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Biomedical subjects

U Conte

Publications and source records attributed to U Conte.

At least 37 records · Page 2Linked to original sources
PubMed1999

Formulation of biphasic release tablets containing slightly soluble drugs.

A new biphasic release system for slightly soluble drugs has been proposed. To enhance the dissolution rate, the drug was milled with a superdisintegrant. Then, double-layer tablets were prepared. One layer was formulated to release the drug in a very short time (fast-release). The other consisted of an extended-release hydroxypropylmethylcellulose (HPMC) matrix. Different HPMC concentrations (10, 16 and 22%) and viscosity grades (Methocel K4, K15 and K100M) were used to obtain different release rates of the drug from the extended-release layer, ketoprofen and praziquantel were used as slightly soluble model drugs. The in vitro dissolution tests of the prepared double-layer systems, showed the desired biphasic behaviour: the drug contained in the fast releasing layer dissolved within the first 15 min, while the drug contained in the prolonged-release layer was released at different times, depending on the formulation of the hydrophilic matrix. In particular, an increase in the percentage and viscosity grade of HPMC, in the extended release layer, leads to a decrease in the drug delivery rate and produces a wide range of different release rates from only a few hours up to 24 h.

Chemistry, Pharmaceutical↗
PubMed1998

In vitro degradation study of polyester microspheres by a new HPLC method for monomer release determination.

Biodegradable polyesters have increasing importance as materials used for the preparation of microspheres. The knowledge of their degradation process is important to prepare microparticulate delivery systems with suitable drug release rates. In this work an in vitro degradation study of empty and drug loaded microspheres is described. Three different polyesters were used: two poly-d, l-lactides of different molecular weight and a poly-d, l-lactide-co-glycolide (50:50). Diazepam has been chosen as the model drug. Solvent evaporation and spray-drying were used as preparation methods. To study the polymer degradation process, a new HPLC method is proposed for the direct and (in the case of the copolymer) simultaneous determination of the monomer(s): lactic acid (LA) and glycolic acid (GA). SEM and particle size analysis highlight the different characteristics of the particles, depending on their preparation method: spray-dried spheres result to be always smaller with respect to particles obtained by solvent evaporation. The results obtained indicate in particular that: the preparation methods play an important role in determining the degradation behaviour of microspheres, as unloaded spray-dried particles are characterized by a higher monomer release rate with respect to microspheres obtained by solvent evaporation; PLGA spheres degrade faster than PDLLA microparticles, according to the higher hydrophilicity of the copolymer; the two monomers are released at a different rate in the case of PLGA (faster for GA, slower for LA); the presence of diazepam increases the polymer degradation rate, with respect to empty particles.

Biocompatible Materials↗
PubMed1998

Formulation and characterization of calcium alginate beads containing ampicillin.

The purpose of this work was the preparation and characterization of calcium alginate beads containing ampicillin. Aqueous solutions of drug and sodium alginate (three viscosity grades) were added drop by drop to aqueous solutions of calcium chloride; the droplets instantaneously formed gel beads, which were then dried. Morphological studies and drug contents, in vitro release, and erosion tests were carried out for the characterization of the prepared beads. The dried particles were characterized by irregular shape and a smooth or rough surface, depending on the viscosity grade of the alginate used. The control of the drug for different time intervals depended on the molecular weight of the polymer used; however, the pH-change test showed that this capacity was much lower in the case of acid-treated particles. The results obtained show that the ampicillin beads prepared are suitable for intramammary therapy.

Alginates↗
PubMed1996

Modulation of the dissolution profiles from Geomatrix multi-layer matrix tablets containing drugs of different solubility.

A new multi-layer tablet design has recently been proposed for constant drug release: Geomatrix Technology (Jago Pharma, Muttenz, Switzerland). It consists in the application of a drug-free barrier layer on one or both bases of an active core (hydrophilic matrix). The partial coating modulates the core hydration process and reduces the surface area available for drug release. The result is an extended release that draws close to a linear profile. The device was mainly intended for soluble drugs, while an excessive reduction of the release rate may be obtained with drugs of low solubility. In this study a new time-dependent polymeric barrier is proposed to control the release of sparingly soluble drugs. Two different barrier compositions (one swellable and one erodible) are applied on active cores containing drugs of different water solubility, Trapidil, Ketoprofen and Nicardipine hydrochlorides, and the drug dissolution patterns of the different multi-layer devices are compared. During dissolution, the swellable barrier swells and gels, but is not eroded, thus acting as a modulating membrane during the release process. The erodible barrier, instead, is progressively removed by the dissolution medium, exposing in time an increasing extent of the planar surface(s) of the core to interaction with the outer environment and to drug release. Both types of coatings are able to control drug release from the devices: the swellable barrier shows a stronger modulation efficiency and is more suitable to modify the delivery pattern of highly soluble drugs; the erodible barrier shows a time-dependent coating effect that provides better control of the dissolution profile of sparingly soluble drugs.

