Polymorphism and devitrification of nifedipine under controlled humidity: a combined FT‐Raman, IR and Raman microscopic investigation

Abstract

FT-Raman and FT-IR spectroscopy and Raman microscopy were employed to identify the structural characteristics of one amorphous and three crystalline phases of nifedipine, a common antihypertension drug of the 1,4-dihydropyridine family. A significant fraction of the nifedipine molecules in the glass are found to be frozen into metastable rotational conformations as a result of melt quenching. Moreover, the effect of relative humidity .RH = 20-80%/ on the onset and rate of crystallization was studied at 40 • C by means of in situ IR and Raman microscopy employing a controlled humidity cell. The nature and the relative abundance of the various crystallization products were analysed on the basis of the corresponding spectra of the neat compounds. Glassy nifedipine is found to crystallize to the thermodynamically stable a-polymorph via a transient metastable b-nifedipine phase. Increasing RH in the range 20-60% is found to favour the surface crystallization of the glass to b-nifedipine. At high RH (80%), b-nifedipine is rapidly converted to a-nifedipine.

Release Problems for Nifedipine in the Presence of Soluplus

“…These band positions and assignments correspond to those reported [27] for α -nifedipine. The same peaks were observed in all the samples examined (especially that containing higher percentages of the drug).…”

“…An intermolecular bond between one of the ester carbonyl and NH group of an adjacent nifedipine molecule is present in the solid state [27] . Similarly soluplus, among other claimed advantages, offers a variety of functional groups, such as the hydroxy groups at the end of the poly-oxyethylene chains, the carbonyl groups of the vinyl acetate moiety and the amide function of the caprolactam portion.…”

Analysis of solid-state transformations of pharmaceutical compounds using vibrational spectroscopy

“…For example, in-situ IR and Raman spectroscopy were used to study the recrystallisation of amorphous nifedipine in a controlled humidity cell at different relative humidities. [143] Increasing the relative humidity decreased the recrystallisation onset time. The authors concluded that in-situ IR and Raman microscopy are useful tools to examine environmental effects on the solid state of an API.…”

“…Paracetamol, ketoprofen, naproxen, ibuprofen [142] Amorphisation in polyethylene oxide matrices at high humidity Storage at high humidity (94% RH) in room temperature Raman spectroscopy Nifedipine [143] Recrystallisation of amorphous nifedipine via metastable b-form to a-nifedipine…”

Raman characterization and chemical imaging of biocolloidal self-assemblies, drug delivery systems, and pulmonary inhalation aerosols: A review

“…24,29 Incorporating an optical microscope and motorized stage into the Raman instrument for spectroscopic chemical imaging by obtaining spectra for a defined 2-dimensional area with a resolution down to 1 μm 12 has further expanded Raman spectroscopy's utility in various structural and molecular investigations. These direct and quantitative Raman chemical imaging ( Figure 3) and mapping ( Figure 4) investigations include biomaterial nanotubes (providing a spatial resolution of~25 nm), 30 drug-polymer-controlled drug delivery systems, 31,32 solid-state polymorphic transformations, [33][34][35][36][37] and drug disposition research. 24,[38][39][40][41][42] The combination of scanning electron microscopy (SEM) and Raman spectroscopy has been applied in single-crystal hydration studies of carbamazepine, in the absence and presence of excipients, where it was demonstrated that defect structures were of greater importance in the initiation of the hydration process than the crystal face.…”