Application of microencapsulated isoflavone into milk

This study was designed to develop a microencapsulated, water-soluble isoflavone for application into milk and to examine the hypocholesterolemic effect of such a milk product in a rat diet. The coating material was medium-chain triglyceride (MCT) and the core material was water-soluble isoflavone. The microencapsulation efficiency was 70.2% when the ratio (w/w) of coating material to core material was 15:1. The isoflavone release from the microcapsules was 8% after 3-day storage at 40 degrees C. In in vitro study, 4.0-9.3% of water-soluble isoflavone in simulated gastric fluid was released in the pH range of 2 to 5 after 60 min incubation; however, in simulated intestinal fluid at pH 8, 87.6% of isoflavone was released from the capsules after 40 min incubation time. In sensory analysis, the scores of bitterness, astringency, and off-taste in the encapsulated isoflavone-added milk were slightly, but not significantly, different from those in uncapsulated, isoflavone-added milk. In blood analysis, total cholesterol was significantly decreased in the isoflavone-added group compared with that in the control after 6-week feeding. Therefore, this study confirmed the acceptability of MCT as a coating material in the microencapsulation of water-soluble isoflavone for application into milk, although a slight adverse effect was found in terms of sensory attributes. In addition, blood total cholesterol was lowered in rats which had been fed a cholesterol-reduced and microencapsulated, isoflavone-added milk for 6 weeks.     

Microencapsulated ascorbic acid for milk fortification

The present study was designed to develop a microencapsulated L-ascorbic acid and iron that could be used to fortify milk and to determine the sensory properties of milk fortified with microencapuslation. Coating material was medium-chain triacylglycerol (MCT), and selected core material was ferric ammonium sulfate and L-ascorbic acid. The highest efficiency of microencapsulation was 95.0% in the ratio of 15:1 as coating to core material. Ascorbic acid release was increased sharply up to 5 d storage as 6.5%. TBA value was the lowest when both capsulated iron and ascorbic acid were added during 12 d storage, compared with other treatments. In sensory analysis, most aspects were not significantly different between control and capsulated ascorbic acid fortified milk at 5 d storage. The present study indicated that the use of microencapsulated ascorbic acid with MCT is effective for fortifying milk. In addition, these results suggest that acceptable milk products can be prepared with microencapsulated ascorbic acid and iron.     

The microencapsulated ascorbic acid release<Emphasis Type="Italic">in vitro</Emphasis> and its effect on iron bioavailability

The present study was carried out to examine the stability of microencapsulated ascorbic acid in simulated-gastric and intestinal situation in vitro and the effect of microencapsulated ascorbic acid on iron bioavailability. Coating materials used were polyglycerol monostearate (PGMS) and medium-chain triacylglycerol (MCT), and core materials were L-ascorbic acid and ferric ammonium sulfate. When ascorbic acid was microencapsulated by MCT, the release of ascorbic acid was 6.3% at pH 5 and 1.32% at pH 2 in simulated-gastric fluids during 60 min. When ascorbic acid was microencapsulated by PGMS, the more ascorbic acid was released in the range of 9.5 to 16.0%. Comparatively, ascorbic acid release increased significantly as 94.7% and 83.8% coated by MCT and PGMS, respectively, for 60 min incubation in simulated-intestinal fluid. In the subsequent study, we tested whether ascorbic acid enhanced the iron bioavailability or not. In results, serum iron content and transferring saturation increased dramatically when subjects consumed milks containing both encapsulated iron and encapsulated ascorbic acid, compared with those when consumed uncapsulated iron or encapsulated iron without ascorbic acid. Therefore, the present data indicated that microencapsulated ascorbic acid with both PGMS and MCT were effective means for fortifying ascorbic acid into milk and for enhancing the iron bioavailability.     

