Stability of microencapsulated B. lactis (BI 01) and L. acidophilus (LAC 4) by complex coacervation followed by spray drying

Microcapsules containing Bifidobacterium lactis (BI 01) and Lactobacillus acidophilus (LAC 4) were produced by complex coacervation using a casein/pectin complex as the wall material, followed by spray drying. The aim of this study was to evaluate the resistance of these microorganisms when submitted to the spray drying process, a shelf-life of 120 days at 7–37°C and the in vitro tolerance after being submitted to acid pH (pH 1.0 and 3.0) solutions besides morphology of microcapsules. Microencapsulated microorganisms were shown to be more resistant to acid conditions than free ones. Microencapsulated L. acidophilus maintained its viability for a longer storage period at both temperatures. The microcapsules presented a spherical shape with no fissures. The process used and the wall material were efficient in protecting the microorganisms under study against the spray drying process and simulated gastric juice; however, microencapsulated B. lactis lost its viability before the end of the storage time.     

Microencapsulation of L. acidophilus (La-05) and B. lactis (Bb-12) and evaluation of their survival at the pH values of the stomach and in bile

Microcapsules were prepared using the probiotic microorganisms Lactobacillus acidophilus (La-05) and Bifidobacterium lactis (Bb-12) and the spray drying technique and cellulose acetate phthalate as the wall material. This study evaluated the resistance of these microorganisms to drying at three temperatures and also the in vitro tolerance of the free and microencapsulated form to pH values and bile concentrations similar to those found in the human stomach and intestine. With an air entry temperature of 130 degrees C and exit temperature of 75 degrees C, the number of viable cells of B. lactis was practically unaltered, whereas the population of L. acidophilus was reduced by two logarithmic cycles. B. lactis was more resistant to the drying process than L. acidophilus under all conditions tested. The morphology of the microcapsules was determined by scanning electron microscopy and the microcapsules presented a rounded external surface containing concavities, a continuous wall with no apparent porosity, average size of 22 microm, moisture content varying from 5.3 to 3.2% and water activity between 0.230 and 0.204. After inoculation into HCl solutions with pH values adjusted to 1 and 2, incubated anaerobically at 37 degrees C, and plated after 0, 1 and 2 h of incubation, microcapsules were effective in protecting the microorganisms, while the populations of both free microorganisms were eliminated after only 1 h at the acidic conditions. Microencapsulated B. lactis and L. acidophilus, both free and microencapsulated, were also resistant after 12h to bile solutions.     

喷雾干燥法制备吡哌酸缓释微囊

用喷雾干燥法制备吡哌酸缓释微囊,以乙基纤维素作囊材,硬脂酸作阻滞剂,制备的微囊能明显延缓药物的释放。药物释放速率随其含量增加而增加,释药的表观扩散系数随微囊粒径降低而降低。家兔体内药物动力学研究结果表明,与片剂相比,吡哌酸微囊口服后,血药浓度维持时间较长。     

Microencapsulation of insulin using a W/O/W double emulsion followed by complex coacervation to provide protection in the gastrointestinal tract

Abstract

Microcapsules containing insulin were prepared using a combination of a W/O/W double emulsion and complex coacervation between WPI (used as a hydrophilic emulsifier) and CMC or SA with further spray drying of the microcapsules in order to provide protection in the gastrointestinal tract. The microcapsules prepared exhibited high encapsulation efficiency and showed the typical structure of a double emulsion. After spray drying of these microcapsules, the integrity of the W/O/W double emulsion was maintained and the biological residual activity remained high when using the combination of 180?°C inlet air temperature and 70?°C outlet air temperature. The microcapsules exhibited low solubility at pH 2 and high solubility at pH 7 so they might protect insulin at acid pH values in the stomach and release it at intestinal pH values. The microcapsules developed in this study seem to be a promising oral delivery vehicle for insulin or other therapeutic proteins.     

Survival of Beijerinckia sp. microencapsulated in carbohydrates by spray-drying

The encapsulation of Beijerinckia sp. cell suspension in different wall materials using the spray drying technique was performed. Mat dextrin, dehydrated glucose syrups, gum acacia and modified starch materials were tested. Cell viability assays were carried out before and after drying and during storage of the products. The surface area and characteristics of the encapsulated powders were examined using BET adsorption of N(2) and scanning electron microscopy, respectively. The residual moisture content and water activity of the powders were also determined. The best results were obtained with the dehydrated glucose syrup, which resulted in products with the greatest per cent survival during the drying process and subsequent storage period. The products obtained with the dehydrated glucose syrup showed more uniform microcapsule surfaces at lower A(w) values and residual moisture content.     

