Characterization of the structures of poly(urea-urethane) microcapsules

A series of poly(urea-urethane) microcapsules containing phthalate derivatives as a core material were prepared by an interfacial polymerization process in order to investigate the structural formation mechanism. Scanning electron microscopy (SEM) analysis for the cross sections of microcapsules revealed the systematic formations of porous structures followed by the formation of core/shell structures. Critical values of the core oil content for the formation of porous and core/shell structures were obtained from SEM results and the critical values were found to be proportional to the solubility parameters of core materials. Dynamic mechanical measurements indicated an amorphous structure of wall membrane and the glass transition temperature was found to decrease with increasing the core oil content suggesting a plasticizing effect. The surface amount of the core oils absorbed in the wall membrane was estimated using time of flight secondary ion spectroscopy analysis and found to increase with increasing the oil content before reaching constant. This tendency was interpreted in terms of the structural formation of the microcapsules. The results obtained in the present investigation were reasonably understood on the basis of swelling theory of wall membrane and the Flory-Huggins interaction parameters of the systems were discussed.     

Encapsulation of chlorothiazide in whey proteins: effects of wall-to-core ratio and cross-linking conditions on microcapsule properties and drug release

A model drug with limited water-solubility, chlorothiazide, was successfully encapsulated in whey protein-based wall systems cross-linked by glutaraldehyde-saturated toluene via an organic phase. The effects of drug content of the core-in-wall suspension and of cross-linking conditions on core retention and on microcapsule size, structure and core release properties were investigated. Spherical, surface cracks-free microcapsules ranging in diameter from approximately 200-1300 microm were obtained. Particle size distribution of microcapsules was affected by core content and cross-linking conditions. Core retention in microcapsules prepared at different cross-linking conditions and different wall-to-core ratios ranged from 48.9-81%, from 42.2-76.1% and from 37.3-67.2% in large (L), medium-size (M) and small (S) microcapsules, respectively. In all cases, drug crystals were physically entrapped and embedded throughout the cross-linked protein matrix. Core release from the microcapsules into enzyme-free simulated gastric fluid was governed by a diffusion-controlled mechanism and did not involve erosion or softening of the wall matrix. Rate of core release was significantly affected by a combined influence of core content, microcapsule size and cross-linking density. Complete core release from L, M and S microcapsule prepared at different wall-to-core ratios and cross-linking conditions ranged from 28.6-81.2 h, from 16.8-28.6 h and from 7.2-15.9 h, respectively. Results suggested that whey protein-based wall matrix cross-linked by GAST may provide significant opportunities in modulating the release of an encapsulated core with a limited water solubility.     

Controlled release captopril microcapsules: effect of ethyl cellulose viscosity grade on the in vitro dissolution from microcapsules and tableted microcapsules

Captopril microcapsules were prepared using four different viscosity grades of ethyl cellulose (core: wall ratios 1:1, 1:2 and 1:3) by temperature induced coacervation from cyclohexane. In vitro dissolution studies in 0.1 M hydrochloric acid showed that the drug release was dependent on the core to wall ratio, the viscosity grade of the ethyl cellulose and thus the total viscosity of the coacervation system. Viscosity grade of greater than 100 c.p. was unsuitable for microencapsulation by coacervation method at the concentration used. The surface characteristics of a 1:2 core to wall ratio were studied by scanning electron microscopy. The surface of the microcapsules prepared with 10 c.p. viscosity grade was comparatively more porous with larger size pores than 50 c.p. viscosity grade of ethyl cellulose. However, 300 c.p. viscosity grade showed incomplete wall formation. The microcapsules did not fragment during dissolution, alter in shape or size, or show evidence of enlargement of the surface pores. The tensile strength of tablets prepared at constant pressure from each batch of microcapsules (mean diameter 675 microns) increased as both the core to wall ratios and the viscosity of ethyl cellulose increased. The dissolution rate of the drug from tableted microcapsules was significantly delayed. The in vitro release gave best correlation with first order release kinetics when compared to zero-order and square-root-of-time equations.     