Biocompatible Materials↗
PubMed1996

Ocular mini-tablets for controlled release of timolol: evaluation in rabbits.

Topical delivery of timolol by inserts or similar controlled-release devices may offer distinct advantages over administration by eyedrops. The purpose of this investigation was the evaluation in rabbits of ophthalmic inserts (denominated mini-tablets, MT) for sustained/controlled release of timolol maleate (TiM). The MTs (diameter 3.5 mm, thickness 1.5 mm, average TiM content 0.34 or 0.68 mg) were prepared by compressing appropriate mixtures of powders with a standard tabletting machine. A thin, rate-controlling membrane was applied over the devices by spraying aqueous dispersions of acrylic copolymers. A first series of different (uncoated and coated) MTs were tested for release of TiM to the lacrimal fluid, using commercial eyedrops (Timoptol 0.5%) as a reference standard. Two MTs (one of which was coated) and the same reference solution were then selected for an ocular absorption study. Analysis of TiM in the aqueous humor indicated that the coated MT was capable of maintaining low and steady levels of TiM for at least 19 h, while the other device, identical but uncoated, produced a prolonged-pulse effect lasting about 8 h. The apparent mean residence time (MRT) of TiM in the aqueous humor was 1.3 h for the reference solution, 3.2 h for the uncoated MT, and 5.7 h for the coated one. The present preliminary results point to the potential validity of coated mini-tablets as simple systems for controlled ocular delivery of timolol.

Absorption↗
PubMed1995

Influence of mucin type on polymer-mucin rheological interactions.

There are numerous in vitro methods with which to investigate the mucoadhesive properties of polymers. One recent method is based on the measurement of rheological interactions between polymer and mucin, which implies the use of mucins isolated from the mucous tissue. The extraction and purification of glycoprotein fraction, which is responsible for rheological interaction, can modify the native structure of mucin or spoil it with exogenous substances. Therefore the particulars of the mucin employed (origin, purification grade, the effect of further treatments such as freezing or freeze-drying) are likely to be critical for the interaction. The aim of this work was to compare some commercial mucins of differing origin and grade of purification for their rheological interaction with well-known mucoadhesive polymers (polyacrylic acid and sodium carboxymethylcellulose). For polyacrylic acid, which is sensitive to ions, we found rheological interaction to be strongly influenced by mucin type. The removal of ions, with dialysis, improved the interaction. For sodium carboxymethylcellulose, which is less sensitive to ions, rheological interaction proved to be less dependent on mucin type and improved upon glycoprotein solubilization.

Acrylic Resins↗
PubMed1994

Modification of the dissolution behaviour of a water-insoluble drug, naftazone, for zero-order release matrix preparation.

The preparation of hydrophilic matrix tablets able to release naftazone, a water-insoluble drug, into an aqueous medium at a constant rate (zero-order dissolution) is described. Enhancement of dissolution rate of the drug was achieved using cross-linked carmellose sodium, beta-cyclodextrin or hydroxypropyl-beta-cyclodextrin. Hypromellose was used as a water-gelling polymer. Tablets could be prepared that released naftazone at a constant rate over 16 h.

Calorimetry, Differential Scanning↗
PubMed1993

Press-coated tablets for time-programmed release of drugs.

A new dry-coated device for the release of drug after a programmable period of time is proposed. It is intended to be used mainly in the therapy of those diseases which depend on circadian rhythms. Some core formulations, characterized by different release rates and mechanisms (containing diltiazem hydrochloride or sodium diclofenac as model drugs), were coated by compression with different polymeric barrier layers (press-coated systems). The shell formulations tested contained either gellable or erodible polymers. The dissolution profiles of uncoated cores and press-coated devices were compared. The gellable and/or erodible characteristics (properties) of the barrier formulations were also examined by means of a penetrometer. The coatings prevent drug release from the core until the polymeric shell is completely eroded or swollen. This delay in release start is not influenced by the core composition and depends only on the shell formulation. Except for the time-lag, the release kinetics of the drug contained in the core are not significantly influenced by the presence of the erodible barrier, but can be widely modulated using a swellable polymeric shell.

Circadian Rhythm↗
PubMed1993

Intraocular pressure reduction and systemic absorption of timolol after administration of one side-coated inserts in rabbits.

