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.     

复凝聚法制备桃金娘油肠溶微囊

目的采用复凝聚法制备桃金娘油肠溶微囊,并对其体外性质进行评价。方法选用海藻酸钠、氯化钙、壳聚糖为囊材采用复凝聚法制备桃金娘油微囊,用扫描电子显微镜(scanning electron microscope,SEM),Beckman Coulter LS 230激光粒度仪表征了微囊表面形态及粒径,采用顶空进样-GC色谱法测定了载药量和包封率。结果正交设计优化处方和工艺如下:海藻酸钠质量浓度为25g.L-1、壳聚糖质量浓度为3 g.L-1、凝聚速度为5 mL.min-1和凝聚时间为60 min,所得微囊粒径为(14.23±1.45)μm,载药质量分数为(11.3±0.4)%,包封率为(73.6±2.5)%。微囊具有耐酸和肠溶性能,表面褶皱,粒径分布均匀。结论复凝聚法可用于桃金娘油肠溶微囊的制备。     

Influence of pH adjustment on microcapsules obtained from complex coacervation of gelatin and acacia

Abstract

The coacervation behaviour of commercial grade gelatin and acacia mixtures was studied with five different acids to adjust the coacervation pH, i.e. HCI, HNO₃, H₂SO₄, acetic acid, and citric acid. The electrical equivalence pH value (EEP) of the polymer mixture was determined by means of a streaming current detector (SCD). With all acids-except H₂SO₄-maximum coacervate yield was observed at the EEP. Using H₂SO₄ the EEP was found at a lower pH value than compared with the point of maximum coacervate yield. The quantity of coacervate at the EEP was significantly reduced in the presence of H₂SO₄ whereas with all other acids, almost no differences were found. The dependence of the coacervate volume on the added amount of acid did not change in parallel to the dry coacervate yield and there was no coincidence of the maximum coacervate volume and the EEP. The barrier properties of the capsule shells of corresponding microcapsules using indomethacin as a model drug were examined by dissolution studies. Indomethacin microcapsules showed the slowest release rate when the coacervation pH was adjusted to the EEP and not to the pH of maximum coacervate yield. As expected from the coacervation behaviour, dissolution profiles of the microcapsules were quite similar even when different acids were used for pH adjustment.     

薄荷油致大鼠肝毒性时量关系及对肝细胞超微结构的影响

目的研究薄荷油致大鼠肝毒性的时效、量效关系以及对肝细胞超微结构的影响。方法大鼠按不同时间点或不同剂量分组,口服给药后检查血清ALT等肝功能指标,光镜或电镜下观察肝组织形态及肝细胞超微结构变化。结果与正常组相比,薄荷油组大鼠血清ALT等肝功能数值升高,于给药后24～48h达到高峰;随着剂量增大,ALT等肝功能指标相应升高(P<0.01)。薄荷油高剂量组对肝组织损伤明显,出现肝细胞核溶解等超微结构变化,与CCl4组相似。结论大鼠一次性口服大剂量薄荷油可造成急性肝脏毒性,并显示一定的毒性时效、量效关系;肝细胞损伤可出现脂肪变性、坏死等结构变化。     

复方莪术油微囊中莪术醇的气相色谱测定

目的：建立莪术油、干蟾皮水溶性提取物微囊制剂和莪术油原料的定量分析方法。方法：用气相色谱法使微囊制剂和原料油中挥发性有效成分达到良好分离,并对主要抗肿瘤成分莪术醇进行定性定是量分析。结果:组分与内标分离良好,莪术醇在0.05－1.6g/L范围内线性关系良好,r=0.9999,高、低二个浓度的日内与日间精密度以及3个浓度加样回收率的相对标准误差均＜2％。结论：本法定量准确可靠,可以作为该制剂与原料油的定性定量分析方法。     

Investigation of the effects of peppermint oil and valerian on rat liver and cultured human liver cells

1. The aim of the present study was to investigate the effects of peppermint oil and valerian on rat liver and cultured human hepatoma cells. 2. Rats received a single oral dose of peppermint oil (8.3-830 microL/kg) or valerian (0.31-18.6 g/kg), or daily oral doses of 83 microL/kg peppermint oil or 3.1 g/kg valerian for 28 days. After 24 h, rats were anaesthetized and measurements made of bile flow, liver function and in vivo sinusoidal area. Livers were then removed for histology. 3. Bile flow was unaffected by any treatment, except acute high-dose peppermint oil (830 microL/kg; 70% increase in flow). No change in liver enzyme activity was found, except for a 45% increase in alkaline phosphatase after chronic peppermint oil. No change in sinusoidal area in vivo or in histology was found following any treatment, although pretreatment with carbon tetrachloride reduced sinusoidal bed area and produced histological damage. Incubation of human hepatoma cells with 0.5 microL/mL (but not 0.05 microL/mL) peppermint oil or 20 mg/mL (but not 2 mg/mL) valerian resulted in increased cell death. 4. In conclusion, the present study demonstrated in vitro toxicity of high doses of valerian and peppermint oil in cultured human hepatoma cells and, at doses 2-3 orders of magnitude greater than those recommended for human use, an increase in rat bile flow after acute peppermint oil and an increase in alkaline phosphatase after chronic peppermint oil.     