The prolongation of the in vitro dissolution of a soluble drug (phenethicillin potassium) by microencapsulation with ethyl cellulose

Microcapsules of phenethicillin potassium as a model water-soluble drug, coated with ethyl cellulose, have been prepared (core: wall ratios 1:1, 1:2 and 1:3) in which the taste has been masked, the odour almost eliminated and the release retarded. Sieve analysis showed that with decreasing core: wall ratios there was a trend towards increasing amounts of larger sized microcapsules. At constant core: wall ratios in vitro release of drug was generally greatest from the larger microcapsules. This result correlated with the surface areas of the microcapsules which became less as the asymmetry of the microcapsules diminished with decrease in microcapsule size. There was a linear relation between the amount of ethyl cellulose and the time for 60% release of drug, and the release pattern was analogous to that from insoluble porous matrices. Scanning electron micrographs showed the microcapsules to be irregularly shaped with circular surface pores, and they did not alter in shape or size during dissolution. Tableting of 1:1 core: wall ratio microcapsules significantly further retarded the dissolution.     

Preparation of microencapsulated liposomes

Liposomal microcapsules were prepared by encapsulating a liposome suspension in a nylon wall formed by the interfacial polymerization technique. The resulting microcapsules were washed in ether to remove the chloroform and cyclohexane. Residual ether was removed by rinsing with distilled water prior to resuspending the microcapsules in aqueous medium. The encapsulation efficiency of the microcapsules toward liposomes was dependent on the lipid composition of the liposomes. The liposomal nylon microcapsules possess sustained release properties when compared with the simple nylon microcapsules.     

Microencapsulation of thyme oil by coacervation

The objective of this work is to develop a novel coacervation process to produce microcapsules of polylactide (PLA) to encapsulate thyme oil that will be used in cosmetics. The novelty of this approach consists of dissolving PLA in dimethylformamide (DMF) which is a good solvent for PLA but in addition has high solubility in water. Upon contact with water, the homogeneous solution of PLA in DMF promotes the precipitation of PLA around the thyme oil core. The produced microcapsules have bimodal particle size distributions in volume with a mean particle size of 40 µm. Microcapsules analysis by microscopy have confirmed the spherical shape, the rough surface and allowed the estimation of the wall thickness around 5 µm. Quantification of the encapsulated thyme oil was performed by gas chromatography and allowed to evaluate the quality of the encapsulated oil and pointed out for a preferential encapsulation of thyme oil apolar compounds.     

Taste masking of diclofenac sodium using microencapsulation.

This study addresses how to mask the undesirable taste of diclofenac sodium (DS) without interfering with an adequate rate of drug release. DS microcapsules were successfully prepared using a system of ethylcellulose (EC)-toluene-petroleum ether. The system was optimized by the construction of the phase diagram and determination of the amount of EC precipitated under different solvent:non-solvent ratios to determine the most appropriate conditions for preparing good microcapsules. Microcrystalline cellulose (Avicel) and lactose were mixed with DS powder and converted into spherical cores by the wet agglomeration technique which facilitated coacervation and formation of thin and uniform microcapsule walls. Diethylphthalate (DEP) and Polyethyleneglycol 600 (PEG) in different concentrations (20 or 40% w/w) were used as plasticizers to impart better elasticity to the microcapsules. The microcapsules were evaluated for DS released against crushed commercial DS enteric coated tablet (Voltaren). The prepared microcapsules were taste evaluated by a taste panel of 10 volunteers. The results revealed that the optimum solvent:non-solvent ratio required for microcapsule formation was 1:2. Microcapsules containing PEG 20% or DEP 40% showed a faster rate of DS release compared to that obtained from other microcapsules and crushed commercial enteric coated tablets (Voltaren). The palatability and the taste of DS were significantly improved by microencapsulation. The extent of taste masking was influenced by the microcapsule core:wall ratio, the presence of additives within the core, the type and concentration of plasticizer and initial core size.     

