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.     

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.     

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。     

单、复凝聚法制备酮康唑微囊的性状和包封率比较

目的:比较单、复凝聚法制备微囊的外观性状和包封率,为进一步研究微囊的制备工艺打下基础。方法:以酮康唑作为囊芯物,用明胶和阿拉伯胶作囊材,采用常规的单、复凝聚法分别制备酮康唑微囊,并在光学显微镜下比较其外观性状;采用单波长紫外分光光度法建立微囊中酮康唑含量测定方法,在此基础上计算其药物包封率。结果:2种方法所得的微囊均为白色粉末,采用单凝聚法得到的微囊平均粒径为32.20μm, 相对包封率为56.11%;复凝聚法制备的微囊则分别为7.99μm和83.42%。结论:采用相分离-凝聚法制备微囊时,复凝聚法所得结果较好。     

Physical factors affecting microencapsulation by simple coacervation of gelatin

Gelatin has been coacervated at 60 degrees C using sodium sulphate. Interfacial tensions between coacervate and supernatant liquid, coacervate and two oils (with and without one of two drugs, clofibrate and chlormethiazole) and supernatant liquid and the oils (+/- drug) have been measured by a drop volume technique, in the presence and absence of one of three surfactants, cetrimide, sodium lauryl sulphate and hexadecyltrimethylammonium lauryl sulphate (double salt). Spreading coefficients calculated from tensions indicate that coacervate should spread readily over oil droplets in presence of double salt, less readily with cetrimide and spreading is unlikely in the presence of sodium lauryl sulphate. The sign of the charge on coacervate droplets and oil droplets was identified under different conditions and showed coacervate droplets and oil droplets have opposite charges except in the presence of sodium lauryl sulphate. Microcapsules were prepared using cetrimide or 'double salt' as emulsifier and release of drug measured. Those prepared with 'double salt' released more slowly than those prepared with cetrimide.     

Application of a hydrodynamic model to microencapsulation by coacervation

The role of the hydrodynamic conditions in determining the characteristics of microcapsules made by coacervation was investigated in this study. The model proposed by Armenante and Kirwan, regarding the mass transfer to microcapsules in a turbulent agitated system, was applied. The working hypothesis was that the microcapsules are formed in microeddies generated by the agitation source. The dimensions of the microeddies, calculated in the vicinity of the agitation source according to Armenante and Kirwan, depend on the physical properties of the liquid medium and are inversely proportional to the power exchanged from the agitation source of the system. The power was determined according to the hydrodynamic rules developed by Rushton et al. The experimental results confirmed the hypothesis of the model. Indeed, a good relationship was found between the calculated size of the microeddies and the measured diameter of the microcapsules. Moreover, the distribution error (the standard deviation of the microcapsule size frequency distribution curve) was found to be proportional to the mean diameter value of the microcapsules and microeddies. This can be explained considering that the microeddies diameter increases by moving away from the agitation source and, consequently, a distribution of microeddies of difference sizes is present in the medium. The distribution error, which represents the difference between the smaller and the larger diameters, is inversely proportional to the exchanged power and, consequently, proportional to the mean diameter.     

Application of a hydrodynamic model to microencapsulation by coacervation

The role of the hydrodynamic conditions in determining the characteristics of microcapsules made by coacervation was investigated in this study. The model proposed by Armenante and Kirwan, regarding the mass transfer to microcapsules in a turbulent agitated system, was applied. The working hypothesis was that the microcapsules are formed in microeddies generated by the agitation source. The dimensions of the microeddies, calculated in the vicinity of the agitation source according to Armenante and Kirwan, depend on the physical properties of the liquid medium and are inversely proportional to the power exchanged from the agitation source of the system. The power was determined according to the hydrodynamic rules developed by Rushton et al. The experimental results confirmed the hypothesis of the model. Indeed, a good relationship was found between the calculated size of the microeddies and the measured diameter of the microcapsules. Moreover, the distribution error (the standard deviation of the microcapsule size frequency distribution curve) was found to be proportional to the mean diameter value of the microcapsules and microeddies. This can be explained considering that the microeddies diameter increases by moving away from the agitation source and, consequently, a distribution of microeddies of difference sizes is present in the medium. The distribution error, which represents the difference between the smaller and the larger diameters, is inversely proportional to the exchanged power and, consequently, proportional to the mean diameter.     

