Effect of process variables on the microencapsulation of vitamin A palmitate by gelatin-acacia coacervation

Microcapsules of vitamin A palmitate were prepared by gelatin-acacia complex coacervation. The effects of colloid mixing ratio, core-to-wall ratio, hardening agent, concentration of core solution, and drying method on the coacervation process and the properties of the microcapsules were investigated. The microcapsules of vitamin A palmitate were prepared using different weight ratios of gelatin and acacia, that is, 2:3, 1:1, and 3:2 under controlled conditions. The other factors studied were 1:1, 1:2, and 1:3 core-to-wall ratios; 30, 60, and 120 min of hardening time; 2, 5, and 10 ml of formaldehyde per 280 g of coacervation system as a hardening agent; and 30%, 40%, and 50% w/w vitamin A palmitate in corn oil as a core material. The drying methods used were air drying, hot air at 40°C, and freeze-drying. The results showed that spherical microcapsules were obtained for all conditions except for 30 min of hardening time, which did not result in microcapsules. The optimum conditions for free-flowing microcapsules with a high percentage of entrapped drug were 1:1 gelatin-to-acacia ratio and 1:2 core-to-wall ratio when hardening with 2 ml formaldehyde for 60 min and using 40% w/w vitamin A palmitate in corn oil as the core concentration. In addition, drying the microcapsules by freeze-drying provided microcapsules with excellent appearance.     

肉桂精油微囊化及其在果蔬保鲜中的应用

目的以壳聚糖、海藻酸钠为壁材,以肉桂精油为芯材,采用复凝聚法制备壳聚糖微胶囊,并将其应用于水果保鲜中。方法通过光学显微镜、扫描电子显微镜、傅里叶转化红外光谱等,确定微胶囊的最佳工艺参数、芯壁比及添加质量分数,并以芒果为实验对象,研究添加不同微胶囊质量分数的壳聚糖溶液对芒果保鲜效果的影响。结果当壳聚糖/海藻酸钠质量比为1∶2,氯化钙质量分数为1%,p H值为5,戊二醛质量分数为60%,交联时间为60 min,芯壁比为4∶1时,制备形成的壳聚糖微胶囊成球效果较好;微胶囊在壳聚糖溶液中的添加质量分数为4%时,以其涂膜的芒果保鲜效果最佳。结论肉桂精油经囊化后有效减少了气味、延缓了挥发,在果蔬保鲜中有较重要的现实研究意义。     

The Physico-Chemical Effect of Coacervation Conditions on the Diffusional Properties and Surface Morphology of Biodegradable Microcapsules

Microcapsules containing kaolin and hydrocortisone 21- acetate (HCAC) were produced through controlled coacervation of a biodegradable block copolymer of d-tartaric acid and 1, 10-octanediol, under Plait and non-Plait compositions. Diffusional studies indicated that the permeability of Plait microcapsules was at least 40% greater than non-Plait microcapsules at the same polymer to core ratio. Scanning electron photomicrographs of the various microcapsules suggested surface morphologic differences among microcapsules produced under Plait and non-Plait solvent conditions.     

The Physico-Chemical Effect of Coacervation Conditions on the Diffusional Properties and Surface Morphology of Biodegradable Microcapsules

Abstract

Microcapsules containing kaolin and hydrocortisone 21- acetate (HCAC) were produced through controlled coacervation of a biodegradable block copolymer of d-tartaric acid and 1, 10-octanediol, under Plait and non-Plait compositions. Diffusional studies indicated that the permeability of Plait microcapsules was at least 40% greater than non-Plait microcapsules at the same polymer to core ratio. Scanning electron photomicrographs of the various microcapsules suggested surface morphologic differences among microcapsules produced under Plait and non-Plait solvent conditions.     

