Eudragit RS Microspheres Research Articles

Moxifloxacin loaded microspheres-composed gel for controlled release and enhanced penetration in ocular tissues: In vitro, ex vivo and in vivo proof of concept

Microspheres-enriched ocular gels are proposed in this work for the loading of a model quinolone antibiotic of broad-spectrum - moxifloxacin hydrochloride (MXF) - as an approach to achieve a controlled release profile and enhance drug's bioavailability in ocular milieu. MXF is a synthetic fluoroquinolone antibacterial agent used for treatment of ocular diseases caused by strains of aerobic gram positive and gram-negative bacteria, besides others. MXF-loaded Eudragit RS microspheres were prepared by emulsion solvent evaporation method, as previously described by us. Optimized microspheres were characterized and then formulated in an ocular gel. Hydrophilic polymeric base HPMC K100 was used as gelling agent. Ocular gel enriched with microspheres was evaluated for its physicochemical parameters, in vitro drug release, ex vivo corneal and scleral permeation and bioadhesion, in vivo primary eye irritation and in vivo efficacy study. The developed MXF microspheres dispersed in an ocular gel showed an in vitro drug release over a period 12 h, improved corneal and scleral penetration and increased therapeutic efficacy with a reduced administration frequency which may contribute to increase patient's compliance to ocular treatment.

Comparison of Microencapsulation by Emulsion-Solvent Extraction/Evaporation Technique Using Derivatives Cellulose and Acrylate-Methacrylate Copolymer as Carriers

Microencapsulation is a useful method to prolong a drug release from dosage forms and to reduce its adverse effect (1) among various available methods. The microencapsulation of hydrophilic active ingredients requires the use of a polar dispersing phase such as a mineral oil. Acetone/paraffin systems are conventionally used. The current study aimed to investigate two different microencapsulation techniques comparatively, water in oil in oil (w/o/o) and oil in oil (o/o), for theophylline (TH) loaded ethylcellulose (EC), cellulose acetate butyrate (CAB), Eudragit RS and RL microspheres with regard to loading efficiency, release and degradation kinetics. Microspheres were prepared by the emulsification method by solvent diffusion/evaporation technique and different polymers which were incorporated into microspheres to control the release rate of drug. Theophylline (TH) was chosen as a model drug. The emulsion technique was investigated for to prepare theophylline microparticles. EC and CAB and acrylatemethacrylate copolymer corresponding to the above ratios were selected as microparticles wall materials. The effects of type polymers on the physical characteristics and dissolution of the microparticles were also studied. However, the TH loading efficiency (for w/o/o emulsion about 90.64% and o/o emulsion about 73.90/5 to 95.90%) and the TH release kinetics were influenced by the microencapsulation technique. The results demonstrated that the o/o microspheres (containing of CAB) was most appropriate, providing a high encapsulation efficiency (95.90%) and low initial burst release (6.45%). The microspheres prepared with CAB polymer showed faster dissolution rate than other polymers with 0.75: 1 drug to polymer ratio. The double emulsion technique with EC as wall material gave the high dissolution efficiency (80.48%) of microcapsules. Eudragit RS microspheres showed higher yield (90%). The release of TH from CAB and Eudragit RL walled microcapsules was slow whilst the release from those of EC and Eudragit RS were faster. The type of polymer and the drug to polymer ratio were found to be the key factors affecting the release profile which could lead to microspheres with desired release behavior.

Influence of aluminum tristearate and sucrose stearate as the dispersing agents on physical properties and release characteristics of Eudragit RS microspheres.

The purpose of this research was to investigate the effects of different concentrations of polymer and sucrose stearate, aluminum tristearate as dispersing agents on microsphere properties and performance. The yield values of microspheres were over the 78%, and the encapsulation efficiencies were found to be ∼735. Particle sizes of microspheres prepared with aluminum tristearate were between 76 and 448 μm, while that of the microspheres containing sucrose stearate were between 521 and 2000 μm. Morphological and physicochemical properties of microspheres were investigated by scanning electron micrography and differential scanning calorimetry (DSC). DSC analysis indicated that verapamil hydrochloride formed a solid solution with acrylic polymers. In vitro release studies were performed using the flow-through cell method. While ∼80% of drug was released from the microspheres containing aluminum tristearate in 480 minutes, the same amount of drug was released from microspheres containing sucrose stearate in only 60 minutes. Chemical structures and concentrations of the dispersing agents were clearly effective on the physical properties of microspheres and their drug-release characteristics.

