Evaluation of electrical conductivity-temperature curves using a mathematical model: temperature-dependent changes during thawing of frozen aqueous pharmaceuticals.

The information contained in the electrical conductivity curves of pharmaceuticals measured as a function of temperature can be represented by a small set of parameters. This is achieved by approximating the electrical conductivity curve as a number of consecutive steps, using a suitable empirical model. The three parameters describing each step are: transition temperature, slope factor and step height. The validity of the calculated transition temperatures was established by applying the model to electrical conductivity curves measured on aqueous solutions of KCl, NaCl and on a KCl-NaCl mixture. It appears that the transition temperatures calculated for these inorganic salts are in good agreement with the respective eutectic temperatures reported in the literature. Subsequently, the method was applied to the corticosteroids prednisolone sodium succinate and prednisolone disodium phosphate. The mathematical model yields a satisfactory fit for both experimental conductivity curves. The actual consequences of freeze-drying an aqueous solution of prednisolone sodium succinate below and above the respective transition temperatures calculated are discussed in relation to the experimental conductivity data.

Pharmacokinetics and miscibility of 4 highly purified porcine insulins: a study in vitro and in healthy volunteers.

In this study 4 new, highly purified porcine insulin preparations (ORGANON) were characterized by their time action profiles and in vitro and in vivo miscibility. These insulin preparations were soluble insulin, and suspensions of amorphous zinc insulin, mixture of 30% amorphous and 70% crystalline zinc insulin and NPH insulin. The time action profiles, assessed with the euglycaemic clamp technique and measurements of plasma insulin levels, in healthy volunteers were very similar to corresponding, already available, insulins of other manufacturers. In vitro miscibility was assessed for the soluble insulin with the 3 intermediate acting insulins in mixing ratios varying from 1:1-1:5. The recovery percentages of added soluble insulin, 75 sec after mixing in a 1:1 ratio with NPH, Tardum and Sub Tardum insulin, were 97.1%, 67.8% and 42.4%, respectively. The recovery of added soluble insulin decreased significantly with time of contact and with lowering of the mixing ratio for all insulins tested. In vivo insulin miscibility was performed for soluble and NPH insulin in a mixing ratio of 2:3, administered immediately after mixing in the syringe. The insulin action profiles were not altered when soluble and NPH insulin were administered after mixing as compared with the separate injections into contralateral thighs. In conclusion, the pharmacokinetics of these highly purified porcine insulins are in agreement with corresponding already available insulins. NPH insulin can be mixed with soluble insulin without affecting the absorption kinetics of either insulin.