permeability
assays are very important determinations at characterization of drug substance.
In light of the FDA's recent guidances, there is an increased awareness of the
potential relevance of dissolution tests but also realizes the need for individualizing
the method on a case by case. The evaluation of dissolution profiles changing the
media to obtain a pH gradient or simulate fed and fasted conditions may be a tool for
predicting bioavailability, and in some cases, replace clinical studies to determine
bioequivalence. The permeability assay is considered to be the development
gold standard for in vitro prediction of in vivo human intestinal permeability and
bioavailability of orally administered drugs (as Caco-2 cells). Although the cost and
the ethics aspects bioavailability testing in animals can be an alternative to predict the
bioequivalence. The association of well-made characterization of drug, the relevant
dissolution profile test and permeability assay gains the maximal information from
which factors could have an impact on the oral bioavailability.
ANALBIOANAL-2010
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