Ionic strength, drug stability

To use liposomes as delivery systems, drug is added during the formation process. Flydrophilic compounds usually reside in the aqueous portion of the vesicle, whereas hydrophobic species tend to remain in the lipid proteins. The physical characteristics and stability of lipsomal preparations depend on pH, ionic strength, the presence of divalent cations, and the nature of the phospholipids and additives used [45 47],... 

Many examples are present in the scientific Uterature underlining the effort in producing kinetic data [9—11]. The Edwards historical study that started the investigation on the mechanism of the hydrolysis of aspirin required hundreds of kinetic experiments [12,13]. Several examples are reported by Carstensen [1] in his review on the subject where, beside the large space dedicated to the determination of the pH-rate profile, the effect of temperature, ionic strength, buffer concentration, and dielectic constant on the stability of drugs was treated. 

Some kinetic data found in literature are referred to the conventional (Sorensen) pH scale [7] or, in a few cases, to the paH scale [7] (paH = —log aH). Application of the conventional pH scale is certainly useful in kinetic experiments which are done for practical purposes (such as stability studies of drugs in solution). Matters are different, however, if it is intended to determine well defined values of the catalytic coefficients fcH or ft oh As mentioned above, the pcH scale is most recommendable for an evaluation of the rate equation from experimental data — particularly if the dependence of the rate on [H+] is complicated. Only if the pcH scale is used, ftH and fcoH values (referred to concentrations) determined with dilute solutions of strong acids or strong bases will be identical with those measured in buffer solutions at the same ionic strength. ... 

There are several parameters that affect the solubility and chemical stability of a drug in solution. The pH of the solution can dramatically affect both the solubility and chemical stability of the drug. Buffer concentration/composition and ionic strength can also have an effect, especially on chemical stability. The hydropho-bic/hydrophilic nature of the drug influences solubility. A typical characterization of a dmg will start with a study of the chemical stability of the drug as a function of pH. The structure of the degradation products will be characterized to determine the mechanism of the degradation reaction. 

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