Asymmetric membrane capsules for delivery of poorly water-soluble drugs by osmotic effects

A non-disintegrating polymeric capsule system, in which asymmetric membrane offers an improved osmotic effect, was used to deliver poorly water-soluble drugs in a control manner. The capsule wall membrane was made by a phase inversion process, in which asymmetric membrane was formed on stainless-steel mold pins by dipping the mold pins into a coating solution containing a polymeric material followed by dipping into a quench solution. This study evaluates the influence of coating formulation that was cellulose acetate (CA), ethylcellulose (EC), and plasticizer (glycerin and triethyl citrate). Results show capsule that made by CA with glycerin (formulation A), which appear in asymmetric structure and are able to release chlorpheniramine maleate (CM) in significant percentage. Two poorly water-soluble drugs of felodipine (FL) and nifedipine (NF) were selected as the model drug to demonstrate how the controlled release characteristics can be manipulated by the design of polymeric capsules with an asymmetric membrane and core formulations. Results show that sodium lauryl sulfate (SLS) is able to promote the release of FL from polymeric capsules prepared with CA with asymmetrical membrane. The addition of solubilizer, including RH40, PVP K-17, and PEG 4000 could enhance the release of FL but with an extent not being related to its solubility. Based on these results, influence of core formulation variables, including the viscosity and added amount of hydroxypropyl methylcellulose (HPMC), the added amount of SLS, and drug loading were examined on the release of NF. It was found that HPMC of 50 cps was suitable to be a thickening agent and both added amount of HPMC and SLS showed a comparable and profoundly positive effect, whereas NF loading had no influence on the drug release percent and rate. There existed a synergistic interaction between HPMC and SLS on the release percent and rate.     

Fatty acid and water-soluble polymer-based controlled release drug delivery system

Sustained release capsule formulations based on three components, drug, water-soluble polymer, and water-insoluble fatty acid, were developed. Theophylline, acetaminophen, and glipizide, representing a wide spectrum of aqueous solubility, were used as model drugs. Povidone and hydroxypropyl cellulose were selected as water-soluble polymers. Stearic acid and lauric acid were selected as water-insoluble fatty acids. Fatty acid, polymer, and drug mixture was filled into size #0 gelatin capsules and heated for 2 h at 50 °C. The drug particles were trapped into molten fatty acid and released at a controlled rate through pores created by the water-soluble polymer when capsules were exposed to an aqueous dissolution medium. Manipulation of the formulation components enabled release rates of glipizide and theophylline capsules to be similar to commercial Glucotrol XL tablets and Theo-24 capsules, respectively. The capsules also exhibited satisfactory dissolution stability after exposure to 30 °C/60% relative humidity (RH) in open Petri dishes and to 40 °C/75% RH in closed high-density polyethylene bottles. A computational fluid dynamic-based model was developed to quantitatively describe the drug transport in the capsule matrix and the drug release process. The simulation results showed a diffusion-controlled release mechanism from these capsules.     

Studies on the development of a microencapsulated delivery system for norbormide,a species-specific acute rodenticide

Norbormide, a selective rat toxicant, was microencapsulated to both mask the flavour and delay the release until after a lethal dose has been ingested by the rat. To this end, gelatine microspheres containing norbormide were made and over coated with either shellac resin or an equal mixture of shellac and Eudragit RS in a fluid-bed coating machine. The microcapsules absorb water, swell and burst to release their contents. In rats an 8 h window is available to delay the release of encapsulated material. In initial experiments, a shellac coating of 20% w/w was established as suitable for delaying the release. A capsule size range of 200-400 microm was selected, from capsule mastication experiment, for oral gavaging and feeding studies in rat. Oral gavage study has demonstrated for the first time that a substantial delay in release of a lethal dose of an acute poison has been achieved by microencapsulation. Feeding test has demonstrated that there is a fine balance between the size and density of the capsules in the bait to overcome mastication of the capsules by rats. A combination of shellac and Eudragit RS resins is a viable polymeric wall material to control the rate of penetration of water in to microcapsules.     

