title: Stability of a hydrophobic drug in presence of hydrous and anhydrous lactose.
abstract: The chemical stability of a hydrophobic Leukotriene receptor antagonist drug was investigated in the presence of lactose (both hydrous and anhydrous) under various humidity and temperature conditions. The effect of wet-granulation and direct-mixing on the stability of the drug was also studied. Mixtures of drug:lactose in the ratio 1:25, 1:50 and 1:100 were prepared and analyzed over a 6 week period after storage at 40, 83 and 97% RH (all at 25 degreesC) and 75% RH at 40 degreesC. The mixtures were subjected to LOD, Karl--Fischer titrimetry, HPLC and DSC analysis to evaluate the amount of moisture pickup, percent potency and presence of drug-moisture-lactose interaction. Mixtures containing lactose anhydrous picked up more moisture and exhibited greater drug degradation than those containing lactose hydrous. Also, mixtures stored under high temperature and humidity condition showed greater moisture uptake than those stored at high humidity alone. Lactose anhydrous becomes hydrated on exposure to high humidity/temperature and storage conditions. The transition state of lactose and not its stable state may be responsible for its greater interaction and subsequent degradation of the drug. Therefore, the normal belief that lactose anhydrous, which has less than 0.5% moisture, should provide greater stability as compared to lactose hydrous, needs to be properly evaluated.
authors.affiliation: Department of Applied Pharmaceutical Sciences, The University of Rhode Island, Kingston, RI, USA.
authors.forename: R
authors.initials: R
authors.lastname: Jain
authors.forename: A S
authors.initials: AS
authors.lastname: Railkar
authors.forename: A W
authors.initials: AW
authors.lastname: Malick
authors.forename: C T
authors.initials: CT
authors.lastname: Rhodes
authors.forename: N H
authors.initials: NH
authors.lastname: Shah
mesh_terms: D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006813:Humidity; D007202:Indicators and Reagents; D007785:Lactose / Q000737:chemistry*; D020024:Leukotriene Antagonists / Q000737:chemistry*; D012492:Salts; D012996:Solutions; D013696:Temperature; D013997:Time Factors; D014867:Water
chemical_list: D007202:Indicators and Reagents; D020024:Leukotriene Antagonists; D012492:Salts; D012996:Solutions; D014867:Water; D007785:Lactose