Effects of the Molecular Weight and Concentration of Polymer Additives, and Temperature on the Melt Crystallization Kinetics of a Small Drug Molecule

Citations Over TimeTop 12% of 2010 papers

Abstract

The purpose of the present study was to investigate the effect of molecular weight (MW) and concentration of a polymeric additive, poly(vinyl pyrrolidone) (PVP), on the crystal growth rate of a small molecule drug, felodipine. PVP samples with three different molecular weights (2−3 × 103 g/mol for PVP K-12, 4−5 × 104 g/mol for PVP K-29/32, and 1−1.5 × 106 g/mol for PVP K-90) were used to study the effect of molecular weight. Optical microscopy was used to measure the growth rates at various temperatures in the range of 70−110 °C. While PVP was found to reduce the crystal growth rate at all temperatures, the inhibitory effect was much greater at lower temperatures. The inhibiting effect of PVP on the crystal growth rate of felodipine increased as a function of polymer molecular weight. The effect of polymer concentration on the crystal growth rate was investigated with varying concentrations of PVP K-29/32 (0.5−4.5 wt %), and a log linear relationship between crystal growth rate and concentration was observed. The calorimetric glass transition temperatures (Tg) of the solid dispersions were not significantly different from the Tg of pure felodipine. IR spectroscopy results indicate that among the PVP polymers of three different MWs, there is no difference in their hydrogen-bonding interactions with felodipine molecules. We present discussions of these experimental results with reference to established thermodynamic theories of crystallization kinetics and mass transfer models.

Related Papers

• → Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine(1996)31 cited
• → Synthesis, Biological Evaluation, Calcium Channel Antagonist Activity, and Anticonvulsant Activity of Felodipine Coupled to a Dihydropyridine−Pyridinium Salt Redox Chemical Delivery System(1996)24 cited
• → Overview of the Safety of Felodipine Based on Clinical Trials in Patients With Hypertension(1997)1 cited
• → Attenuation of renal ischaemic injury by felodipine(1991)9 cited
• Domestic felodipine extended release tablets vs imported felodipine extended release tablets in treating hypertension(2002)