Gliadin matrices for microencapsulation processes by simple coacervation method

The aim of this study was to use a vegetal protein (gliadin) as a wall-forming component to produce microcapsules. The microencapsulation technique employed was the simple coacervation method and the encapsulated product was a non-food oil, hexadecane. Hexadecane was emulsified by a gliadin solution and the coacervation phenomena induced by adding a salt-solution in the continuous phase of the emulsion containing gliadin. The study of the coacervation conditions has shown that the richer in protein the continuous phase, the smaller the quantity of salt required. The main problem of the microencapsulation process by salting-out was to control the capsule size and the agglomeration of the capsules. This study succeeded in preventing the agglomeration phenomenon by adjusting the kinetics of the salt addition. When the feed rate of salt solution was very slow, this aggregation was considerably decreased. The suitable quantity of cross-linker (glutaraldehyde) to harden the microcapsules was determined by an electrophoresis method. The effect of different process parameters (gliadin concentration, quantity and addition kinetics of the coacervation agent, cross-linker concentration) was studied with regard to the final microcapsule characteristics (shape, size, composition, and mechanical resistance evaluated by a centrifugation test).     

Gliadin matrices for microencapsulation processes by simple coacervation method

The aim of this study was to use a vegetal protein (gliadin) as a wall-forming component to produce microcapsules. The microencapsulation technique employed was the simple coacervation method and the encapsulated product was a non-food oil, hexadecane. Hexadecane was emulsified by a gliadin solution and the coacervation phenomena induced by adding a salt-solution in the continuous phase of the emulsion containing gliadin. The study of the coacervation conditions has shown that the richer in protein the continuous phase, the smaller the quantity of salt required. The main problem of the microencapsulation process by salting-out was to control the capsule size and the agglomeration of the capsules. This study succeeded in preventing the agglomeration phenomenon by adjusting the kinetics of the salt addition. When the feed rate of salt solution was very slow, this aggregation was considerably decreased. The suitable quantity of cross-linker (glutaraldehyde) to harden the microcapsules was determined by an electrophoresis method. The effect of different process parameters (gliadin concentration, quantity and addition kinetics of the coacervation agent, cross-linker concentration) was studied with regard to the final microcapsule characteristics (shape, size, composition, and mechanical resistance evaluated by a centrifugation test).     

Characterization of albumin-acacia complex coacervation.

Complex coacervation between oppositely charged albumin and acacia mixtures has been studied, and the applicability of the various theoretical treatments of complex coacervation (the Voorn-Overbeek, Veis-Aranyi, Nakajima-Sato, and Tainaka theories) to this system has been assessed. Under optimum conditions where maximum coacervate yield occurred, the Voorn-Overbeek theory appeared to apply. However, away from the optimum coacervation conditions, coacervate sol formation was observed, which is in accordance with the Veis-Aranyi and Tainaka theories. Microelectrophoretic measurements were used to determine optimum pH and ionic strength conditions for maximum coacervation, based on the method of Burgess & Carless (1984). The effects of pH and ionic strength on coacervate yield are reported. Around the optimum conditions for maximum coacervation a viscous coacervate phase and a relatively clear equilibrium phase are formed.     

Characterization of albumin-alginic acid complex coacervation

Complex coacervation of albumin and alginic acid has been investigated to characterize this process, and to prepare a microencapsulation system suitable for the encapsulation of live cells, protein and polypeptide drugs. The optimum conditions of pH, ionic strength and total polyion concentration were in accordance with predictions based on the method of Burgess & Carless (1984). Albumin/alginic acid complex coacervation appears to fit the Vies-Aranyi model for complex coacervation. Coacervation was limited compared with other polypeptide/polysaccharide systems such as gelatin and acacia, with albumin/alginic acid complex precipitates rather than complex coacervates forming under certain conditions. In particular coacervation was limited to concentrations below 0.5% w/v. At concentrations between 0.35 and 0.5% w/v both complex coacervation and precipitation occurred, and at concentrations above 0.5% w/v only precipitation was detected. The albumin/alginic acid complex coacervate is very viscous and this together with the limited conditions governing the occurrence of coacervation makes this system unsuitable for the preparation of microcapsules.     

