Applicability of the one-step DVS method for the determination of amorphous amounts for further different hydrophilic and hydrophobic drugs |
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| Institution: | 1. Department of Pharmaceutics and Biopharmaceutics, Christian Albrecht University Kiel, Grasweg 9a, 24118 Kiel, Germany;2. Boehringer Ingelheim, Binger Straße 173, 55216 Ingelheim am Rhein, Germany;1. School of Physics and Materials Science, Anhui University, Hefei 230601, PR China;2. Institute of Plasma Physics, Chinese Academy of Sciences, P.O. Box 1126, Hefei 230031, PR China;3. University of Science and Technology of China, Hefei 230026, PR China;1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC 3052, Australia;2. CSIRO Materials Science and Engineering, Bayview Avenue, Clayton, VIC 3168, Australia;3. Ian Wark Research Institute, University of South Australia, Mawson Lakes, SA 5095, Australia;4. Melbourne School of Engineering, The University of Melbourne, VIC 3010, Australia;1. Pharmaceutics Research Laboratory, Arundel Building, School of Life Sciences, University of Sussex, BN1 9QJ, Brighton, UK;2. Colorcon Inc., Global Headquarters, 275 Ruth Road, Harleysville, PA, 19438, USA;3. Surface Measurement Systems, Unit 5, Wharfside, Rosemont Road, Alperton, London, HA0 4PE, UK;4. School of Pharmacy and Biomolecular Sciences, Huxley Building, University of Brighton, Brighton, BN2 4GJ, UK;1. Boreskov Institute of Catalysis SB RAS, Prospekt Akad. Lavrentieva 5, 630090 Novosibirsk, Russian Federation;2. Novosibirsk State Technical University, Prospekt K. Marksa 20, 630092 Novosibirsk, Russian Federation;3. Department of Chemistry and Green-Nano Materials Research Center, Kyungpook National University, Sankyuck-Dong, Buk-Ku, Daegu 702-701, Republic of Korea;4. Novosibirsk Institute of Organic Chemistry SB RAS, Prospekt Akad. Lavrentieva 9, 630090 Novosibirsk, Russian Federation;1. Surfaces and Particle Engineering Laboratory (SPEL), Department of Chemical Engineering, Imperial College London, South Kensington Campus, London SW7 2AZ, UK;2. Bristol-Myers Squibb Co., One Squibb Drive, New Brunswick, NJ 08902, USA;3. Bristol-Myers Squibb Pharmaceuticals, Reeds Lane, Moreton, Wirral CH46 1QW, UK |
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| 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 8 bar, 1–3 grinding cycles), respectively. |
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| Keywords: | Dynamic vapor sorption Moisture sorption isotherms Amorphous content Organic solvent Glass transition Re-crystallization event |
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