Microencapsulation of higher hydrocarbon phase change materials by in situ polymerization

Three higher hydrocarbon phase change materials (PCMs) with melting points of 25, 40 and 50 degrees C were microencapsulated by in situ polymerization of amino-aldehyde resins. Trimethylolmelamine (TMM) and hexamethoxymethylolmelamine (HMMM) were studied as amino-aldehyde pre-polymers for microcapsule wall formation, in combination with emulsifying/modifying agents based on styrene-malein anhydride copolymers (SMA) of different molecular weights and different styrene-maleic acid anhydride ratios. Microcapsule sizes, size distribution and wall permeability were analysed. A mathematical model was developed for comparing the mechanical resistance of different batches of microcapsules, produced at different TMM-SMA ratios. Larger microcapsules with thicker walls and larger pores (M(LAR)) expressed lower resistance to breakage than slightly smaller microcapsules with thinner walls and finer pore structure (M(SMA)). Mathematical data were confirmed by a smudging colouration test. Laboratory microencapsulation process parameters were optimized to obtain impermeable microcapsules with improved mechanical stability. The process was transferred into a 10l pilot reactor for two PCMs with melting points of 25 and 40 degrees C. Dry powder of microencapsulated PCMs was obtained by spray drying of aqueous microcapsule suspensions.     

Microencapsulation of higher hydrocarbon phase change materials by in situ polymerization

Three higher hydrocarbon phase change materials (PCMs) with melting points of 25, 40 and 50°C were microencapsulated by in situ polymerization of amino-aldehyde resins. Trimethylolmelamine (TMM) and hexamethoxymethylolmelamine (HMMM) were studied as amino-aldehyde pre-polymers for microcapsule wall formation, in combination with emulsifying/modifying agents based on styrene-malein anhydride copolymers (SMA) of different molecular weights and different styrene-maleic acid anhydride ratios. Microcapsule sizes, size distribution and wall permeability were analysed. A mathematical model was developed for comparing the mechanical resistance of different batches of microcapsules, produced at different TMM-SMA ratios. Larger microcapsules with thicker walls and larger pores (M_LAR) expressed lower resistance to breakage than slightly smaller microcapsules with thinner walls and finer pore structure (M_SMA). Mathematical data were confirmed by a smudging colouration test. Laboratory microencapsulation process parameters were optimized to obtain impermeable microcapsules with improved mechanical stability. The process was transferred into a 10?l pilot reactor for two PCMs with melting points of 25 and 40°C. Dry powder of microencapsulated PCMs was obtained by spray drying of aqueous microcapsule suspensions.     

Microencapsulation of phenobarbital by spray polycondensation.

A new method for the microencapsulation of solids is described. It is based on the polycondensation of amphiphilic and, thus, tensioactive precondensates on a melamine-formaldehyde base on the surface of suspended particles during spray drying. A film-forming agent, preferably one that reacts chemically with the resin, is indispensable for spray drying and also for the formation of an efficient membrane around the drug particles. The resulting microcapsules are essentially spherical and have, after appropriate curing, a sustained-release effect in vitro. The factors that most influence the formation and properties of the microcapsules are the composition (qualitative and quantitative), pH, and viscosity of the suspension.     

Microencapsulation of ascorbic acid: effect of process variables on product characteristics

This study deals with a comparative investigation of the characteristics of ascorbic acid microcapsules prepared by different methods, such as thermal phase separation, melt dispersion, solvent evaporation and spray drying. Scanning electron microscopy (SEM), release tests and size distribution were used for the evaluation of product characteristics. The results show that microencapsulated ascorbic acid could prevent the ascorbic acid colour change, retard its core release rate, and generally mask its acid taste. In the thermal phase separation, molecular weight (Mw) of ethyl cellulose (EC) and the addition of polyisobutylene (PIB) significantly influenced the aggregation and release rate of microcapsules. In the melt dispersion method, spherical particles were prepared by using carnauba. The ascorbic acid release rate was found to be slower in the case of carnauba-encapsulated ascorbic acid than that made by EC using other methods. In the solvent evaporation method, a higher Mw of EC and the addition of plastizer were also found to be important for good encapsulation. In the spray drying method, loss of ascorbic acid was found to be minimum during microencapsulation. Starch and beta-cyclodextrin encapsulated ascorbic acid delayed the degradation of ascorbic acid during storage at 38 degrees C and relative humidity 84.0%.     