离心造粒法制备托拉塞米缓释小丸胶囊及其释放度考察

目的:制备托拉塞米缓释小丸胶囊。方法:采用离心造粒粉末层积法制备托拉塞米小丸,用丙烯酸树脂水分散体包衣,并对包衣小丸的释药特征进行探讨。结果:微晶纤维素(MCC)空白母核32～40目的收率约80.2%,含药素丸20～24目收率约87.6%,使用Eudragit NE30D包衣液,包衣增重10%。托拉塞米缓释胶囊体外释药行为较好地符合Higuchi方程。结论:在优化的工艺条件下可制得表面光滑、圆整度高的托拉塞米缓释小丸。     

The release of immobilized substances from Symplex capsules

A new procedure of microencapsulation was studied with regard to substance release and quantification of diffusion processes on the capsule membrane. The permeability behaviour on the capsule membrane was especially studied in metabolites, which are essential for immobilized biological objects (i.g. preimplantative mammal embryos). Peptide and proteohormones, cyanmethemoglobin and proteins were enclosed in simple and multiple Symplex Capsules. All substances examined are able to pass the Symplex membrane. The speed of release is influenced by the size of the capsule, the ion force, temperature, concentration of immobilized substances as well as their linear and globular structur. Compared with simple capsules the release of substances from multiple capsules was delayed. Corresponding to the results found under the experimental design described the Symplex membrane can be considered as coating for the compartmentation of cells, that allows the passage of essential substances for the immobilized objects. The method of microencapsulation used and described has various ways of application.     

Controlled release of dual drug-loaded hydroxypropyl methylcellulose matrix tablet using drug-containing polymeric coatings.

A dual drug-loaded hydroxypropylmethylcellulose (HPMC) matrix tablet simultaneously containing drug in inner tablet core and outer coated layer was formulated using drug-containing aqueous-based polymeric Eudragit RS30D dispersions. Effects of coating levels, drug loadings in outer layers, amount and type of five plasticizers and talc concentration on the release characteristics were evaluated on the characteristics in simulated gastric fluid for 2 h followed by a study in intestinal fluids. Melatonin (MT) was selected as a model drug. The surface morphology of dual drug-loaded HPMC tablets using scanning electron microscope (SEM) was smooth, showing the distinct coated layer with about 75-microm coating thickness at the 15% coating level. Unlike the uncoated and conventionally coated HPMC tablet, the dual drug-loaded HPMC matrix tablet gave a biphasic linear release, showing a zero-order for 4 h (first) followed by another zero-order release when fitted using linear regression (r(2) = 0.99). As the coating levels (15, 25%) increased, the release rate was further decreased. The biphasic release profiles of dual drug-loaded HPMC matrix tablet was unchanged except when 25% coating level containing 0.5% drug concentration was applied. As the drug concentration in polymeric coating dispersion increased (0.25-1.0%), the amount of drug released increased. The time for the first linear release was also advanced. However, the biphasic release pattern was not changed. The biphasic release profiles of dual drug-loaded HPMC matrix tablet were highly modified, depending on the amount and type of five plasticizers. Talc (10-30%) in coating dispersion as an anti-sticking material did not affect the release profiles. The current dual drug-loaded HPMC matrix tablet, showing biphasic release profiles may provide an alternative to deliver drugs with circadian rhythmic behaviors in the body but needs to be further validated in future in human studies. The dual drug-loaded coating method is also interesting for the modified release of poorly water-soluble drugs because solubilizers and other additives can be added in drug-containing polymeric coating dispersions.     

In vitro and in vivo studies of sustained-release floating dosage forms containing salbutamol sulfate

Peroral sustained-release floating capsules containing salbutamol sulfate were formulated using different combinations of hydrocolloids of natural and semi-synthetic origin. The floating properties and release rate characteristics were determined for the capsules in simulated gastric fluid USP XXI and HCl (0.1 mol.l-1) as dissolution media. Also, a marketed sustained-release non-floating capsule containing salbutamol sulfate was studied for its release rate characteristics. The floating capsule formulated showed a Higuchian release profile while the marketed product released only about 80% of the total dose in the stipulated 12 h in the dissolution medium. In vivo X-ray studies of the abdomen were carried out to locate the floating and non-floating (fabricated) dosage forms at various time intervals of uniform duration. The floating capsule definitely indicated a residence time (up to 8-9 h) in the stomach greater than for the non-floating capsule.     