复凝聚法制备磁性微胶囊及其磁响应特性

采用复凝聚法,以亲油改性的纳米Fe3O4为磁性颗粒,白油为分散介质,明胶、阿拉伯胶为壁材,在不同工艺条件下制备磁性微胶囊.通过激光粒度分析仪测试微胶囊的粒径及粒径分布,采用光学显微镜和扫描电子显微镜(SEM)观察微胶囊的表面形貌及分散状态,借助磁铁和振动样品磁强计(VSM)测试微胶囊的磁响应性能.结果表明,反应溶液pH=3.8、芯壁比1∶1时,微胶囊收率最高;搅拌速率为600r/min时,微胶囊的粒径分布最均匀;在pH=3.8、芯壁比1∶1、搅拌速率600r/min条件下制备的微胶囊形状规整性及单分散性好,且囊壁透明、表面光滑,具有良好的磁响应性能,可应用于磁泳显示和靶向药物传输领域.     

Development of self-microemulsifying drug delivery system for oral delivery of poorly water-soluble nutraceuticals

The objective of the study was to develop a self-microemulsifying drug delivery system (SMEDDS), also known as microemulsion preconcentrate, for oral delivery of five poorly water-soluble nutraceuticals or bioactive agents, namely, vitamin A, vitamin K2, coenzyme Q₁₀, quercetin and trans-resveratrol. The SMEDDS contained a 1:1 mixture (w/w) of Capmul MCM NF (a medium chain monoglyceride) and Captex 355 EP/NF (a medium chain triglyceride) as the hydrophobic lipid and Tween 80 (polysorbate 80) as the hydrophilic surfactant. The lipid and surfactant were mixed at 50:50 w/w ratio. All three of the SMEDDS components have GRAS or safe food additive status. The solubility of nutraceuticals was determined in Capmul MCM, Captex 355, Tween 80, and the SMEDDS (microemulsion preconcentrate mixture). The solubility values of vitamin A palmitate, vitamin K2, coenzyme Q₁₀, quercetin, and trans-resveratrol per g of SMEDDS were, respectively, 500, 12, 8, 56, and 87?mg. Appropriate formulations of nutraceuticals were prepared and filled into hard gelatin capsules. They were then subjected to in vitro dispersion testing using 250?mL of 0.01 N HCl in USP dissolution apparatus II. The dispersion test showed that all SMEDDS containing nutraceuticals dispersed spontaneously to form microemulsions after disintegration of capsule shells with globule size in the range of 25 to 200?nm. From all formulations, except that of vitamin K2, >80–90% nutraceuticals dispersed in 5–10?min and there was no precipitation of compounds during the test period of 120?min. Some variation in dispersion of vitamin K2 was observed due to the nature of the material used (vitamin K2 pre-adsorbed onto calcium phosphate). The present report provides a simple and organic cosolvent-free lipid-based SMEDDS for the oral delivery of poorly water-soluble nutraceuticals. Although a 50:50 w/w mixture of lipid to surfactant was used, the lipid content may be increased to 70:30 without compromising the formation of microemulsion.     

准均匀分散电子墨水微胶囊的制备研究

在明胶阿拉伯胶复合凝聚过程中,通过控制十二烷基硫酸钠(SDS)浓度和搅拌速度,制备了准均匀分散的电子墨水微胶囊。实验表明:随着SDS浓度和搅拌速度的增加,囊芯液滴的平均粒径减小;同时,囊芯液滴的平均粒径的对数与搅拌速度的对数呈现出良好的线性关系。在最佳实验条件(SDS 0.01%(质量分数),搅拌速度800r/min)下获得的微胶囊大小均匀且形状规则、表面光滑无粘连,平均粒径约为40μm,湿胶囊壁厚约为2μm。     

自修复微胶囊复合材料的制备及力学性能研究

为了提高树脂基复合材料的使用寿命,以脲醛树脂为壁材,双环戊二烯为囊芯,通过原位聚合法制备了内含修复液的微胶囊,探讨了反应过程中脲醛量比及乳化剂用量等对微胶囊表面形貌和结构的影响.通过优化工艺条件制备出表面致密的微胶囊,并将微胶囊埋植在环氧树脂基体中制备复合材料.采用扫描电镜对胶囊进行形貌表征,运用快速傅里叶变换红外光谱...     

