A Provisional Biopharmaceutical Classification of the Top 200 Oral Drug Products in the United States, Great Britain, Spain, and Japan

Abstract

Orally administered, immediate-release (IR) drug products in the top 200 drug product lists from the United States (US), Great Britain (GB), Spain (ES), and Japan (JP) were provisionally classified based on the Biopharmaceutics Classification System (BCS). The provisional classification is based on the aqueous solubility of the drugs reported in readily available reference literature and a correlation of human intestinal membrane permeability for a set of 29 reference drugs with their calculated partition coefficients. Oral IR drug products constituted more that 50% of the top 200 drug products on all four lists, and ranged from 102 to 113 in number. Drugs with dose numbers less than or equal to unity are defined as high-solubility drugs. More than 50% of the oral IR drug products on each list were determined to be high-solubility drugs (55-59%). The provisional classification of permeability is based on correlations of the human intestinal permeabilities of 29 reference drugs with the calculated Log P or CLogP lipophilicity values for the uncharged chemical form. The Log P and CLogP estimates were linearly correlated (r2 = 0.79) for 187 drugs. Metoprolol was chosen as the reference compound for permeability and Log P or CLogP. A total of 62-69.0% and 56-60% of the drugs on the four lists exhibited CLogP and Log P estimates, respectively, greater than or equal to the corresponding metoprolol value and are provisionally classified as high-permeability drugs. We have compared the BCS classification in this study with the recently proposed BDDCS classification based on fraction dose metabolism. Although the two approaches are based on different in vivo processes, fraction dose metabolized and fraction dose absorbed are highly correlated and, while depending on the choice of reference drug for permeability classification, e.g., metoprolol vs cimetidine or atenolol, show excellent agreement in drug classification. In summary, more than 55% of the drug products were classified as high-solubility (Class 1 and Class 3) drugs in the four lists, suggesting that in vivo bioequivalence (BE) may be assured with a less expensive and more easily implemented in vitro dissolution test.

Co-crystals of diflunisal and isomeric pyridinecarboxamides – a thermodynamics and crystal engineering contribution

“…Thus, co-crystal research formation spurs interest from pharmaceutical industry, especially for those APIs whose oral bioavailability is solubility limited, classes II and IV of the Biopharmaceutical Classification System (BCS) 22 . For this kind of drugs, besides cocrystals, binary eutectic mixtures, for instance, are also relevant [23][24][25][26] due to their increased surface area and the potential for increasing dissolution rate.…”

Cholinium-based ionic liquids with pharmaceutically active anions

“…24 Nowadays, close to 40% of the marketed immediate-release oral drugs are categorized as practically insoluble (<0.1 mg ml À1 ). 25 The poor aqueous solubility of drug candidates plays one of the major roles in drug research and development. The low aqueous solubility of orally administered drugs leads to limited dissolution rate and low bioavailability.…”

Dissolution behavior of co-amorphous amino acid-indomethacin mixtures: The ability of amino acids to stabilize the supersaturated state of indomethacin

“…In these cases, the limited water solubility may become a major challenge for successful formulation. Takagi approximately 40% of these drugs were considered as being practically insoluble [4]. In particular, the impact of higher lipophilicity was noteworthy among newly discovered and developed drugs.…”