Use of microcapsules as timed-release parenteral dosage form: application as radiopharmaceutical imaging agent.

The development of a new type of parenteral dosage form is described. A system of microencapsulation was formulated which produced microcapsules containing a water-soluble core material. The basic microencapsulation system could be altered to produce microcapsules with varied timed-release characteristics. Tracer methodology was employed as a sensitive and versatile analytical tool for the development and evaluation of the microencapsulation system. The core material was labeled by neutron activation after microcapsule formulation, which eliminated the radiation hazard and contamination problems that could occur during formulation with a labeled core material. Both in vitro and in vivo testing showed that the release patterns of labeled core material could be altered and detected. The microcapsules developed have potential as a timed-release parenteral dosage form and as an organ-imaging radiopharmaceutical.     

Encapsulated microcapsules

A microencapsulation procedure has been developed which allows an oil slurry of microcapsules to be filled into soft gelatin capsules. Ethylcellulose solutions in ethyl acetate can be desolvated by the addition of light liquid paraffin so that an ethylcellulose coat is deposited on a core material such as aspirin. Approximately 1% of the aspirin is imperfectly encapsulated. The use of light liquid paraffin enables the slurry to be filled directly into soft gelatin capsules without the usual filtering, drying, and redispersion steps.Different release characteristics can be devised by varying the ratio of ethylcellulose to drug. In vitro release into a simulated gastric juice shows that essentially first-order kinetics exist for periods up to 12 hours.     

Formulation and characterization of the microencapsulated entomopathogenic fungus Metarhizium anisopliae MA126

Bioinsecticides are expected to be used for controlling major species of aphids. The present study explored a liquid phase coating technique for the formulation of microencapsulated conidia of the entomopathogenic fungus Metarhizium anisopliae MA126. Various parameters for microencapsulation were investigated. The biopolymers sodium alginate, hydroxypropyl methyl cellulose (HPMC) and chitosan were tested as coating materials. Calcium chloride was used as the cross-linking agent for converting soluble sodium alginate into an insoluble form. To improve the efficiency of microencapsulation, the additives of HPMC, dextrin, chitosan or HPMC/chitosan in various ratios (1 : 1, 1 : 3 and 3 : 1) were used as the coating materials. The particle size of a bare microcapsule was less than 30 microm. Larger size microcapsules were produced using vortex method by comparison with that using homogenization method. The latter method, however, was easy to scale up. The effect of coating materials on the morphology and encapsulation efficiency of the microcapsules was also studied. The best encapsulation efficiency (78%) was using HPMC as the additive of the coating material. The next was dextrin (70%). By measuring the germination rate, the results showed that the activity was approximately 80% of the initial after 6 months of storage at 4 degrees C, while that of the bare conidia was less than 50% stored in identical conditions.     

Microencapsulation of theophylline in composite wall system consisting of whey proteins and lipids

Theophylline was microencapsulated in composite whey protein-based wall systems containing different proportions of dispersed apolar filler, anhydrous milkfat. Wall emulsions exhibited uni-modal particle size distribution and had a mean particle size of 0.36-0.38 microm. Microcapsules were cross-linked by glutaraldehyde-saturated toluene via an organic phase. Spherical microcapsules ranging in diameter from 150 to larger than 700 microm were obtained and exhibited some surface cracks that could be attributed to the fragile nature of a peripheral, highly cross-linked 'shell' layer around the capsules. Core content ranged from 46.9-56.6% (w/w) and filler content ranged from 12.0-33.4% (w/w). Core and filler retention during microencapsulation ranged from 84.9-96.9%) and from 85.1-89.6%, respectively. Core retention was proportionally related to the proportion of filler embedded in the wall matrix. Core release into SGF and SIF was affected by microcapsule size, type of dissolution medium and wall composition. Rate of core release was inversely proportional to filler content of the wall matrix. This could be attributed to effects of filler content on diffusion through the wall matrix and probably on swelling properties of microcapsules. Results indicated that incorporation of apolar filler in wall matrix of whey protein-based capsules provided the means to enhance retention of a water-soluble core during the microencapsulation process and to decrease the rate of core release into aqueous dissolution media.     

