Air Jet Mill Research Articles

Improvement of pulverization efficiency for micro-sized particles grinding by uncooled high-temperature air jet mill using a computational simulation

The high-temperature-uncooled-developed air jet mill system (AJMS) is one of the most effective grinding technologies for uniformed particle size. AJMS is the core technology in raw material manufacturing technology to grind and classify materials efficiently with a classifier that crushes raw materials by high-pressure compressible nozzles at high temperature into micro size particles and separates them by the desired size by using the centrifugal force of the rotor. However, the characteristics of grinding and classifying are affected by internal factors with occurring of complexed physical phenomena. To overcome the challenge, we used a discrete element model (DEM) and Computational fluid dynamics (CFD) simulation to clarify the relationship of the correlation with the actual design variables by predicted the motion of particles with the operating conditions and obtained optimized conditions. This research is described pulverization models of the AJMS with particle-structure interactions through optimized design value from DEM. Based on these results, we suggest a design method of AJMS to grinding the ceramic particles 2.86 μm of an average and 1.32 μm of a standard deviation from 14,000 rpm of the classifying rotor.

Sugarcane Bagasse Ash Micronized Using Air Jet Mills for Green Pozzolan in Brazil

This study provided a basis for new possibilities concerning the use of the sugarcane bagasse ash as a green pozzolanic addition to the Portland cement composite. To that effect, a simple micronization method using air jet milling without any other additional thermal procedure was used to control the characteristics of ash particles. This procedure not only maintains the required characteristics of the residues but can also improve some of them. Sugarcane bagasse ash is a residue produced on large scale in Brazil by ethanol and sugar plants as a result of the burning of sugarcane bagasse in energy cogeneration. The residue used in this study was initially characterized by scanning electron microscopy, granulometric and specific mass analyses, N2 adsorption measurements, X-ray diffraction, X-ray fluorescence spectroscopy, and thermogravimetric analysis with differential thermal analysis. Pozzolanic ash activity was evaluated according to the axial compressive strength at 28 days and the modified Chapelle methods. The results showed that the milling fly sugarcane bagasse ash samples presented satisfactory pozzolanic activity.

Influence of micronization on the physical properties of salbutamol sulfate as a model drug used in dry powder inhalation

Abstract Purpose: Investigation of the crystallinity of salbutamol sulfate a model drug used in the dry powder inhalation formulation. Materials and Methods: Salbutamol sulfate was supplied kindly by Lindopharm (Hilden, Germany). Salbutamol sulfate was milled using an air jet milling process, the particle size and morphology were determined using laser diffraction and the scanning electron microscopy. The drug was subjected to conditioning through storage at 52.8% and 75% relative humidity for 24 h, 1 week, and 2 weeks, respectively. The drug crystallinity was investigated using differential scanning calorimetry (DSC), X-ray diffraction, and water vapor sorption techniques. Results and Discussion: Conditioning of salbutamol sulfate after micronization lowers the glass transition (Tg) temperature of the amorphous parts present at particle surface, which enhances particle mobility for more rearrangement associated with water expelling. This transformation may result in deviation from the original particle size obtained after milling out of respirable range. DSC and X-ray diffraction show no detectable amorphous drug since no detectable Tg observed. Alternatively, water vapor sorption shows a small amount of amorphous salbutamol sulfate at the particle surface, which recrystallizes at 52.8% relative humidity after approximately 2 weeks of conditioning. Conclusion: The amorphous regions can be generated in crystalline materials during processing. The level of amorphous materials can affect every step of pharmaceutical formulation, storage, and stability. However, quantification of low levels of amorphous content still poses considerable challenge. This study confirms that, the water vapor sorption technique is useful in the quantification of a small amount of drug amorphous content.

