Mara Lovrecich

Investigation of surface properties of some polymers by a thermodynamic and mechanical approach: possibility of predicting mucoadhesion and biocompatibility

Mucoadhesive properties of several polymers, such as sodium alginate, hydroxypropylmethyl cellulose, scleroglucan, xanthan gum, polyacrylic acid (Carbopol), and poly co-(methyl vinyl ether-maleic anhydride) (Gantrez), have been investigated by comparing a thermodynamical and a mechanical approach. Surface properties of polymers in the dry state have been studied by contact angle measurements and thermodynamical parameters derived by using different equations. This tensile adhesive strength of polymers in hydration conditions was measured by a modified DuNoy tensiometer. Comparison of the two different approaches has allowed us to conclude that thermodynamical consideration on surface energy can be used to evaluate mucoadhesive properties of materials. Data obtained with the two methods yielded a good linear correlation. Calculation of surface free energy of the considered materials also allowed a prediction of the water-polymer interface free energy: biocompatibility, defined according to the minimal interfacial free energy concept, could consequently be evaluated.

Effect of ageing on the release of indomethacin from solid dispersions with Eudragits

Abstract The effect of ageing on the release of indomethacin from coprecipitates with Eudragit RS, Eudragit E and blends of these polymers was studied. DSC thermograms were carried out to control the glass transition temperature (Tg) of polymers and the physical state of indomethacin after 2 and 3 years of storage in closed containers at room temperature. The rotating disk method was used on compressed powders in order to test drug release under controlled conditions. Data treatments were carried out in order to verify modifications in the diffusion coefficient and mechanism of drug release. Results indicated that, for all the systems investigated, randomness was reduced within the polymeric network during storage, and this observation was confirmed by the appearance of a peak at the polymeric Tg. The drug diffusion coefficient from Eudragit RS was not influenced by storage, while, in the case of Eudragit E and a blend of polymers, a significant reduction of the diffusion coefficient was noticed after 3 years, probably due to an interaction between the drug and Eudragit E.

Dissolution Rate of Griseofulvin from Solid Dispersions with Poly(Vinylmethylether/Maleic Anhydride)

AbstractA solid dispersion technique with poly(vinylmethylether/ maleic anhydride) (PVM/MA) and its half esters has been used to enhance griseofulvin dissolution.A marked increase of the dissolution rate and solubility of griseofulvin contained in these solid dispersions was observed compared with that of drug alone and that of physical mixture with the carrier.Differences in dissolution rates resulted from the molecular weight and the chemical structure of the carrier.X-Ray powder diffractometry, differential scanning calorimetry (DSC) and wettability tests were employed to investigate the nature of the studied forms.

Morphology and surface properties of blends of Eudragit RS with different poly(ethylene glycol)s

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.

Chemometric Modelling of Dissolution Rates of Griseofulvin From Solid Dispersions With Polymers

AbstractThe quantitative relationship between the release rate of griseofulvin and the chemical and physical properties of a series of polymers, used for the preparations of solid dispersions, was investigated by the application of multiple regression analysis (MRA), partial least square analysis (PLS) and a new non linear chemometric procedure called CARSO (Computer Aided Response Surface Optimization).It was confirmed that the degree of crystallinity of griseofulvin and the wettability of the powder samples are important in the dissolution mechanism and in the prediction of dissolution profiles of griseofulvin from these solid dispersions.

Lipidic composite materials: interface modifying agent effect on bulk and surface properties

Abstract Blends of an amphiphilic polymer and a low molecular weight lipidic component with and without an interface modifying agent (IMA) were prepared. The bulk composition of the blends was analysed using differential scanning calorimetry (DSC); surface mapping was performed using a wettability test. In the binary system, a eutectic at T = 47.5°C was detected for each blend with the lipidic component; the surface analysis showed a surface excess of the more lipophilic component. No modification in the eutectic temperature was detected upon addition of an IMA (ternary system), whereas composition of the eutectic point was shifted towards higher percentages of the lipidic component. Moreover, the surface excess of the lipidic constituent was decreased. An evaluation of these finding indicated that: (i) at normal operative temperatures ( T = body temperature), two separated phases are present in the composite material. The composition of each phase is predetermined by the experimental one; (ii) the surface composition does not reflect the bulk composition, with a surface excess of the more lipophilic component; (iii) IMA acts as a compatibilizing agent, modifying both the eutectic point and the surface composition. It is thus shown how slight modifications of the bulk composition can cause large changes on the material surfaces.

Effect of loading parameters on theophylline release from polystyrene beads

Abstract Various parameters of preparation of theophylline loaded by solvent swelling on polystyrene beads were evaluated. The resulting samples were characterized by X-ray photoelectron spectroscopy, differential scanning calorimetry, X-ray diffractometry, electron scanning microscopy and wettability test. The release of drug was carried out in pH 7.5 buffer medium and a biphasic process was seen. An initial phase was adequately described by a cube-root of undissolved drug equation and a terminal phase by a square-root of time equation. Drug-polymer systems, washed with water to remove the surface drug before the release study, exhibit a diffusion mechanism controlled by the Higuchi equation.

Characterization of Drug Loading into Swellable Polymers by Surface Analysis

Swellable polymers can be used in the pharmaceutical dosage forms either to control the release process or to improve the solubility and the dissolution rate of slightly soluble drugs. In the former case slowly swellable polymers are used, such as crosslinked polyvinyl alcohol 1 ,ethylene/vinylacetate copolymers 2 , crosslinked hydroxyethyl-metacrylate 3 ; the swelling mechanism of these polymers largely influences the drug release process 4 . In the later case, polymers with a high swelling rate are used, such as crosslinked polyvinyl pyrrolidone5–7, crosslinked casein and crosslinked sodium carboxymethylcellulose 8 .