EFFECT OF SURFACE CHARACTERISTICS OF THEOPHYLLINE ANHYDRATE POWDER ON HYGROSCOPIC STABILITY

Abstract— The hygroscopicity of theophylline anhydrate has been investigated by gas adsorption and hydration kinetic methods. Type I theophylline anhydrate was obtained by recrystallization from distilled water at 95°C, and type II was obtained by dehydration of theophylline monohydrate. The X‐ray diffraction pattern of types I and II agreed with the data of theophylline anhydrate. However, the diffraction peaks of the (200) and (400) planes of type I were much stronger than those of type II. The particles of type I were clear crystalline‐like single crystals. However, the particles of type II had many cracks. The gas affinity balance (H/N) of type II, measured by gas adsorption, was about 7 times that of type I. After the hygroscopicity of types I and II had been tested at various levels of relative humidity (RH) at 35°C, type I was stable at less than 82% RH, but transformed into the monohydrate at more than 88% RH. Type II was stable at less than 66% RH and transformed into the monohydrate at less than 75% RH. The hydration data of type I at 88% RH and type II at 75% RH were calculated for hydration kinetics using various solid‐state kinetic models, but no particular model could be preferred from these data. 1990 Royal Pharmaceutical Society of Great Britain