Air Jet Mill 공법과 PMMA의 단분산성이 프레스드 파우더의 밀착성 및 발림성 향상에 대한 연구

베이스메이크업 중의 하나인 프레스드 파우더는 주요 품질 속성으로 밀착성과 발림성이다. 일반적으로 메이크업 화장료에서 밀착성을 향상시키면 반대속성인 발림성이 저하되기 때문에 밀착성과 발림성을 동시에 충족시키는데 한계가 있었다. 본 연구에서는 두 가지 주요 속성을 만족시키기 위해서 air jet mill 공정을 시도하였고, lauroyl lysine (LL)과 sodium cocoyl glutamate (SCG)의 혼합물로 습식 코팅 처리한 sericite를 적용하여 밀착성을 향상시켰다. 또한, 분산성이 단분산성을 이루고 있는 polymethyl methacrylate (PMMA)와 diphenyl dimethicone/ vinyl diphenyl dimethicone/ silsesquioxane crosspolymer (DDVDDSC)를 적용하여 발림성을 향상시켜 서로 양립하기 어려운 두 가지 품질 속성을 모두 만족시켰다. air jet mill 공정은 제약, 식품 산업에서 주로 적용되고 있으며 화장품 분야에서는 파우더 소재 가공을 위해 사용되고 있는 공법이다. 본 연구에서는 air jet mill 공정을 제조 공정단계에서 접목시켜 최적의 입경인 <TEX>$6.8{\mu}m$</TEX>의 화장료를 완성할 수 있었다. 그리고, EDS 매핑으로 Ti 원소가 화장료에서 전체적으로 고르게 분포하고 있음을 확인하였고, SEM 분석을 통하여 판상 입자의 모서리 부분이 둥글게 가공처리 됨을 확인하였다. 이는 화장 도구를 이용하여 화장료를 취하여 피부에 도포할 때, 발림성이 향상되는 효과를 줄 수 있다고 판단된다. 피부 친화성이 우수한 LL과 저자극이면서 코코넛에서 유래한 SCG를 습식 코팅하여 sericite의 밀착성을 더욱 향상시켰다. 그리고, PMMA의 분산성과 형태가 발림성에 미치는 영향을 평가하기 위해서 SEM을 분석하였다. 유사한 형태를 갖는 구형 및 진구형에서도 분포도가 균일하고 단분산상일 때 발림성 효과가 더욱 증가하는 것으로 나타났다. PMMA의 단분산성과 입경에 따른 발림성을 동마찰계수 측정으로 확인하였고, 최적의 함량을 결정하였다. 그리고, 실리콘 러버 파우더 종류에 따른 발림성과 경도, 낙하안정성 등을 확인하여 DDVDDSC를 결정하였다. 최종적으로 PMMA의 단분산성과 실리콘 러버 파우더가 발림성에 영향을 끼치는 것을 알 수 있었다. 이와 같은 화장료는 적정한 경도를 갖으면서도 낙하안정성이 우수하며, 경시에 따른 안정성도 우수하였다. 본 연구 결과를 통해 본 논문에서 제시하는 프레스드 파우더의 밀착성과 발림성을 향상시킬 수 있는 한 가지 방법으로 활용될 수 있을 것이라 판단된다. The key quality attributes of the pressed powder, one of base makeup products, are skin-affinity and spreadability. In general, there was a limit to meet skin-affinity and spreadability simultaneously, which are opposite attributes each other. In this study, air jet mill process was tried to satisfy two main properties. Skin-affinity was improved by a wet coating of sericite with a mixture of lauroyl lysine (LL) and sodium cocoyl glutamate (SCG). The application of mono-dispersed polymethyl methacrylate (PMMA) and diphenyl dimethicone/vinyl diphenyl dimethicone/silsesquioxane crosspolymer (DDVDDSC) improved both qualities. Air jet mill process has been mainly applied in the pharmaceutical and food industries, and is a method used for processing powder materials in cosmetic field. In this study, we were able to complete makeup cosmetics with an optimum particle size <TEX>$6.8{\mu}m$</TEX> by combining the air jet mill process at the manufacturing stage. It was confirmed that the Ti element was uniformly distributed throughout the cosmetics by EDS mapping, and that the corners of the tabular grains were rounded by SEM analysis. It is considered that this can provide an effect of improving the spreadability when the cosmetic is applied to the skin by using a makeup tool. LL with excellent skin compatibility and SCG derived from coconut with little skin irritation were wet coated to further enhance the adhesion of sericite. SEM images were analyzed to evaluate effect of the dispersion and uniformity of PMMA on spreadability. With the spherical shapes of similar size, it was found that the spreading effect was further increased when the distribution was homogeneously mono-dispersed. The dispersion and spreadability of PMMA were confirmed by measuring the kinetic friction and optimal content was determined. The silicone rubber powder, DDVDDSC, was confirmed by evaluating the hardness, spreading value, and drop test. Finally, it was found that the dispersion of PMMA and silicone rubber powder affected spreadability. Such makeup cosmetics have excellent stability in drop test while having appropriate hardness, and good stability over time. Taken together, it is concluded that air jet mill process can be utilized as a method to improve skin-affinity and spreadability of the pressed powder.

