Microencapsulation of caffeic acid and its release using a w/o/w double emulsion method: Assessment of formulation parameters

Caffeic acid (CAF)has numerous health benefits mainly due to its antioxidant, antibacterial and fungicide properties. However, its incorporation in skin care products as anti-aging and the photoprotective agent is still limited due to its solubility and stability in oily matrices or solutions balanced with the skin pH. In this research, CAF–ethyl cellulose (EC) microparticles were produced by water-in-oil-water double emulsion solvent evaporation encapsulation technique using a biocompatible polymer, EC, as a coating material and a surfactant, polyvinyl alcohol, as a stabilizer of the double emulsion. The study assessed the influence of formulation parameters as the solubility of the polymer in organic solvents and the polymer concentration on microparticles final characteristics. CAF–EC microparticles were characterized by product yield, encapsulation efficiency, mean particle size, particle size distribution and polydispersity and imaged by scanning light microscopy. In vitro release profiles were obtained in water and octanol to mimic oily based and water-based matrices balanced with the skin pH. In vitro release kinetics studies were carried out to investigate the release pattern of CAF in simulated cosmetic formulations. Both the product yield and the encapsulation efficiency were found to be dependent on the solubility of the polymer in the organic phase. The product yield was mainly affected by operational factors such as the sticking and the agglomeration of the polymer to the walls and the magnet stirring during microparticles hardening and results from the encapsulation efficiency revealed that an increase of the polymer concentration led to an increase of the encapsulation efficiency. The usage of a water-soluble solvent contributed to a decrease in the mean particle size and reduction of polydispersity with higher polymer concentrations. The polymer concentration, the polymer solubility in the organic phase and the amount of CAF entrapped shown to affect the release in water, whereas the release in octanol was mainly independent of the amount of CAF entrapped in EC microparticles. The double emulsion solvent evaporation technique and the assessment of the selected formulation conditions have given significant and innovative insights on the microencapsulation of bioactive ingredients for cosmetics formulations.     

Comparative study of encapsulated vildagliptin microparticles produced by spray drying and solvent evaporation technique

Vildagliptin (VLG), an antihyperglycemic drug, having high water solubility and shorter elimination half-life. This leads to administer VLG frequently to maintain its therapeutic efficacy. Hence the goal of this work was to formulate sustained release polymeric VLG microparticles by spray drying technique using 3² full factorial design (Design-Expert Software). Ethyl cellulose (EC) and span-80 were used as encapsulating material and surfactant, respectively. This work furthermore assessed the probability of encapsulating VLG by single emulsion oil in oil (o/o) solvent evaporation technique. The resultant microparticles from these two methods were evaluated to demonstrate the significant differences in their particle size, percentage yield, drug loading (DL), encapsulation efficiency (EE), in vitro drug release, surface morphology, and drug–polymer compatibility. EE of microparticles prepared by spray drying and solvent evaporation technique was in the range of 71.42–89.87% and 51.79–64.03%, respectively. The in vitro drug release study from the microparticles prepared by both methods was conducted for 12?h. Microparticles prepared by solvent evaporation technique showed incomplete VLG release in 12?h. To visualize the effects of independent factors (polymer and surfactant amount) on dependent factors (EE and DL), 2D contour and 3D surface plots were constructed. Significant variations in microparticles’ physicochemical properties were observed with two formulation techniques. Optimum EE and sustained drug release of VLG–EC microparticles were conclusive using spray drying and solvent evaporation techniques.     

Preparation of poly(L‐lactide) microparticles by a supercritical antisolvent process with a mixed solvent

Poly(L ‐lactide) (PLLA) microparticles were prepared by a supercritical antisolvent (SAS) process with a mixed solvent. Five factors, namely, the molar percentage of acetone, pressure, temperature, flow rate, and concentration of the solution, were optimized by a four‐level orthogonal array design. By analysis of variance, the concentration of the solution showed a significant effect on the PLLA microparticle size. The effects of the mixed solvent (dichloromethane/acetone) at different mixing ratios, pressures, and temperatures on the morphology of the PLLA microparticles were also investigated. The thermal properties of PLLA before and after the SAS process were studied by differential scanning calorimetry. The results indicate that the molar percentage of acetone had a significant effect on the morphology of the PLLA microparticles. The microparticles prepared with the mixed solvent were much smaller than those prepared with dichloromethane alone under the same conditions. Furthermore, the particle size distribution was more uniform in the case of the mixed solvent. The particle size decreased with increasing pressure, whereas it showed no significant change with increasing temperature. The results also show that the thermal properties of PLLA could be improved through the SAS process. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

