Moisture sorption analysis

3 Integrated Approaches to the Solid State Characterization of Salts and Co-crystals 

The identification of two (or more) components in a material by chemical methods alone can infer salt, co-crystal or solvate formation when one or both of the components is a liquid or a gas under ambient conditions. For example, when elemental or evolved gas analysis reveals that HCl or HBr, both gases under STP conditions, are present, salts are very likely to be formed, although rare cases of co-crystals have been reported. This was the case for a molecular HCl complex found for the mono-HCl salt of A - (15)-l-[2-(l- [(3S,4R)-l-/ert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl piperidin-4-yl)-5-chloro-phenyl]ethyl acetamide, wherein two equivalents of HCl were confirmed through elemental analysis, AgNOs titration and TG-MS.Remarkably, not one, but four crystal forms of this most unusual bis-HCl salt complex were identified, despite the presence of only one relatively basic site in the molecule. While HCl (or HBr) incorporation in a crystal usually signals salt formation and stoichiometric solvent retention generally points to solvate formation, the 

Single crystal neutron diffraction single crystal X-ray diffraction powder X-ray diffraction solid-state NMR spectroscopy 

Single crystal neutron diffraction single crystal X-ray diffraction solid-state NMR analysis vibrational spectroscopy X-ray photoelectron spectroscopy Environmental (VT, VRH) XRPD VT SSNMR spectroscopy Raman/IR spectroscopy thermal analysis hot stage microscopy moisture sorption analysis slurry equilibration Moisture sorption analysis 

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Wettability Contact angle tensiometer Moisture sorption Dynamic moisture/vapor sorption analysis... 

In essence, the test battery should include XRPD to characterize crystallinity of excipients, moisture analysis to confirm crystallinity and hydration state of excipients, bulk density to ensure reproducibility in the blending process, and particle size distribution to ensure consistent mixing and compaction of powder blends. Often three-point PSD limits are needed for excipients. Also, morphic forms of excipients should be clearly specified and controlled as changes may impact powder flow and compactibility of blends. XRPD, DSC, SEM, and FTIR spectroscopy techniques may often be applied to characterize and control polymorphic and hydrate composition critical to the function of the excipients. Additionally, moisture sorption studies, Raman mapping, surface area analysis, particle size analysis, and KF analysis may show whether excipients possess the desired polymorphic state and whether significant amounts of amorphous components are present. Together, these studies will ensure lotto-lot consistency in the physical properties that assure flow, compaction, minimal segregation, and compunction ability of excipients used in low-dose formulations. 

Moisture sorption kinetics by neat epoxies were measured using gravimetric analysis using a Mettler balance which was accurate to +0.05 mg. This technique was described in detail elsewhere 137). Another method was used to monitor the sorp-... 

York, P. Analysis of moisture sorption hysteresis in hard gelatin capsules, maize starch, and maize starch drug powder mixtures. J. Pharm. Sci. 1981, 33, 269-273. 

The influence of sorbed moisture on chemical stability and the flow and compaction of powders and granulations is well established. The moisture content and hygroscopicity of excipients is particularly important as total product processing as well as finished product stability can be affected. Hygroscopicity, moisture-sorption isotherms, and equilibrium moisture content can be determined by thermogravimetric analysis and Karl Fisher titration methods. 

The effects of temperature and relative humidity on the kinetics of moisture sorption in epoxy materials for microelectronics encapsulation are not generally known. In a previous paper QJ we examined moisture sorption as a function of temperature under conditions of 100 percent relative humidity. Conjugate sorption measurements were combined with mechanical, dielectric and thermal methods of analysis to examine moisture related micro-structural alterations. 

Aerospace epoxy resina--Contlnued dyn2unlc mechanical analysis, 134-38 hardness, 129,143 moisture sorption... 

It should be stressed, that a successful analysis of solvated crystal forms requires additional methods besides those mentioned with true polymorphs. Such methods are, for example, thermogravimetry or Karl-Fischer titration and moisture sorption/desorption analysis for hydrates. In order to perform studies... 

X-ray diffraction methods (powder, single crystal) Spectroscopy (UV, IR, Raman, solid-state NMR) Thermal analysis, microcalorimetry, solubility determination, vapour pressure determination Moisture sorption Microscopy and micromeritics... 

Besides thermal, diffractometric, and moisture sorption techniques, there are ample other techniques, as aforementioned, that are commonplace for the analysis of the various structural features of ASD. Table 14.1 lists various techniques and brief descriptions for their measuring principles relevant to ASD. The details of working principle and various other applications of these techniques are available elsewhere. Some representative and relevant references are also included in Table 14.1. Tables 14.2-14.8 portray the structural characteristics measurable by various these techniques and also possible hurdles and interferences. 

Moisture sorp- Moisture sorption tion analysis isotherm... 

Figure 530. DMA data for samples of an amorphous aromatic polyamid-imide polymer containing various amounts of moisture the data indicate a decrease in Tg of over 100°C with 4.25% moisture sorption. [From Hiltz and Keough (1991) reprinted with permission of the North American Thermal Analysis Society.]...

The structural characteristics and moisture sorption properties of two kinds of nylon-6/clay hybrids were investigated by Murase et The moisture sorption isotherms of the hybrid samples were a typical sigmoid shape similar to that of the pure nylon-6 sample, even if the extent of moisture regain of the hybrid films was comparatively low. All the isotherms obtained were explained through quantitative analysis in terms of the BET multilayer adsorption theory and complementally with the aid of the FloryHuggins solution theory. 

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