Towards quality by design in pharmaceutical manufacturing: modelling and control of air jet mills

Milling is an important step in pharmaceutical manufacturing as it not only determines the final formulation of the drug product, but also influences the bioavailability and dissolution rate of the active pharmaceutical ingredient (API). In this respect, the air jet mill (AJM) is most commonly used in the pharmaceutical industry as it is a non-contaminating and non-degrading self-classifying process capable of delivering narrow particle size distributions (PSD). Keeping the principles of Quality by Design in mind, the Critical Process Parameters (CPPs) of the AJM have been identified to be the pressures at the grinding nozzles, and the feed rate which affect the PSD, surface charge and the morphology of the product (i.e. the Critical Material Attributes (CMAs)). For the purpose of this research, the PSD is considered to be the only relevant CMA. A population balance based model is proposed to simulate the dynamics milling operation by utilizing the concept of breakage functions. This model agrees qualitatively with experimental observations of the air jet mill unit present at Janssen Pharmaceutica but further steps for model validation need to be carried out.

Study on the Performance of an Air-Jet Mill by varying operating Parameters

In the present work, performance of an Air-Jet Mill was studied. Although jet mill has several advantages but it is still an energy intensive process as only 2% - 5% of the energy supplied is used to create new surfaces. In the present work some trial runs are performed by varying the operating parameters of the jetmill. Product quality is the factor which determines whether determines whether a specific grinding technique is appropriate. The roduct of a jet mill is a fine powder with a well defined and narrow particle size distribution. The RPM and blower alue conditions were varied and the results were tabulated. The optimum conditions for the desired quality and production rate of the jet mill in the plant are determined.

Implementation of design of experiments approach for the micronization of a drug with a high brittle–ductile transition particle diameter

Objective: To optimize air-jet milling conditions of ibuprofen (IBU) using design of experiment (DoE) method, and to test the generalizability of the optimized conditions for the processing of another non-steroidal anti-inflammatory drug (NSAID).Methods: Bulk IBU was micronized using an Aljet mill according to a circumscribed central composite (CCC) design with grinding and pushing nozzle pressures (GrindP, PushP) varying from 20 to 110 psi. Output variables included yield and particle diameters at the 50th and 90th percentile (D50, D90). Following data analysis, the optimized conditions were identified and tested to produce IBU particles with a minimum size and an acceptable yield. Finally, indomethacin (IND) was milled using the optimized conditions as well as the control.Results: CCC design included eight successful runs for milling IBU from the ten total runs due to powder “blowback” from the feed hopper. DoE analysis allowed the optimization of the GrindP and PushP at 75 and 65 psi. In subsequent validation experiments using the optimized conditions, the experimental D50 and D90 values (1.9 and 3.6 μm) corresponded closely with the DoE modeling predicted values. Additionally, the optimized conditions were superior over the control conditions for the micronization of IND where smaller D50 and D90 values (1.2 and 2.7 μm vs. 1.8 and 4.4 μm) were produced.Conclusion: The optimization of a single-step air-jet milling of IBU using the DoE approach elucidated the optimal milling conditions, which were used to micronize IND using the optimized milling conditions.