The object of this study was to test whether flat, circular ophthalmic inserts releasing drug only from one side, would show improved activity parameters and reduced systemic absorption. To this purpose, uncoated and one-side coated hydroxypropylcellulose inserts containing timolol were prepared and evaluated. An acrylic copolymer (Eudragit RS) was used as coating material. Timolol release from inserts was studied both in vitro and in vivo. Timolol release in vitro from the coated inserts was much slower than from the uncoated ones, due to the smaller releasing surface area. Compared with timolol eyedrops (0.5%, 50 microliters), administration of 250 micrograms of timolol in uncoated or coated inserts produced a significantly greater hypotensive effect at 6 and 8 hr post instillation in rabbits with artificially increased intraocular pressure. The coated inserts containing 62.5 micrograms of timolol antagonised isoproterenol-induced ocular hypotension significantly more than timolol eyedrops (0.5%, 12.5 microliters) and uncoated inserts containing 62.5 micrograms of timolol. Both uncoated and coated inserts provided a significant sustaining of timolol release in tear fluid and decreased systemic peak concentrations of timolol with respect to the eyedrop control. However, one-side coated inserts failed to show significant improvements with respect to the uncoated samples.

Absorption↗
PubMed1992

New oral system for timing-release of drugs.

Polymeric barriers applied by compression have already been used to control drug release rate from matrix tablets. In this paper, polymeric barrier layers, used to prepare and develop a new device able to release the drug after a programmable period of time, are described. Some matrix core formulations, containing Trapidil or Sodium Diclofenac as a model drug, were dry-coated using either a swellable or an erodible shell. This coating prevents drug release from the core until the polymeric layer is not completely eroded or swollen. The time-lag can be modified by changing the barrier formulation and/or the coating thickness. Also drug release profiles (release rate and kinetics), can be widely modified changing the barrier layer characteristics.

Delayed-Action Preparations↗
PubMed1990

A swellable polymer as carbamazepine dissolution rate enhancer.

A superdisintegrant (cross-linked sodium carboxymethylcellulose, Ac-Di-Sol was used for the enhancement of the dissolution rate of carbamazepine, an anti-epileptic drug characterized by very low water solubility. Three different drug/polymer systems were prepared: a physical mixture and two loaded systems obtained using a solvent evaporation method and a spraying method. In vitro dissolution tests showed that the dissolution rate in water of carbamazepine from all the systems prepared (compared with that of the pure drug) always increases, particularly in the case of the physical mixture and of the loaded system obtained with the spraying method, while DSC analysis shows that no drug amorphisation has occurred.

Carbamazepine↗
PubMed1989

Swelling-restricted minimatrices for controlled release of drugs. Preliminary in-vivo studies.

A preliminary in-vivo study was performed on a new modified release system which contained diltiazem hydrochloride. The system consisted of swellable minimatrices that were coated with an acrylic polymeric film. The film thickness, because of its pH-dependent solubility, might represent a critical variable with regard to in-vivo release. In order to evaluate the influence of such a variable on in-vivo behaviour, two minimatrices formulations with differing film thickness were tested versus a commercial tablet. The in-vivo study, which was based on a balanced incomplete block design, involved six volunteers in two sequences. The drug was quantified in plasma by an HPLC method. Computation and statistical analysis of pharmacokinetic parameters were performed by means of SIPHARR package (Simed, F). The results show that the approach of film coating, in order to modify the release rate from minimatrices, is feasible, but it must be improved; in particular the results point to the necessity of reducing the film susceptibility to pH changes.

Adult↗
PubMed1988

Swelling-activated drug delivery systems.

A previous paper dealt with the preparation of an in vitro programmable zero-order drug delivery system in which the area of the surface exposed to the dissolution medium and the macromolecular relaxation of polymer controlled the release of the drug. In the present study, the preparation of similar delivery systems is described, in which differing drugs and polymers were used to ascertain the mechanism governing the drug-release kinetics. The movement of the interfaces between solvent and system was measured during drug release in systems with varying composition. The results indicate that the synchronization of the movement of swelling and eroding fronts at the solvent-system interface determines the achievement of the linear-release kinetics of such swelling activated systems and that the swelling and dissolution characteristics of the polymer employed for core preparation govern front movement.

Chemical Phenomena↗
PubMed1987

Bioavailability of indomethacin from a modified release system containing indomethacin as the lysine salt.

The bioavailability of a new controlled release formulation of indomethacin lysine salt in tablets was tested in 6 healthy humans against a conventional indomethacin lysinate formulation in capsules. Both contained 100 mg of the drug, i.e. 70 mg indomethacin. Peak plasma levels were lower and more lasting and the AUC was higher with the new controlled release formulation. The latter on average produced active plasma levels for 12 h, and so it can be recommended for twice daily administration.

Biological Availability↗