Interraction of pharmeceuticals with schardinger dextrins VI. Interactions of β-cyclodextrin, sodium deoxycholate, and deoxycholic acid with amines and pharmaceutical agents
✍ Scribed by John L. Lach; Wayne A. Pauli
- Publisher
- John Wiley and Sons
- Year
- 1966
- Tongue
- English
- Weight
- 622 KB
- Volume
- 55
- Category
- Article
- ISSN
- 0022-3549
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✦ Synopsis
Data are presented for the interactions of p-cyclodextrin and sodium deoxycholate with 11 pharmaceutical agents in aqueous solution. Three of the compounds were also studied as to possible reactivity with deoxycholic acid. Interactions were observed with all of the systems studied. Similar solubility isotherms were obtained for the three pharmaceuticals when interacted with both deoxycholic acid and its sodium salt indicating possible similarities in the reaction mechanisms for these two complexing agents. T h e larger molecules showed a lower degree of interaction with both B-cyclodextrin and sodium deoxycholate, indicating the importance of molecular size and structure for optimum reactivity. Stoichiometries could he determined for several of the interactions due to the presence of plateau regions in their solubility isotherms. Formation constants and free energies of formation are also reported for a number of the insoluble complexes.
HE IMPORTANCE of molecular complex forma-Ttion in pharmaceutical formulation is certainly evident. ilpplications of this type of interaction can be made in the area of drug solubilization, stabilization, etc. The problem of stabilization is of particular interest in t h a t numerous attempts have been made to retard degradation of pharmaceutical compounds. These include pH considerations, changes in solvent systems, antioxidants, and complex salt formation. The use of molecular complex formation in this area represents a relatively new approach t o this problem of stability (1-5). CompJexation b y means of inclusion formation has been used successlully in the stabilization of labile drugs such as benzocaine, vitamin A, and various fatty acids (6, 7). This mode of protection for an unstable molecule offers definite advantages in that the entire molecule can be shielded from its surroundings. It has also been recognized that complexes not only influence the stability and appearance of phartnaceutical preparations, but may also exert some influence on the pharmacological and even biochemical mechanisms b y which they operate.
The previous paper of this series dealt with a study of the interactions of 0-cyclodextrin with a series of phenvl-substituted carboxylic acids in an effort to explain more clearly the nature of cyclodextrin interaction in aqueous solution. It was the objective of this study to investigate and com-