Preparation of slab-shaped lactose carrier particles for dry powder inhalers by air jet milling

Dry powder inhalers are often formulated by attaching micronized drug particles onto carrier particles, which are generally lactose. In this study, commercially available lactose was air jet milled to produce unique slab-like coarse carrier particles, which have larger and rougher surfaces compared to other commercially available lactose. Two key processing factors, i.e., classifier speed and jet milling pressure, were systematically investigated. The largest fraction of slab-like particles in the resulting powder was obtained at a classifier speed of 3000 rpm. The slab-like coarse carrier particles are expected to exhibit superior performance than commercial lactose due to their unique surface properties.

In vitro characterization of insulin containing thiomeric microparticles as nasal drug delivery system

This study focused on a novel two step preparation method for the generation of insulin containing thiomer microparticles. The first step utilized the interpolymer complexation between poly(vinyl pyrrolidone) (PVP) and poly(acrylic acid) (PAA) or poly(acrylic acid)-cysteine (PAA-Cys), respectively, in the presence of insulin. Thereafter lyophilized coprecipitates were micronized via air jet mill. Particles were evaluated regarding size, morphology, insulin release and the effect on ciliary beat frequency of human nasal epithelial cells in vitro. Results displayed mean particle sizes of 2.6±1.6μm and 2.8±1.7μm for PAA/PVP/insulin and PAA-Cys/PVP/insulin microparticles, respectively, in a range where volitional impaction of particles on nasal epithelium takes place. Multi unit dosage forms showed in addition release for the incorporated insulin and nasal safety as to results of ciliary beat frequency studies (CBF). The introduced jet milled microparticles might in conclusion display a safe nasal insulin drug delivery system leading to improved absorption.

Removal of lead(II) from aqueous solution using modified palygorskite, contribution of inverse gas chromatography

Four modified palygorskite powders that had been milled in mortar, in air jet mill, in Pulverisette0 vibrating ball mill and treated with hydrochloric acid were used as adsorbents for lead removal from an aqueous solution. The adsorbents were characterized by nitrogen adsorption, size measurement, mercury porosimetry and scanning electron microscopy. Inverse gas chromatography at infinite dilution and finite concentration was also implemented to determine surface properties of the four samples, in particular the irreversibility indexes, a measurement of high-energy sites.In a second part, batch adsorption experiments were carried out to study the effect of mechanical and chemical treatments on lead adsorption properties of the powder. The isotherm analysis indicated that the Langmuir model could represent the adsorption data. The sample ground in Pulverisette0 presented the highest cationic exchange capacity and led to the highest adsorption capacity despite the relatively low specific surface area and the complete destruction of the fibrous morphology of the raw powder. A correlation was shown between the cationic exchange capacity and irreversibility indexes obtained with isopropanol.

Effect of mill type on the size reduction and phase transformation of gamma alumina

The influence of stress modes and comminution conditions on the effectiveness of particle size reduction of a common catalyst support; γ-Alumina is examined through a comparative assessment of three different mill types. Air jet milling is found to be the most effective in reducing particle size from a d90 of 37µm to 2.9µm compared to planetary ball milling (30.2µm) and single ball milling (10.5µm). XRD and TEM studies confirm that the planetary ball mill causes phase transformation to the less desired α-Alumina resulting in a notable decrease in surface area from 136.6m2/g to 82.5m2/g as measured by the BET method. This is consistent with the large shear stresses under high shear rates prevailing in the planetary ball mill when compared to the other mill types. These observations are consistent with a shear-induced phase transformation mechanism brought about by slip on alternate close packed oxygen layers from a cubic close packed to a hexagonal close packed structure.

