title: Spontaneous crystalline-to-amorphous phase transformation of organic or medicinal compounds in the presence of porous media, part 3: effect of moisture.
abstract: OBJECTIVE
  Amorphization of crystalline compounds using mesoporous media is a promising technique to improve the solubility and drug release of poorly-soluble compounds. The objective of this paper is to understand the effect of moisture on the capacity and performance of vapor-phase mediated amorphization.
  
  
  METHODS
  Mesoporous silicon dioxide (SiO(2)) and crystalline naphthalene were used as the model system. The effect of moisture on the amorphization capacity of naphthalene was determined using adsorption chambers with various levels of relative humidity. Enthalpy and capacity of water vapor adsorption on SiO(2) were measured using isothermal microcalorimetry and thermogravimetry.
  
  
  RESULTS
  Moisture not only suppressed the amorphization capacity of naphthalene, but reversed an already-amorphized formulation as well. On the other hand, through the same competitive interaction, improved drug release and enhanced solubility were obtained. The initial supersaturation was followed by an entropy-driven crystallization. In addition, moisture-induced siloxane bond fracture was found at normal processing conditions, which led to the changes in silica surface chemistry. However, the implication in amorphization has not reached a definitive conclusion.
  
  
  CONCLUSIONS
  Humidity during processing and storage must be carefully controlled for this type of amorphous formulation. Further investigation is needed to better understand the moisture-induced changes of silica.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, The University of Connecticut, 69 North Eagleville Rd, Unit 3092, Storrs, Connecticut, 06269, USA.
authors.forename: Ken K
authors.initials: KK
authors.lastname: Qian
authors.forename: Dale E
authors.initials: DE
authors.lastname: Wurster
authors.forename: Robin H
authors.initials: RH
authors.lastname: Bogner
mesh_terms: D000327:Adsorption; D002151:Calorimetry / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D006813:Humidity; D009281:Naphthalenes / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D044367:Phase Transition; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry*; D012833:Siloxanes / Q000737:chemistry; D012995:Solubility; D013818:Thermogravimetry / Q000379:methods
chemical_list: D009281:Naphthalenes; D004364:Pharmaceutical Preparations; D012833:Siloxanes; C031721:naphthalene; D012822:Silicon Dioxide