Microencapsulation using poly(DL-lactic acid). III: Effect of polymer molecular weight on the release kinetics

Poly(DL-lactic acid) [DL-PLA] microcapsules containing phenobarbitone (PB) were prepared using a w/o emulsion-evaporation method. DL-PLA of three different molecular weights, 20,200, 13,300 and 5,200 were used to prepare microcapsules of nominal core: polymer (C:P) ratios of 1 : 2, 1 : 2.5, 1 : 3 and 1 : 4. The release of PB was investigated in aqueous buffer of pH 2, pH 7 and pH 9 at 37 degrees C and found to follow a square root of time dependent release mechanism. The first order and zero order release mechanisms were disproved by the lower correlation coefficient of the release data as compared to that of the t1/2 mechanism. These microcapsules showed an initial burst phase release followed by a lag phase, during which time little PB was released. This lag time was affected by the polymer molecular weight and pH of the buffer. The polymer matrix was hydrated during the lag phase and a steady state release occurred. The steady state release rate per unit specific surface area (Kh2/SSA) was found to increase exponentially with the increase in core loading of the microcapsules. However the extent of normalized release rate reduced linearly with the increase in polymer molecular weight at any particular core loading (e.g. 20 per cent or 30 per cent). Increases in the normalized steady state release rate with an increase in buffer pH could be correlated to PB solubility in the dissolution medium. PB release from these microcapsules was diffusion controlled. However, swelling and erosion also contributed to the release process.     

The effect of microcapsule size on the oxidative decomposition of core material.

The factors that affect the size of microcapsules and the oxidation of their benzaldehyde core have been examined. The pH of the preparation changed the overall size of the microcapsules which reached a maximum diameter at pH 4.1. The size of the core droplets also varied with the preparative pH and their oxidation rate depended on the bulk droplet size rather than their surface area. A rapid oxidation of benzaldehyde associated with the microcapsule wall resulted in a preliminary peak in the oxidation curve. Explanations for these phenomena are discussed.     

The effect of microcapsule size on the oxidative decomposition of core material*

The factors that affect the size of microcapsules and the oxidation of their benzaldehyde core have been examined. The pH of the preparation changed the overall size of the microcapsules which reached a maximum diameter at pH 4·1. The size of the core droplets also varied with the preparative pH and their oxidation rate depended on the bulk droplet size rather than their surface area. A rapid oxidation of benzaldehyde associated with the microcapsule wall resulted in a preliminary peak in the oxidation curve. Explanations for these phenomena are discussed.     

A contribution to the evaluation of microcapsules by light microscopy.

Light microscopy has been used for the evaluation of the internal and external structure of dry microcapsules. The method involves surface and penetrative staining with various dyes after which the microcapsules were embedded in suitable optically translucent material. Using this method the core material, its shape and position within the microcapsules either in total or as subunits of the core are clearly distinguishable from the wall material. The surface characteristics of the microcapsules can be observed with either light or fluorescent microscopy after staining with a fluorescent dye. Furthermore, it is a relatively simple and inexpensive method by comparison with the scanning electron microscopy. The natural character of microcapsules, without any artificial structures, has been maintained. It could serve as a routine auxiliary method for complex evaluation or control of the microencapsulation process and its optimization.     

