Drug substances biopharmaceutical properties

Formulation design is based on the physical, chemical, and biopharmaceutical properties of a drug substance. A formulation for direct compression is composed of active pharmaceutical ingredients and other inactive ingredients such as fillers, binders, dis-integrants, flow aids, and lubricants. Simplicity is the basis of good formulation design. Minimally, a direct compression tablet formulation must meet requirements for manufacturability, uniformity of dose, physical and chemical stability, appropriate dmg release profiles, and bioavailability. In addition, the formulation must meet many quality standards and special requirements to ensure the efficacy and safety of the product. 

Drug Properties. In keeping with the QbD concept, the physicochemical and biopharmaceutical properties of drug substance should be characterized for a better... 

A rational approach to dosage form design requires a complete understanding of the physicochemical and biopharmaceutical properties of the drug substance. For example, the successful design of an efficacious oral dosage form requires an understanding of the... 

Figure 3.1 The Biopharmaceutics Classification System as defined by Amidon et al. [6]. The BCS is a classification of drug substances according to their solubility and permeability properties, in orderto stand forthe most fundamental viewofthe drug intestinal absorption process following oral administration.

Depending on the structure of the organization, the contents of the preformulation report may be included in several different reports. Typically, the analytical profile may be issued by the analytical development group, and specifications of the drug substance may be issued by the QC laboratory. Physicochemical property determination, stability, compactibility, and pharmaceutical properties may be reported by the basic pharmaceutics or physical pharmacy group. The biopharmaceutical group may issue the report with KADME and bioavailability data. 

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... 

Several substance properties can affect dissolution and/or solubility, such as purity particle size and distribution surface area and the presence of polymorphs, hydrates or other solvates or amorphous forms. To avoid misleading or inconclusive results in extensive solubility or dissolution studies, it is important to characterise the drug substance form with respect to such properties, especially in the later biopharmaceutical preformulation phase. Methods for such characterisation are described in more detail in Chapters 3 and 7. 

Physicochemical and Biopharmaceutical Properties of Drug Substances and Pharmacokinetics... 

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