Release of Theophylline from Ethyl Cellulose Mecrocapsues Alone and in Conjuction with Fat Embedded (Precirol®) Granules and Hydroxypropyl Methycellulose

Abstract

Microcapsules of theophylline with ethyl cellulose were prepared by coacervation technique using cabosil® (silicon dioxide) as separant. Tablets were prepared from microcapsules, microcapsules + theophylline fat embedded granules, and microcapsules and hydroxypropyl methylcellulose 4000 (HPMC). Release was studied in vitro by the rotating basket method. Prolonged release of theophylline was observed from microcapsules with no drug dumping. The release from microcapsules was of first-order whereas that from all the tablet formulation was diffusion controlled according to the Higuchi model. Good correlation was found between release rate and core:wall ratio for all the systems. Decrease in hardness of tablets made from microcapsules alone decreased the release rate, indicating damage of microcapsules during compression. The tablets compressed from fat embedded granules, microcapsules with fat embedded granules, and microcapsules with HPMC gave a desired release for a 74 hour sustained release preparation.     

聚甲基丙烯酸甲酯包覆十二醇微胶囊的制备及表征

以相变物质正十二醇(DA)为芯材,聚甲基丙烯酸甲酯(PMMA)为壁材,采用悬浮聚合法制备了正十二醇-聚甲基丙烯酸甲酯(DA@PMMA)微胶囊。通过差示扫描量热仪(DSC),扫描电镜(SEM),透射电镜(TEM),傅里叶变换红外光谱仪(FIIR)和热重分析仪(TGA)等仪器对微胶囊进行检测表征。结果表明:当工艺为苯乙烯-马来酸甘钠盐(SMA)加入量占DA质量的7.5%,偶氮二异丁腈(AIBN)加入量占单体甲基丙烯酸甲酯(MMA)质量的7.5%,芯材壁材质量比为2∶1,搅拌速度为1 000r/min时,所制备的微胶囊整体性能最好。DA@PMMA微胶囊为球形,平均粒径26μm,DA@PMMA微胶囊中DA的质量分数为66%。DA@PMMA微胶囊的熔化焓和结晶焓分别是137.6J/g和132.8J/g。TGA和FIIR的分析表明,DA@PMMA微胶囊具有良好的性能。     

Controlled Release Kinetics of Captopril From Tableted Microcapsules

Abstract

Different viscosity grades ethylcellulose coated captopril microcapsules were prepared using temperature induced coacervation method from cyclohexane containing 2% Tween 80. Microcapsules were compressed directly into tablets. In vitro dissolution was carried out in 0.1 N HCl at 37°C using the rotating basket method. Release from tablets of all the batches was extensively prolonged in comparison to the respective microcapsules. The longest time for 70% drug release was shown by microcapsules (55min) and tablets (378 min) of the batch E-2. Release rate constants, correlation, determination and regression coefficients were calculated for the first-order, zero-order and Higuchi's equations. The best fit of release kinetics with the highest correlation and determination coefficients was achieved with the first-order followed by Higuchi's plot.     

溶剂挥发法制备苯乙烯微胶囊

采用简单易控制的溶剂挥发法成功制备了聚砜材料包覆苯乙烯的自修复微胶囊,通过核磁共振氢谱(1H-NMR)、扫描电子显微镜(SEM)、元素分析仪和热重分析仪(TGA)对微胶囊的化学结构、表面形貌及其热性能进行了研究.结果表明,选择0.5％的聚乙烯醇表面活性剂,700 r/min乳化转速、芯壁比2∶1时制得的微胶囊表面光滑,体积平均粒径为120μm,并且分布比较窄,微胶囊在室温下具有一定缓释性.     

Gelatin-Acacia Complex Coacervation as a Method for Ketoprofen Microencapsulation

Ketoprofen microcapsules were prepared by complex coacervation between gelatin and acacia, and dried with different methods: isopropanol addition, spray-drying, and freeze-drying, Successively, microparticles were analyzed by infrared thembalance, ultraviolet spectroscopy, optical and scanning electron microscopy, and sieves; and subjected to dissolution studies in order to examine parameters such as yield, moisture content, encapsulation percentage, morphology of solid particles, particle size, and dissolution behavior. Provided that encapsulation and drying methods did not affect ketoprofen dissolution profiles, the most appropriate drying method for industrial purposes was spray-drying.     

