Drug release from ammonio-methacrylate-coated diltiazem particles: influence of the reservoir on membrane behavior.

Drug-layered sugar spheres 15, 45, and 64% potent were made such that each had the same particle size distribution. The particles were coated to the same coat thickness with an ammonio polymethacrylate formulation, and drug release was measured in two media. The products exhibited a sigmoidal release pattern, where a lag time was followed by relatively rapid drug release.

The influence of surfactants and additives on drug release from a cationic eudragit coated multiparticulate diltiazem formulation.

A cationic polymethacrylate coated multiparticulate diltiazem formulation exhibited sigmoidal drug release. Lag time prior to drug release was influenced by dissolution media, coat thickness, and by the nature of additives included in the formulation. Incorporation of up to 5% w/w sodium lauryl sulfate (SLS) in the coating membrane resulted in substantial increases in lag times in acidic and neutral media.

Drug-polymer interaction and its significance on the physical stability of nifedipine amorphous dispersion in microparticles of an ammonio methacrylate copolymer and ethylcellulose binary blend.

Using spectroscopic and thermal analysis, this study investigated drug-polymer interaction and its significance on the physical stability of drug amorphous dispersion in microparticles of an ammonio polymethacrylate copolymer (Eudragit RL) (RL) and ethylcellulose (EC) binary blend (RL/EC = 2:1 w/w) prepared for use in controlled release of poorly water-soluble drugs. Solid dispersion of the model drug, nifedipine in the microparticles could be described as an ideal amorphous mixture for drug loadings up to 11% w/w. The antiplasticizing effect of the polymer blend was indicated by a significant increase in the glass transition point from approximately 50 degrees C for the amorphous nifedipine to approximately 115 degrees C for its solid solution.

Ammonio polymethacrylate-coated diltiazem: drug release from single pellets, media dependence, and swelling behavior.

Drug release from single pellets was measured on an easily assembled flow-through system. Despite heterogeneity between pellets, the sum of the individual results resembled drug release from an ensemble. A typical pellet displayed a long lag followed by rapid release.

Assessment of dynamic image analysis as a surrogate dissolution test for a coated multiparticulate product.

Dynamic image analysis (DIA) was used to measure particle diameter (D50) of in-process samples removed during fluid bed coating. A single, rapid measurement gave D50 to within 4 mum. Samples removed at intervals of 2% weight gain were readily distinguishable by DIA and by their drug release profiles.

Nifedipine molecular dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blends for controlled drug delivery: effect of matrix composition.

The objective of this study is to explore matrix-type microparticles, comprising a solid dispersion of drug with an ammonio methacrylate copolymer and ethylcellulose binary blend, for use in the controlled release of a poorly water-soluble drug, nifedipine. Microparticles consisting of an ethylcellulose N7 (N7) and Eudragit RL (RL) binary blend at different ratios were prepared using phase-separation methodology. The effects of matrix composition on microparticle properties were evaluated by polarized light microscopy, differential scanning calorimetry (DSC), FT-infrared and UV-visible spectroscopy, stability, and drug release studies.

Thermogravimetric analysis for the determination of water release rate from microcrystalline cellulose dry powder and wet bead systems.

The purpose of this work was to determine the total amount of water contained in dry powder and wet bead samples of microcrystalline cellulose, MCC, (Avicel PH-101), taken from various stages of the extrusion/marumerization process used to make beads and to determine the kinetic rates of water release from each sample. These samples were allowed to equilibrate in controlled humidity chambers at 25 degrees C. The total amount of water in each sample, after equilibration, was determined by thermogravimetric analysis (TGA) as a function of temperature.

Nifedipine solid dispersion in microparticles of ammonio methacrylate copolymer and ethylcellulose binary blend for controlled drug delivery. Effect of drug loading on release kinetics.

In order to elucidate the controlled-release mechanism of a poorly water-soluble drug from microparticles of ammonio methacrylate copolymer and ethylcellulose binary blend prepared by a phase-separation method, nifedipine-loaded microparticles with different levels of drug loading were evaluated by micromeritic properties, drug physical state, matrix internal structure, drug dissolution, and release modeling. Drug release study indicated that nifedipine release from the microparticles followed the Fickian diffusion mechanism, which supported the study hypothesis that as a result of formation of a nifedipine molecular dispersion, nifedipine dissolution inside the matrix was no longer the rate-limiting step for drug release, and the drug diffusion in matrix became the slowest step instead. Moreover, study results indicated that even though drug loading did not significantly affect the microparticle size distribution and morphology, nifedipine release rate from those microparticles was more or less influenced by the level of drug loading, depending on matrix formulation.

