Linear Nonisothermal Stability Studies

Complexes of Ergot Alkaloids and Derivatives IV: Investigations into the Nature of Ergot Alkaloid—Xanthine Complexes

“…The kinetic method was not employed because of the absence of a suitable reaction for study, thus leaving solubility analysis. This mode has previously been found to be practicable in the study of proteinaceous ergot derivatives, although certain problems have arisen from their erratic solubility properties (3)(4)(5)(6).…”

“…This mutual attraction is exemplified by: (a) increased solubility; (b) increased dissolution-rate constant, and ( c ) altered partitioning-rate constants depending on pH. These changes are noted on inclusion of xanthines as compared to the alkaloids alone (3)(4)(5)(6). Recent biological results (7) were found to be in good agreement with the postulation that complex formation leads to increased enteral absorption of ergotamine and ergot alkaloids.…”

“…In the course of investigating the physicochemical nature of the combination, several ergot alkaloids and their analogs, such as ergotamine, 9,lO-dihydroergocristine, and methysergide, have been observed to possess the capacity for interaction with caffeine and other xanthines in aqueous solution (3)(4)(5)(6). This mutual attraction is exemplified by: (a) increased solubility; (b) increased dissolution-rate constant, and ( c ) altered partitioning-rate constants depending on pH.…”

Non-isothermal stability by linear heating: a fast method for preformulation stability screening of drugs at the discovery and development interface

“…Non-isothermal stability by linear heating (LNISO) has been explored as an accelerated method for predicting the long-term stabilities and shelf-lives of pharmaceuticals for almost five decades (Yoshioka et al 1987(Yoshioka et al , 1988Zoglio et al 1968). However, this method has never been systematically evaluated across numerous compounds in a single study and compared directly to conventional isothermal stability method.…”

“…These studies used a Monte Carlo simulation method and not actual experimental data. A much earlier study by Zoglio, et al highlighted the usefulness of the LNISO method in stability screening of drugs in different pharmaceutical formulations (Zoglio et al 1968). However, no comprehensive studies have been conducted to show that stability parameters predicted by the LNISO method are reproducibly in good agreement with the same parameters obtained by the conventional Arrhenius stability method.…”