title: The crystallinity of cellulose controls the physical distribution of sorbed water and the capacity to present water for chemical degradation of a solid drug.
abstract: The purpose of the research was to investigate the effect of moisture content of cellulose on the degradation of a drug in binary mixtures with cellulose. Physical mixtures of acetylsalicylic acid and two forms of cellulose, either microcrystalline cellulose or low crystalline cellulose, in the proportion 1:1 were stored at 50°C at a series of relative humidities (0-90%) for up to 175 days. The degradation rate constant of the drug increased with increased cellulose moisture content in a bi-regional fashion, with a low and a high degradation rate region. The shift from region 1 to 2 occurred at higher moisture content for the low crystalline cellulose. The relationships between rate constant and the temperature of maximum endothermic value overlapped for the two celluloses. It is proposed that the amount of water available for degradation of a solid drug is controlled by the water presenting capacity of cellulose which is dependent of the mechanism of sorption of water in cellulose. The water sorption of water can for cellulose satisfactorily be described by a two-site residence model with cellulose crystallinity as the structural correlate to the distribution between the two residence sites.
authors.affiliation: Department of Pharmacy, Uppsala University, Box 580, Uppsala SE-751 23, Sweden.
authors.forename: Mina Heidarian
authors.initials: MH
authors.lastname: Höckerfelt
authors.affiliation: Department of Pharmacy, Uppsala University, Box 580, Uppsala SE-751 23, Sweden. Electronic address: goran.alderborn@farmaci.uu.se.
authors.forename: Göran
authors.initials: G
authors.lastname: Alderborn
mesh_terms: D000327:Adsorption; D002152:Calorimetry, Differential Scanning; D002482:Cellulose / Q000737:chemistry*; D003460:Crystallization; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000737:chemistry*; D008956:Models, Chemical; D011208:Powders; D013499:Surface Properties; D013678:Technology, Pharmaceutical; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D005079:Excipients; D011208:Powders; D014867:Water; D002482:Cellulose
keywords: Cellulose; Crystallinity; Moisture content; Solid drug degradation; Sorption sites; Water attachment