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Microencapsulation for low cost, high volume, pharmaceutical applications


This method is based on the preparation of a dispersion of the active material in an organic phase. The method comprises the following steps: - Preparing a dispersion of the active material in an organic phase (dichloromethane, chloroform) containing a polymer, - Adding a second polymer (silicone oil) or a solvent (cyclohexane), to make the polymer desolvate and precipitate onto the particles of the active material, - Pouring the formulation into an excess of organic solvent, such as heptane, cyclohexane, isopropyl myristate, to extract methylene chloride or chloroform and harden the microcapsules, - Filtering and drying the microcapsules. It was discovered that the simple non-aqueous coacervation method is not suitable as caffeine is soluble in the dichloromethane solvent.
In this process, the model drug is extracted by supercritical carbon dioxide and expanded at medium pressure (60 bar) through a nozzle. At the same time, a polymer dissolved in an organic solvent is injected in the precipitation vessel through the same nozzle. At this medium pressure, expansion of the caffeine supercritical solution, due to pressure reduction, induces drug precipitation (RESS) and volumetric expansion of the polymer solution, due to carbon dioxide dissolution in the organic solvent, leads to polymer precipitation (SAS). By carefully choosing precipitation temperature and pressure, production of encapsulated caffeine particles seems to be possible. The sample obtained from run 1 was observed by scanning electron microscope (JEOL- JSM-T330A). The SEM observation showed that needles of caffeine are agglomerated with the polymer and form spherical structures.
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The molecular encapsulation of caffeine (CAF) by hydroxypropyl-â-cyclodextrin (HPBCD) has been studied through fluorescence emission enhancement measurements in aqueous solutions at 25?C. The aim of this Case Study was to determine the association constant between the HPBCD and caffeine, KCD:CAF, which has been evaluated using a non-linear regression analysis of the experimental fluorimetric data. With Cyclodextrin, the association constant for caffeine was 290 M-1. Values of association constants in the range 200-10.000 M-1 are regarded as being appropriate for controlled drug release.
Case studies were undertaken by a number of partners to look at the comparisons of the various methods of microencapsulation. It was agreed that the best choice of active substance to encapsulate would be Caffeine. This has application in both the food and pharmaceutical industries and there had been limited amount of microencapsulation work done on this substance. The work done was organised into a typical manual sheet and included the following: an introduction indicating the name of the technique used, the material and methods for evaluation of the product, the results and discussion, the conclusion and the references.
The encapsulating material used was melted hydrogenated palm oil (GV 60) mixed with caffeine powder at 65°C. The Caffeine contents were 10% (W/W). This is a useful method, but there is always some part of the Caffeine, which is not completely encapsulated. This results in a more or less important burst effect at the dissolution tests. The lower and the finer the active content, the larger the microbeads, the smaller the burst effect and the slower the release. The encapsulation may result in a complete taste masking. This may be useful to some applications in pharmaceutical and veterinary fields.
This method involves forming an oil-in-water emulsion of a solution of the polymer in a relatively volatile organic solvent (e.g. dichloromethane), which also contains the material to be microencapsulated, either in solution or as a fine particle suspension. The organic solvent is allowed to partition into the aqueous phase and then evaporated, leaving solid microspheres. With poly (lactic acid) [PLA] in dichloromethane/water simple emulsion, caffeine loading was negligible (0.04%). This method is not suitable due to solubility of caffeine in water. The double emulsion (water-in-oil-in-water) method may be more suitable.
Parma carried out experimental work into the formation of Caffeine microparticles obtained by Spray Drying. This technique is a one step process of liquid feed (solution, suspension or emulsion) into a dried particulate form. This is an effective and efficient microencapsulation method, and the results obtained in the present work show the feasibility of preparing nasal powders of Caffeine by Spray Drying. The excipients used strongly influenced the morphological properties of particles, while particle size was in the range 5-25 micrometre.
This method is based on the preparation of a double emulsion water-in-oil-in-water (w/o/w). The inner aqueous phase is the solution of the active material. This process comprises the following steps: - Preparing a concentrated aqueous solution of active material, - Preparing an inverse w/o emulsion of the above solution in an oily phase, using a low HLB emulsifier, such as a sorbitane alkyl ester or an alkylglyceryl succinate, - Emulsifying this primary emulsion in water containing gelatine and polyphosphate at ~ 45°C, - Lowering the pH of the outer aqueous phase to induce the phase separation of polymers and the formation of coacervates. Then, these insoluble polymer coacervates adsorb onto the surface of the oil droplets to form the microcapsule wall, - Cooling the medium at 10°C, - Cross-linking the microcapsule wall with a difunctional reactive compound (dialdehyde, dicetone) or tannins. - Collecting the microcapsules by sieve filtration and washing them with water to eliminate the excess of polymers and the unreacted cross-linker. Caffeine loading of 3% was achieved, with particle size in the range 100-500 m. These microparticles are mainly used to encapsulate aqueous solutions. The microcapsules crosslinked by glutaraldehyde cannot be used in food applications.
This process consists of a liquid feed which can be a fusion, a dispersion, an emulsion, a suspension, a sol or a solution. A common feed solution consists of an alginate solution (although Hydrogenated Palm Oil and Gelatine were also tested) with a dispersed or solved ingredient. The liquid is forced through several nozzles of diameters between 30 and 3000 µm. By vibrating, the flow breaks up into equally sized droplets, which are forced by surface tension to spherical form. The liquid is then solidified by solutions of a multifold loaded metallic-ion. The embedding in waxes shows problems, because stable suspensions could not be produced. Aqueous solutions with the binder alginate lead to solidification (acidic reaction of Caffeine). The embedding tests of Caffeine in gelatine were very successful. Both matrix embedded microspheres with up to 55wt% of Caffeine and encapsulated, aqueous and organic solutions of Caffeine could be produced (Core-Shell type microcapsules).
Microspheres containing caffeine, and coated with an enteric polymer, were prepared by emulsion/solvent evaporation procedures. Two different polymers were used: cellulose acetate phthalate (CAP) and Eudragit S 100. Mannitol was used as an excipient in the preparation of these microparticles. With the acetone/liquid paraffin system, high loadings of 85-95% were achieved, with particle sizes 500-1000ìm. This is a good method for water-soluble materials, but it is difficult to achieve small particle sizes with it.
The Rapid Expansion of Supercritical Solutions concept consists in saturating a supercritical fluid with the substrate(s), then depressurising this solution through a heated nozzle into a low pressure chamber in order to cause an extremely rapid nucleation of the substrate(s) in form of very small particles - or fibres, or films when the jet is directed against a surface - that are collected from the gaseous stream. The powder was observed by scanning electron microscope (JEOL- JSM-T330A). This showed caffeine needles and hydrogenated palm oil organized in a complex network.