ABSTRACT
A novel mathematical model for the water transport into and drug release from hydroxypropyl methylcellulose (HPMC) tablets is presented. Fick's second law of diffusion is used to describe the mass transfer processes in the three-component system drug/polymer/water. Numerical solutions of the respective set of partial differential equations are provided, considering axial and radial diffusion within cylindrical tablets. It is shown that the diffusion coefficients strongly depend on the water concentration (parameters quantifying this dependence have been determined). Swelling of the device is considered using moving boundary conditions, whereas dissolution processes are neglected. Experiments proved the applicability of the theory. The practical benefit of the new model is to calculate the required shape and dimensions of HPMC tablets to achieve a desired release profile.
Subject(s)
Excipients/chemistry , Methylcellulose/analogs & derivatives , Algorithms , Chemical Phenomena , Chemistry, Physical , Diffusion , Hypromellose Derivatives , Kinetics , Methylcellulose/chemistry , Models, Theoretical , Surface Properties , Tablets , Water/chemistryABSTRACT
Ion exchange resins were incorporated into hydroxypropylmethylcellulose (HPMC) matrix tablets to modify the release of oppositely charged drugs. The drug release from HPMC tablets containing drug-resin complexes was significantly slower than from HPMC tablets containing drug without resin. A physical mixture of drug and ion exchange resin (cationic drug, propranolol HCl, with the cation exchange resin, Amberlite IRP 69, or the anionic drug, sodium diclofenac, with the anion exchange resin, cholestyramine (Duolite ATP-143)) resulted in almost the same drug release as tablets containing preformed drug-resin complexes. Upon contact with the dissolution medium, a gel layer formed rapidly around the solid tablet core and the complex between the drug and the resin formed in situ within the gelled regions. No effect of pH of the dissolution medium (0.1 N HCl or pH 7.4 phosphate buffer) or resin counterion was observed with the strong cation exchanger, Amberlite IRP 69. The resin was dissociated at both pH-values, allowing drug binding. With the weak cation exchange resin, Amberlite IRP 88, in situ complex formation and retardation was only observed in pH 7.4 buffer but not in 0.1 N HCl because of the non-ionization of the carboxyl groups. The drug release depended also on the amount and particle size of the resin particles and the type of carrier. The use of smaller resin particles eliminated the burst release seen with larger resin particles. Upon comparing different carrier materials, a rapid formation of the gel layer was important for the in situ complex formation. The drug release was in the order of Gelucire 54/02 (glyceryl palmitostearate) > polyethylene oxide 400K > HPMC K15M.
Subject(s)
Adrenergic beta-Antagonists/chemistry , Delayed-Action Preparations/chemistry , Ion Exchange Resins/chemistry , Methylcellulose/analogs & derivatives , Propranolol/chemistry , Protease Inhibitors/chemistry , Adrenergic beta-Antagonists/administration & dosage , Chemistry, Pharmaceutical/methods , Hypromellose Derivatives , Ion Exchange Resins/administration & dosage , Methylcellulose/administration & dosage , Methylcellulose/chemistry , Propranolol/administration & dosage , Protease Inhibitors/administration & dosage , Tablets/chemistryABSTRACT
Interactions between endogenous cholesterol and cyclodextrins have been investigated by several researchers, and they found altered skin penetration of some drugs, membrane disruption, and extraction of cholesterol from the large lipoprotein particles or animal fat. In the present study, an inclusion complex composed of cholesterol and hydroxypropyl-beta-cyclodextrin (HPbetaCD) prepared by lyophilization was investigated and characterized in order to confirm these interactions. Five grams of cholesterol were dispersed in 50 ml of 73.2 mM HPbetaCD aqueous solution, mixed for 2 days, and the filtrate lyophilized. A phase solubility study was performed by mixing an excess amount of cholesterol with an aqueous solution containing increasing amounts of HPbetaCD. The amount of cholesterol in solution after mixing for 2 days at 25 degrees C was determined by HPLC. The inclusion complex was characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry, and differential scanning calorimetry (DSC). An Ap-type Higuchi phase solubility diagram, DSC, FTIR, and X-ray diffraction demonstrated the formation of an inclusion complex. DSC thermograms indicated that the endothermic peaks of cholesterol and physical mixture of cholesterol with HPbetaCD due to the fusion of drug crystals, were absent in DSC thermograms obtained on the freeze dried inclusion complex. FTIR spectra indicated that some of the absorption peaks in the lyophilized inclusion complex were different from that of the physical mixture of cholesterol and HPbetaCD. X-ray diffraction patterns showed that the pure cholesterol and a physical mixture of cholesterol and HPbetaCD exhibited crystalline characteristics whereas the lyophilized inclusion complex and HPbetaCD displayed amorphous characteristics. The results indicated that the formation of a cholesterol/HPbetaCD inclusion complex is more water soluble than cholesterol alone.
Subject(s)
Cholesterol/chemistry , Cyclodextrins/chemistry , beta-Cyclodextrins , 2-Hydroxypropyl-beta-cyclodextrin , Calorimetry, Differential Scanning , Chemical Phenomena , Chemistry, Physical , Solubility , X-Ray DiffractionABSTRACT
A high-performance liquid chromatographic method for the determination of diazolidinyl urea (DU) in a cream formulation is described. The aqueous phase of the emulsion was separated by centrifugation, removed, filtered, diluted and applied onto the HPLC system. DU was detected by ultraviolet absorption at a wavelength of 214 nm. The calibration curve was linear over the range of 79-553 micrograms/ml, and identical when determined on consecutive days. The relative standard deviation for repeat determinations was less than 0.5%. Recoveries were 97.74-101.72%. This analytical method is useful for quantitation of DU in cream formulations.
Subject(s)
Anti-Infective Agents/analysis , Chromatography, High Pressure Liquid/methods , Urea/analogs & derivatives , Administration, Topical , Anti-Infective Agents/administration & dosage , Reproducibility of Results , Spectrophotometry, Ultraviolet , Urea/analysisABSTRACT
The influence of simulated high-fat meals on drug release from beads coated with modified-release ethylcellulose coating formulations was investigated as a function of plasticizer type and concentration, and coating level. Ethylcellulose-coated beads were soaked in peanut oil prior to testing to simulate the influence of concomitant administration of the dosage form with ingestion of fatty meals. The USP apparatus 3 dissolution procedure was employed to study the drug release properties of the beads. It was found that the ethylcellulose-coated beads plasticized with either triethyl citrate (TEC) or dibutyl sebacate (DBS) had faster drug release rates after the peanut oil treatment. Scanning electron microscopy (SEM) revealed that the peanut oil soak caused the polymeric films to detach from the surface of the bead, producing a series of uneven ridges and cracks in the coating. Modulated differential scanning calorimetry (DSC) demonstrated that the glass transition temperature was increased for DBS-plasticized films soaked in peanut oil, and that it was not influenced for TEC plasticized films. Similar results were found for the puncture strength, percent elongation, and modulus of elasticity for the DBS- and TEC-plasticized films soaked in peanut oil. The results verified that the DBS was solubilized and extracted from the plasticized film during the peanut oil soak, and that the film plasticized with the TEC was not significantly affected by the peanut oil soak. Drug release was influenced by the plasticizer type and concentration, and coating level applied to the beads.