Effect of solvent on surface wettability of electrospun polyphosphazene nanofibers

Two kinds of biodegradable polymers, poly(ε‐caprolactone) (PCL) and poly[(alanino ethyl ester)_0.67 (glycino ethyl ester)_0.33 phosphazene] (PAGP), were electrospun by using four different solvents. All PCL nanofibrous mats had similar surface water contact angles independent of solvents. However, it was found that the water contact angles of PAGP nanofibrous mats were 102.2° ± 2.3°, 113.5° ± 2.2°, 115.8° ± 1.4°, and 119.1° ± 0.7°, respectively, when trifluoroethanol, chloroform, dichloromethane, and tetrahydrofuran were used as a solvent. This difference was supposed mainly due to phosphorous and nitrous atoms in PAGP being dragged to fiber surface with solvent evaporation during the solidification of nanofibers, because of the strong interaction between positive phosphorous atoms and electronegative atoms in solvents. This interaction was confirmed by Fourier Transform Infrared, and the accumulation of phosphorous and nitrous atoms in the solvent‐casting PAGP film surface was identified by X‐ray photoelectron spectrometry analysis. PCL samples did not show the solvent‐controlled surface wettability because it contained fewer polar atoms. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

Estimation of particle size distributions from focused beam reflectance measurements based on an optical model

A popular in situ particle characterization technique, which can be applied without dilution, is the focused beam reflectance measurement (FBRM^®). The FBRM probe measures a chord length distribution (CLD) which is different from a particle size distribution (PSD). In order to compare results obtained by an FBRM probe with other measurement technologies such as laser diffraction, it is necessary to reconstruct the PSD from a measured CLD. For this reconstruction a measurement model and an inversion procedure are required. Most FBRM models presented in the literature assume that an FBRM records a geometric chord which can be deduced from a two-dimensional projection of the particle silhouette. In previous work [Kail, N., Briesen, H., Marquardt, W., 2008. Analysis of FBRM measurements by means of a 3D optical model. Powder Technology 185 (3), 211-222] it has been demonstrated that FBRM data show significant deviations from this geometric model. Consequently, an estimation of a PSD using such a geometric FBRM model will fail. A novel FBRM model is developed in this work. This model imitates the chord discrimination algorithm used in a Lasentec D600L FBRM system and takes the intensity profile of the laser beam and the optical aperture of the probe into account. The model is ideally suited for the estimation of a PSD from a measured CLD using a sequential, linear inversion routine, as proposed in this work. The novel FBRM model and the inversion procedure are evaluated using small, mono-disperse polystyrene beads, large ion-exchanger beads, and α-lactose-monohydrate particles. The applicability of the FBRM for PSD measurements is discussed on the basis of these results.     

On‐line monitoring of chord distributions in liquid–liquid dispersions and suspension polymerizations by using the focused beam reflectance measurement technique

The on‐line monitoring of the droplet/particle size distributions is very important to ensure the quality and applicability of various products in heterogeneous systems. For this reason, the main objective of the present work was to study the usage of the focused beam reflectance measurement (FBRM) technique for monitoring of liquid–liquid dispersions (styrene dispersion in aqueous solutions) and suspension polymerization of styrene. To do better understand the FBRM technique in these systems, the effects of surfactant concentrations, agitation speed and ambient light were evaluated during the in‐line monitoring of average chord lengths and chord‐length distributions (CLD) at different operation conditions in batch experiments. In addition, a preliminary investigation of the optimal probe position was conducted in the polymerization experiments. It is shown that the FBRM technique is sensitive to variations of particle sizes in the characteristic ranges of particle diameters of typical styrene suspension polymerizations, being useful for monitoring and also control applications that require the on‐line characterization of CLD in real time in liquid–liquid dispersions and polymerization systems. POLYM. ENG. SCI., 56:309–318, 2016. © 2015 Society of Plastics Engineers     

