Effects of Moisture on the Growth Rate of Felodipine Crystals in the Presence and Absence of Polymers

Abstract

The purpose of this study was to examine how moisture affects the growth rate of felodipine crystals from amorphous systems. Amorphous felodipine films with 0-10% w/w poly(vinylpyrrolidone) (PVP) or hypromellose acetate succinate (HPMCAS) were prepared by spin coating and stored at room temperature at different relative humidities (RHs). Linear growth rates were determined using optical microscopy. Crystals grown from felodipine alone had the fastest growth rate under all conditions. An approximately log-linear relationship between crystal growth rate and storage RH was observed between 13% and 80% RH. Above 80% RH, an abrupt 15-40-fold increase in growth rate occurred, producing crystals of a different morphology. Polymeric additives decreased crystal growth rates, more so with increasing polymer concentration. Growth rates from PVP-containing films increased with increasing storage RH, but thosefor HPMCAS systems did not. Below 52% RH, PVP was the better growth inhibitor; above 64% RH, HPMCAS inhibited crystal growth more effectively. At high RH, the dependence of crystal growth rate on PVP concentration was vastly reduced probably as a result of moisture-induced drug-polymer phase separation.Polymeric additives were thus found to inhibit the crystal growth rate of felodipine in the presence of moisture, with the extent of the inhibition dependent on a number of different factors.

Using Flory–Huggins phase diagrams as a pre-formulation tool for the production of amorphous solid dispersions: a comparison between hot-melt extrusion and spray drying

“…In the 2000-1500/cm region, a single, sharp carbonyl peak was observed at 1744/cm for HPMCAS and 1667/cm for PVPK15, respectively, while for Soluplus peaks at 1739/cm and 1638/cm are associated with the carbonyl groups in the vinyl acetate and caprolactam segments. [19] These specified groups could potentially interact with drug molecules within the solid dispersion and significantly influence the performance of the final product.…”

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

“…The solid-state physical instabilities associated with ASDs include amorphous–amorphous phase separation (AAPS) and/or the conversion of the amorphous drug to a crystalline form (crystallization), both of which negate the solubility advantage of ASDs. AAPS is a phenomenon wherein distinct drug-rich and polymer-rich amorphous phases are formed throughout the ASD matrix, which initially consisted of molecularly mixed drug and polymer 31 . These drug-rich phases are more prone to crystallization due to the reduction in the inhibitory effect of the polymer.…”

Exploring molecular reorientations in amorphous and recrystallized felodipine at the microscopic level

“…Molecular reorientation will be investigated using 1 H NMR (nuclear magnetic resonance), 13 C CP-MAS NMR and QENS methods for temperatures below T g , while the recrystallization process will be monitored by the NMR relaxation method. 13 FLD is the subject of interest of many researchers [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] and can be treated as a model system, but so far little is known about molecular reorientations in the amorphous form of FLD. Interest was focused mainly on the study of various aspects of the stabilization of the amorphous form of FLD 19,[22][23][24]35,36 and recrystallization processes.…”

“…Interest was focused mainly on the study of various aspects of the stabilization of the amorphous form of FLD 19,[22][23][24]35,36 and recrystallization processes. 18,20,21,[25][26][27][28][29][30][31][32][33] The aforementioned studies were performed mostly at the macroscopic level. The exceptions are papers, 14,15 in which the authors analyzed how the amorphization of a series of dihydropyridines (including FLD) inuences intermolecular hydrogen bonds, using optical spectroscopy (FTIR and Raman) methods.…”