The current cyclodextrin (CD) literature is reviewed concerning synthesis, characterization, and pharmaceutical relevant applications of CD derivatives. Although natural CDs have been used extensively to improve pharmaceutical properties, the effects of chemically modified CDs on the solubility, dissolution rate, and stability of drugs are overproportional. Concerning the parenteral application, the major interest is focussed on highly water-soluble, randomly substituted hydroxyalkyl derivatives of beta- and gamma-CD such as 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD). Although the heptakis-(2,6-di-O-methyl)-beta-cyclodextrin is applied in the pharmaceutical field, 2-HP-beta-CD is predestined as a parenteral drug carrier owing to its weak hemolytic activity and intrinsically amorphous character. A minimal average degree of substitution is especially preferred when 2-HP-beta-CD is used as solubilizer of pharmaceuticals for the use in parenteral applications. The influence of the type, degree, and pattern of substitution of the CDs, as well as substituent effects of the guest molecule is elucidated.

The notorious degradation susceptibility of peptides is a major obstacle to their use as medicinal drugs. Assays with which the stability of peptides in complex proteolytic environments can be determined are thus indispensable for peptide drug development. Herein, we describe a new peptide proteolysis assay that meets that demand. It unites the high-throughput capacity of heterogeneous with the well-defined kinetic characteristics of homogeneous assay formats and operates on the cleavage-caused loss of a detection handle. We have confirmed the assay's accuracy with well-defined model interactions and proved its high versatility and robustness with a representative application where we determined the half-lives of 375 different peptides in a crude intestinal protease preparation. With this reliable, reproducible, and efficient assay the enzyme kinetics of any peptide-protease interaction is accessible even for complex protease solutions.

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