预聚合条件对密胺树脂相变微胶囊包覆效率的影响

通过改变预聚合条件制备了一系列密胺树脂相变微胶囊,采用扫描电镜(SEM)、差示扫描量热仪(DSC)和热重分析仪(TG)对其进行表征。探究了微胶囊包覆效率的计算方法,并结合SEM的测试结果,系统地研究了甲醛与三聚氰胺(F/M)摩尔比、预聚合时间和预聚体质量分数等因素对包覆效率(E_n)的影响。实验结果表明,采用DSC-TG联用的方法计算得到的E_n可以更准确地表征相变微胶囊的包覆情况。E_n随F/M摩尔比的增加和预聚合时间的缩短而增大,随预聚体质量分数的增加先增大后减小。当F/M摩尔比为2.5,预聚合时间为30min,预聚体质量分数为10%时,所制备微胶囊的E_n可以达到88.6%。     

毒死蜱/脲醛树脂微胶囊的制备工艺优化及缓释动力学

随着人们健康与环保意识的不断加强,农药施用量大、效率低、高残留等问题日益受到人们的重视,对农药进行微胶囊化,有助于有效解决当前农药使用过程中所面临的问题。采用脲醛树脂作为壁材,以十二烷基硫酸钠为乳化剂,采用原位聚合法制备毒死蜱/脲醛树脂微胶囊。研究了乳化剂种类和用量、pH值、酸化时间对微胶囊粒径及其分布的影响,并进一步探讨微胶囊的载药量、包封率及释放动力学。结果表明,采用3%(质量分数)的十二烷基硫酸钠为乳化剂,在酸化时间为90min、酸化终点pH值为2.5、搅拌速度为1 200r/min、芯壁比为1∶3、固化温度为60℃时,所制备的毒死蜱/脲醛树脂微胶囊的粒径分布窄,平均粒径约为113μm,载药量达53%以上,包封率达62%以上。毒死蜱/脲醛树脂微胶囊的缓释性能及动力学研究结果显示,所制备的毒死蜱/脲醛树脂微胶囊的缓释效果明显,10天内能释放90%的药物,释放过程遵循Fick扩散机理。可见,制备的毒死蜱/脲醛树脂微胶囊具有较高的载药量、较好的包封率以及缓释性能,可进一步开发为新型的农药制剂,并为开发缓释农药新剂型提供理论支持与实践参考。     

Micromeritic Properties of Nitrofurantoin Microcapsules

Abstract

In our previous study, we have prepared nitrofurantoin microcapsules using carboxymethylcellulose (CMC) and aluminium sulphate by a coacervation technique. In the present study, the micromeritics of these microcapsules were investigated in terms of standardization of the crude materials employed, the microcapsules product and the dosage forms prepared from these microcapsules. The microcapsules were prepared with a 1:1 core: wall ratio and sieved into three particle sizes. Both the micromeritic properties of the pure drug and the polymer were studied by determining their bulk volume and weight, tapping volume and weight, fluidity, angle of repose, weight deviation, particle size distribution, density and porosity, The particle size range went from approximately 250μm to 3000μm with a peak between 900μm and 1350μm. The results indicate that the flowability and the particle size of the resultant microcapsules were much increased compared with the raw materials. As the microcapsule size increases the porosity also increases but the density decreases.

The weight deviation of the microcapsules first sieved then filled into hard gelatin capsules was carried on according to the USP XXII. Hard gelatin capsule size was found by Lindenwald-Tawashi nomogram as number 3. The geometric mean diameters and the geometric standard deviation of microcapsules were calculated as 750 pm for number distribution and 1275μm for weight distribution and 1.52 for number and weight distribution respectively.

In addition to evaluate whether some kind of glidant will be needed during tableting of microcapsules and filling of them into hard gelatines, “Hausner ratio and consolidation indexes” were calculated.

