Preparation of Polymeric Microcapsules: Formulation Studies

Air-filled microcapsules were prepared by freeze-drying different oil-in-water emulsions containing biodegradable polyester as the wall-forming material. The aim of this work was to find an acceptable formulation with respect to the microcapsule suspension and the stability of the emulsion during the production process. The influence of various formulation parameters (concentrations of mannitol, polymer, and surfactant; pH; oil-in-water phase ratio) was investigated in a factorial design. The results were treated by ordinary least-square (OLS) regression and partial least-square regression (PLSR). In a previous work, air-filled microcapsules were successfully made using human serum albumin as the surfactant in the emulsion . In the present work, a new block copolymer based on poly(ethylene glycol) (PEG) was implemented as the surfactant to replace human serum albumin. It was found that the new block copolymer is a suitable replacement for human serum albumin. The concentration of the polymer in water and the concentration of the surfactant in the oil phase and the interaction between these variables had a significant influence on the stability of the emulsion at 60°C. A surfactant concentration of approximately 2% (w/v) in water was necessary when the concentration of the wall-forming polymer was below 5% (w/v) in (-)-camphene. The concentration of the polymer in the oil phase influenced the yield, measured as the volume concentration of particles in suspension per milligram of polymer added and as acoustic effect per milligram of polymer. Low levels of polymer concentration in (-)-camphene (<5% w/v) gave the highest yield. Excess polymer in the oil phase did not form microcapsules, but precipitated in the suspension or was included in the wall of the microcapsules. Addition of mannitol protected the microcapsules from being destroyed during freeze-drying and resulted in freeze-dried products with few cracks, little shrinkage, and higher suspension yield.     

Engineering of poly(ε-caprolactone) microcarriers to modulate protein encapsulation capability and release kinetic

Drug delivery applications using biodegradable polymeric microspheres are becoming an important means of delivering therapeutic agents. The aim of this work was to modulate the microporosity of poly(ε-caprolactone) (PCL) microcarriers to control protein loading capability and release profile. PCL microparticles loaded with BSA (bovine serum albumin) have been de novo synthesized with double emulsion solvent evaporation technique transferred and adapted for different polymer concentrations (1.7 and 3% w/v) and stabilizer present in the inner aqueous phase (0.05, 0.5 and 1% w/v). SEM (scanning electron microscope) and CLSM (confocal laser scanning microscope) analysis map the drug distribution in homogeneously distributed cavities inside the microspheres with dimensions that can be modulated by varying double emulsion process parameters. The inner structure of BSA-loaded microspheres is greatly affected by the surfactant concentration in the internal aqueous phase, while a slight influence of polymer concentration in the oil phase was observed. The surfactant concentration mainly determines microspheres morphology, as well as drug release kinetics, as confirmed by our in-vitro BSA release study. Moreover, the entrapped protein remained unaltered during the protein encapsulation process, retaining its bio-activity and structure, as shown through a dedicated gel chromatographic analytical method.     

Phase diagram studies of microcapsule formation using hydroxypropyl methylcellulose phthalate

Abstract

Microcapsules of hydroxypropyl methylcellulose phthalate were prepared using a non-aqueous emulsion method. The study was designed to determine the region of microcapsule formation in the ternary system of mineral oil, acetone and polymer and to present the data by means of phase diagrams. Increasing amounts of sorbitan monooleate were added to mineral oil to determine the effect of surfactant concentration on the phase diagram. The effect of sorbitan monooleate, sorbitan trioleate and sorbitan monolaurate on the microcapsule region of the phase diagram was also investigated. Particle size analysis was carried out to determine if the concentration and type of surfactant used had a significant effect on the size of the microcapsules obtained. Tartrazine was encapsulated as a model drug and its dissolution was studied in acidic and neutral mediums. The results indicate that the addition of sorbitan monooleate increased the microcapsule region of the phase diagram and sorbitan trioleate had a similar effect. However, the microcapsule region in the phase diagram decreased when sorbitan monolaurate was used. The particle size increased with increasing concentration of polymer, irrespective of the type and concentration of surfactant used.     