Effect of processing parameters on the formation of spherical multinuclear microcapsules encapsulating peppermint oil by coacervation

The gelatin/gum arabic multinuclear microcapsules encapsulating peppermint oil were prepared by coacervation. The effect of various processing parameters, including the core/wall ratio, wall material concentration, pH value, as well as stirring speed on the morphology, particle size distribution, yield and loading was investigated. When the wall material concentration or the core/wall ratio increased, the morphology of multinuclear microcapsules changed from spherical to irregular and the average particle size increased, the optimal wall material concentration and the core/wall ratio were 1% and 2:1, respectively. The multinuclear spherical microcapsules with desired mean particle size can be manufactured by modulating the pH value and stirring speed. The ideal preparation conditions were pH 3.7 at 400 rpm of stirring speed. The yield of multinuclear microcapsules encapsulating peppermint oil by coacervation was approximately 90% and the processing parameters had very slight influence on the yield. When transglutaminase was used as the cross-linker instead of formaldehyde, morphology, mean particle size, yield and loading remained the same as that hardening with formaldehyde, but the particle size distribution became narrower.     

Effect of processing parameters on the formation of spherical multinuclear microcapsules encapsulating peppermint oil by coacervation

The gelatin/gum arabic multinuclear microcapsules encapsulating peppermint oil were prepared by coacervation. The effect of various processing parameters, including the core/wall ratio, wall material concentration, pH value, as well as stirring speed on the morphology, particle size distribution, yield and loading was investigated. When the wall material concentration or the core/wall ratio increased, the morphology of multinuclear microcapsules changed from spherical to irregular and the average particle size increased, the optimal wall material concentration and the core/wall ratio were 1% and 2:1, respectively. The multinuclear spherical microcapsules with desired mean particle size can be manufactured by modulating the pH value and stirring speed. The ideal preparation conditions were pH 3.7 at 400?rpm of stirring speed. The yield of multinuclear microcapsules encapsulating peppermint oil by coacervation was ～90% and the processing parameters had very slight influence on the yield. When transglutaminase was used as the cross-linker instead of formaldehyde, morphology, mean particle size, yield and loading remained the same as that hardening with formaldehyde, but the particle size distribution became narrower.     

Microencapsulation of eugenol by gelatin-sodium alginate complex coacervation

Present study describes microencapsulation of eugenol using gelatin-sodium alginate complex coacervation. The effects of core to coat ratio and drying method on properties of the eugenol microcapsules were investigated. The eugenol microcapsules were evaluated for surface characteristics, micromeritic properties, oil loading and encapsulation efficiency. Eugenol microcapsules possessed good flow properties, thus improved handling. The scanning electron photomicrographs showed globular surface of microcapsules prepared with core: coat ratio1:1.The treatment with dehydrating agent isopropanol lead to shrinking of microcapsule wall with cracks on it. The percent oil loading and encapsulation efficiency increased with increase in core: coat ratio whereas treatment with dehydrating agent resulted in reduction in loading and percent encapsulation efficiency of eugenol microcapsules.     

Characteristics of ethylcellulose microcapsules of sulfisoxazole

Sulfisoxazole, a chemotherapeutic agent, was microencapsulated with ethylcellulose by means of phase separation from cyclohexane by temperatture change. The size distribution was determined by use of standard sieves and the effect of core to wall ratio was noted. To examine their shapes and surface characteristics, the microcapsules were observed with a scanning electron microscope. Release of the drug from microcapsules into pH 7.5 buffer medium was studied. The release pattern was found to have similar properties to the release of a drug from an insoluble porous matrix reported. The apparent diffusion coefficient of sulfisoxazole was measured for the transport of the drug from the core of microcapsules into the surrounding sink condition. The apparent diffusion coefficient increased with increasing capsule size.     

Some factors affecting the microencapsulation of pharmaceuticals with cellulose acetate phthalate

Phase diagrams were prepared to indicate the region of microcapsule formation for the following system: cellulose acetate phthalate, light mineral oil, acetone: 95% ethanol solvent, and sorbitan monooleate. The microencapsulation of pharmaceuticals having widely different solubility properties was carried out. Various factors affecting microencapsulation, namely trituration, order and time of addition of the pharmaceutical, core size, and the core to coat ratio, were investigated. The evidence for a mechanism of microencapsulation is also presented. The phase diagrams showed that microcapsules readily formed when the cellulose acetate phthalate concentration was in the 0.93-3.85% range and the polymer solvent concentration was in the 7-16% range. Aggregation of microcapsules was minimized at low solvent concentrations. Pharmaceuticals could be microencapsulated regardless of their solubility in the polymer solvent or hardening liquid. The size of the microencapsulated pharmaceutical increased as the core:coat ratio increased to a maximum of 1.5:1. There is an upper size limit of the pharmaceuticals which can be coated.     