Impact of the type of emulsifier on the physicochemical characteristics of the prepared fish oil-loaded microcapsules

Fish oil microcapsules were successfully prepared from fish oil-in-water emulsions using chitosan as shell material and anionic surfactants sodium dodecyl sulphate (SDS), sodium dodecylbenzenesulfonate (SDBS), sodium cholate (cholate), and sodium deoxycholate (DOC) as emulsifiers. The type of emulsifier influenced the physicochemical characteristics of the prepared microcapsules to different extents. The microcapsules formed with DOC showed the least mean effective diameter (MED) of 500?nm. Emulsion formed with DOC exhibited the smallest MED of 100?nm. The emulsions showed negative zeta potential values which became positive after encapsulation with chitosan. The surfactants showed little influence on thermal stability. Microcapsule suspensions showed creaming over storage. Fish oil at higher loading in SDS microcapsules showed higher primary and secondary oxidation. All microcapsules showed sustained release but the values varied depending upon the surfactants. The emulsion and microcapsules formed with DOC showed better morphology and stability despite its lower loading and encapsulation efficiency.     

Optimisation of the microencapsulation of lavender oil by spray drying

Background: Lavender oil consists of around 100 components and is susceptible to volatilisation and degradation reactions.

Aim: Microencapsulate lavender oil by spray drying using a biocompatible polymeric blend of gum acacia and maltodextrin to protect the oil components. Effect of total polymer content, oil loading, gum acacia, and maltodextrin proportions on the size, yield, loading, and encapsulation efficiency of the microparticles was investigated.

Methods: Morphology and oil localisation within microparticles were assessed by confocal laser scanning electron microscope. Structural preservation and compatibility were assessed using Fourier transform infra-red spectroscopy, differential scanning calorimetry, and gas chromatography–mass spectrometry.

Results: Lavender microparticles of size 12.42?±?1.79?µm prepared at 30 w/w% polymer concentration, 16.67 w/w% oil loading, and 25w/w% gum acacia showed maximum oil protection at high loading (12?mg w/w%), and encapsulation efficiency (77.89 w/w%).

Conclusion: Lavender oil was successfully microencapsulated into stable microparticles by spray drying using gum acacia/maltodextrin polymeric blend.     

Effect of the cross-linking agent and drying method on encapsulation efficiency of orange essential oil by complex coacervation using whey protein isolate with different polysaccharides

Orange essential oil was microencapsulated by complex coacervation with whey protein isolate (WPI): carboxymethylcellulose (CMC), WPI:sodium alginate (SA) and WPI:chitosan (CH). Effect of pH, protein:polysaccharide ratio and solid concentration on coacervation efficiency were selected for the best coacervation conditions. Tannic acid (TA), sodium tripolyphosphate, oxidised tannic acid and transglutaminase enzyme (TG) were used as cross-linking agents. Highest encapsulation efficiency (EE) for wet coacervated microcapsules ranged from 88% to 94%. Microcapsules were freeze and spray dried to evaluate their effect on its integrity. EE was higher than 80% in freeze dried coacervated microcapsules with and without cross-linking agent, but they formed a solid cake. Spray-dried samples formed a free fluid solid (10–20?µm), where the systems WPI:CMC and WPI:CH cross-linked with TA and TG, respectively showed the highest EE (47% and 50% respectively), representing 400% improvement compared to the samples without cross-linking.     

Effect of oil loading on microspheres produced by spray drying

Oil-loaded microspheres were produced by spray drying emulsions consisting of fish oil and modified starch suspensions with different oil loadings. The emulsion stability was assessed by oil droplet size analysis. Microspheres were characterized in terms of size, morphology, yield and microencapsulation efficiency. It was found that an increase in oil loading resulted in emulsions containing larger oil droplets. This corresponded with larger mean microsphere diameters and rounder microspheres. However, high oil loadings produced lower yields and affected microencapsulation efficiencies.     