Preparation of ferromagnetic microcapsules for hyperthermia using water/oil emulsion as a reaction field

Hyperthermia is a minimally invasive cancer treatment. As hyperthermia thermoseeds, ferromagnetic microcapsules of 20–30 μm in diameter have attracted much attention since their embolization effect cuts off the nutrition supply into cancer cells, ensuring that the microcapsules efficiently reach the tumor. In the present study, ferromagnetic microcapsules were prepared via iron hydroxide precipitation from a water/oil emulsion and subsequent hydrothermal treatment. The fundamental conditions for obtaining microcapsules of suitable size were investigated. The diameter of the obtained microcapsules tended to decrease as rotation speed increased during emulsion preparation or surfactant concentration in the oil phase. The sphericity of the microcapsules was improved at low surfactant concentration. A large amount of 20–30 μm-diameter magnetite microcapsules were obtained when the rotation speed and surfactant concentration were fixed at 1500 rpm and 0.35 mass%, respectively. The obtained microcapsules embedded in agar phantom exhibited heat generation under an alternating magnetic field.     

Emulsion Spray-Drying for the Preparation of Albumin-Loaded PLGA Microspheres

The purpose of this work was to study the encapsulation of bovine serum albumin (BSA) in polylactide-co-glycolide (PLGA) microspheres using an emulsion/spray-drying method. Albumin was dissolved in an aqueous phase (w) in the presence of surfactant and emulsified in an organic phase containing the polymer (o). To stabilize the emulsion, different types of surfactant (Pluronic® F68, Pluronic F127, sodium oleate, dioctylsulfosuccinate) were added to the aqueous phase. The w/o emulsion was spray-dried to obtain BSA-loaded PLGA microspheres. The effect of type of surfactant on microsphere characteristics was evaluated. The microspheres were characterized for their morphology by scanning electron microscopy (SEM) and granulometric analysis; drug content determination and in vitro dissolution tests were performed. Results showed that the emulsion/spray-drying method is suitable for obtaining small microparticles (2-5 μm) characterized by high drug payloads (70%-80% encapsulation efficiency). The type of surfactant affects the microsphere shape and BSA release behavior.     

Phenylpropanolamine HCl Microcapsules: Preparation and release studies

Microcapsules of phenylpropanolamine HCL were prepared by three techniques, viz. coacervation-phase separation, air suspension, and pan coating, using different polymers and/or waxes as wall-forming materials.

Formulations showed reasonable dissolution behaviour, viz. microcapsules prepared by air suspension with polymer level of 20% polyvinyl acetate copolymer (PVAC) associated with 40% carnauba wax (II) and microcapsules prepared by pan coating with polymer level of 25% Rodopace^R (III), were evaluated for their absorption rates by demonstrating their toxicities compared to pure grug (I) by the LD₅₀ method. Toxicity assessment showed close agreement between the increase in lethal dose and the decrease in dissolution rate and revealed that Formula III has more prolonged action than Formulae II and I.     

Antioxidant coating of micronsize droplets for prevention of lipid peroxidation in oil-in-water emulsion

Fast lipid peroxidation in emulsified oils results in carcinogens formation and product rancidity. Prevention of oxidative degradation in oil-in-water emulsion has been achieved by encapsulating of each droplet of dispersed phase in antioxidant multilayer coating shell. The fabrication comprised placing a surface-active ionic emulsifier at the oil/water interface followed by stepwise alternate adsorption a biocompatible polyelectrolyte and antioxidant layers. Uncoupled polyelectrolyte macromolecules and antioxidant were thoroughly removed from formulation, thus the protection was entirely attributed to the droplets' shell. The experiments were performed using linseed oil, the richest source of highly unstable omega-3 alpha linolenic essential fatty acid. Bovine serum albumin (BSA) was exploited as an anionic emulsifier. The biodegradable coating shell was formed of poly-l-arginine (PARG) and dextran sulfate (DS) applied as a polycation and a polyanion respectively. Tannic acid (TA) known as a natural antioxidant and possessing antimicrobial properties was used as a protective remedy. Oil microdroplets coated with TA-containing shell displayed physical-chemical and mechanical stability in aqueous phase and over freeze-drying process as determined by ζ-potential measurements, dynamic light scattering (DLS), and confocal laser scanning microscopy (CLSM). Oxidation of emulsified oil was monitored by formation of malondialdehyde (MDA) in the samples quantified by Thiobarbituric Acid Reactive Substances (TBARS) assay. Coating shell with an incorporated layer of TA effectively suppressed oxidation in water-dispersed oil droplets and affected iron-catalyzed oxidation over 15 days of incubation at 37 °C in 0.3 mM FeBr2 solution. Antioxidant activity of TA-containing shell assembled around each oil droplet was found to be higher than that of mixed tocopherols (MT) added to linseed oil in concentration of 10000 ppm.     

