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.     

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.     

尼莫地平肠溶微囊的制备及体外释放度考察

目的：优化尼莫地平肠溶微囊的制备工艺并对其体外释放度进行考察。方法：以纤维醋法酯（CAP）为载体材料,利用单凝聚法,通过正交试验设计,考察囊材与囊芯比、溶解cAP所需磷酸氢二钠pH值及量、span-80量及凝聚剂用量、成囊温度等因素对微囊包封率及载药量的影响,初步筛选出最佳处方工艺条件。此外,还建立了紫外分光光度法测定微囊的栽药量与包封率,考查其体外释放度。结果：所得微囊外观圆整,测得平均包封率为80．4％,平均载药量为41．7％。结论：该制备方法简单易行,所制得的微囊肠溶效果理想。     

两种减肥药的表面增强拉曼光谱研究

目的：研究盐酸西布曲明与盐酸芬氟拉明的表面增强拉曼光谱,对比它们的拉曼固体光谱,对表面增强拉曼光谱中的分子振动模式进行识别。方法：使用便携式拉曼光谱仪时盐酸西布曲明与盐酸芬氟拉明的表面增强拉曼光谱与拉曼固体谱进行考察。结果：研究表明,药物分子-银胶体系的pH对盐酸西布曲明与盐酸芬氟拉明的增强效应有较大的影响,这是pH对药物分子-银胶体系的凝聚状态和药物分子存在状态综合影响的结果。结论：本方法可以作为分析不同pH情况下盐酸西布曲明与盐酸芬氟拉明分子在纳米表面吸附情况。     

Solid lipid nanoparticles carrying lipophilic derivatives of doxorubicin: preparation,characterization, and in vitro cytotoxicity studies

Doxorubicin (DOXO) lauroyl ester and amide were proposed as lipophilic derivatives and entrapped in SLNs. DOXO derivatives-loaded SLNs were spherical shaped, had 200–300?nm mean diameters and showed 80–94% w/w drug entrapment efficiencies. The effect of DOXO derivatives-loaded SLNs and free DOXO on cell growth was examined by MTT and colony-forming assays on four different tumour cell lines: a pancreatic, CFPAC-1, a lung, A549, and two ovarian, A2780 and A2780res (DOXO-resistant). The results obtained with MTT and colony-forming assay show that although DOXO displayed an inhibition of cell proliferation greater or similar to DOXO lauroyl amide-loaded SLNs on all cell types, the effect induced by DOXO lauroyl ester-loaded SLNs was higher and concentration-dependent, and it was the only one maintained at 10^?5?mM concentration. Only DOXO lauroyl ester-loaded SLNs were able to induce a 40% inhibitory effect on A2780 res cell line up to 10^?4?mM concentration.     

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.     

The design of flexible ciprofloxacin-loaded PLGA implants using a reversed phase separation/coacervation method

The purpose of this research is to design and characterize flexible PLGA-based implants for the controlled release of ciprofloxacin hydrochloride for up to 6 weeks in vitro. This research uses a reversed phase separation/coacervation method to fabricate flexible PLA and PLGA: excipient implants with dichloromethane/mineral oil as solvent/non-solvent. Physical characterization was performed using thermal and mechanical analyses. Drug loading and release studies were performed with ciprofloxacin HCl as the model drug. Release kinetics was modeled to elucidate possible mechanisms of drug release. Four polymer-excipient combinations with glass transition temperatures less than 20 °C and representing a wide range of Young’s moduli were shown to entrap up to 8% of ciprofloxacin HCl that could be released at a controlled rate for 65 days in vitro. The release rate could consistently fit a ternary Gaussian pattern with an R² > 0.99. It was postulated that these release patterns could be related to ciprofloxacin that was loosely or poorly bound (burst release), trapped within the polymer matrix, or encapsulated by the polymer. These studies show that flexible implants can be fabricated from PLGA-based polymers for the controlled release of ciprofloxacin hydrochloride for up to 6 weeks in vitro.     

In vitro and in vivo evaluation of carbamazepine-loaded enteric microparticles

The objective of the study was to prepare and evaluate carbamazepine-loaded enteric microparticles produced by a novel coacervation method. An aqueous polymeric stabilizer solution was added to an organic carbamazepine/Eudragit L100-55 solution. Water, which is a non-solvent for the drug and the enteric polymer, caused phase separation and the formation of coacervate droplets. These droplets hardened into microparticles upon further addition of the aqueous phase. The microparticles were characterized with respect to particle size distribution, morphology, encapsulation efficiency, yield, physical state and physical stability of the drug, wettability, in vitro release and in vivo bioavailability. Microparticles with a smooth surface and dense structure were obtained with high encapsulation efficiency (>85%) and yield (>90%). The drug was in a non-crystalline state in the matrix and physically stable for 5 months at room temperature. Under sink conditions, the drug dissolution rate from the microparticles was significantly enhanced compared to the physical mixture and to the pure drug; the release profile of the microparticles was stable after 5 months. Under non-sink conditions, an unstable supersaturated solution of carbamazepine was obtained from microparticles with the subsequent formation of needle-shaped crystals. The high surface area and good wettability of the microparticles, the non-crystalline state of the drug in the matrix and the fast dissolution rate contributed to a significantly enhanced oral bioavailability from the microparticles when compared to the physical mixture.     

Cross-linking of soybean protein isolate–chitosan coacervate with transglutaminase utilizing capsanthin as the model core

Abstract

Transglutaminase (TG) is an alternative coacervate cross-linking agent to aldehydes due to its safety. In this work, the cross-linking conditions of soybean protein isolate (SPI)–chitosan coacervates with TG-utilizing capsanthin as the model core were optimized and its cross-linking effectiveness was compared with that of glutaraldehyde. Results indicated that the optimum capsanthin microcapsule cross-linking conditions were as follows: a suspension pH of 6.0, an incubation duration of 3?h, a TG concentration of 18.75?U/g SPI and a reaction temperature of 45?°C. Under these conditions, TG provided a cross-linking effectiveness comparable with that of glutaraldehyde in regards to microcapsule stability against swelling in 80?°C water and heating at 150?°C. Differential scanning calorimetry analysis revealed that TG cross-linking increased the integrity of the microcapsule walls. It was concluded that the SPI–chitosan coacervation pair has potential applications in the food industry in terms of cross-linker safety and effectiveness.     

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).