Effect of the shell-forming polymer ratio on the encapsulation of tea tree oil by complex coacervation as a natural biocide

Abstract

The aim of this study was to develop footwear materials with antimicrobial properties using microencapsulated Tea Tree oil (TTO) as a natural biocide. For that purpose, gelatine–carboxymethylcellulose based microcapsules containing TTO were synthesised by a complex coacervation process. Furthermore, the influence of the gelatine (G)/sodium carboxymethylmethyl cellulose (CMC) ratio (G/C) on the microcapsule properties, as well as in the microencapsulation oil efficiency, was evaluated. The microcapsules were characterised by different experimental techniques and applied to footwear materials (leather and textile) to evaluate their performance. The microcapsule durability under different conditions, such as rubbing and ironing, was analysed in order to simulate shoe manufacturing and shoe wearing. The properties of the microcapsules obtained by complex coacervation, using gelatine and sodium carboxymethylcellulose as shell-forming polymers, are determined by the ratio between those two polymers (G/C). The results obtained showed a notable effect of G/C ratio on the formation of the coacervate during the synthesis process and also on the encapsulation efficiency of the antimicrobial oil, with the optimal value for the G/C ratio being around 10.     

Effect of formulation and processing factors on the characteristics of biodegradable microcapsules of zidovudine

Abstract

Biodegradable microcapsules of zidovudine (AZT) were prepared using poly-(lactide/glycolide) by the solvent evaporation technique. The objective of this project was to focus on the effect of several formulation and processing factors on the efficiency of encapsulation, surface morphology, and drug release profiles. When the drug was incorporated as powder or as aqueous suspension containing a high amount of insoluble particles, to the organic phase the surface of the microcapsules was appeared to be wrinkled. The efficiency of encapsulation decreased when AZT powder was dispersed directly into the organic solvent instead of adding as an aqueous solution. When the relative volume of the aqueous phase containing 1% PVA was changed from 25 up to 125% of the volume of the organic phase, the efficiency of encapsulation, surface morphology, and release profiles did not change significantly. The efficiency of encapsulation decreased from 9 to 3·8% when the drug loading was increased from 10 to 50% of the weight of the polymer.     

Effect of microwave heating with different exposure times on physical and chemical parameters of olive oil

This study reflects the effect of different microwave heating times (1, 3, 5, 10 and 15 min) on physical and chemical characteristics of three Portuguese olive oils from three protected designation of origin (PDO), “Azeite de Trás-os-Montes PDO”, “Azeites da Beira Interior PDO”, and “Azeite de Moura PDO”. The parameters evaluated were free acidity, peroxide value, specific extinction coefficients (K₂₃₂ and K₂₇₀), color and chlorophylls and carotenoids content. A differential pulse voltammeter was also used to monitor the changes in α-tocopherol content. The results showed that microwave heating produce losses in the quality of the different analysed olive oils. The heating time did not promote the occurrence of hydrolysis in the samples since no changes in free acidity values were found. All other parameters were affected by exposure time in a similar way: in the firsts 3 min no marked changes were observed, after that the quality of the oil decrease significantly. The microwave heating time also affects the total chlorophylls, carotenoids and α-tocopherol contents which clearly decreased as long as the exposure time increases. After 15 min of heating the electrochemical signal, due to the α-tocopherol, disappear completely in the voltamogram.     

Effect of processing variables on the release and particulate properties of sustained release amoxicillin microcapsules prepared by emulsion solvent evaporation

This study reports the preparation of amoxicillin microcapsules by an emulsion solvent evaporation process. In particular the effect of processing variables including the dimension and position of stirring paddle and container; volume of continuous phase versus dispersion phase; stirring speed and encapsulation temperature on the release and particulate properties of the amoxicillin microcapsules were determined. When the diameter of the paddle was half of that of the container and the clearance between the paddle and the bottom of the vessel was 1/4 of the total volume in the vessel, almost no material stuck to the inside wall of the beaker and uniform microcapsules were prepared. Very uniform, round microcapsules were also prepared with a high yield when V(acetone): V(light mineral oil) = 1 : 3 and 1 : 5 because these systems ensured the formation of uniform emulsions. Physical evaluation of the microcapsules also showed that optimum drug release was achieved when the microcapsules were round, did not aggregate, were protected from the burst effect, the stirring speed for preparation was between 600-800 rpm and evaporation temperature was 25 degrees C. Microcapsules prepared using these ideal conditions achieved constant amoxicillin release for up to 12 h.     