表面活性剂浓度对乳胶基质平均粒径的影响和机理分析

乳胶基质内相液滴的平均粒径大小直接反映了可燃剂和氧化剂的混合均匀程度,是影响乳化炸药爆炸性能和稳定性能的重要因素。主要研究了油相中表面活性剂浓度对乳胶基质内相液滴平均粒径的影响。使用5种含有不同表面活性剂浓度的外相材料制备乳胶基质,并且使用激光粒度仪测试了所有样品的平均粒径。实验结果表明:油相材料中表面活性剂的浓度越大,则制备出的乳胶基质平均粒径越小。然后通过表面张力的理论分析和外相动力粘度的实验测试,进而分析出增加表面活性剂降低乳胶基质的平均粒径的机理:表面活性剂的增加导致了外相材料的动力粘度的增大,进而使乳胶基质平均粒径变小,和表面张力无关。     

以高岭石稳定的Pickering乳液为模板制备高岭石聚脲微胶囊及相变性能研究

相变微胶囊以其优异的储热性能被广泛用于建筑节能等领域,但是,由于传统相变微胶囊常以表面活性剂所稳定的乳液为模板,由单一高分子聚合物形成囊壁,导致其热稳定性和储热性能较低。本文通过在高岭石稳定的水/石蜡乳液界面处引发异佛尔酮二异氰酸酯和水发生聚合反应,成功获得了囊壁为高岭石聚脲包封客体为石蜡的相变微胶囊。结果表明:相变微胶囊形貌规整呈球形,微胶囊平均粒径为42μm并可通过调控乳液液滴大小实现尺寸调控;该微胶囊的石蜡包封率达85.3%,相变点为49.6℃,热分解温度为218℃,相变潜热高达175.7 J/g。以高岭石稳定的Pickering乳液为模板所制备的相变微胶囊具有良好的热稳定性和相变潜热,有望作为相变储热材料应用于节能领域。     

Formation of Janus TiO2 nanoparticles by a pickering emulsion approach applying phosphonate coupling agents

Anisotropic surface modification of TiO2 nanoparticles was achieved applying a Pickering emulsion approach. TiO2 nanoparticles were prepared by sol-gel routes which allowed an excellent control over their size and morphology. The obtained colloids were further used as stabilizers in the formation of oil-in-water Pickering emulsion. For reasons of comparison, also commercially available titanium dioxide nanoparticles (Evonik AEROXIDE TiO2 P25) were used in the functionalization experiments. An organophosphorus coupling agent present in the oil phase coordinated to the surface of the anatase nanoparticles. In such a way an anisotropic surface modification of the particles was achieved which increased the stability of the Pickering emulsion. Spectroscopic studies revealed the presence of organophosphorus coupling agents which exhibited a covalent bonding to the surface of the particles. Thermogravimetric analyses confirmed a lower surface coverage of the particles modified in emulsion compared to those modified in suspension. Reactions of organophosphorus coupling agents containing an additional methacrylate group applying an organic monomer (methyl methacrylate) as the oil phase of the Pickering emulsion resulted in hybrid TiO2@polymer spheres. Spectroscopic characterization of the resulting particles revealed that the phosphonates were coordinated to the TiO2 surface and at the same time copolymerized with the MMA within the oil droplet. Morphological investigations of the isolated final product showed that the material was composed of polymer spheres with the stabilizing TiO2 nanoparticles on their surface.     

Antimicrobial activity of microencapsulated lemongrass essential oil and the effect of experimental parameters on microcapsules size and morphology

Lemongrass (Cymbopogom citratus) essential oil, known due to its broad-spectrum antimicrobial activity, was microencapsulated by simple coacervation. Poly(vinyl alcohol) (PVA, 78,000 Da and 88 mol% degree of hydrolysis) crosslinked with glutaraldehyde was used as wall-forming polymer. The influence of stirring rate and oil volume fraction on the microcapsule size distribution were evaluated. Sodium dodecil sulphate (SDS) and Poly(vinyl pirrolidone) were tested in order to avoid microcapsules agglomeration during the process. Depending on the experimental conditions, microcapsules in the range of 10 μm to 250 μm were obtained. Microcapsules presenting no agglomeration were obtained when SDS at 0.03 wt.% was used. The composition and the antimicrobial properties of the encapsulated oil were determined, demonstrating that the process of microencapsulation did not deteriorate the encapsulated essential oil.     