Investigation of the milling capabilities of the F10 Fine Grind mill using Box-Behnken designs

Size reduction or milling of the active is often the first processing step in the design of a dosage form. The ability of a mill to convert coarse crystals into the target size and size distribution efficiently is highly desirable as the quality of the final pharmaceutical product after processing is often still dependent on the dimensional attributes of its component constituents. The F10 Fine Grind mill is a mechanical impact mill designed to produce unimodal mid-size particles by utilizing a single-pass two-stage size reduction process for fine grinding of raw materials needed in secondary processing. Box–Behnken designs were used to investigate the effects of various mill variables (impeller, blower and feeder speeds and screen aperture size) on the milling of coarse crystals. Response variables included the particle size parameters (D10, D50and D90), span and milling rate. Milled particles in the size range of 5–200μm, with D50 ranging from 15 to 60μm, were produced. The impeller and feeder speeds were the most critical factors influencing the particle size and milling rate, respectively. Size distributions of milled particles were better described by their goodness-of-fit to a log-normal distribution (i.e. unimodality) rather than span. Milled particles with symmetrical unimodal distributions were obtained when the screen aperture size was close to the median diameter of coarse particles employed. The capacity for high throughput milling of particles to a mid-size range, which is intermediate between conventional mechanical impact mills and air jet mills, was demonstrated in the F10 mill. Prediction models from the Box–Behnken designs will aid in providing a better guide to the milling process and milled product characteristics.

The Study and Preparation of Petroleum Coke Oil Slurry for Diesel Engine

An amount of 1.8 μm of ultra-fine petroleum coke was prepared by air jet mill and used to prepare the petroleum coke oil slurry for a diesel engine. The results indicated that the viscosity of the slurry decreased from 587 to 305 mPa·S, when the amount of additive NDZ-105 increased from 0 to 2 wt%. The coke oil slurry was used in the modified R180 diesel engine, and the results showed that the engine maximum power reduced by 19% compared with burning diesel fuel, and the smoke emission was 2–5 times higher than burning diesel fuel.

Modeling of continuous self‐classifying spiral jet mills part 1: Model structure and validation using mill experiments

The objective of this work is to develop a milling model for a continuous self‐classifying spiral air jet mill. Its foundation is a population balance model with selection and breakage distribution functions that have been related to a minimal number of mill‐dependent and powder‐dependent parameters. Initially, experimentation is required to determine the mill‐dependent parameters for a specific mill, by milling a “base” powder at multiple operating conditions. Powder‐dependent parameters can be determined from either mill experiments or from material characterization measurements that require small amounts of powder (presented in Part 2). Ultimately, the milling model presented successfully predicts the product particle size using as inputs the feed particle‐size distribution and mill operating conditions. Three crystalline powders, sodium bicarbonate, lactose monohydrate, and sucrose, have been used to test the proposed milling model. © 2014 American Institute of Chemical Engineers AIChE J 60: 4086–4095, 2014

Micronized/ultramicronized palmitoylethanolamide displays superior oral efficacy compared to nonmicronized palmitoylethanolamide in a rat model of inflammatory pain.

