ABSTRACT
Inclusion complex between warfarin and beta-cyclodextrin was obtained to improve the in vitro bioavailability of the drug in acidic media. Inclusion complexation in solution was studied by phase solubility technique. The apparent stability constant was influenced by the pH of the medium ranging from 633.26 M(-1) (at pH 1.2, where the drug was in unionised form) to 99.81 M(-1) (at pH 7.4, where the drug was in ionised form). Phase solubility study showed an AL-type diagram indicating the formation of an inclusion complex in 1:1 molar ratio. Solid binary mixtures of the drug with beta-cyclodextrin were prepared by several methods (physical mixing, kneading, co-evaporation, freeze-drying). Physicochemical characterizations were performed using differential scanning calorimetry, powder X-ray diffractometry and dissolution studies. Preparation method influenced the physicochemical properties of the binary mixtures. An inclusion complex was obtained by freeze-drying, and it showed a high solubility and drug dissolution rate. The physical stability of the complex was also studied. After one year storage in glass container at room temperature no significant changes were detected in the diffractogram, thermogram and dissolution profile of the freeze-dried product.
Subject(s)
Chemistry, Pharmaceutical/methods , Cyclodextrins/analysis , Warfarin/analysis , Calorimetry, Differential Scanning/methods , Cyclodextrins/chemistry , Drug Carriers/analysis , Drug Carriers/chemistry , Drug Stability , Freeze Drying/methods , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Solubility , Time Factors , Warfarin/chemistry , X-Ray Diffraction/methodsABSTRACT
The purpose of this study was to investigate the morphology and surface properties of blends of Eudragit RS, a hydrophobic polymer mainly used for film coating, and poly(ethylene glycol)s (PEG), amphiphilic polymers used as softeners for films. Blends of Eudragit RS and PEGs were prepared as films using the casting technique from methylene chloride. The morphology of those films was evaluated by scanning electron microscopy before and after treatment with water. Sessile drop technique was used to measure solid/liquid contact angles in order to calculate surface free-energy parameters and to investigate phase separation using the Cassie-Baxter approach. Films containing 20, 40, 50, and 60% PEG 3400 and PEG 6000 appeared morphologically unchanged after treatment with water; no phase separation was noticed. Films containing PEG 14,000 after treatment with water showed the presence of a solid emulsion in the range 40, 50, and 60% PEG; a multiple solid emulsion was shown for films containing 60% PEG 20,000. The presence of two-phase systems was shown using contact angle measurements and results were in agreement with microscopic analysis. Calculated surface free-energy parameters indicated that PEG 3400 and 20,000 in a critical concentration of 10% can modify surface parameters of Eudragit RS: for PEG 6000 and 14,000 this critical concentration was found to be between 10 and 20%. The surface polarity of PEG 3400, 6000, and 14,000 was found to be drastically reduced upon addition of 5% Eudragit RS; spontaneous surface layering of Eudragit RS could be reasonably hypothesized for PEG 3400. This study revealed that surface parameters of a polymer can be modified in the presence of a relatively small amount of a second material.
Subject(s)
Acrylic Resins/chemistry , Pharmaceutical Preparations/chemistry , Polyethylene Glycols/chemistry , Microscopy, Electron, Scanning , Surface PropertiesABSTRACT
Regular spherical microspheres of 220-260 microns average size have been prepared from vinylpyrrolidone/vinylacetate copolymer using a solvent evaporation method. Griseofulvin has been incorporated into these microspheres and its physical characterization has been carried out by differential scanning calorimetry (DSC), X-ray diffractometry and X-ray photoelectron spectroscopy. An increase of solubility was observed only with the 1:3 drug/polymer microspheres and the comparison of the dissolution profiles of microspheres with pure griseofulvin resulted in an enhancing effect. Furthermore the release rate of griseofulvin, incorporated into the microspheres, was shown to be biphasic and dependent upon the penetration of water into the microspheres, hydration and dissolution of the polymer and finally dissolution of the drug.
Subject(s)
Griseofulvin/chemistry , Microspheres , Pyrrolidinones/chemistry , Vinyl Compounds/chemistry , Chemical Phenomena , Chemistry, Pharmaceutical/methods , Chemistry, Physical , Evaluation Studies as Topic , Kinetics , SolubilityABSTRACT
The kinetics of hydrolysis of indomethacin and related compounds was studied in an alkaline medium at 25 degrees C in the presence of anionic (sodium dodecyl sulfate) and cationic (hexadecyltrimethylammonium bromide) surfactants. The rate-surfactant profiles for rate inhibition in the presence of sodium dodecyl sulfate and rate enhancement in the presence of hexadecyltrimethylammonium bromide were analyzed in terms of the current theory of micellar effects.
Subject(s)
Indomethacin/analysis , Cetrimonium , Cetrimonium Compounds , Hydrolysis , Indomethacin/analogs & derivatives , Kinetics , Micelles , Models, Chemical , Sodium Dodecyl SulfateABSTRACT
The hydrolysis of 1-(4-nitrophenyl)-3-methyltriazene in aqueous solution has been studied over a pH range of 3-14. The effect of the anionic and cationic surfactants (sodium lauryl sulfate and hexadecyltrimethylammonium bromide) on the rate of hydrolysis was investigated. The quaternary ammonium bromide causes a rate decrease at all pH values studied, while sodium lauryl sulfate enhances the acid-catalyzed hydrolysis and decreases the observed rate constants in the pH-independent region. The results are discussed in terms of the current theory of micellar effects.
Subject(s)
Surface-Active Agents , Triazenes , Cetrimonium , Cetrimonium Compounds , Chemical Phenomena , Chemistry, Physical , Hydrolysis , Kinetics , Micelles , Sodium Dodecyl SulfateABSTRACT
The kinetics of the hydrolysis of indomethacin and related compounds were studied in an alkaline medium at 25 degrees. The pseudo-first-order rate constants were evaluated from log absorbance versus time plots in the ultraviolet. These compounds showed a second-order rate constant at low concentrations of hydroxide ion and a first-order rate constant at higher concentrations of hydroxide ion.
Subject(s)
Indomethacin/analogs & derivatives , Chemistry, Pharmaceutical , Hydrolysis , Kinetics , Spectrophotometry, UltravioletSubject(s)
Imidazoles , Carbon Isotopes , Chemical Phenomena , Chemistry, Physical , Magnetic Resonance Spectroscopy , ProtonsABSTRACT
The synthesis and pharmacological activity of several adamantane derivatives and analogs of tilorone are described as part of a systematic research on potential antiviral compounds and/or interferon inducers.
