Miscibility Behavior and Formation Mechanism of Stabilized Felodipine-Polyvinylpyrrolidone Amorphous Solid Dispersions

• Published in: Drug development and industrial pharmacy 2005-01, Vol.31 (6), p.473-489
• Main Authors: Karavas, Evangelos, Ktistis, Georgios, Xenakis, Aristotelis, Georgarakis, Emmanouel
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Differential Thermal Analysis - methods; Drug Carriers - chemistry; Drug Compounding - methods; Drug Stability; Enhanced release; Felodipine; Felodipine - chemistry; Felodipine - pharmacokinetics; Formation mechanism; General pharmacology; Hydrogen bond; Medical sciences; Microscopy, Acoustic - methods; Miscibility behavior; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Povidone - chemistry; Solid dispersions; Solubility; Spectroscopy, Fourier Transform Infrared - methods; Temperature; X-Ray Diffraction - methods
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639040500215958

In the present study, solid dispersion systems of felodipine (FEL) with polyvinylpyrrolidone (PVP) were developed, in order to enhance solid state stability and release kinetics. The prepared systems were characterized by using Differential Scanning Calorimetry, X-Ray Diffraction, and Scanning Electron Microscopy techniques, while the interactions which take place were identified by using Fourier Transformation-Infrared Spectroscopy. Due to the formation of hydrogen bonds between the carbonyl group of PVP and the amino groups of FEL, transition of FEL from crystalline to amorphous state was achieved. The dispersion of FEL was found to be in nano-scale particle sizes and dependent on the FEL/PVP ratio. This modification leads to partial miscibility of the two components, as it was verified by DSC and optimal glass dispersion of FEL into the polymer matrix since no crystalline structure was detected with XRD. The above deformation has a significant effect on the dissolution enhancement and the release kinetics of FEL, as it causes the pattern to change from linear to logarithmic. An impressive optimization of the dissolution profile is observed corresponding to a rapid release of FEL in the system containing 10% w/w of FEL, releasing 100% in approximately 20 min. The particle size of dispersed FEL into PVP matrix could be classified as the main parameter affecting dissolution optimization. The mechanism of such enhancement consists of the lower energy required for the dissolution due to the amorphous transition and the fine dispersion, which leads to an optimal contact surface of the drug substance with the dissolution media. The prepared systems are stable during storage at 40 ± 1°C and relative humidity of 75 ± 5%. Addition of sodium docusate as surfactant does not affect the release kinetics, but only the initial burst due to its effect on the surface tension and wettability of the systems.