Double emulsions stabilized with hybrids of natural polymers for entrapment and slow release of active matters

Targeting the central nervous system: in vivo experiments with peptide-derivatized nanoparticles loaded with Loperamide and Rhodamine-123.

The invention relates to a liquid methacrylic acid copolymer composition that contains a release adjusting agent and a pharmacological agent. The composition forms a solid film upon drying, and is capable of accomplishing the sustained release of the pharmacological agent such as to permit its use in the treatment or prevention of dental or dermatological conditions.

Liquid polymer composition, and method of use

Recent advances in recombinant DNA technology have resulted in development of many new protein drugs. Due to the unique properties of protein drugs, they have to be delivered by parenteral injection. Although delivery of protein drugs by other routes, such as pulmonary and nasal routes, has shown some promises, to date most protein drugs are administered by parenteral routs. For long-term delivery of protein drugs by parenteral administration, they have been developed, and the currently used microencapsulation methods are reviewed here. The microencapsulation methods have been divided based on the method used. They are: solvent evaporation/extraction; phase separation (coacervation); spray drying; ionotropic gelation/polyelectrolyte complexation; interfacial polymerization; and supercritical fluid precipitation. Each method is described for its applications, advantages, and limitations.

Microencapsulation methods for delivery of protein drugs

In vitro and in vivo evaluation of an oral sustained-release floating dosage form of amoxycillin trihydrate

Polylactic acid (PLA) microspheres containing soluble dyes as water-soluble model compounds were prepared using the water-in-oil-in-water (w/o/w) emulsion solvent evaporation method. Addition of electrolytes such as NaCl or CaCl2 into the external aqueous phase significantly improved brilliant blue (BB) entrapment efficiency compared to the case of no additives. NaCl was the most effective for obtaining high entrapment efficiency (80–90% of theoretical BB content). The average diameter of the obtained microspheres was in the region of 10–20 μm in all cases. PLA microspheres containing 5 and 10% (w/w) BB exhibited the so-called burst release. The release rate decreased with decrease in the internal aqueous droplet volume in the preparation process. In particular, with PLA microspheres containing 5% (w/w) BB, those prepared with the smallest internal droplet volume (63 μl), the initial burst release was reduced significantly, and 50% (w/w) of the loaded BB remained in the microspheres for 7 days.

Preparation and characterization of polylactic acid microspheres containing water-soluble dyes using a novel w/o/w emulsion solvent evaporation method

The objective of this study was to produce biodegradable poly(lactide-co-glycolide) (PLGA; 50/50) microspheres by an oil-in-oil (o/o) solvent evaporation method to prolong the in vitro release of ovalbumin (OVA) as a model protein. The effects, on loading efficiency, microsphere yield, morphology and drug release, of two dispersing agents, aluminium tristearate and Span 80, in mineral oil were examined. PLGA 50/50 microspheres containing OVA powder (sieved through a 53 microns mesh) were prepared using an o/o solvent evaporation method. When aluminum tristearate was employed as a dispersing agent, the loading efficiency and yield of OVA had maximum values of 89 and 72% at 0.15% (w/v) aluminum tristearate, respectively. Morphology studies suggested that the obtained microspheres were spherical, and had a smooth surface. The diameters of the microspheres ranged between 100 and 200 microns. The loading efficiency, or yield, for microspheres decreased significantly above or below 0.15% (w/v) aluminum tristearate, and microspheres with irregular shapes were observed. The minimum sedimentation volume ratio (F) was obtained at a dispersity of carbon black particles in ethanol containing 0.15% (w/v) aluminum tristearate by a sedimentation study, and the cloudy supernatant suggested a deflocculated suspension. However, on the contrary, when Span 80 was added into the mineral oil as a dispersing agent, the concentration of Span 80 had little or no effect on the characteristics of the prepared microspheres. Drug loadings (60-70%) were obtained within the Span 80 concentrations employed in the present study (0.05-1.0% (w/v)). The yields were also in the same levels. The microspheres prepared in mineral oil containing Span 80 had an average diameter less than 50 microns in all cases. Sustained-release characteristics were demonstrated for PLGA microspheres prepared in mineral oil containing aluminum tristearate as a dispersing agent, even though a burst release at the initial phase was observed. This initial burst release from PLGA microspheres was reduced to some extent by micronization of the OVA powder using a planetary-type ball mill. However, PLGA microspheres prepared in mineral oil containing Span 80 as a dispersing agent, exhibited a large initial burst release. This burst release seems to be due to the smaller size of microspheres and the OVA powder adhering to the surface of PLGA microspheres (confirmed by scanning electron microscope (SEM) study).

Microencapsulation of ovalbumin in poly(lactide-co-glycolide) by an oil-in-oil (o/o) solvent evaporation method

Two methods of microencapsulation of amoxicillin, an orally administered antibiotic, were studied. One is based on dispersion of gelatin-amoxicillin mixture in liquid paraffin followed by drying and hardening with formalin-isopropanol treatment; the other is based on dispersion of ethylcellulose—amoxicillin mixture in purified water containing sodium lauryl benzene sulphonate. The microcapsules were recovered as discrete, free-flowing fine granules with a particle diameter of about 250–1000 μm. Dissolution of amoxicillin from ethylcellulose microcapsules was suppressed considerably with a zero-order dissolution pattern in solutions of various pH. Gastric-emptying-controlled rabbits were used for the in vivo evaluation of gelatin and ethylcellulose microcapsules. The ethylcellulose microcapsule containing 25 per cent amoxicillin showed a significantly sustained release pattern of amoxicillin. To establish a suitable design and for the evaluation of the sustained release microcapsules, a nomogram wa...

Preparation and biopharmaceutical evaluation of microcapsules of amoxicillin.

Eudragit RS, RS-RL, RL and S microcapsules containing ketoprofen were prepared by the solvent evaporation process in oil phase. The sustained release effect of these microcapsules and Oruvailr`, the representative commercial product of ketoprofen, was evaluated by the pH shift dissolution method and in beagle dogs, respectively. The dissolution patterns of ketoprofen from Eudragit RS, RS-RL and RL microcapsules were independent of the pH of the dissolution medium, and its dissolution rate increased with increasing content of ketoprofen in microcapsules. But the dissolution pattern of ketoprofen from Eudragit S microcapsules and Oruvailr` was found to depend on the pH of the dissolution medium. The rank order of the dissolution rate of ketoprofen from Eudragit RS, RS-RL and RL microcapsules containing 30 and 40 per cent (w/w) ketoprofen was sufficiently clear as to enable prediction of the relative bioavailability of ketoprofen from these microcapsules. In vivo evaluation using beagle dogs, sustain...

Shigeru Goto

Papers

Preparation and characterization of polylactic acid microspheres containing water-soluble dyes using a novel w/o/w emulsion solvent evaporation method

Microencapsulation of ovalbumin in poly(lactide-co-glycolide) by an oil-in-oil (o/o) solvent evaporation method

Preparation and biopharmaceutical evaluation of microcapsules of amoxicillin.

Evaluation of the sustained release properties of Eudragit RS, RL and S (acrylic resins) microcapsules containing ketoprofen in beagle dogs˚