The results obtained suggest that sustained release dosage forms of nitrofirantoin can be prepared from the obtained microcapsules as far as the micromeritic properties is concerned and the microencapsulation changed the micromeritic properties of the crude materials significantly.     

Micromeritic Properties of Nitrofurantoin Microcapsules

In our previous study, we have prepared nitrofurantoin microcapsules using carboxymethylcellulose (CMC) and aluminium sulphate by a coacervation technique. In the present study, the micromeritics of these microcapsules were investigated in terms of standardization of the crude materials employed, the microcapsules product and the dosage forms prepared from these microcapsules. The microcapsules were prepared with a 1:1 core: wall ratio and sieved into three particle sizes. Both the micromeritic properties of the pure drug and the polymer were studied by determining their bulk volume and weight, tapping volume and weight, fluidity, angle of repose, weight deviation, particle size distribution, density and porosity, The particle size range went from approximately 250μm to 3000μm with a peak between 900μm and 1350μm. The results indicate that the flowability and the particle size of the resultant microcapsules were much increased compared with the raw materials. As the microcapsule size increases the porosity also increases but the density decreases.

The weight deviation of the microcapsules first sieved then filled into hard gelatin capsules was carried on according to the USP XXII. Hard gelatin capsule size was found by Lindenwald-Tawashi nomogram as number 3. The geometric mean diameters and the geometric standard deviation of microcapsules were calculated as 750 pm for number distribution and 1275μm for weight distribution and 1.52 for number and weight distribution respectively.

In addition to evaluate whether some kind of glidant will be needed during tableting of microcapsules and filling of them into hard gelatines, “Hausner ratio and consolidation indexes” were calculated.

The results obtained suggest that sustained release dosage forms of nitrofirantoin can be prepared from the obtained microcapsules as far as the micromeritic properties is concerned and the microencapsulation changed the micromeritic properties of the crude materials significantly.     

Gelatin-Acacia Complex Coacervation as a Method for Ketoprofen Microencapsulation

Abstract

Ketoprofen microcapsules were prepared by complex coacervation between gelatin and acacia, and dried with different methods: isopropanol addition, spray-drying, and freeze-drying, Successively, microparticles were analyzed by infrared thembalance, ultraviolet spectroscopy, optical and scanning electron microscopy, and sieves; and subjected to dissolution studies in order to examine parameters such as yield, moisture content, encapsulation percentage, morphology of solid particles, particle size, and dissolution behavior. Provided that encapsulation and drying methods did not affect ketoprofen dissolution profiles, the most appropriate drying method for industrial purposes was spray-drying.     

山梨醇磷酸酯蜜胺盐的合成

采用非溶剂法经过二步反应合成了膨胀型阻燃剂山梨醇二磷酸酯蜜胺盐(SDM).首先三氯氧磷和山梨醇反应得到山梨醇磷酸酯二磷酰氯(SDD),然后SDD再与蜜胺反应,得到SDM并将其微胶囊化,研究了反应物配比、反应温度、反应时间等因素对产品收率的影响以及微胶囊化SDM的阻燃性能.认为SDD最适宜的合成条件为:nSOR:npoc=1:3,在100℃下反应40 min,SDD的收率为74%;SDM最佳合成条件为:nsdD:nMEL=1:2,反应温度为140℃,反应时间为2 h,SDM收率约为8l%.     

广藿香油微胶囊的制备与性能

以广藿香油为芯材,壳聚糖(CTS)、壳聚糖季铵盐(HACC)、阿拉伯胶(GA)为壁材,采用复凝聚法制备了广藿香油微胶囊。采用扫描电子显微镜(SEM)、激光粒度仪、傅立叶红外光谱(FT-IR)对微胶囊进行表征,并对其热稳定性、缓释性、抗菌性进行了研究。结果表明,微胶囊球形规则、分散性好,湿囊的平均粒径为10.8μm,微胶囊化提高了广藿香油的热稳定性。在相对湿度24%,37℃密封环境中储藏20 d,微胶囊对金黄色葡萄球菌、大肠杆菌的最小杀菌浓度分别为1.25 mg/mL和2.5 mg/mL。