Measuring the particle size of a known distribution using the focused beam reflectance measurement technique

The accuracy of the focused beam reflectance measurement (FBRM) probe, which measures a chord length distribution, from Mettler-Toledo Lasentec^® has been explored. A particle video microscope (PVM) probe, which provides in situ digital images, was used as a direct visual method to test the reliability of the FBRM results. These probes can provide in situ particle characterization at high pressures. The FBRM has been used to study emulsions and ice and clathrate hydrate formation. The ability of the FBRM to accurately characterize unimodal and bimodal distributions of particles and droplets and to measure agglomeration events was investigated. It was found that while the FBRM can successfully identify system changes, certain inaccuracies exist in the chord length distributions. Particularly, the FBRM was found to oversize unimodal distributions of glass beads, but undersize droplets in an emulsion and was unable to measure full agglomerate sizes. The onset of ice and hydrate nucleation and growth were successfully detected by the FBRM, but quantitative analysis of the particle and agglomerate sizes required simultaneous PVM measurements to be performed.     

Preparation of ethyl cellulose microcapsules containing perphenazine and polymeric perphenazine based on acryloyl chloride for physical and chemical studies of drug release control

The preparation of microcapsules containing perphenazine by solvent evaporation using ethyl cellulose is described. The microparticles are formed after solvent evaporation and polymer precipitation. The drug was dissolved in a polymer solution and emulsified into an aqueous phase to form microcapsules. To study the effects on particle size, encapsulation efficiency and morphology, three different molecular weights of ethyl cellulose (M_w=47000, 71000 and 99000) were used. Covalent bonding of drugs to polymers via hydrolytically or enzymatically cleavable covalent bond was achieved for sustained drug delivery. The release rate of perphenazine from these systems was investigated. © 1998 Society of Chemical Industry     

Determination of non-spherical particle size distribution from chord length measurements. Part 2: Experimental validation

In this paper, the theory on the translation of a measured chord length distribution (CLD) into its particle size distribution (PSD), which was developed in the first part of this study [Li and Wilkinson, 2005. Determination of non-spherical particle size distribution from chord length measurements. Part 1: theoretical analysis. Chemical Engineering Science 60, 3251-3265], has been validated using experimental results. CLDs were measured using the Lasentec focused beam reflectance measurement (FBRM) with three different materials, spherical ceramic beads and non-spherical plasma aluminium and zinc dust particles. Meanwhile, the particle shape and PSD of each material were also investigated by image analysis (IA). Comparison of the retrieved PSDs with the measured PSDs by IA shows that the PSD can be retrieved from a measured CLD successfully using the proposed iterative nonnegative least squares (NNLS) method based on the PSD-CLD model.     

An investigation of the droplet size distributions in a cyclone reactor for liquid-liquid heterogeneous reactions using FBRM and PVM

A multi-element process coupled cyclone reactor for the liquid-liquid heterogeneous reaction was proposed. This paper presents the investigation of dispersed phase droplet size distributions near the wall surface using FBRM and PVM. To translate a chord length distribution (CLD) measured by the FBRM instrument into its droplet size distribution (DSD), a CLD-DSD transformation model was proposed. Moreover, the effects of operational parameters on the droplet size distributions were studied. The results show that the total inlet flow plays a decisive role on the dispersed phase droplet size distributions, while the influence of feed ratio is mainly reflected in inhibiting the probability of droplet coalescence. In comparison, the influence of overflow ratio on the droplet size distributions can be neglected.     

Effect of Solvent on Nanoparticle Production of β‐Carotene by a Supercritical Antisolvent Process

Production of micro‐ to nano‐sized particles of β‐carotene was investigated by means of solution‐enhanced dispersion by supercritical fluids (SEDS). β‐Carotene was dissolved in dichloromethane (DCM), N,N‐dimethylformamide (DMF), n‐hexane, or ethyl acetate, and supercritical CO₂ served as an antisolvent. The effects of the organic solvents, operating pressure, and temperature were examined. The morphologies of the particles produced by the SEDS were observed by field emission‐scanning electron microscopy and particle sizes were determined by image analysis. Irregularly shaped microparticles were produced in the system with DCM and DMF solution. Plate‐like microparticles were generated by using n‐hexane solution and irregular nanoparticles by ethyl acetate solution. The optimum operating conditions were found to be ethyl acetate as solvent in a defined pressure and temperature range.     

