Polymorphic Transformation of Pravastatin Sodium Monitored Using Combined Online FBRM and PVM

Abstract

Polymorphic transformation of pravastatin sodium in a mixture of isopropanol and water was studied by use of online focused beam reflectance measurement (FBRM) and particle vision measurement (PVM). It is shown that the form A polymorph transformed to the stable polymorph, form B. It was speculated that in the transformation process there was an agglomeration and breakage phenomenon. The transformation mechanism was identified as solution-mediated phase transformation. Influences of temperature, solvent composition, and stirrer speed on the transformation process were examined. It can be seen from the FBRM monitoring results that higher temperature, larger ratio of water to isopropanol, and higher stirrer speed can increase the transformation process.

Problems, potentials and future of industrial crystallization

“…The latter can be applied for solution concentration measurements [31] and to monitor polymorph and solvate conversations in real-time [28,32,33]. Furthermore, in situ imaging techniques for the direct observation of the appearance and growth of crystals such as PVM (particle vision monitor) were developed recently [34]. A number of in-line and online monitoring techniques were developed and are still evolving.…”

Detection of the II–I Etiracetam solvent-mediated polymorphic transformation through the online monitoring of the suspension apparent viscosity

“…The Focused Beam Reflectance Measurement (FBRM s ), Particle Vision and Measurement (PVM) and Raman probes are commonly used for tracking the changes of the crystals over time while the Attenuated Total Reflectance Fourier Transformed Infra-Red (ATR-FTIR) or Near Infra-Red (NIR) probes are used for the monitoring of the evolution of the solute concentration in the solution over time [7]. Many applications have been developed (i) involving a single PAT measurement probe: ATR-FTIR [8], NIR [9], FBRM s [10,11] or Raman [12], or (ii) using a combination of several probes such as FBRM s and PVM [13], FBRM s , PVM and Raman [14], FBRM s and ATR-FTIR [15], Raman and NIR [11], FBRM s , PVM, Raman and ATR-FTIR [16], etc.…”

Polymorphism Solvatomorphism 2008

“…In another study, focused beam reflectance measurement (FBRM) data were used to monitor the orthorhombic‐to‐monoclinic phase transformation of paracetamol in ethanol solutions, since the transition was accompanied by a change in crystal morphology from octahedrons to needles 143. The FBRM technique was used in conjunction with particle vision measurement to study the transformation of pravastatin sodium metastable Form‐A into the stable Form‐B in an aqueous isopropanol solvent system 144…”