Novel aqueous chitosan-based dispersions as efficient drug delivery systems for topical use. Rheological, textural and release studies.

The use of a novel cross-linked thiolated chitosan (CTS) was investigated as the main component of aqueous dispersions (at 1% and 3% w/v) for topical drug delivery systems. The nonionic theophiline (Th) and the cationic diltiazem(.)HCl (Dt) (at 0.

Invivo absorption behaviour of theophylline from starch-methyl methacrylate matrix tablets in beagle dogs.

This study evaluates in vivo the drug absorption profiles from potato starch-methyl methacrylate matrices(*) using theophylline as a model drug. Healthy beagle dogs under fasting conditions were used for in vivo studies and plasma samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA method). Non-compartmental and compartmental (population approach) analysis was performed to determine the pharmacokinetic parameters.

Synthesis and characterization of a novel chitosan-N-acetyl-homocysteine thiolactone polymer using MES buffer.

We report a new "green" approach to synthesize a novel thiolated chitosan conjugate, chitosan-N-acetyl-homocysteine thiolactone (chitosan-AcHcys) using a "Good's buffers", 2-(N-morpholino)ethanesulfonic acid (MES). After that, the crosslinked Xr-chitosan-AcHcys was obtained only in the presence of air, without other reactants. The chitosan-AcHcys spectrum shows a partial incorporation of the thiolactone onto the polymer backbone.

In vitro release testing of matrices based on starch-methyl methacrylate copolymers: effect of tablet crushing force, dissolution medium pH and stirring rate.

Direct-compressed matrix tablets were obtained from a variety of potato starch-methyl methacrylate copolymers(1) as sustained-release agents, using anhydrous theophylline as a model drug. The aim of this work was to investigate the influence of the copolymer type, the tablet crushing force and dissolution variables such as the pH of the dissolution medium and the agitation intensity on the in vitro drug release behaviour of such matrices. Commercial sustained-release theophylline products (Theo-Dur(®) 100mg, Theolair(®) 175 mg) were used as standards.

Drug diffusion from disperse systems with a hydrophobically modified polysaccharide: Enhancer vs Franz cells.

This study assesses the capacity of a new hydrophobically modified polysaccharide -hydroxypropyl cellulose-methyl methacrylate - to control drug release in semisolid formulations. The dispersed systems contain the new polymer, Igepal CO520 as surfactant and theophylline as model drug at three concentrations (0.5, 1 and 1.

Compaction properties, drug release kinetics and fronts movement studies of matrices combining mixtures of swellable and inert polymers. III: effect of polymer substitution type.

Theophylline radial release from cellulose derivatives with different substitution type (HPMC K4M, HPC H, MC A4M) matrix tablets has been modulated by the introduction of a new inert polymeric excipient, at different proportions (75, 50, 25%). The new polymer was hydroxypropylcellulose-methyl methacrylate (HCMMA), which was dried either in a vacuum oven (OD-HCMMA) or freeze-dried (FD-HCMMA). MC A4M and its mixtures presented the best compaction properties results, especially mixed with FD-HCMMA, according to 100% mixtures.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: drug release and fronts movement kinetics.

A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility.

Tapioca starch graft copolymers and Dome Matrix® modules II. Effect of modules assemblage on riboflavin release kinetics.

This paper studies the Riboflavin release from systems made of assembled modules of Dome Matrix® technology using tapioca starch-ethylmethacrylate (TSEMA) and tapioca hydroxypropylstarch-ethylmethacrylate (THSEMA) graft copolymers produced by two different drying methods. Two different shape modules were manufactured for this study, i.e.

Tapioca starch graft copolymers and Dome Matrix modules assembling technology. I. Effect of module shape on drug release.

This paper studies the Riboflavin release from compressed disc modules of Dome Matrix(R) technology using tapioca starch-ethylmethacrylate (TSEMA) and tapioca hydroxypropylstarch-ethylmethacrylate (THSEMA), graft copolymers produced by two different drying methods. The comparison with the release behaviour of similar HPMC modules was performed. Two different shape modules have been made, identified as female and male modules, in order to obtain their assemblage by interlocking the disc bases.

