INCREASE IN THE RATE OF MOISTURE GAIN BY HYGROSCOPIC DRUGS IN THE PRESENCE OF NON-HYGROSCOPIC WATER-SOLUBLE SUBSTANCES: STUDY OF THE GENERALIZATION OF THIS HITHERTO UNKNOWN PHENOMENON, EXPLANATION TO ITS OCCURRENCE AND IMPLICATIONS IN FORMULATION DEVELOPM

The purpose of this study was to explore whether the increase in rate of moisture gain by hygroscopic drugs in the presence of non-hygroscopic water- soluble substances (NHWSS) was a generalized phenomenon. Also, the aims were t o provide explanat ion for the occurrence of this hithert o unknown phenomenon, and t o explore it s implicat ions in formulat ion development . An indicat ion t o the prevalence of this phenomenon was provided earlier, when moisture gain studies were carried out on ethambutol hydrochloride (E) in the presence of isoniazid (H). Specific ratios of E (a known hygroscopic drug) and H (a NHWSS) were found to gain moisture at a higher rate than the former alone. In the present invest igat ion, E and benzyl penicillin (BP) (bot h hygroscopic drugs) were separately combined wit h a variety of NHWSS, viz., gabapentin, ascorbic acid, pyrazinamide and glycine, apart from H. The compounds were mixed in the ratios from 100:0 w/w to 0:100 w/w. The mixtures were exposed to accelerated conditions of temperature and humidity (40 0C/75% RH) and moisture gain was determined with t ime. The rat e of moisture gain was higher for several mixtures than pure hygroscopic substances, although total moisture gain was more for the pure drugs than any ratio of mixture of hygroscopic drug and NHWSS. This provided confirmation that the phenomenon was of general occurrence. To gain further insight, rate of moisture gain was correlated to structural descriptors of NHWSS calculated using CODESSA, DRAGON and Hyperchem. The results indicated that increased rate of moisture gain by the combination of hygroscopic compounds and NHWSS was perhaps due to removal of water by NHWSS molecules for the purpose of hydration, forcing the hygroscopic substance to withdraw more moisture from the environment. The study suggests that formulations containing hygroscopic material and NHWSS together should be given critical consideration during formulation development, packaging selection and stability testing, as they can gain moisture at a faster rate than normal products.