Assessment of the physical properties and stability of mixtures of tetracycline hydrochloride ointment and acyclovir cream

Abstract

In dermatology, ointments are often mixed as part of drug therapy, but mixing often leads to incompatibility. Three combinations of tetracycline ointment (TC-o) and acyclovir cream (ACV-cr) were prepared at a TC-o:ACV-cr ratio of 1:1 using a brand-name ACV-cr and two generic ACV-cr (samples TC-o+ACV-A, TC-o+ACV-B, and TC-o+ACV-C). Microscopic examination revealed separation in TC-o+ACV-C. Viscosity and elasticity measurement indicated that the storage modulus (G') and loss modulus (G″) of each of the TC-o+ACV-cr mixtures behaved similarly to those of an ACV-cr and the loss tangent (tanδ) behaved similarly to that of a TC ointment. In addition, differences in the storage modulus (G') and loss modulus (G″) of the TC-o+ACV-cr mixtures were noted. To assess stability, each TC-o+ACV-cr mixture was stored away from direct sunlight at 25 °C and an RH of 84% and at 4 °C (in a refrigerator). HPLC revealed that the ACV content in each TC-o+ACV-cr mixture remained at 95-105% for up to 14 days under both sets of storage conditions. A decline in TC content in each TC-o+ACV-cr mixture was not noted with storage at 4 °C but was noted over time with storage at 25 °C and an RH of 84%. In addition, significant differences in the percent decline in TC content in each TC-o+ACV-cr mixture occurred with storage at 25 °C and an RH of 84%. Thus, differences in physical properties and stability may occur when combining brand-name and generic drugs, and temperature and humidity may be the cause of the TC-o's incompatibility.