title: Probing the effect of drug loading and humidity on the mechanical properties of solid dispersions with nanoindentation: antiplasticization of a polymer by a drug molecule.
abstract: Amorphous solid dispersions of clotrimazole in the polymer Kollidon VA64 were prepared as films in concentrations from 0% to 100% in 10% by weight increments. Nanoindentation was performed on each film at 18% and 49% relative humidity to assess the effect of drug loading and humidity on the mechanical properties of the solid dispersions. Although the addition of clotrimazole to the polymer reduces the glass transition temperature of the system as measured by differential scanning calorimetry, the hardness, reduced elastic modulus, and storage modulus were found to increase to values greater than those of either pure component up to drug loadings of approximately 60% by weight. Further addition of clotrimazole to the system resulted in decreased hardness and moduli with increased drug load. Dynamic vapor sorption of the dispersions shows that the hygroscopicity of the system is reduced as clotrimazole is added to the polymer.
authors.affiliation: Merck Research Laboratories, Merck and Co., Inc., Summit, New Jersey, United States. matthew.lamm@merck.com
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Lamm
authors.forename: Amanda
authors.initials: A
authors.lastname: Simpson
authors.forename: Michael
authors.initials: M
authors.lastname: McNevin
authors.forename: Celeste
authors.initials: C
authors.lastname: Frankenfeld
authors.forename: Richard
authors.initials: R
authors.lastname: Nay
authors.forename: Narayan
authors.initials: N
authors.lastname: Variankaval
mesh_terms: D002152:Calorimetry, Differential Scanning; D003022:Clotrimazole / Q000737:chemistry*; D004355:Drug Stability; D006813:Humidity; D015394:Molecular Structure; D011205:Povidone / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D017155:Wettability
chemical_list: D011205:Povidone; D003022:Clotrimazole