Synthesis of maltodextrin-grafted-cinnamic acid and evaluation on its ability to stabilize anthocyanins via microencapsulation

In this work, maltodextrin-grafted-cinnamic acid (MD-g-CA) was synthesised and used as wall material to improve the stability of purple sweet potato anthocyanins (PSPa) via microencapsualtion. MD-g-CA was prepared through esterification in a two-step convenient synthesis procedure and characterised using infra-red (IR) spectroscopy. The IR data indicated the typical ester carbonyl stretching at around 1721?cm^?1. Moreover, MD-g-CA could give about 40% inhibition of DPPH radical and present excellent UV-absorption, which were notably better than that of native MD. Maltodextrin (MD) and MD-g-CA were used to prepare PSPa microcapsules by spray drying. The stability of PSPa was evaluated by UV-Vis analysis. The microcapsules produced by MD-g-CA showed a spheres-like appearance with some cracks. Storage tests revealed that the degradation rate of PSPa embedded by MD-g-CA was much lower than that of free PSPa under the same condition. Thus, MD-g-CA could be used as an effective wall material to improve stability of anthocyanins.     

Visualization and quantification of polymer distribution in microcapsules by confocal laser scanning microscopy (CLSM)

Confocal laser scanning microscopy (CLSM) was employed in order to characterize microcapsules. Microcapsules were prepared by complex coacervation: gelatin and arabic gum were labelled with fluorescent markers. In the capsule wall a homogeneous distribution for both gelatin and arabic gum throughout the capsule wall was depicted. By the use of CLSM and a computational image analysis the quantification of the labelled polymer in the wall material was possible. Adding fluorescently labelled casein as a macromolecular model compound to the coacervation process, a gradiental distribution in the wall material was observed with highest concentration of casein at the oil-wall interface. The influence of casein concentration on its deposition behaviour in the capsule wall was imaged successfully and thereafter quantified by computational image analysis.     

Microencapsulation of ascorbic acid: effect of process variables on product characteristics

This study deals with a comparative investigation of the characteristics of ascorbic acid microcapsules prepared by different methods, such as thermal phase separation, melt dispersion, solvent evaporation and spray drying. Scanning electron microscopy (SEM), release tests and size distribution were used for the evaluation of product characteristics. The results show that microencapsulated ascorbic acid could prevent the ascorbic acid colour change, retard its core release rate, and generally mask its acid taste. In the thermal phase separation, molecular weight (M_w) of ethyl cellulose (EC) and the addition of polyisobutylene (PIB) significantly influenced the aggregation and release rate of microcapsules. In the melt dispersion method, spherical particles were prepared by using carnauba. The ascorbic acid release rate was found to be slower in the case of carnauba-encapsulated ascorbic acid than that made by EC using other methods. In the solvent evaporation method, a higher M_w of EC and the addition of plastizer were also found to be important for good encapsulation. In the spray drying method, loss of ascorbic acid was found to be minimum during microencapsulation. Starch and beta-cyclodextrin encapsulated ascorbic acid delayed the degradation of ascorbic acid during storage at 38°C and relative humidity 84.0%.     

Survival of Beijerinckia sp. microencapsulated in carbohydrates by spray-drying

The encapsulation of Beijerinckia sp. cell suspension in different wall materials using the spray drying technique was performed. Mat dextrin, dehydrated glucose syrups, gum acacia and modified starch materials were tested. Cell viability assays were carried out before and after drying and during storage of the products. The surface area and characteristics of the encapsulated powders were examined using BET adsorption of N₂ and scanning electron microscopy, respectively. The residual moisture content and water activity of the powders were also determined. The best results were obtained with the dehydrated glucose syrup, which resulted in products with the greatest per cent survival during the drying process and subsequent storage period. The products obtained with the dehydrated glucose syrup showed more uniform microcapsule surfaces at lower A_w values and residual moisture content.     

Effect of kynurenic acid on the viability of probiotics in vitro

Probiotics are bacteria that are commercially available as dietary supplements. One of the important properties of probiotics is their ability to survive in the intestine. Recent evidence has identified kynurenic acid (KYNA) as a bactericidal constituent of intestinal fluid. These data led us to study the influence of KYNA on the viability of selected probiotics. We found that KYNA supported the growth of bacteria in the probiotics Acidolac (Lactobacillus acidophilus, Bifidobacterium) and Lakcid Forte (Lactobacillus rhamnosus) or retarded the growth of bacteria from the Acidolac, BioGaia (Lactobacillus reuteri Protectis), Dicoflor (Lactobacillus rhamnosus GG), Lacium (Lactobacillus plantarum) and Trilac (Lactobacillus acidophilus, Lactobacillus delbrueckii subsp. bulgaricus, Bifidobacterium animalis subsp. lactis) probiotics depending on its concentration. KYNA did not affect the viability of bacteria from the probiotic Linex (Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12). Our results suggest a potential role of KYNA in the regulation of bacterial growth in the digestive system.     