Cross-linking of hard gelatin carbamazepine capsules: effect of dissolution conditions on in vitro drug release.

The aim of this study was to determine if the use of both enzyme and surfactant in the dissolution medium changes the in vitro drug release from cross-linked hard gelatin capsules containing a water-insoluble drug. Hard gelatin capsules were cross-linked by a controlled exposure to formaldehyde resulting in different stressed capsules and carbamazepine (CBZ) was chosen as a drug model. In vitro dissolution studies were conducted using simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) with enzymes. Sodium lauryl sulfate (SLS) was added in the dissolution medium at a concentration of 2% m/v both in SGF and SIF with pepsin and pancreatin, respectively. The percentage of CBZ dissolved was reduced by increasing the degree of gelatin cross-linking. For unstressed hard gelatin capsules, 36% of the CBZ was released after 1 h, lowering to 5% for highly stressed hard gelatin capsules in the SGF. A similar effect was observed with SIF. In the case of moderately stressed hard gelatin capsules, addition of enzyme in the dissolution medium enhanced the percentage of CBZ dissolved. The dissolution level increased from 12% to 39% in SGF with pepsin for hard gelatin capsules cross-linked with 1500 ppm formaldehyde. On the contrary, the use of enzyme in the dissolution medium did not increase the dissolution of CBZ from highly stressed hard gelatin capsules. Surprisingly, the addition of SLS in the medium did not allow the release of the CBZ both in SGF and in SIF. The results of this study demonstrate that the use of enzyme in the dissolution medium is justified for moderately cross-linked hard gelatin capsules. However, the action of a surfactant added in the medium containing enzyme remains unclear.     

Formulation and characterization of the microencapsulated entomopathogenic fungus Metarhizium anisopliae MA126

Abstract

Bioinsecticides are expected to be used for controlling major species of aphids. The present study explored a liquid phase coating technique for the formulation of microencapsulated conidia of the entomopathogenic fungus Metarhizium anisopliae MA126. Various parameters for microencapsulation were investigated. The biopolymers sodium alginate, hydroxypropyl methyl cellulose (HPMC) and chitosan were tested as coating materials. Calcium chloride was used as the cross-linking agent for converting soluble sodium alginate into an insoluble form. To improve the efficiency of microencapsulation, the additives of HPMC, dextrin, chitosan or HPMC/chitosan in various ratios (1 : 1, 1 : 3 and 3 : 1) were used as the coating materials. The particle size of a bare microcapsule was less than 30 µm. Larger size microcapsules were produced using vortex method by comparison with that using homogenization method. The latter method, however, was easy to scale up. The effect of coating materials on the morphology and encapsulation efficiency of the microcapsules was also studied. The best encapsulation efficiency (78%) was using HPMC as the additive of the coating material. The next was dextrin (70%). By measuring the germination rate, the results showed that the activity was ～80% of the initial after 6 months of storage at 4°C, while that of the bare conidia was less than 50% stored in identical conditions.     

克拉霉素缓释胶囊的制备与体外释放度研究

目的:制备克拉霉素缓释胶囊,考察不同包衣增质量对其体外释放特性的影响。方法:采用流化床包衣工艺,以3%羟丙基甲基纤维素为黏合剂,乙基纤维素水分散体(Surelease?)为缓释包衣材料,制备克拉霉素缓释胶囊。采用高效液相色谱法测定不同包衣增质量胶囊的体外释放度,并与进口缓释片的释放度进行比较。结果:成功制备克拉霉素缓释胶囊,包衣增质量为5%、8%、11%的自制缓释胶囊与进口缓释片比较,体外释放曲线相似因子f2分别为40.3、66.8、53.3。结论:该制剂制备工艺可行,包衣增质量为8%的克拉霉素缓释胶囊体外释放与进口缓释片基本一致。     

