Monitoring Temperature Effect on the Polymorphic Transformation of Acitretin Using FBRM−Lasentec

Abstract

Polymorphs have a tendency to undergo solution-mediated transformation from one form to another during crystallization. Various in situ techniques explored for understanding the crystallization process include, Raman spectroscopy, near-infrared spectroscopy (NIR), and focused beam reflectance measurement (FBRM). Both Raman and NIR techniques are used for polymorphic identification. FBRM has gained much popularity as an ideal technique for studying and improving particle size. The crystallization process can be improved using FBRM by studying the meta-stable zone, temperature of crystallization, and primary and secondary nucleation. This FBRM technique offers a quick and time-saving approach along with insight on the particle size of the product. The same technique can be used during scale up to understand and monitor crystallization processes. This report describes a different application of FBRM, which involves monitoring the changes in chord length distribution as a result of polymorphic transformation associated with temperature during crystallization. Needle-shaped Form III of acitretin undergoes solvent-mediated transformation to cube-shaped Form II. This polymorphic transformation is monitored by monitoring the chord length distribution.

Raman, UV, NIR, and Mid‐IR Spectroscopy with Focused Beam Reflectance Measurement in Monitoring Polymorphic Transformations

“…Mid-IR Discrimination between polymorphic forms of solids [11,12] ATR-UV/Vis Solvent-mediated polymorphic transformation monitoring in batch crystallization (changes in solute concentration) [13][14][15][16] NIR Determination of the polymorphic ratio of solid mixtures [17][18][19] NIR Solvent-mediated polymorphic transformation monitoring [18,20] Raman Determination of the polymorphic ratio of solid mixtures [21][22][23][24][25] FT-Raman, FTIR Comparison between the two techniques in determining the polymorphic ratio of solid mixtures [26,27] Raman Cocrystallization of carbamazepine and nicotinamide monitoring [28] Raman Solvent-mediated polymorphic transformation monitoring [29,30] Raman, FBRM, PVM Study on the impact of operating parameters on polymorphic transformation of D-mannitol [31] Raman Measurement of the total solid concentration in a polymorphic system [32,33] Raman Measurement of solute concentration in a polymorphic system [34,35] FBRM Solvent-mediated polymorphic transformation monitoring [36][37][38][39][40] Raman, NIR, UV/Vis Solvent-mediated polymorphic transformation monitoring [41,42] Raman Feedback strategies to control polymorphs of carvedilol [43,44] Raman, NIR Application of quantitative Raman spectroscopy using a good calibration practice (GCP) procedure [45] a) b) Crystallization Process Informatics System (Cry-PRINS) software. CryPRINS provides a communication interface via file transfer, OPC (Object linking and embedding ...…”

Polymorphism and Solvatomorphism 2010

“…177 dehydration was not allowed by the positions of the water molecules in the crystal lattice. 150 The temperature dependence of the solubilities of naproxen sodium in methanol-water and ethanol-water solutions was used to map the solvatomorphs that could be crystallized under various conditions, as well as establishing the transition points at which the various solid-state forms could be in equilibrium.…”

“…160 The 2010 literature also contained a number of additional reports regarding the phase transformations among polymorphs and solvatomorphs of other organic compounds. Although some of these substances may have only limited pharmaceutical significance, the references summarized in Table 3, [161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177] are collected to pique the interests of appropriately directed investigators.…”

Investigation of a solution‐mediated phase transformation of pranlukast DMF solvate to hemihydrate

“…Both online and off‐line analytical technologies have been reported to investigate solution‐mediated phase transformation. Online analytical technologies include hot stage polarized microscope, in situ Raman spectroscopy , in situ attenuated total reflectance Fourier transform infrared spectroscopy , focused beam reflectance measurement (FBRM) , ect. Off‐line analytical technologies include powder X‐ray diffraction (PXRD) , differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), etc.…”