Effect of different dispersing agents on the characteristics of Eudragit microspheres prepared by a solvent evaporation method

Eudragit RS microspheres containing verapamil HCl for oral use were prepared using three different dispersing agents: aluminium tristearate, magnesium stearate and sucrose stearate, by a solvent evaporation method. The effects of the type and concentration of the dispersing agents and the inner phase polymer concentration on the size and T63.2% (the time at which 63.2% of the drug is released) of microspheres were determined by multiple linear regression analysis. The morphology of microspheres was characterized by scanning electron microscopy. The surface of microspheres prepared with sucrose stearate was smoother and non-porous and the drug release from these microspheres was the fastest. When aluminium tristearate or magnesium stearate were used as dispersing agents, the particle size of microspheres became smaller. Increasing amounts of these two dispersing agents led to the accumulation of their free particles onto the surfaces of the microspheres. The drug release from the microspheres was slower than that of the microspheres from sucrose stearate depending on their hydrophobic structures. According to the results of the multiple linear regression analysis among the dispersing agents used, aluminium tristearate showed the best correlation between the examined input (dispersing agent and polymer concentrations) and output (T63.2% and particle size) variables.

Preparation and in vitro evaluation of Eudragit microspheres containing acetazolamide

The aim of this study was to prepare and evaluate Eudragit (RS and RL) microspheres containing acetazolamide. Microspheres were prepared by solvent evaporation method using acetone/liquid paraffin system. The influence of formulation factors (stirring speed, polymer:drug ratio, type of polymer, ratio of the combination of polymers) on particle size, encapsulation efficiency and in vitro release characteristics of the microspheres were investigated. The yields of preparation and the encapsulation efficiencies were high for all formulations the microspheres were obtained. Mean particle size changed by changing the polymer:drug ratio or the stirring speed of the system. Although acetazolamide release rates from Eudragit RS microspheres were very slow and incomplete for all formulations, they were fast from Eudragit RL microspheres. When Eudragit RS was added to Eudragit RL microsphere formulations, release rates slowed down and achieved the release profile suitable for peroral administration.

The influence of chitosan on in vitro properties of Eudragit RS microspheres.

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using acetone/liquid paraffin solvent system and their properties were compared with Eudragit RS microspheres without chitosan, prepared in our previous study. Different stirring rates were applied (400-1200 rpm) and drug content, Higuchi dissolution rate constant, surface and structure characteristics of the microspheres were determined for each size fraction. An increase in average particle size with a reduction of stirring rate appeared in limited interval in both series. The average particle size of microspheres without chitosan, prepared at the same stirring rate, was smaller. Pipemidic acid content increased with increasing fraction particle size, but not with increasing stirring rate as it was observed for microspheres without chitosan. We presume that high pipemidic acid content in larger microspheres is a consequence of cumulation of undissolved pipemidic acid particles in larger droplets during microspheres preparation procedure. Pipemidic acid release was faster from microspheres with chitosan and no correlation between Higuchi dissolution rate constant and stirring rate or fraction particle size was found, though it existed in the system without chitosan. Structure and surface characteristics of microspheres observed by scanning electron microscope (SEM) were not changed significantly by incorporation of chitosan. But in contrast with microspheres without chitosan, the surface of chitosan microspheres was more porous after three hours of dissolution. It is supposed that the influence of particle size fraction and stirring rate on release characteristics is expressed to a great extent through porosity and indirectly through total effective surface area, but the incorporation of highly soluble component i.e. chitosan salt hides these effects on drug release. In conclusion, changes in biopharmaceutical properties due to varying stirring rate and fraction particle size exhibited the same direction as those reported for the microspheres without chitosan, although they are less expressed because of increased experimental variability, likely caused by chitosan.

Preparation of 3,4-diaminopyridine microparticles by solvent-evaporation methods.

The present study compares two methods of preparation of microparticles of 3,4-diaminopyridine (3,4-DAP) for the treatment for multiple sclerosis and Lambert-Eaton myasthenia syndrome. Poly( epsilon -caprolactone) microparticles were prepared with a solvent-evaporation W/O method. The 3,4-DAP was dispersed in dichloromethane, leading to a suspension. The dispersion and the solidification of the dichloromethane droplets in an aqueous phase have led to microparticles of 55.3+/-34.7 microm. The incorporation of the drug by milligram of powder was very low (1.91 micrograms/mg) and the scanning electron microscopy (SEM) did not show any crystal but marks of dissolved crystals were observed on the polymeric surface. EudragitRS microspheres containing 3,4-DAP were prepared by a solvent-evaporation technique using light mineral oil as continuous phase. The drug and the polymer were completely dissolved in an acetone solution, used as discontinuous phase. This formulation have led to a higher incorporation of the drug (88.25 micrograms/mg). The particle size was 91.8+/-44.3 microm. The observation, by SEM, shows many crystals on the surface and inside the microparticles. A slow-release of the drug in a phosphate buffer pH 7.4 was observed (50% in 60 min and about 70% in 4 h).