The effects of substrate size, surface area, and density on coat thickness of multi-particulate dosage forms.

Drugs layering experiments were performed in a fluid bed fitted with a rotor granulator insert using diltiazem as a model drug. The drug was applied in various quantities to sugar spheres of different mesh sizes to give a series of drug-layered sugar spheres (cores) of different potency, size, and weight per particle. The drug presence lowered the bulk density of the cores in proportion to the quantity of added drug.

Particle size distributions of inert spheres and pelletized pharmaceutical products by image analysis.

Image analysis was used to measure particle size distributions (PSDs) of ensembles of 425 to 1400 microm-size materials. Repeatability of a measurement, suitable sample sizes, and methods of sampling were assessed. Two lots of inert spheres were compared prior to drug layering in a Glatt GPCG-5 rotor.

A multi-mechanistic drug release approach in a bead dosage form and in vivo predictions.

Our previous study has successfully prepared a combination of immediate release, enteric coated, and controlled release (CR) beads and mathematically modeled in vitro drug release characteristics of the combination based on the release profiles of individual beads. The objectives of the present study are to evaluate the combination and individual beads in vivo and to mathematically model in vivo drug input characteristics of the combination based on the in vivo input of individual beads. Beagle dogs were used as an animal model, and theophylline as a model drug.

A multi-mechanistic drug release approach in a bead dosage form and in vitro/in vivo correlations.

An in vitro/in vivo relationship of a combined multi-mechanistic dosage form has now been established in the literature. In our previous study, we successfully prepared a combination of immediate release, enteric coated, and controlled-release (CR) beads and mathematically modeled in vitro and in vivo drug release characteristics of the combination based on the release profiles of individual beads. The objective of the present study is to develop in vitro/in vivo correlations (IVIVC) for three individual beads and the combination using theophylline as a model drug and the beagle dog as an animal model.

A multimechanistic drug release approach in a bead dosage form and in vitro predictions.

The objective of this study was to prepare a combination of immediate release, enteric coated, and controlled release (CR) beads and to mathematically model in vitro drug release characteristics of the combination based on the release profiles of individual beads. Uncoated beads were manufactured by using extrusion/spheronization technology. Fluid-bed bottom spraying was used for coating: Eudragit-L-30D for enteric coating and Eudragit-NE-30D for CR coating.

Melt granulation and heat treatment for wax matrix-controlled drug release.

The purpose of this study was to evaluate sustained drug release after melt granulation and heat treatment. Theophylline (anhydrous) and phenylpropanolamine hydrochloride (PPA) were used as model drugs. Compritol 888 ATO (Glyceryl Behenate NF) was incorporated as the wax matrix material.

Release of cyclobenzaprine hydrochloride from osmotically rupturable tablets.

Osmotically rupturable systems were developed and the release of cyclobenzaprine hydrochloride (model drug) from the systems was investigated. Systems were designed using mannitol (osmotic agent) and increasing amounts of polyethylene oxide (PEO, a water-swellable polymer) surrounded by a semipermeable membrane. When placed in an aqueous environment, osmotic water imbibition into the systems distended and swelled the systems until the membrane ruptured and released the active compound to the outside environment.

Investigation of cyclobenzaprine hydrochloride release from oral osmotic delivery systems containing a water-swellable polymer.

Oral osmotic delivery systems containing polyethylene oxide (PEO, a water-swellable polymer) were designed and the release of cyclobenzaprine hydrochloride (model drug) from the devices was investigated. The systems consisted of model drug, mannitol (osmotic agent), and increasing amounts of PEO surrounded by a semipermeable membrane drilled with a delivery orifice. There was a decrease in drug release rate with PEO in the core.

An adjusted pharmacokinetic equation for predicting drug levels in vivo based on in vitro square root of time release kinetics.

An adjusted pharmacokinetic equation that predicts in vivo plasma drug profiles for controlled release (CR) dosage forms having square root of time drug release kinetics has been derived. The CR hydrogel tablets containing hydroxypropyl methylcellulose (HPMC) were formulated with theophylline and Fast Flo lactose, to produce tablets with HPMC K100MP content of 30% w/w. Plasma profiles in vivo were determined from four male beagle dogs.

The effect of controlled release tablet performance and hydrogel strength on in vitro/in vivo correlation.

The impact of controlled release (CR) formulations having different gel strength values (gamma) on in vivo tablet performance and the in vitro/in vivo correlation of the formulations was investigated. The CR tablets containing either hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), or carbomer were formulated with theophylline and Fast Flo lactose to produce tablets with a polymer content of 8 and 30% w/w. gamma was measured using a previously reported method.