The effects of absorbed water on the properties of amorphous mixtures containing sucrose

• Published in: Pharmaceutical research Vol. 16; no. 7; pp. 1119 - 1124
• Main Authors: SHAMBLIN, S. L, ZOGRAFI, G
• Format: Journal Article
• Language: English
• Published: New York, NY Springer 01.07.1999; Springer Nature B.V
• Subjects: Absorption; Acrylates - administration & dosage; Acrylates - chemistry; Biocompatible Materials - chemistry; Biological and medical sciences; Chemical Phenomena; Chemistry, Physical; Chloride; Crystallization; General pharmacology; Glass - chemistry; Humidity; Medical sciences; Molecular weight; Pharmacology. Drug treatments; Physicochemical properties. Structure-activity relationships; Polymers; Polyvinyls - administration & dosage; Polyvinyls - chemistry; Potassium; Povidone - administration & dosage; Povidone - analogs & derivatives; Povidone - chemistry; Pyrrolidines; Pyrrolidinones - administration & dosage; Pyrrolidinones - chemistry; Sucrose; Sucrose - chemistry; Sugar; Temperature; Vinyl Compounds; Water - chemistry; Differential scanning calorimetry; Freeze drying; Pyrrolidone(vinyl) polymer; Sucrose; Crystallization; Water content; Molecular interaction; Water absorption; Water vapor; X ray diffraction; Glass transition temperature; Physicochemical properties
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1023/A:1018960405504

To measure the water vapor absorption behavior of sucrose-poly(vinyl pyrrolidone) (PVP) and sucrose-poly(vinyl pyrrolidone co-vinyl acetate) (PVP/VA) mixtures, prepared as amorphous solid solutions and as physical mixtures, and the effect of absorbed water on the amorphous properties, i.e., crystallization and glass transition temperature, Tg, of these systems. Mixtures of sucrose and polymer were prepared by co-lyophilization of aqueous sucrose-polymer solutions and by physically mixing amorphous sucrose and polymer. Absorption isotherms for the individual components and their mixtures were determined gravimetrically at 30 degrees C as a function of relative humidity. Following the absorption experiments, mixtures were analyzed for evidence of crystallization using X-ray powder diffraction. For co-lyophilized mixtures showing no evidence of crystalline sucrose, Tg was determined as a function of water content using differential scanning calorimetry. The absorption of water vapor was the same for co-lyophilized and physically mixed samples under the same conditions and equal to the weighted sums of the individual isotherms where no sucrose crystallization was observed. The crystallization of sucrose in the mixtures was reduced relative to sucrose alone only when sucrose was molecularly dispersed (co-lyophilized) with the polymers. In particular, when co-lyophilized with sucrose at a concentration of 50%, PVP was able to maintain sucrose in the amorphous state for up to three months, even when the Tg was reduced well below the storage temperature by the absorbed water. The water vapor absorption isotherms for co-lyophilized and physically mixed amorphous sucrose-PVP and sucrose-PVPNA mixtures at 30 degrees C are similar despite interactions between sugar and polymer which are formed when the components are molecularly dispersed with one another. In the presence of absorbed water the crystallization of sucrose was reduced only by the formation of a solid-solution, with PVP having a much more pronounced effect than PVP/VA. The effectiveness of PVP in preventing sucrose crystallization when significant levels of absorbed water are present was attributed to the molecular interactions between sucrose, PVP and water.