The influence of stirring rate on biopharmaceutical properties of Eudragit RS microspheres

Eudragit RS microspheres containing pipemidic acid, as a model drug, were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system. The aim of the work was to evaluate the influence of stirring rate on the average particle size, particle morphology, drug content and release kinetics, as well as the influence of particle size on microsphere morphology, drug content and release kinetics. Stirring rate has been found to significantly influence the average diameter of microspheres. The average diameter decreases as the stirring rate increases. This can be explained by production of a finer dispersion of droplets when higher stirring rates are applied and, consequently, by the formation of smaller microspheres. With increasing stirring rate and increasing fraction particle size the drug content also increases. It is assumed that this dependence is a consequence of an uneven diffusion of the drug from the inner to the outer emulsion phase, and an uneven encapsulation of drug particles during the preparation. Drug release follows the Higuchi model. As seen from SEM photographs, larger microspheres are more porous and the microspheres produced at higher stirring rates are more porous than those produced at lower stirring rates. This explains the unexpected finding that the release rate increases as the fraction particle size and the stirring rate increase.

Radiolabelling of polymer microspheres for scintigraphic investigations by neutron activation. 3. Changes in the physical properties of Eudragit RS-sulphapyridine microspheres from incorporating samarium oxide

Eudragit RS microspheres containing sulphapyridine and samarium oxide (Sm 2O 3) have been prepared using a solvent evaporation process. Microspheres containing 1.1% w/w Sm 2O 3 were smaller, had a higher density, and released encapsulated drug significantly more slowly than samples containing no Sm 2O 3. Electron microscopy revealed that in the presence of Sm 2O 3, the size and number of pores in the microsphere surface was markedly reduced, suggesting that it may be exerting an effect at the organic:aqueous interface during microsphere formation.

Encapsulation of 5-aminosalicylic acid into Eudragit RS microspheres and modulation of their release characteristics by use of surfactants

An emulsification-solvent evaporation technique has been used to produce microspheres containing 5-aminosalicylic acid from the acrylate-methacrylate copolymer, Eudragit TM RS. Two emulsifiers were used in the preparation procedure, either sodium dodecyl sulphate (SDS) or Tween 20, at a range of concentrations. Microspheres could be produced with both surfactants, although the yield using SDS was very low. The rate of drug release was found to be dependent on the concentration of emulsifier used to produce the microspheres. For example, microspheres produced using 0.25% w/v SDS released their encapsulated drug instantaneously on dissolution testing, whereas microspheres produced without surfactant provided prolonged release of drug ( t 50% > 360 min). Low temperature scanning electron microscopy revealed for these two systems that the differences in release resulted from different degrees of porosity in the microsphere drug-polymer matrix.

Fourier transform-Raman spectroscopy for the qualitative and quantitative characterization of sulfasalazine-containing polymeric microspheres.

FT-Raman spectroscopy (FTRS) has been used to characterize microspheres produced from the pharmaceutical polymer Eudragit RS containing a range of concentrations of the drug sulfasalazine. While pure sulfasalazine produced an intense and complex Raman spectrum, the spectrum of drug-free Eudragit RS microspheres was considerably weaker in intensity and contained only a few prominent Raman scattering peaks. In spectra of the drug-polymer microspheres, peaks arising from the individual components could be identified. This enabled a quantitative analysis to be undertaken by calculating the ratio between the area of a sulfasalazine peak and the area of a Eudragit RS peak for each microsphere spectrum. A correlation was shown between the peak area ratio and the microsphere sulfasalazine content. FTRS was then applied to a series of microsphere samples which had been dissoluted into pH 7 buffer for 1, 3, 6, 9, 12, or 24 hr. For each spectrum, the drug-polymer peak area ratio was determined and this in turn enabled calculation of the residual drug content of the microsphere sample. FTRS-calculated data showed good agreement with microsphere drug content values determined spectrophotometrically.