Compaction properties, drug release kinetics and fronts movement studies from matrices combining mixtures of swellable and inert polymers. II. Effect of HPMC with different degrees of methoxy/hydroxypropyl substitution.

The aim of this paper is the modification of the release behaviour of hydrophilic HPMC-based matrices of different substitution degree (E4M, F4M, K4M) by the introduction of a new inert polymeric excipient hydroxypropylcellulose-methyl methacrylate (HCMMA) at different proportions (75:25, 50:50 and 25:75). The product (HCMMA) was dried either in a vacuum oven--OD copolymers--or freeze-dried-FD copolymers. HPMC E4M formulations showed the worst compaction properties.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: physicochemical and technological characterisation.

Nowadays, graft copolymers are being used as an interesting option when developing a direct compression excipient for controlled release matrix tablets. New graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS) were synthesised by free radical polymerization and alternatively dried in a vacuum oven (OD) or freeze-dried (FD). This paper evaluates the performance of these new macromolecules and discusses the effect of the carbohydrate nature and drying process on their physicochemical and technological properties.

Determination and pharmacokinetic profile of liposomal foscarnet in rabbit ocular tissues after intravitreal administration.

The treatment of ocular diseases affecting the posterior segment of the eye, such as cytomegalovirus (CMV) retinitis, requires the access of the drugs to the vitreous humor. Foscarnet inhibits replication of herpesviruses, including CMV. The drug's encapsulation in liposomes is meant not only to increase activity and to prolong the effect of the drug, but also to reduce its toxicity.

Drug release behaviour from methyl methacrylate-starch matrix tablets: effect of polymer moisture content.

The aim of this work was to study the effect of the initial moisture content of the polymer on the tabletting and drug release behaviour of controlled release inert matrices elaborated with methyl methacrylate (MMA)-starch copolymers. The copolymers, obtained by free radical polymerisation and dried by two different methods (oven-drying or freeze-drying), were equilibrated at different relative humidities (0%, 25%, 50% and 75% RH) at room temperature. From these copolymers, matrix systems were directly compressed containing either a slightly water-soluble drug (anhydrous theophylline) or a freely water-soluble drug (salbutamol sulphate), and their compaction properties and in vitro dissolution profiles were evaluated.

Compaction properties, drug release kinetics and fronts movement studies from matrices combining mixtures of swellable and inert polymers: effect of HPMC of different viscosity grades.

The aim of this paper is the modification of the release behaviour of hydrophilic HPMC-based matrices of different viscosity grade by the introduction of a new inert polymeric excipient hydroxypropylcellulose-methyl methacrylate (HCMMA). The drug released could be control by both mechanisms, the swelling rate from the hydrophilic matrices, and the porosity, tortuosity and water uptake capacity from inert matrices. The effects of drying methods, presence or absence of viscosity (HCMMA in relation with HPMC), proportion of two polymers and different viscosity grade of HPMC were studied.

Surface tension and rheology of aqueous dispersed systems containing a new hydrophobically modified polymer and surfactants.

This article reports data supporting that the hydroxypropyl cellulose-methyl methacrylate (HCMMA) hydrophobically modified polymer studied is surface-active at the air-water interface due to its amphiphilic nature. Surface tension measurements of diluted solutions point to the formation of a complex between this copolymer and a polyoxyethylene nonylphenyl ether non-ionic surfactant of high HLB. Conversely, no indications of specific interactions were found either with a polyoxyethylene nonylphenyl ether non-ionic surfactant of intermediate HLB or with an anionic surfactant such as sodium dodecyl sulfate (SDS).

Influence of moisture content on the mechanical properties of methyl methacrylate-starch copolymers.

The water vapour sorption-desorption behaviour of graft copolymers (hydroxypropylstarch-methyl methacrylate -HSMMA- and carboxymethylstarch-methyl methacrylate -CSMMA-) synthetised by free-radical polymerisation and alternatively dried by oven (OD) or freeze-drying (FD) techniques was investigated in a previous paper. The aim of the present study was to analyse the influence of the amount and distribution of water molecules on the flow and compaction characteristics of this family of methyl methacrylate-starch copolymers. Products were stored at constant temperature (25 degrees C) and different relative humidity conditions (RH).

Water sorption-desorption behaviour of methyl methacrylate-starch copolymers: effect of hydrophobic graft and drying method.

