Physicochemical characterization dissolution rate

Anderberg, E.K., and Nystrom, C. (1990), Physicochemical Aspects of Drug Release X. Investigation of the Applicability of the Cube Root Law for Characterization of the Dissolution Rate of Fine Particulate Materials, Intemat. J. of Pharma., 62, 143-151. 

H-K Chan, S Venkataram, DJW Grant, Y-E Rahman. Solid state properties of an oral iron chelator, l,2-dimethyl-3-hydroxy-4-pyridone and its acetic acid solvate. I Physicochemical characterization intrinsic dissolution rate and solution thermodynamics. J Pharm Sci 80 677-685, 1991. 

The preparation of salts is frequently undertaken to improve the physicochemical properties of an ionizable compound. Most often, improvement of solubility and dissolution rate is desired. However, improvement in crystallinity (e.g., melting point), stability, or hygro-scopicity may be possible (1,2). Figure 18.1 shows the solubility of several salts of terfena-dine and the free base as a function of pH. Development of salts, particularly soluble salts of insoluble compounds, is not without challenge, however. Complete characterization of salt forms is needed (4). If the salt is very soluble, precipitation of the insoluble free base (or free acid) may occur in uivo under physiological pH conditions. 

Chemical development Proof of structure and configuration are required as part of the information on chemical development. The methods used at batch release should be validated to guarantee the identity and purity of the substance. It should be established whether a drug produced as a racemate is a true racemate or a conglomerate by investigating physical parameters such as melting point, solubility and crystal properties. The physicochemical properties of the drug substance should be characterized, e.g. crystallinity, polymorphism and rate of dissolution. 

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