Higher Drug Release Rate Research Articles

5-Fluorouracil in vesicular phospholipid gels for anticancer treatment: entrapment and release properties

Vesicular phospholipid gels (VPG), i.e. highly concentrated liposomal dispersions, are suitable for entrapping substances such as anticancer drugs with particular high encapsulation efficiencies (EE). We prepared different formulations of VPG with 30% (w/w) lipid containing 5-fluorouracil (5-FU) by high pressure homogenization and analysed their EE and drug release. Using mixtures of hydrogenated soy phosphatidylcholine and cholesterol with molar ratios ranging from 55/45 to 75/25, a decreasing amount of cholesterol correlated with an increasing EE, which is probably due to a reduced amount of smaller vesicles and number of lamellae. Using a 5-FU solution of pH 8.6 for VPG preparation, an EE of approximately 40% was found after redispersion of the gel to a liposomal dispersion and separation of free drug from liposomal drug by size exclusion chromatography. The reduced EE for preparations with lower pH values was attributed to a fast initial drug release due to the increased drug lipophilicity below the p K a value of 8. After redispersion of a VPG of pH 8.0, an initially faster release of about a third of the entrapped drug was found during the first 20 min, followed by stable entrapment over many hours. The rapid initial release may be due to the portion of liposomes smaller than 40 nm in diameter, determined by photon correlation spectroscopy. Cryo electron microscopic pictures show a lentil-like shape of these small liposomes. The membrane defects on the edges are probably the reason for the very high initial drug release rate. The half-life time of the release of 5-FU from intact FU-VPG at both pH 7.4 and 8.0 was found to be in the order of 4–5 h and the kinetics are typical for matrix-controlled drug diffusion. The in vitro data of 5-FU loaded VPG suggest their applicability as implants with controlled release properties or, after redispersion, as intravenously injected liposomal formulations.

Biopharmaceutical characterization of topical liposome formulations bearing 5-fluorouracil

Liposome dispersions and liposome gel formulations for topical administration were evaluated as modified release delivery systems for 5-fluorouracil. Drug substance has been entrapped in the internal aqueous compartment of liposomes during the preparation. The concentration of 5-fluorouracil in the hydration medium was varied and the effect on the liposome characteristics was considered. Liposome gel formulations were prepared by incorporation of liophylized liposomes into a structured vehicle of chitosan. The decrease of the amount of aqueous phase bearing total drug quantity (drug/aqueous phase ratio from 1:100, 1:60, 1:40) led to an increase of the percentage of liposome-entrapped drug, and decreased percentage of drug release, while particle size analysis showed no changes in vesicle size. Liposome gel formulations showed initially a higher drug release rate in comparision with liposome dispersions, which could be related to the release of “free” 5-fluorouracil, leaked from liposomes due to the process of liophylization. This was followed by slower release (after 1.5 hour) as a result of the influence of the viscosity of the gel matrix.

Release of Pentoxifylline from Xanthan Gum Matrix Tablets

Pentoxifylline-controlled release tablets were prepared using xanthan gum. The effects of polymer concentration, rotation speed, ionic strength, and pH of the dissolution medium on the release of the water-soluble pentoxifylline were studied. The release rate decreased with increasing polymer concentration in the tablet, which was reflected in the increase in the mean dissolution time. A higher rotation speed and increased ionic strength of the dissolution medium resulted in a higher rate of drug release of xanthan-based tablets. A higher release rate of pentoxifylline was also observed using acidic dissolution medium.

Influence of Thermal Processing on the Properties of Chlorpheniramine Maleate Tablets Containing an Acrylic Polymer

The purpose of this investigation was to determine the effects of thermal processing and post-processing thermal treatment on the release properties of chlorpheniramine maleate (CPM) from matrix tablets containing Eudragit® RS PO and triethyl citrate (TEC). CPM tablets containing Eudragit RS PO with and without TEC were prepared by direct compression (DC), high shear hot-melt granulation (HMG), and hot-melt extrusion (HME). X-ray diffraction patterns showed that the CPM was distributed in Eudragit RS PO at the molecular level following HME. The thermogravimetry analysis (TGA) profiles of CPM, Eudragit RS PO, and TEC demonstrated that these materials were thermally stable during both the high shear HMG and HME processes. The tablets were subjected to post-processing thermal treatment by storing the tablets at 60°C in open containers for 24 hr. Tablets prepared by DC showed the highest drug release rate constant of 36.2%hr−1/2. When 4% TEC was incorporated into the formulation, the drug release rate constant for the directly compressed tablets decreased to 32.4%hr−1/2. After high shear HMG and HME of the powder blend containing 4% TEC, the drug release rate constant decreased to 30.8 and 13.8%hr−1/2 for the respective processes. The drug release rate constants for all tablets decreased following post-processing thermal treatment. The reduction in release rate was due to an increase in the intermolecular binding and entanglement between drug molecules and polymer molecules that occurred during thermal processing. Post-processing thermal treatment of the hot-melt extrudates had a minimal effect on the drug release rate since the HME process enhanced the drug and polymer entanglement to a greater extent.

Degradation and drug release characteristics of monosize polyethylcyanoacrylate microspheres.

Monosize, biodegradable poly(ethylcyanoacrylate) (PECA) microspheres with a diameter of 1.3 microns were prepared by a relatively new polymerization method, the so-called phase inversion polymerization. The effects of pH and temperature on the degradation behavior of PECA particles were investigated. PECA microspheres were degraded mainly by surface erosion. The degradation rate increased with increasing pH temperature. A model drug, i.e. 2,4-dinitrophenylhydrazine (DNPH) was loaded into the monosize PECA microspheres during polymerization. The drug incorporation into the PECA microspheres increased with increasing initial drug concentration in the monomer phase. Drug release from the PECA microspheres was investigated at different pH. Higher drug release rates were observed in the neutral and alkaline media as compared with the acidic medium.

In VitroDrug Release from Matrix Tablets Containing a Silicone Elastomer Latex

AbstractA silicone elastomer latex was evaluated as a wet-granulating agent in preparing controlled release matrix tablets containing a water soluble active ingredient. A one-half fractional factorial statistical design was used to investigate the effect of five different formulation and non-formulation variables on the in vitro release characteristics of the drug from the matrix tablets. Tablets containing a high percent of fumed colloidal silica exhibited a faster drug release rate. A high drug to polymer ratio in the tablets was also shown to result in a faster release of the drug. Granules dried at a higher temperature (80°C vs. 60°C) produced tablets with a slower drug release rate. The release of the drug was shown to be pH dependent. A higher drug release rate was obtained in a dissolution medium with a lower pH (1.2 vs. 6.8).