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.     

Use of polyacrylate dispersions for spray coating phenobarbital. 1: Production and in vitro study of microcapsules

The production of microcapsules (model drug: phenobarbital) using aqueous polyacrylate dispersions by means of spray drying is described. The influence of the following factors on formation and quality of the microcapsules is discussed: particle size of the drug, composition of the polyacrylate, viscosity of the spray material and quantitative relation between the drug and the coating material. The morphology of the microcapsules is investigated by means of light and screen electronic microscopy. The liberation of the drug is evaluated. Mainly dry spheric microcapsules arise in a one-working step. Their properties are influenced by variation of the polyacrylate composition. The liberation of the drug decreases with decreasing drug concentration (80-20%) and in dependence of the polyacrylate dispersion for spray coating and the resulting film.     

Preparation and evaluation of abietic acid microcapsules by a solvent evaporation technique.

Abietic acid was isolated from rosin N Grade (ISI) by a simple process and the product was further standardized. Sulphadiazine microcapsules were prepared by the solvent evaporation technique, using abietic acid as a wall-forming material. Discrete, spherical and free-flowing microcapsules were obtained by phase separation induced by solvent evaporation using bentonite as a solid emulsifier. The prepared microcapsules were evaluated for drug content, wall thickness, flow properties, size distribution, density and in vitro dissolution studies in gastric fluid. The effect of various process variables such as agitation speed, coat-core ratio, etc., on the micromeritic and release characteristics has been described.     

A Novel Method for Determination of Sterility of Microcapsules and Measurement of Viability of Encapsulated Organisms

A method of determining the viability of microencapsulated microorganisms (Bacillus Calmette Guerin) is reported. This method was also used to measure the effectiveness of aseptic production of mi-crocapsules in maintaining the interior of the microcapsules free from contamination by microorganisms. This method is advantageous over conventional plating methodology, as plating can only determine external contamination of microcapsules and similar devices. It involves the detection of ¹⁴CO₂, which is generated by the metabolism of ¹⁴C-labeled fatty acid in the growth medium by encapsulated microorganisms. The method depends on the semiper-meable nature of the microcapsule walls, which allows passage of ¹⁴C-palmitic acid and ¹⁴CO₂. BCG organisms encapsulated within an alginate-polylysine-alginate microcapsule (5–15 µm) (1) were shown to be viable, and no contaminating organism(s) was present. Methods suitable for the aseptic production and freeze drying of alginate–polylysine–alginate BCG microcapsules, which retain the viability of the organisms, are reported.     

Microcapsules formulated in the enteric coating copolymer Eudragit L100 as delivery systems for oral vaccination against infections by gastrointestinal nematode parasites

Microcapsules using the copolymer of methacrylic acid (Eudragit L100) were formulated for oral delivery of vaccines against the enteral/parenteral nematode parasite Trichinella spiralis. Antigenic preparations from first stage larvae (L1) of T. spiralis were microencapsulated in Eudragit L100. The microcapsules prepared by the spray drying method were resistant to acid pH, although the antigen was rapidly released under neutral and basic environmental conditions. The native protein conformation and biological activity was preserved in the microcapsules, as assessed by SDS-PAGE and ELISA. When administered to NIH mice, the antigen loaded microcapsules protected against infection by T. spiralis at both the intestinal and muscular levels, the worm burden diminishing by 45.58 and 53.33%, respectively. Furthermore, following administration of the microparticles an increase of the serum IgG1 response, a marker for the Th2 type response, was evident. These results indicate that microcapsules formulated with anionic biocompatible polymers such as Eudragit may be useful for oral vaccination against nematode infections.     

喷雾干燥工艺对含药微囊机械性质的影响

目的以经过机械处理微囊相对未经机械处理微囊吸湿质量的增加率为指标,表征微囊机械性质,考察喷雾干燥的工艺参数对微囊机械性质的影响。方法设计一实验方法模拟生产过程中对微囊的磨擦、剪切等物理机械作用,计算经机械处理微囊相对未经机械处理微囊的吸湿质量增加率。采用单因素,考察进风温度、供液速度和雾化气流速对微囊机械性质的影响。结果喷雾干燥各工艺参数均影响微囊的机械性质,随着进风温度的提高、供液速度的增加、雾化气流速的增大,微囊机械性质先减弱再增强。结论微囊机械性质是微囊的一个重要的质量标准,通过评价微囊的机械性质,可作为微囊工艺优化的重要评价指标。