Biopharmaceuticals molecular structure

At one end of the analytical spectrum is the bioassay, which can demonstrate what biological activity the biopharmaceutical molecule may possess, regardless of molecular structure. At the other end are structural methods that elucidate the molecular structure of the molecule, regardless of biological activity. Somewhere in the middle of the spectrum is the ELISA. 

We have developed a two-step procedure for the in silico screening of compound libraries based on biopharmaceutical property estimation linked to a mechanistic simulation of GI absorption. The first step involves biopharmaceutical property estimation by application of machine learning procedures to empirical data modeled with a set of molecular descriptors derived from 2D and 3D molecular structures. In silico methods were used to estimate such biopharmaceutical properties as effective human jejunal permeability, cell culture permeability, aqueous solubility, and molecular diffusivity. In the second step, differential equations for the advanced compartmental absorption and transit model were numerically integrated to determine the rate, extent, and approximate GI location of drug liberation (for controlled release), dissolution, and absorption. Figure 17.3 shows the schematic diagram of the ACAT model in which each one of the arrows represents an ordinary differential equation (ODE). 

If the drug substance is suspected to be surface active, which will be indicated by the molecular structure, the surface-active properties should be further investigated during the biopharmaceutical preformulation phase. The potential for micelle formation should be investigated and, if relevant, the CMC and the CMT should be determined. CMC is determined by measuring a colligative property such as conductivity, surface tension or osmotic pressure... 

Standard technology (e.g., high-performance liquid chromatography) used to characterize NCEs can also be used for biopharmaceuticals, but many of these techniques are not useful for analyzing the large, complex molecular structures of most biopharmaceuticals. Therefore, additional standards had been developed specifically for biopharmaceuticals. 

Quantitative Structure-Property Relationship Analysis of Drugs Pharmacokinetics Within the Framework of Biopharmaceutics Classification System Using Simplex Representation of Molecular Structure... 

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