BackgroundThe fatty acid amide palmitoylethanolamide (PEA) has been studied extensively for its anti-inflammatory and neuroprotective actions. The lipidic nature and large particle size of PEA in the native state may limit its solubility and bioavailability when given orally, however. Micronized formulations of a drug enhance its rate of dissolution and reduce variability of absorption when orally administered. The present study was thus designed to evaluate the oral anti-inflammatory efficacy of micronized/ultramicronized versus nonmicronized PEA formulations.MethodsMicronized/ultramicronized PEA was produced by the air-jet milling technique, and the various PEA preparations were subjected to physicochemical characterization to determine particle size distribution and purity. Each PEA formulation was then assessed for its anti-inflammatory effects when given orally in the carrageenan-induced rat paw model of inflammation, a well-established paradigm of edema formation and thermal hyperalgesia.ResultsIntraplantar injection of carrageenan into the right hind paw led to a marked accumulation of infiltrating inflammatory cells and increased myeloperoxidase activity. Both parameters were significantly decreased by orally given micronized PEA (PEA-m; 10 mg/kg) or ultramicronized PEA (PEA-um; 10 mg/kg), but not nonmicronized PeaPure (10 mg/kg). Further, carrageenan-induced paw edema and thermal hyperalgesia were markedly and significantly reduced by oral treatment with micronized PEA-m and ultramicronized PEA-um at each time point compared to nonmicronized PeaPure. However, when given by the intraperitoneal route, all PEA formulations proved effective.ConclusionsThese findings illustrate the superior anti-inflammatory action exerted by orally administered, micronized PEA-m and ultramicronized PEA-um, versus that of nonmicronized PeaPure, in the rat paw carrageenan model of inflammatory pain.

Influence of different dry milling processes on the properties of an attapulgite clay, contribution of inverse gas chromatography

The effect of dry milling processes on the surface properties of an attapulgite clay, also called palygorskite, was investigated by carrying out experiments with different types of grinding devices. Ground products were then characterized by size measurement, scanning electron microscopy, X-ray diffraction, adsorption–desorption of N2 and inverse gas chromatography at infinite dilution (IGC-ID) as well as finite concentration conditions (IGC-FC). These analyses were performed to evaluate the changes in particle size distribution, morphology, crystallinity and surface properties of attapulgite powder, respectively. Among the tested dry grinding devices, grinding in an air jet mill (Alpine 50 AS) and a vibratory ball mill (Pulverisette 0) led to the most significant particle size reduction. SEM photomicrographs showed that a breakage of the fibrous structure took place during dry grinding. Moreover, long grinding in Pulverisette 0 resulted in the complete destruction of fibre morphology followed by agglomeration. XRD analysis showed that whatever the grinding process, the microstructure of the attapulgite was not affected. IGC confirmed that only grinding in Pulverisette 0 affected the surface properties notably. In this case, the most significant decreases were observed in the dispersive component of the surface energy (164 to 116mJ/m2) and in the specific surface area obtained with the octane probe (114.5m2/g to 62.6m2/g) by IGC-ID and IGC-FC, respectively. At the same time, a modification of the distribution functions of the adsorption energies (DFAE), giving information about surface heterogeneity, was noticed.

Solid Dispersions Prepared by Continuous Cogrinding in an Air Jet Mill

Embedding a poorly water-soluble drug as a solid dispersion in a hydrophilic carrier by cogrinding is a possible strategy for enhancing the drug dissolution rate. Although general interest in continuous processes for manufacturing drug formulations has increased, many publications still focus on batch processes. The jet mill used in this study is a promising tool for continuous cogrinding. Investigation of different drug-to-carrier ratios (griseofulvin/mannitol) demonstrated that a drug load of 10% is best suited to investigate the enhanced dissolution behavior. To gain deeper insight into the underlying mechanisms, the coground dispersion is compared with different physical mixtures in terms of physicochemical properties and dissolution behavior. Differential scanning calorimetry and X-ray powder diffraction were used to verify the crystalline structure of the coground formulation. On the basis of the Hixson-Crowell model, particle size reduction was ruled out as the main reason for dissolution enhancement. An increase of surface free energies because of grinding is shown with contact angle measurements. Confocal Raman microscopy investigations revealed the drug's bulk dispersity in the coground formulation as an additional factor for the increased dissolution rate. In conclusion, the continuous cogrinding approach is a promising technique to prepare the drug in a rapidly dissolving, yet crystalline, form.

