Understanding the Effect of API Properties on Bioavailability Through Absorption Modeling

Selection of API phase is one of the first decision points in the formulation development process. Subsequent to phase selection, the focus shifts to the API physical properties such as particle size. Oftentimes, such properties are closely monitored throughout the drug development, as they can have a direct impact on the formulation bioperformance. The purpose of this mini-review was to describe the potential for application of absorption modeling in understanding the effect of API properties on bioavailability. Examples are provided to demonstrate how absorption modeling can be applied both early on to set the formulation strategy as well as during the development process to help with setting of specifications around the API. Limitations of the existing models and areas of possible expansion of such tools are also discussed.

[1]  R. J. Hintz,et al.  The effect of particle size distribution on dissolution rate and oral absorption , 1989 .

[2]  Michael Brandl,et al.  Physicochemical Properties of the Nucleoside Prodrug R1626 Leading to High Oral Bioavailability , 2008 .

[3]  Lawrence X. Yu,et al.  In vitro testing of drug absorption for drug 'developability' assessment: forming an interface between in vitro preclinical data and clinical outcome. , 2004, Current opinion in drug discovery & development.

[4]  Rainer H. Müller,et al.  Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique , 1998 .

[5]  G. Amidon,et al.  Molecular properties of WHO essential drugs and provisional biopharmaceutical classification. , 2004, Molecular pharmaceutics.

[6]  A. Noyes,et al.  The rate of solution of solid substances in their own solutions , 1897 .

[7]  Michael B. Bolger,et al.  Application of Gastrointestinal Simulation for Extensions for Biowaivers of Highly Permeable Compounds , 2008, The AAPS Journal.

[8]  Kiyohiko Sugano,et al.  Theoretical dissolution model of poly-disperse drug particles in biorelevant media. , 2008, Journal of pharmaceutical sciences.

[9]  Lawrence X. Yu,et al.  A provisional biopharmaceutical classification of the top 200 oral drug products in the United States, Great Britain, Spain, and Japan. , 2006, Molecular pharmaceutics.

[10]  Lawrence X. Yu An Integrated Model for Determining Causes of Poor Oral Drug Absorption , 1999, Pharmaceutical Research.

[11]  J. Dressman,et al.  Mixing-tank model for predicting dissolution rate control or oral absorption. , 1986, Journal of pharmaceutical sciences.

[12]  J Dressman,et al.  Improving drug solubility for oral delivery using solid dispersions. , 2000, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[13]  Gloria Kwei,et al.  The role of biopharmaceutics in the development of a clinical nanoparticle formulation of MK-0869: a Beagle dog model predicts improved bioavailability and diminished food effect on absorption in human. , 2004, International journal of pharmaceutics.

[14]  G L Amidon,et al.  Transport approaches to the biopharmaceutical design of oral drug delivery systems: prediction of intestinal absorption. , 1996, Advanced drug delivery reviews.

[15]  Filippos Kesisoglou,et al.  Nanosizing--oral formulation development and biopharmaceutical evaluation. , 2007, Advanced drug delivery reviews.

[16]  Yatindra Joshi,et al.  Development of clinical dosage forms for a poorly water soluble drug I: Application of polyethylene glycol-polysorbate 80 solid dispersion carrier system. , 2004, Journal of pharmaceutical sciences.

[17]  Erich Brunner,et al.  Reaktionsgeschwindigkeit in heterogenen Systemen , 1904 .

[18]  D. Flanagan,et al.  General solution for diffusion-controlled dissolution of spherical particles. 1. Theory. , 1999, Journal of pharmaceutical sciences.

[19]  Martin Kuentz,et al.  A strategy for preclinical formulation development using GastroPlus as pharmacokinetic simulation tool and a statistical screening design applied to a dog study. , 2006, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[20]  Walter Schmitt,et al.  PK-Sim®: a physiologically based pharmacokinetic ‘whole-body’ model , 2003 .

[21]  B Agoram,et al.  Predicting the impact of physiological and biochemical processes on oral drug bioavailability. , 2001, Advanced drug delivery reviews.

[22]  Jennifer B Dressman,et al.  Classification of orally administered drugs on the World Health Organization Model list of Essential Medicines according to the biopharmaceutics classification system. , 2004, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[23]  G. Amidon,et al.  Absorption potential: estimating the fraction absorbed for orally administered compounds. , 1985, Journal of pharmaceutical sciences.

[24]  Abu T M Serajuddin,et al.  Salt formation to improve drug solubility. , 2007, Advanced drug delivery reviews.

[25]  Kevin C. Johnson,et al.  Guidance in the Setting of Drug Particle Size Specifications to Minimize Variability in Absorption , 1996, Pharmaceutical Research.

[26]  Kevin C. Johnson,et al.  Dissolution Modeling: Factors Affecting the Dissolution Rates of Polydisperse Powders , 1993, Pharmaceutical Research.

[27]  W. Nernst,et al.  Theorie der Reaktionsgeschwindigkeit in heterogenen Systemen , 1904 .