Fibrin-Based Drug Delivery Systems. II. The Preparation and Characterization of Microbeads

An emulsion method was employed to prepare fibrin beads having different sizes in this study. The oil phase of emulsion system was consisted of mineral oil with various amount of oleic acid as surfactant. Fibrin was converted from fibrinogen with thrombin in Tris buffer solution, then the mixture was emulsified into the oil phase forming droplets. After curing for one hour, 400 ul of glutaraldehyde solution (0.5% v/v) was added to minimize coagulation. The recovery of fibrin beads was simply done by decanting the oil phase and washing the residual with diethyl ether once and then with a mixture of isopropanol and n-hexane (1:3) containing 0.2% w/v Tween 80 twice. As expected, increasing the amount of oleic acid in the oil phase decreased the size of fibrin beads. It is due to the decrease of interfacial tension with increasing oleic acid amount. The presence of macromolecules showed no interference on the formation of fibrin beads except lysozyme. The diffusion characteristics of fibrin beads was evaluated using macromolecules of different molecular weight as model. The size of fibrin beads affected the penetration rate, whereas the effect of molecular weight of macromolecules was inconclusive. An exponential equation was able to approximate the penetration of macromolecules into fibrin beads during the late-time period. The possibility of using fibrin beads as the carrier to deliver protein drugs was appreciated.     

Use of polymer nanoparticles as functional nano-absorbents for low-molecular weight hydrophobic pollutants

To use amphiphilic polymer nanoparticles as a new nano-absorbent for improving environmental process, urethane acrylate nonionomer (UAN) chain having hydrophobic polypropylene oxide-based segment and hydrophilic polyethylene oxide-based segment at the same backbone was synthesized and dispersed as nanoparticles at water phase without using a surfactant or dispersion agent. These UAN nanoparticles were converted to crosslinked amphiphilic polymer (CAP) nanoparticles through soap-free emulsion polymerization and suspension agent-free suspension polymerization process. Emulsion polymerization process exhibited higher conversion of polymerization compared to suspension polymerization process. CAP nanoparticles showed interfacial activity and solubilize hydrophobic pollutants (phenanthrene and toluene) like surfactant micelles. This result indicates possible application of CAP nanoparticles as nano-absorbent for improving efficiency of soil washing and micellar-enhanced ultrafiltration (MEUF) process.     

凸棒颗粒稳定的橄榄油／水型Pickering乳状液的制备条件及形成机理研究

选取凹凸棒作为乳化剂,系统研究pH、颗粒浓度、油相体积分数以及不同价态盐对橄榄油／水型Pickering乳状液稳定性的影响,结果表明,体系pH在4～9范围内可制备出稳定的乳状液;颗粒浓度的提高可增强乳液的分层和聚结稳定性;乳液液滴直径随油相体积分数的增加先增大后减小;无机盐的引入不会对乳液相及水相的体积产生影响,但对乳液液滴的尺寸分布影响显著,其中NaCl浓度的增加有利于乳状液液滴数均直径的增加,而CaCl2浓度增加时,乳状液液滴数均直径呈现先增大后减小的变化趋势。研究表明,凹凸棒可作为一种新型纳米乳化剂应用于绿色乳状液的制备。     

Preparation Methods of Biodegradable Microspheres on Bovine Serum Albumin Loading Efficiency and Release Profiles

The solvent evaporation and multiple phase methods for preparing poly-(d, l) lactide microspheres of bovine serum albumin (BSA) were compared. The effects of poly (vinyl alcohol) concentration and external aqueous phase temperature on the loading efficient of BSA microspheres prepared by multiple phase emulsion method were evaluated as well. The BSA loading efficient of microspheres by multiple phase emulsion method was much higher than that by solvent evaporation method. The high aqueous solubility of BSA contributes to the low loading efficieny in the solvent evaporation method, suggesting that this method is inappropriate for proteins with high water solubility. The loading efficieny of microspheres, whcih were prepared by multiple phase emulsion method, increased with PVA concentration but decreased with external aqueous phase temperature. The burst phenomenon of release profiles of microspheres was influenced by poly (vinyl alcohol) concentrations and the external aqueous phase temperature. Considering the duration sustained release, 0.5% w/v of poly (vinyl alcohol) is most appropriate among the concentrations tested for preparing BSA microspheres by multiple phase emulsion method.     