离心造粒法制备盐酸坦索罗辛缓释微丸胶囊的工艺影响因素及体外释放度考察

目的:制备盐酸坦索罗辛缓释微丸。方法:采用离心造粒粉末层积法制备盐酸坦索罗辛微丸。通过考察主机转速、喷浆泵转速、供粉速度、喷枪雾化条件、抛光时间、包衣增重对微囊收率的影响,确定各因素较佳水平;制备微晶纤维素空白丸芯和盐酸坦索罗辛含药微丸,并在此基础上进行丙烯酸树脂水分散体包衣,对包衣微丸的释药特征进行探讨。结果:微丸成丸的最佳工艺参数为主机转速200r·min-1,喷浆泵转速20r·min-1,供粉速度50r·min-1,喷气压力0.5MPa,喷气流量10～15L·min-1,抛光时间5min,包衣增重11%。3批样品经放大试验,测得微晶纤维素空白丸芯、含药微丸、包衣微丸的收率分别是97.5%、95.4%、96.8%。缓释微丸胶囊体外释药行为较好地符合零级方程。结论:采用离心造粒法在优化的工艺条件下可制得符合要求的盐酸坦索罗辛缓释微丸。     

Formulation parameters affecting the performance of coated gelatin capsules with pulsatile release profiles

The objective of this study was to develop and evaluate a rupturable pulsatile drug delivery system based on soft gelatin capsules with or without a swelling layer and an external water-insoluble but -permeable polymer coating, which released the drug after a lag time (rupturing of the external polymer coating). The swelling of the gelatin capsule itself was insufficient to rupture the external polymer coating, an additional swelling layer was applied between the capsule and the polymer coating. Croscarmellose sodium (Ac-Di-Sol) was more effective as a swelling agent than low and high molecular weight hydroxypropylmethyl cellulose (HPMC; E5 or K100M). Brittle polymers, such as ethyl cellulose (EC) and cellulose acetate propionate (CAPr), led to a better rupturing and therefore more complete drug release than the flexible polymer coating, Eudragit RS. The lag time of the release system increased with higher polymer coating levels and decreased with the addition of a hydrophilic pore-former, HPMC E5 and also with an increasing amount of the intermediate swelling layer. The water uptake of the capsules was linear until rupture and was higher with CAPr than with EC. Soft gelatin capsule-based systems showed shorter lag times compared to hard gelatin capsules because of the higher hardness/filling state of the soft gelatin capsules. The swelling pressure was therefore more directed to the external polymer coating with the soft gelatin capsules. Typical pulsatile drug release profiles were obtained at lower polymer coating levels, while the release was slower and incomplete at the higher coating levels. CAPr-coated capsules resulted in a more complete release than EC-coated capsules.     

Microencapsulation of theophylline in composite wall system consisting of whey proteins and lipids

Theophylline was microencapsulated in composite whey protein-based wall systems containing different proportions of dispersed apolar filler, anhydrous milkfat. Wall emulsions exhibited uni-modal particle size distribution and had a mean particle size of 0.36-0.38 µm. Microcapsules were cross-linked by glutaraldehyde-saturated toluene via an organic phase. Spherical microcapsules ranging in diameter from 150 to larger than 700 µm were obtained and exhibited some surface cracks that could be attributed to the fragile nature of a peripheral, highly cross-linked 'shell' layer around the capsules. Core content ranged from 46.9-56.6% (w/w) and filler content ranged from 12.0-33.4% (w/w). Core and filler retention during microencapsulation ranged from 84.9-96.9% and from 85.1-89.6%, respectively. Core retention was proportionally related to the proportion of filler embedded in the wall matrix. Core release into SGF and SIF was affected by microcapsule size, type of dissolution medium and wall composition. Rate of core release was inversely proportional to filler content of the wall matrix. This could be attributed to effects of filler content on diffusion through the wall matrix and probably on swelling properties of microcapsules. Results indicated that incorporation of apolar filler in wall matrix of whey protein-based capsules provided the means to enhance retention of a water-soluble core during the microencapsulation process and to decrease the rate of core release into aqueous dissolution media.