The influence of HLB on the encapsulation of oils by complex coacervation

Abstract

Microcapsules are used for the formulation of drug controlled release and drug targeting dosage forms. Encapsulated hydrophobic drugs are often applied as their solutions in plant oils. The uptake of the oils in the complex coacervate microcapsules can be improved by the addition of surfactants. In this study, soybean, olive and peanut oils were chosen as the representatives of plant oils. The well characterized complex coacervation of gelatin and acacia has been used to produce the microcapsules. The amount of encapsulated oil has been determined gravimetrically. The encapsulation of the oils was high (75–80%). When the surfactants with HLB values from 1.8 to 6.7 were used, the amount of encapsulated oil was high (65–85%). A significant decrease of the oil content in the microcapsules was found when Tween 61 with HLB = 9.6 had been added into the mixture. No oil was found inside the microcapsules from the coacervate emulsion mixture containing Tween 81 (HLB = 10) and Tween 80 (HLB = 15), respectively. The results of the experiment confirm the dependence of hydrophobic substance encapsulation on the HLB published recently for Squalan     

Physicochemical characterization and enzymatic degradation of casein microcapsules prepared by aqueous coacervation

The use of biopolymers in sustained release systems has been studied by many research groups because of the bioavailability and biodegradability of these compounds. Casein is a natural biopolymer whose degradation results in biologically utilisable compounds. The objective of the present study was to assess the potential of casein microcapsules (CAS/MC) as sustained release systems using acetaminophen as a model drug. CAS/MC were prepared by aqueous coacervation in lactate buffer containing gelatin, hydroxypropyl cellulose (HPC) and lecithin. After preparation, the microcapsules were treated, or not, with glutaraldehyde as a cross-linking agent. CAS/MC were loaded using two distinct procedures, either by dissolving 50% of the drug (w/w), relative to casein, in the polymer dispersion or by dissolving the drug in the coacervating solution. The drug present in CAS/MC was quantified by HPLC after an enzymatic degradation assay, and the CAS/MC were analysed by scanning electron microscopy and thermal analysis (differential scanning calorimetry and thermogravimetrical analysis). Loading of the drug was ~ 8% (w/w), with high resistance to enzymatic attack. The absence of an acetaminophen melting peak indicated that there was no drug present on the surface of the cross-linked systems. In addition, loading was accompanied by a reduction of the specific heat capacity of the systems, which suggests a decrease in stability. The outer morphology of the encapsulating polymer was affected by the process of microencapsulation. The data suggest that the microencapsulation process of aqueous coacervation and cross-linking is appropriate for the preparation of microencapsulated systems for sustained drug delivery.     

Effect of pamidronate in a rat hypercalcemia model induced by cholecalciferol.

Pamidronate (disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate, CGP 23339A, CAS 57248-88-1) has been show to provide a potent antihypercalcemic effect through the inhibition of calcium release from the bone. The time course study on the antihypercalcemic effect of pamidronate was performed using a rat hypercalcemia model induced by orally administered cholecalciferol. The onset of the antihypercalcemic effect was observed within 48 h after a single i.v. injection of pamidronate at 1 mg/kg and this effect was sustained for 19 days. The time course of the antihypercalcemic effect of pamidronate in combination with calcitonin was also examined in the same model. The onset of the antihypercalcemic effect was observed within 4 h after combination therapy with a single i.v. injection of pamidronate at 1 mg/kg and successive i.m. injections of calcitonin at 3.2 IU/kg and the effect was of sufficient duration. These results suggest that pamidronate has a pronounced effect in controlling hypercalcemia and provides a long-lasting effect by a single i.v. administration. Moreover, the use of pamidronate in combination with calcitonin may be useful when a quicker onset of action is required clinically.     

Formulation of curcumin-loaded solid lipid nanoparticles produced by fatty acids coacervation technique

Curcumin (CU) loaded solid lipid nanoparticles (SLNs) of fatty acids (FA) were prepared with a coacervation technique based on FA precipitation from their sodium salt micelles in the presence of polymeric non-ionic surfactants. Myristic, palmitic, stearic, and behenic acids, and different polymers with various molecular weights and hydrolysis grades were employed as lipid matrixes and stabilisers, respectively. Generally, spherical-shaped nanoparticles with mean diameters below 500?nm were obtained, and using only middle-high hydrolysis, grade-polymer SLNs with diameters lower than 300?nm were produced. CU encapsulation efficiency was in the range 28-81% and highly influenced by both FA and polymer type. Chitosan hydrochloride was added to FA SLN formulations to produce bioadhesive, positively charged nanoparticles. A CU-chitosan complex formation could be hypothesised by DSC analysis, UV-vis spectra and chitosan surface tension determination. A preliminary study on HCT-116 colon cancer cells was developed to evaluate the influence of CU-loaded FA SLNs on cell viability.     

