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Drug release modulation by physical restrictions of matrix swelling

Abstract Swellable matrix systems with anomalous release kinetics are suitable solutions for drug release control for oral administration. Generally, the release rate modulation is achieved through the use of different types of polymer or the employment of soluble or insoluble fillers. The resulting release mechanism depends on the relative importance of tablet relaxation and drug diffusion rates. By adjusting these two rates, it is possible simultaneously to control the release mechanism and the release rate. In this work, we present the results obtained by changing the relaxation rate of the matrix by means of the application of impermeable coatings that partially cover the matrix. The applied impermeable coating modifies the relaxation rate of the matrix by affecting the dimension of the swelling of the plain matrix while leaving the diffusion characteristics of the drug practically intact. The overall result is that the original kinetics of the uncoated matrix is shifted towards constant release, dependent on the extension and position of the impermeable coating.

Characterization and selection of vaginal Lactobacillus strains for the preparation of vaginal tablets

Aims: To characterize and select Lactobacillus strains for properties that would make them a good alternative to the use of antibiotics to treat human vaginal infections.

Multi-layered hydrophilic matrices as constant release devices (GeomatrixTM systems)

Abstract In recent years many attempts have been made to modify drug release profiles from hydrophilic matrix tablets. Recently a new method based on the application of an inert impermeable coating on different sides of a matrix tablet was proposed. The coating delays the interaction of the matrix with the dissolution medium. In this way the hydration rate of the active core is slowed and its release surface is reduced. As a result the release extent is increased, while the dissolution profile tends to shift toward constant drug release compared with the uncoated matrix. In this article the design and technological development (up to the industrial production) of these types of devices is described: the film coatings are replaced by a polymeric barrier applied on the tablet bases during tableting. The effectiveness, the reproducibility and the technological characteristics of the new multi-layer systems are described.

Preparation and characterization of ampicillin loaded methylpyrrolidinone chitosan and chitosan microspheres

Ampicillin was embedded in microparticles made of a new derivative of chitosan: methylpyrrolidinone chitosan. They were prepared using different drug-to-polymer weight ratios and by a spray-drying technique. Spray-dried drug-loaded chitosan microspheres were prepared for comparison. The microparticles were characterized by scanning electron microscopy (SEM), particle size analysis, differential scanning calorimetry (DSC) and in vitro drug release. Microbiological assay was performed using different bacterial strains. Spray-dried microspheres of almost spherical shape, smooth surface and narrow size distribution were always obtained. Ampicillin loaded into both polymer matrices showed amorphous behaviour as determined by DSC. Drug-loaded microspheres resulted to control the drug release in a 30-120 min range, depending on chitosan type. Thermal denaturation of the microspheres does not modify drug release rate. The results of the microbiological assay show that the loading of ampicillin into chitosans is able to maintain or improve the anti-bacterial activity of the drug.

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.

High molecular weight polyethylene oxides (PEOs) as an alternative to HPMC in controlled release dosage forms

High molecular weight polyethylene oxides (PEOs) have recently been proposed as an alternative to hydroxypropylmethylcellulose (HPMC) in controlled release matrix tablets. In this study, we compared the performance of PEO and HPMC polymers when employed in the Geomatrix technology, a versatile, well-known method to achieve extended release of drugs at a constant rate. Four core formulations were prepared, containing a soluble drug (diltiazem) and, alternatively, PEO or HPMC of two different viscosity grades. These formulations have the same composition except for the polymer employed. Similarly, four barrier formulations were also prepared, which only differ in the kind of polymer employed. Three-layer Geomatrix systems were then prepared using these core and barrier formulations. The release profiles of the different three-layer systems obtained were compared, to verify if PEO could efficiently replace HPMC in this type of dosage form. The results show that slower release rates can be obtained from the plain matrices containing HPMC compared to PEO, moreover HPMC, used in the barrier formulations, is generally more efficient in controlling drug release rate in three-layer Geomatrix systems.

Dissolution behaviour of hydrophilic matrix tablets containing two different polyethylene oxides (PEOs) for the controlled release of a water-soluble drug. Dimensionality study

Hydrophilic matrix tablets containing polyethylene oxides as the retarding polymer have been successfully employed in the controlled release of drugs. To evaluate the relative influence of drug diffusion and polymer erosion mechanisms in the drug delivery process, we studied the hydration behaviour of matrix tablets containing a water-soluble drug and PEOs of two different molecular weights: Polyox WSRN 1105 (Mw = 0.9 x 10(6)) and Polyox WSRN 301 (Mw = 4 x 10(6)). The hydration rate, the extent of swelling, and the erosion rate of matrices containing the polymer, the drug and tableting excipients were evaluated in comparison to tablets made of pure polymer. The results of these studies on function of the release behaviour were then discussed. The results show that the higher molecular weight PEO swells to a greater extent and tends to form, upon hydration, a stronger gel, which is therefore less liable to erosion, if compared to the lower molecular weight PEO. This difference in the erosion behaviour can explain the different efficiencies of the two polymeric products in modulating the delivery rate of the water-soluble drug. Moreover, the presence of other soluble components (drug and excipients) in the dosage form enhances the erosion trend of the tablets with a consequent reduction of the efficiency of the polymer in drug release control.

Swelling characteristics of hydrophilic matrices for controlled release New dimensionless number to describe the swelling and release behavior

Abstract Drug release mechanisms of swellable systems for controlled drug administration were investigated. The variations of the matrix relaxation and drug diffusion rates were quantified, by measuring the surface area exposed during matrix swelling and drug release as a function of impermeable coating coverage and location. Four different types of matrices, partially coated on various sides, were investigated in order to elucidate the role of the swelling behavior on the release from such delivery systems, especially in view of the three-dimensional nature of the swelling phenomenon. Dependence of the release kinetics on the matrix surface area was assesed. A new dimensionless number, the swelling area number, Sa, was defined for evaluating the significance of the relative rate of matrix swelling variation and drug diffusivity. The systems studied were produced by partial coverage of the release area of tablets by an impermeable coating.

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.

Technological and biological evaluation of tablets containing different strains of lactobacilli for vaginal administration

Ten strains of lactobacilli were evaluated for the administration of viable microorganisms to restore the normal indigenous flora in the treatment of urogenital tract infections (UTI) in women. As the strains considered are facultative anaerobes, optimization of the production process was particularly critical to preserve bacterial viability. The microorganisms were formulated in single- and double-layer vaginal tablets. The two layers were characterized by different release properties: one is an effervescent composition that ensures a rapid and complete distribution of the active ingredient over the whole vaginal surface; while the second is a sustained release composition capable of releasing the lactobacilli over a longer period of time. Three different retarding polymers were tested, and all the formulations and tablets were evaluated in terms of technological processability, bacterial viability and stability, and cell adhesion properties of the microorganisms. From the results obtained, three out of ten strains appear particularly suitable for their application in the treatment of UTI. A larger batch of tablets made with a mixture of the three strains was then evaluated, confirming the feasibility of their industrial production and a good bacterial viability in the final dosage form.