A new family of graft copolymers combining hydrophilic and hydrophobic components have recently been proposed as direct compression excipients. Copolymers were synthetised by free radical copolymerisation of starch derivatives with methyl methacrylate (MMA) and were alternatively dried by oven or freeze-drying techniques. The aim of this study was to investigate the water vapour sorption-desorption behaviour of these copolymers, focusing on the influence of variables such as the hydrophobic component and the drying process.

Drug release kinetics and fronts movement studies from methyl methacrylate (MMA) copolymer matrix tablets: effect of copolymer type and matrix porosity.

Several methyl methacrylate (MMA) copolymers have recently been proposed as an alternative for the formulation of controlled-release matrix tablets. Copolymers were synthesised by free radical copolymerisation of methyl methacrylate with starch or cellulose derivatives and were alternatively dried by oven or freeze-drying techniques. Both the chemical composition and the drying technique were demonstrated to have a considerable influence on the physical properties of the copolymers.

The influence of carbohydrate nature and drying methods on the compaction properties and pore structure of new methyl methacrylate copolymers.

Methyl methacrylate (MMA) copolymers have recently been proposed as an alternative in controlled-release matrix tablets. The aims of this study were to assess the potential value of these copolymers as direct compression excipients and to investigate relationships between the physical and structural properties of the polymers and the compression behaviour of the powders and the microstructural properties of the tablets. Copolymers were synthesised by free radical copolymerisation of MMA with starch or cellulose derivatives and were alternatively dried by oven or freeze-drying techniques.

Fronts movement as a useful tool for hydrophilic matrix release mechanism elucidation.

The purpose of this study was to modify the fronts movement method proposed by Colombo et al. in order to apply it to uncoloured drugs and hydrophilic non-swellable matrices. Matrix tablets were prepared using theophylline as a model drug and sodium carboxymethylcellulose (NaCMC) or a new graft copolymer, hydroxypropylcellulose methylmethacrylate dried by lyophilization (HCMMAL), as polymer carriers.

Determination of the glass transition temperatures of some new methyl methacrylate copolymers using modulated temperature differential scanning calorimetry (MTDSC).

Purpose: The purpose of this study was to determine the glass transition temperatures of new graft copolymers using Modulated Temperature Differential Scanning Calorimetry (MTDSC), and to assess the differences between starch and cellulosic derivatives of methyl methacrylate and between two different drying methods used in their preparation.

Methods: Graft copolymers of methyl methacrylate were synthesized and dried by oven or freeze-drying. Surface area measurements and different thermal analysis techniques (Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TGA) and MTDSC) were used to characterize these copolymers.

Effect of Explotab on the tabletability of a poorly soluble drug.

The efficiency of a superdisintegrant (Explotab) in a direct-compression formulation containing a poorly water soluble drug (albumin tanate) at high dosage was investigated. An experimental design with two variables, applied pressure and concentration of Explotab, enabled its effects on the tableting and the mechanical properties of the final tablets to be determined. Differential scanning calorimetry was performed to study the interactions between drug and excipients.

Effect of compression speed and pressure on the physical characteristics of maltodextrin tablets.

The present paper studies the effect of applied pressure (0-300 MPa) and compression speed (8 and 40 cycles/min) on the physical characteristics of four varieties of maltodextrins for direct compression. The materials were tableted by using a single-punch tablet machine. On the basis of the mechanical properties it seems to be reasonable to propose a limit in the plastic deformation and consequently bonding between particles.

Comparative study of flow parameters of excipients for direct compression excipients determined using a ring shear.

In a previous research it has been attempted to define the selective criteria for excipients used in direct compression by measuring their flow rate and their flow regularity. The control of flowability of Avicel PH 101 and Cellutab has now been realized using a ring shear cell. A comparison of results obtained shows a different behavior in both excipients.

[The effect of two lubricants (magnesium stearate and pruv) in the formation of tablets of four anti-ulcer agents/ by means of direct compression].

In this research we study the influence of two lubricants-Magnesium Stearate and Pruv--on the tablets elaboration of Cimetidine, Ranitidine, Famotidine and Pirenzepine by direct compression. The presence of 0.5% of lubricants improved the flow of all the formulations, but especially the Famotidine's formulation.