Physicochemical characterization and enzymatic degradation of casein microcapsules prepared by aqueous coacervation

The use of biopolymers in sustained release systems has been studied by many research groups because of the bioavailability and biodegradability of these compounds. Casein is a natural biopolymer whose degradation results in biologically utilisable compounds. The objective of the present study was to assess the potential of casein microcapsules (CAS/MC) as sustained release systems using acetaminophen as a model drug. CAS/MC were prepared by aqueous coacervation in lactate buffer containing gelatin, hydroxypropyl cellulose (HPC) and lecithin. After preparation, the microcapsules were treated, or not, with glutaraldehyde as a cross-linking agent. CAS/MC were loaded using two distinct procedures, either by dissolving 50% of the drug (w/w), relative to casein, in the polymer dispersion or by dissolving the drug in the coacervating solution. The drug present in CAS/MC was quantified by HPLC after an enzymatic degradation assay, and the CAS/MC were analysed by scanning electron microscopy and thermal analysis (differential scanning calorimetry and thermogravimetrical analysis). Loading of the drug was approximately 8% (w/w), with high resistance to enzymatic attack. The absence of an acetaminophen melting peak indicated that there was no drug present on the surface of the cross-linked systems. In addition, loading was accompanied by a reduction of the specific heat capacity of the systems, which suggests a decrease in stability. The outer morphology of the encapsulating polymer was affected by the process of microencapsulation. The data suggest that the microencapsulation process of aqueous coacervation and cross-linking is appropriate for the preparation of microencapsulated systems for sustained drug delivery.     

Formulation of curcumin-loaded solid lipid nanoparticles produced by fatty acids coacervation technique

Curcumin (CU) loaded solid lipid nanoparticles (SLNs) of fatty acids (FA) were prepared with a coacervation technique based on FA precipitation from their sodium salt micelles in the presence of polymeric non-ionic surfactants. Myristic, palmitic, stearic, and behenic acids, and different polymers with various molecular weights and hydrolysis grades were employed as lipid matrixes and stabilisers, respectively. Generally, spherical-shaped nanoparticles with mean diameters below 500?nm were obtained, and using only middle-high hydrolysis, grade-polymer SLNs with diameters lower than 300?nm were produced. CU encapsulation efficiency was in the range 28–81% and highly influenced by both FA and polymer type. Chitosan hydrochloride was added to FA SLN formulations to produce bioadhesive, positively charged nanoparticles. A CU-chitosan complex formation could be hypothesised by DSC analysis, UV–vis spectra and chitosan surface tension determination. A preliminary study on HCT-116 colon cancer cells was developed to evaluate the influence of CU-loaded FA SLNs on cell viability.     

Encapsulation of lipophilic drugs within enteric microparticles by a novel coacervation method

Enteric microparticles were prepared by a novel microencapsulation method in order to improve the oral bioavailability of lipophilic drugs. This method involved the addition of an aqueous polymer solution to an organic enteric polymer solution containing lipophilic drugs. In contrast to classical coacervation microencapsulation methods, the drugs were initially also dissolved and not dispersed in the organic polymer solution. The hydrophilic polymer (hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC) and Poloxamer 407) was dissolved in the aqueous phase and acted as a stabilizer for the coacervate droplets, preventing their coalescence and leading to the formation of enteric microparticles. The size of the enteric microparticles decreased with higher concentrations of the hydrophilic polymers, a higher pH of the aqueous polymer solution, a higher content of carboxyl groups of the enteric polymer and with better polymer solvents. Amide-containing lipophilic drugs, such as carbamazepine, lidocaine and cyclosporine A, were successfully encapsulated in the enteric microparticles in a non-crystalline state and were physically stable for 5 months. The high solubility of carbamazepine in the enteric polymer (>30%, w/w), a high partition coefficient between polymer-rich/-poor regions and strong drug/polymer interactions contributed to the high drug encapsulation efficiency (90%, w/w). In contrast, carboxyl-containing drugs (indomethacin, ibuprofen) and hydroxyl-containing drug (17beta-estradiol hemihydrate) crystallized inside or outside the polymeric matrix due to their low solubility in the enteric polymer.