Synthesis of hydroxyapatite nanopowders by sol-gel emulsion technique

Hydroxyapatite nanopowders were synthesized by a sol-gel emulsion technique by varying the concentration of a non-ionic surfactant in the organic phases (oil phase) of water-in-oil (w/o) emulsion. Calcium acetate dissolved in distilled water and phosphorous pentoxide dissolved in 2-butanol were used as starting precursors. The prepared sol was emulsified in a support solvent (cyclohexane) containing 2, 4 and 5 volume% of surfactant (Span 80), followed by the addition of triethylamine, for gelation. The gel powders thus obtained were calcined at different temperatures up to 750??C. Characterization was done using XRD, SEM and TEM. Pellets were made from the developed HAP powders and tested for its biocompatibility after their immersion in the simulated body fluid.     

Preparation Methods of Biodegradable Microspheres on Bovine Serum Albumin Loading Efficiency and Release Profiles

The solvent evaporation and multiple phase methods for preparing poly-(d, l) lactide microspheres of bovine serum albumin (BSA) were compared. The effects of poly (vinyl alcohol) concentration and external aqueous phase temperature on the loading efficient of BSA microspheres prepared by multiple phase emulsion method were evaluated as well. The BSA loading efficient of microspheres by multiple phase emulsion method was much higher than that by solvent evaporation method. The high aqueous solubility of BSA contributes to the low loading efficieny in the solvent evaporation method, suggesting that this method is inappropriate for proteins with high water solubility. The loading efficieny of microspheres, whcih were prepared by multiple phase emulsion method, increased with PVA concentration but decreased with external aqueous phase temperature. The burst phenomenon of release profiles of microspheres was influenced by poly (vinyl alcohol) concentrations and the external aqueous phase temperature. Considering the duration sustained release, 0.5% w/v of poly (vinyl alcohol) is most appropriate among the concentrations tested for preparing BSA microspheres by multiple phase emulsion method.     

Optimization of process parameters for the extraction of chromium (VI) by emulsion liquid membrane using response surface methodology

The emulsion liquid membrane technique was used for the extraction of hexavalent chromium ions from aqueous solution of waste sodium dichromate recovered from the pharmaceutical industry wastewater. The liquid membrane used was composed of kerosene oil as the solvent, Span-80 as the surfactant and potassium hydroxide as internal reagent. Trioctyl amine and Aliquat-336 were used as carriers. The emulsion stability was carried out at different surfactant concentration, agitation speed and emulsification time. Statistical experimental design was applied for the optimization of process parameters for the extraction of chromium by emulsion liquid membrane. The effects of process parameters namely, agitation speed, membrane to emulsion (M/E) ratio and carrier concentration on the extraction of chromium were optimized using a response surface method. The optimum conditions for the extraction of chromium (VI) using response surface methodology for Trioctyl amine were: agitation speed – 201.369 rpm, M/E ratio – 0.5887% (v/v) and carrier concentration – 4.0932% (v/v) and for Aliquat-336: agitation speed – 202.097 rpm, M/E ratio – 0.5873% (v/v) and carrier concentration – 3.9211% (v/v). At the optimized condition the maximum chromium extraction was found to be 89.2% and 96.15% using Trioctyl amine and Aliquat-336, respectively.     

Microencapsulation of Sulfadiazine with Cellulose Acetate Pethalate

Microencapsulation of a relatively insoluble drug sulfadiazine was carried out by allowing drops of' a suspension of the drug in an aqueous cellulose acetate phthalate solution to fall into an acetic acid hardening solution. Spherical microcapsules could readily be obtained when a surfactant polyoxyethylene 20 sorbitan monooleate was added to the suspensior. Increased drug concentration in the suspension yielded larger microcapsules with shorter disintegration times. The incorporation of viscosity agents into the suspension yielded microcapsules with altered disintegration times     

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.