Buffer controlled release of indomethacin from ethylcellulose microcapsules

The rate of release of indomethacin from ethylcellulose microcapsules prepared by coacervation was studied using internal buffer, dibasic sodium phosphate (DSP), to increase the solubility of the core. The dissolution rate of the drug was determined in phosphate buffer solutions of varying pH and concentration. The role of the stagnant diffusion layer at the microcapsule surface was also evaluated by changing the mixing in the dissolution test. Indomethacin release was accelerated considerably with increasing amounts of DSP in the core. DSP increases the pH inside the microcapsules, thus enhancing the release of the acidic drug. Increasing bulk solution pH increased the release rate of indomethacin, the enhancing effect being more pronounced with buffered microcapsules. Neither increasing phosphate concentration of the bulk solution nor increasing mixing of the microcapsules influenced the rate of release of indomethacin from unbuffered capsules. With buffered capsules the increase in phosphate concentration of bulk solution prevented leaching out of internal phosphate increasing the release rate of indomethacin. The release of indomethacin also accelerated slightly with increasing mixing.     

Preparation and evaluation of celecoxib-loaded microcapsules with self-microemulsifying core

The purpose of this study was to prepare alginate microcapsules with a self-microemulsifying system (SMES) containing celecoxib in the core. An Inotech IE-50 R encapsulator equipped with a concentric nozzle was used to prepare the microcapsules. The encapsulated SMES was shown to increase celecoxib solubility over that of the pure drug more than 400-fold. Microcapsules prepared with a high SMES:celecoxib ratio exhibited distinct core vesicles containing liquid SMES. By modifying the SMES and including an additional chitosan coating, drug loading in the range from 12–40% could be achieved with the degree of encapsulation ranging from 60–82%. Alginate microcapsules loaded with SMES and celecoxib showed increased dissolution rate of celecoxib over that of alginate microcapsules loaded with celecoxib or of the celecoxib alone. Compared to the previous report, drug loading capacity was significantly improved, enabling the formulation of dosage forms which are of suitable size for peroral application.     

Evaluation of the Properties of Ethylcellulose-Cellulose Triacetate Microcapsules Containing Theophylline Prepared by Different Microencapsulation Techniques

Abstract

Using cellulose triacetate as an added complementary coating material in preparing sustained-release ethylcellulose-cellulose triacetate microcapsules of theophylline, three microencapsulation techniques were investigated. Ethylcellulose-cellulose triacetate composite microcapsules, ethylcellulose-cellulose triacetate dual-walled microcapsules and ethylcellulose microcapsules containing cellulose triacetate matrices were prepared using the non-solvent addition phase separation method. The effects of cellulose triacetate on the release of theophylline from the different ethylcellulose-cellulose triacetate microcapsules were obtained from dissolution studies. The results showed that the release rates of ethylcellulose-cellulose triacetate microcapsules were slower than those obtained from the ethylcellulose microcapsules prepared with similar core to wall ratios. The ethylcellulose microcapsules containing cellulose triacetate matrices had longer release half-times and smaller surface areas than the other capsule preparation. The release patterns of theophylline from the different ethylcellulose-cellulose triacetate microcapsules fitted first-order kinetics. Scanning electron micrographs showed that the surfaces of various ethylcellulose-cellulose triacetate microcapsules were different from those of theophylline, cellulose triacetate matrices of cellulose triacetate microcapsules, and that the surface morphology of ethylcellulose-cellulose triacetate microcapsules was affected by the preparative method.