野油菜黄单胞菌中gumD基因的过表达对产黄原胶的影响

目的在野油菜黄单胞菌58(Xc58)中过量表达产胶基因gumD,提高黄原胶发酵产量和质量。方法通过PCR扩增、重组质粒构建、三亲本接合等方法,将重组质粒pBBR-gumD转入原始菌Xc58。结果工程菌与原始菌相比,黄原胶产量提高11.19%,黏度提高6.31%,重均分子质量提高20.21%,乙酰基含量提高77.07%,丙酮酸含量下降6.34%。结论改造后的菌株的黄原胶发酵产量和质量都较原始菌株有所提高。     

花椒籽油对大鼠动脉粥样硬化的作用研究

目的探究花椒籽油对大鼠脂质代谢的影响,从而探讨其对动脉粥样硬化的作用。方法 24只健康SD大鼠随机分为3组:对照组、高脂组、花椒籽油组,对照组普通饲料喂养,其余两组均高脂饲料喂养,花椒籽油组同时给予花椒籽油灌胃,8周后腹主动脉采血,测定其TC、TG、HDL-C的含量。结果与高脂组相比,花椒籽油组血清TC、TG显著降低(P<0.01,P<0.05),HDL-C显著升高(P<0.01)。结论花椒籽油可有效降低高脂大鼠的TC、TG含量,升高HDL-C含量,对大鼠的动脉粥样硬化形成有一定的防治作用。     

正交设计研究酸枣仁油与柏子仁油配伍对小鼠自主活动的影响

目的观察酸枣仁油与柏子仁油合用对小鼠自主活动的影响,探讨酸枣仁油与柏子仁油配伍的合理性及配伍的最佳组合。方法采用正交设计进行拆方研究,确定因子数和水平,按正交表L9(34)设计,将小鼠分为9个组,每组重复5次,分别给予不同的剂量组合,并观察小鼠用药后的自主活动次数。结果酸枣仁油及柏子仁油均能减少小鼠自主活动次数(P<0.05),两者之间有交互作用(P<0.05)。结论酸枣仁油和柏子仁油均为主要因素,两者配伍合理并且最佳组合为酸枣仁油与柏子仁油均为5.0mL·kg-1。     

东阿阿胶对体外培养的癌症放疗病人外周血淋巴细胞的影响

目的观察东阿阿胶对体外培养的癌症放疗病人外周血淋巴细胞的影响。方法SD大鼠东阿阿胶灌胃给药3d后取血制备含药血清;取放疗病人外周血,经淋巴细胞分离液分离出淋巴细胞,接种于96孔培养板,东阿阿胶含药血清按分组刺量加入培养孔中,阳性对照为胸腺肽,37℃,5％CO2培养一定时间后,上流式细胞仪测定增殖率、T淋巴细胞活化抗原的表达、淋巴细胞表型及Th1／Th2细胞的比例。结果与对照组相比,不同剂量含东阿阿胶血清均能显著促进丝裂原诱导的淋巴细胞增殖．促进淋巴细胞活化,提高CD3^＋（T细胞）、CD3^＋CD56^＋CD16^＋（NK细胞）的比例和CD3^＋CD4^＋／CD3^＋CD8^＋比值,增加Th1,降低Th2。结论东阿阿胶能解除或减轻肿瘤和放疗对免疫系统产生的抑制作用,有助于免疫细胞对肿瘤的应答。     

Influence of formulation and process parameters on the release characteristics of ethylcellulose sustained-release mini-matrices produced by hot-melt extrusion

Mini-matrices (multiple unit dosage form) with release-sustaining properties were developed by hot-melt extrusion (cylindrical die: 3 mm) using metoprolol tartrate as model drug and ethylcellulose as sustained-release agent. Dibutyl sebacate was selected as plasticizer and its concentration was optimized to 50% (w/w) of the ethylcellulose concentration. Xanthan gum, a hydrophilic polymer, was added to the formulation to increase drug release. Changing the xanthan gum concentration modified the in vitro drug release: increasing xanthan gum concentrations (1%, 2.5%, 5%, 10% and 20%, w/w) yielded a faster drug release. Zero-order drug release was obtained at 5% (w/w) xanthan gum. Using kneading paddles, smooth extrudates were obtained when processed at 60 °C. At least one mixing zone was required to obtain smooth and homogeneous extrudates. The mixing efficacy and drug release were not affected by the number of mixing zones or their position along the extruder barrel. Raman analysis revealed that metoprolol tartrate was homogeneously distributed in the mini-matrices, independent of screw design and processing conditions. Simultaneously changing the powder feed rate (6–25–50 g/min) and screw speed (30–100–200 rpm) did not alter extrudate quality or dissolution properties.     

黑老虎挥发油成分的GC-MS分析

目的对黑老虎含有的挥发油成分进行分析。方法用水蒸气蒸馏后,采用GC-MS联用技术。结果从黑老虎挥发油中分离出151种化学成分,鉴定出其中的45个,占挥发油总量的64.56%,其中相对含量在1%以上的有18个。结论黑老虎挥发油中主要成分为异石竹烯、δ-榄香烯、乙酸龙脑酯、δ-荜澄茄烯、β-古芸烯、γ-依兰油烯及其水合物。