title: Applicability of the one-step DVS method for the determination of amorphous amounts for further different hydrophilic and hydrophobic drugs.
abstract: In a former publication the authors showed that low amounts of amorphous content (LOQ of 0.5%) in a hydrophobic model API (Ciclesonide) can be measured with an individually adjusted one-step dynamic organic vapor sorption (DVS). In this investigation the applicability is tested on various APIs which differ in lipophilicity (poor water solubility) and hygroscopicity (absorption of water). The vapor sorption method proved to be applicable in almost all cases. Moisture sorption isotherms were determined for all five investigated crystalline and amorphous APIs. However, it was necessary to select the parameters individually for each API. The used solvents (water, methanol, isopropanol and methylene chloride) and the humidity-levels (0.05 p/p0 until 0.5 p/p0) were chosen carefully because otherwise the amorphous amounts switch to their crystalline counterparts and are not detectable. The production of fully amorphous samples (absence of crystalline material measured by DSC, mDSC and XRPD) was optimized over several trials. As successfully methods proved ball-milling, freeze-drying, spray-drying and/or quench cooling. In the next step these fully amorphous amounts were blended with crystalline starting material to calibration curves (Turbula blender, influence of electrostatic charge to homogeneity) for the calculation of amorphous content. In summary, the following presented methods were used to determine and quantify low amorphous amounts (between 1.5% and 17.0%) in jet-milled powders (grinding pressure of 8bar, 1-3 grinding cycles), respectively.
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Grasweg 9a, 24118 Kiel, Germany. Electronic address: tmueller@pharmazie.uni-kiel.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Müller
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Grasweg 9a, 24118 Kiel, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Scherließ
authors.affiliation: Boehringer Ingelheim, Binger Straße 173, 55216 Ingelheim am Rhein, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schiewe
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Grasweg 9a, 24118 Kiel, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Smal
authors.affiliation: Boehringer Ingelheim, Binger Straße 173, 55216 Ingelheim am Rhein, Germany.
authors.forename: Claudius
authors.initials: C
authors.lastname: Weiler
authors.affiliation: Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Grasweg 9a, 24118 Kiel, Germany. Electronic address: hsteckel@pharmazie.uni-kiel.de.
authors.forename: Hartwig
authors.initials: H
authors.lastname: Steckel
mesh_terms: D065966:Absorption, Physicochemical; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D057927:Hydrophobic and Hydrophilic Interactions; D010316:Particle Size; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods* / Q000592:standards; D014835:Volatilization; D014867:Water / Q000737:chemistry
chemical_list: D004364:Pharmaceutical Preparations; D014867:Water
keywords: Amorphous content; Budesonide (PubChem CID: 5281004); Ciclesonide (PubChem CID: 444033); Dynamic vapor sorption; Formoterol fumarate (PubChem CID: 23581795); Glass transition; Glibenclamide (PubChem CID: 3488); Ipratropium bromide monohydrate (PubChem CID: 16738693); Moisture sorption isotherms; Organic solvent; Re-crystallization event; Salbutamol sulfate (PubChem CID: 161912)