On-line observation of the crystal growth in the case of the non-typical spherical crystallization methods of ambroxol hydrochloride

Abstract

Spherical agglomeration (SA) of four products was observed by the focused beam reflectance measurement (FBRM), conclusions, similarities, differences were summarized and the agglomeration mechanism was revealed.  The same was performed in the case of cooling crystallization with an alternating temperature profile (ATP) as well.  Crystallization types were compared in case of using a double-walled glass reactor of 250 ml with a total solvent volume of 80 ml and, as a scale-up, a jacketed reactor of 750 ml with a total solvent volume of 500 ml, while applying different types of agitation.  The effect of the addition of more cycles to the ATP methods was investigated. Light microscopic exposures prove significant differences between the SA and the ATP products.

Spherical Cocrystallization—An Enabling Technology for the Development of High Dose Direct Compression Tablets of Poorly Soluble Drugs

“…The pairwise intermolecular interaction energy was estimated using CrystalExplorer and Gaussian09W with experimental geometry of GSF-Acs monohydrate and GSF (Form I, CSD refcode: GRISFL06). − The hydrogen positions were normalized to standard neutron diffraction values before calculation using the B3LYP-D2/6-31G­(d,p) electron densities model. The total intermolecular interaction energy for a given molecule is the sum of the electrostatic, polarization, dispersion, and exchange-repulsion components with scale factors of 1.057, 0.740, 0.871, and 0.618, respectively.…”

Design of Experiments for Optimization of the Lactose Spherical Crystallization Process

“…Estimate n ðe; rÞ ¼ Estimateðe; rÞ Mean responseðrÞ (5) where Estimate n (e, r) is the normalized estimate of the effect e on the response r. It can be seen that the effects on yield, D10, D50 and span were generally greater than the effects on the other responses. This is in agreement with the CV values in the summary statistics (Table 3), which further supported the sensibility of the built models.…”

Design, Development, and Analysis of an Automated Sampling Loop for Online Monitoring of Chiral Crystallization

“… 23 , 24 Raman spectroscopy can also measure species concentrations including enantiomers 25 as well as determine polymorphism. Particle size distributions (PSDs) can be determined using FBRM 26 and PVM. 27 In FBRM, chord lengths and chord length distributions can be determined on-line and these can then be used to derive PSDs.…”

“…ATR–FTIR and ATR–UV/vis are used to determine the concentration of species from the absorption spectrum often using advanced multivariate analysis techniques such as partial least-squares regression (PLSR) (as used in this work). , Raman spectroscopy can also measure species concentrations including enantiomers as well as determine polymorphism. Particle size distributions (PSDs) can be determined using FBRM and PVM . In FBRM, chord lengths and chord length distributions can be determined on-line and these can then be used to derive PSDs.…”