Significant process improvements developed in recent years have resulted in the production of a better quality of insulin suitable for formulation as soluble insulin at a neutral pH. The neutral regular insulin (NRI) selected for study and clinical trial was an unbuffered preparation obtained by simple neutralization of an acid regular insulin solution (ARI) to pH 7.4. Buffering appeared unnecessary and either phenol or methylparaben may be used as a preservative. Beef and pork insulins were readily soluble at neutral pH which suggested that purity is the prerequisite for solubility.
NRI was compared with commercial ARI prepared from the same zinc-insulin crystals. NRI was shown to be more stable when stored at room temperature or above. Degradation reactions in NRI were similar to those in ARI but occurred at a slower rate. Mixtures of NRI or ARI with prolonged acting insulins showed comparable biological activity even though ARI affects the pH of the mixture.
The results of this investigation have shown NRI to possess sufficient advantage over ARI to warrant consideration as a pharmaceutical form of soluble regular insulin and as a replacement for the conventional acidic form.