溶剂蒸发法制备高效氯氟氰菊酯微胶囊及其性能表征

针对高效氯氟氰菊酯使用过程中对人体皮肤的刺激性以及对水生生物的高毒性,以乙基纤维素为壁材,二氯甲烷为溶剂,通过设计L9（34）正交试验,采用溶剂蒸发法制备高效氯氟氰菊酯微胶囊,同时对微胶囊的理化性质和缓释特性进行表征。根据微胶囊平均粒径和未包封率的综合评分确定最佳制备工艺为：25%二氯甲烷,0.75%乙基纤维素,2%乳化剂,剪切8 min。扫描电子显微镜观察发现,所制微胶囊具有粒径大小均匀,表面光滑等特性;红外光谱图表明,高效氯氟氰菊酯被乙基纤维素包埋;释放特性曲线也表明微胶囊具有较好的缓释性能。该工艺操作简单,制备周期短,成囊性好,可为农药微胶囊的制备提供有效途径。     

Monitoring of cell growth using the focused beam reflectance method

In this paper the use of a focused beam reflectance measurement (FBRM) particle characterisation probe was investigated as a tool for monitoring the growth of the filamentous bacteria Streptomyces natalensis. The optimum operating parameters of the probe were identified, and it was found that the sample agitation rate had the largest effect on the mean value of a number of statistics of the chord length distribution (CLD) measured by the FBRM probe. A series of fractions of the particle size distribution was generated by sieving. It was found that the mean chord length measured by the probe responded to changes in the size distribution examined, increasing from 57.2 µm to 69.9 µm with an increase in the upper particle size from 180 µm to 300 µm. It was also found that the average total counts measured by the probe also increased with increasing sample concentration. This relationship was further investigated and it was found that in the normal range of biomass levels experienced in a fermentation (up to 4.0 g dm^?3) there was an apparently linear relationship between counts and concentration. However, as concentration was increased further the relationship became increasingly non‐linear. Copyright © 2004 Society of Chemical Industry     

Development of mefenamic acid–loaded polymeric microparticles using solvent evaporation and spray-drying technique

Ethyl cellulose (EC) and Eudragit RL-100 (ERL-100) were used for the preparation of sustained released microparticles of mefenamic acid (MFN) by using oil-in-oil (o/o) solvent evaporation as well as spray drying. A Plackett-Burman design was employed using Design-Expert software. The resultant microparticles were characterized for their size, surface morphology, encapsulation efficiency, and drug release. Imaging of microparticles was performed by field emission scanning electron microscopy. The drug and polymer interaction was investigated by Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffractometry (XRPD). The microparticles showed encapsulation efficiency in the range of 29.44 to 89.20% by solvent evaporation and 83.73 to 96.69% by spray drying. The surface of the microparticles was smooth, round, and regular, without any erosion and cracking. The size of the microparticles was found to be in the range of 6.55 to 41.1 µm. FTIR analysis confirmed no interaction of MFN with the polymers. XRPD showed the dispersion of the drug within the microparticle formulation. These results helped in finding the optimum formulation variables for encapsulation efficiency (EE) of microparticles.     

Establishment of a solvent map for formation of crystalline and amorphous paclitaxel by solvent evaporation process

This study intended to establish a solvent map for formation of crystalline and amorphous paclitaxel by a solvent evaporation process. Crystalline paclitaxel was produced by evaporation with polar solvents (acetone, acetonitrile, ethanol, isobutyl alcohol, methanol, methyl ethyl ketone, and n-butyl alcohol) having a polarity index above 4.00. On the other hand, amorphous paclitaxel was produced by evaporation with non-polar solvents (methylene chloride, n-butyl chloride, and toluene) having a polarity index of about 4.00 or lower. The formation of paclitaxel was very closely associated with the polarity index of the organic solvent used in the solvent evaporation process. In the case of crystalline paclitaxel, the higher the polarity index and the lower the viscosity of the organic solvent (n-butyl alcohol, methyl ethyl ketone, and acetonitrile), the higher the degree of crystallinity. In the case of amorphous paclitaxel, the shape and size of particles varied according to the solvent (methylene chloride, n-butyl chloride, and toluene) used in the solvent evaporation process.     