Physico-chemical characterisation of surface modified particles for inhalation

Surface modification of drugs for inhalation is a possibility to influence interparticulate forces. This can be necessary to achieve a sufficient aerosolisation during powder inhalation as the cohesiveness of the micronised drug can be reduced. In addition, the interaction with propellants in pressurised metered dose inhaler can be changed. This can be used to improve the physical stability of the suspension based formulations. A dry particle coating process was used for the alteration of particle surfaces. The blending of micronised salbutamol sulphate (SBS) with different concentrations of magnesium stearate (Mgst) or glycerol monostearate (GMS) was followed by co-milling with an air jet mill. The powder properties were characterised by SEM, EDX, laser diffraction, BET and inverse gas chromatography. Physical mixtures generated by Turbula blending were compared to co-milled samples. A slight particle size reduction was determined. The Mgst deposition on SBS particles was detected by EDX measurements. The dispersive surface energy of SBS is lowered and the energy distribution is more homogenous for the co-milled samples. This study proves the application of co-milling for surface modification in the inhalation area.

PARTICLE SIZE REDUCTION OF ACECLOFENAC BY USING SURFACTANTS AND MICRONIZATION FOR NANOCARRIER ENTRAPMENT

The Aceclofenac (2-[(2, 6- dichlorophenyl) amine] phenylacetoxyacetic acid) is a Non-Steroidal Anti-Inflammatory category of drug, which is water insoluble drug of BCS class-II which has low solubility and high permeability phenomenon. The particle size reduction technique is used to solubilize the aceclofenac. The particle size of aceclofenac in bulk form is 140-200 microns. In this experiment, The 35 microns particle size was reduced in powder form from 140-200 microns by using Air jet mill and 17.08 microns size was reduced by using dynomill and 33.62 microns particle size was reduced by using Tween 80 as surfactant as considered as lowest particle size. The Labrasol and Na. CMC were also used in this experiment. The equipments used to reduce particle size of aceclofenac are ultra-Turrax (Ultra-sonication), Air jet mill and Dynomill. These all instruments used to reduce the particle size of aceclofenac are safe and not any chemical compound was added in any of the method described above. This study was used to see the uniform nature of the nano- and micro-particles entrapping the aceclofenac drug obtained by High shear homogenization, high pressure homogenization, Solvent-Diffusion evaporation and membrane contactor methods. If the particle size of aceclofenac cannot be reduced less than 14 microns then at the time of Permeation studies the same particle size will enter in Stratum corneum of Skin and entrapped in the carrier matrix. And formation of microns sized particles will obtained while preparing Solid lipid nanoparticles. Keywords: Solubilization, Particle size reduction, Air jet mill, high shear homogenizer, particle size analyzer, Dynomill

HEC-cysteamine particles: influence of particle size, zeta potential, morphology and sulfhydryl groups on permeation enhancing properties

Within this study, the influence of particle size and zeta potential of hydroxyethyl cellulose–cysteamine particles on permeation enhancing properties was investigated. Particles were prepared by four different methods namely ionic gelation, spray drying, air jet milling and grinding. Particles prepared by grinding were additionally air jet milled. All particles were characterized in terms of particle size and zeta potential. The transport of fluorescein isothiocyanate-dextran 4 (FD4) across Caco-2 cell monolayers in the presence of these particles and the decrease in transepithelial electrical resistance (TEER) was evaluated. The cytotoxic effect of the particles was investigated using resazurin assay. Nanoparticles displaying a zeta potential of 3.3 ± 1.3 mV showed the highest enhancement of FD4 transport among all particles with a 5.83-fold improvement compared to buffer only. Due to the larger particle size, particles generated by grinding exhibited a lower capability in opening of tight junctions compared to smaller particles generated by air jet milling. In addition, the results of the transport studies were supported by the decrease in the TEER. All particle formulations tested were comparatively non-cytotoxic. Accordingly, the zeta potential and particle size showed a significant impact on the opening of tight junctions and hence could play an important role in the design of hydroxyethyl cellulose (HEC)-cysteamine-based nano- and micro-particles as drug delivery systems.