Optimization of Formulation Variables to Increase Antigen Entrapment in PLGA Particles

Efficient antigen entrapment is a key factor in preparation of poly (lactide-co-glycolide) acid (PLGA) vaccine formulations when the antigen is of short supply. This study presents a systematic approach in the testing of formulation variables with the objective to increase antigen entrapment in particles when the antigen stock concentration was low. Some of the experimental variables tested were poly (vinyl) alcohol (PVA) concentration in the inner (W₁) and outer (W₂) aqueous phase, W₁/oil (O) phase ratio and choice of organic solvent. The double emulsion solvent evaporation technique was applied to prepare PLGA particles with sonication as the emulsifying force. To measure antigen entrapment efficiency, the antigen (bovine serum albumin, BSA) was isotope labeled with ¹²⁵iodine (¹²⁵I). Our results demonstrated that a low PVA concentration in the inner aqueous (W₁) phase was beneficial to achieve a high encapsulation efficiency of antigen. On the contrary, in the outer aqueous (W₂) phase, a high PVA concentration favored antigen entrapment. We also demonstrated that decreasing the W₁ to O/polymer ratio contributed to increased entrapment efficiency. Testing different organic solvents (ethyl acetate, dichloromethane and chloroform), either alone or in combination, revealed that using chloroform as solvent resulted in the highest encapsulation of antigen and the highest production yield. Some of the results presented in this work are in disagreement with well-established formulation variables from previous studies.     

二元溶剂体系对泡沫传输制备聚苯乙烯微球的影响

采用二氯甲烷（DCM）和丙酮（AC）组成二元溶剂体系,考察了二元溶剂体系对制备聚苯乙烯（PS）微球时泡沫的传输和微球性能的影响,并探讨了对应的作用机理。实验结果表明,随着AC质量分数的增加,体系的出泡温度升高,PS微球的平均粒径下降且粒径分布逐渐变窄,微球的结构由多孔逐渐演变为中空。这主要是由于AC对水具有一定的亲和性,会往连续相迁移,改变连续相的表面张力,并在油水界面形成一个AC/DCM的混合液膜层,该液膜层改变了溶剂挥发的过程,最终实现对微球粒径和结构的调控。     

Effect of casting solvent on characteristics of hexanoyl chitosan/polylactide blend films

Blend films of hexanoyl chitosan (H‐chitosan) and polylactide (PLA) were cast from corresponding blend solutions in chloroform, dichloromethane, or tetrahydrofuran. Thermal degradation behavior of the as‐prepared blend films was intermediate to those of the pure components and no significant effect from the type of the casting solvent was observed. All of the blend films exhibited one composition‐dependent glass transition temperature, but the results only suggested partial miscibility of the components in the amorphous phase at “low” contents of H‐chitosan. As revealed by solvent etching technique, the as‐prepared blend films prepared from the blend solutions in chloroform and dichloromethane showed extensive phase separation of the two components, with the minor phase forming into discrete domains throughout the matrix. Both thermal and X‐ray analyses showed that the apparent degree of crystallinity of the PLA component in the blends decreased monotonically with increasing H‐chitosan content and the choice of the casting solvent did not have an effect on the structure of PLA crystals. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Halogen‐free solvent for oxidative carbonylation of bisphenol A to polycarbonate

Halogen‐free solvents for oxidative carbonylation of bisphenol A to polycarbonate using carbon monoxide were investigated. Tetrahydorofuran, γ‐butyrolacton, and acetophenone, which dissolve both bisphenol A and polycarbonate, gave a polycarbonate yield that was lower than using a halogenated solvent of dichloromethane. On the other hand, propylene carbonate that has a carbonate bond gave a polycarbonate yield the same as using dichloromethane. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007