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1.
Tewa-Tagne P Degobert G Briançon S Bordes C Gauvrit JY Lanteri P Fessi H 《Pharmaceutical research》2007,24(4):650-661
Purpose Spray-drying process was used for the development of dried polymeric nanocapsules. The purpose of this research was to investigate
the effects of formulation and process variables on the resulting powder characteristics in order to optimize them.
Materials and Methods Experimental designs were used in order to estimate the influence of formulation parameters (nanocapsules and silica concentrations)
and process variables (inlet temperature, spray-flow air, feed flow rate and drying air flow rate) on spray-dried nanocapsules
when using silica as drying auxiliary agent. The interactions among the formulation parameters and process variables were
also studied. Responses analyzed for computing these effects and interactions were outlet temperature, moisture content, operation
yield, particles size, and particulate density. Additional qualitative responses (particles morphology, powder behavior) were
also considered.
Results Nanocapsules and silica concentrations were the main factors influencing the yield, particulate density and particle size.
In addition, they were concerned for the only significant interactions occurring among two different variables. None of the
studied variables had major effect on the moisture content while the interaction between nanocapsules and silica in the feed
was of first interest and determinant for both the qualitative and quantitative responses. The particles morphology depended
on the feed formulation but was unaffected by the process conditions.
Conclusion This study demonstrated that drying nanocapsules using silica as auxiliary agent by spray drying process enables the obtaining
of dried micronic particle size. The optimization of the process and the formulation variables resulted in a considerable
improvement of product yield while minimizing the moisture content. 相似文献
2.
《European journal of pharmaceutics and biopharmaceutics》2009,71(3):828-838
Quality by design (QBD) refers to a holistic approach towards drug development. Important parts of QBD include definition of final product performance and understanding of formulation and process parameters. Inhalation of proteins for systemic distribution requires specific product characteristics and a manufacturing process which produces the desired product. The objective of this study was to understand the spray drying process of insulin intended for pulmonary administration. In particular, the effects of process and formulation parameters on particle characteristics and insulin integrity were investigated. Design of experiments (DOE) and multivariate data analysis were used to identify important process parameters and correlations between particle characteristics. The independent parameters included the process parameters nozzle, feed, and drying air flow rate and drying air temperature along with the insulin concentration as a formulation parameter. The dependent variables included droplet size, geometric particle size, aerodynamic particle size, yield, density, tap density, moisture content, outlet temperature, morphology, and physical and chemical integrity. Principal component analysis was performed to find correlations between dependent and independent variables. Prediction equations were obtained for all dependent variables including both interaction and quadratic terms. Overall, the insulin concentration was found to be the most important parameter, followed by inlet drying air temperature and the nozzle gas flow rate. The insulin concentration mainly affected the particle size, yield and tap density, while the inlet drying air temperature mainly affected the moisture content. No change was observed in physical and chemical integrity of the insulin molecule. 相似文献
3.
Morten Jonas Maltesen Simon Bjerregaard Lars Hovgaard Svend Havelund Marco van de Weert 《European journal of pharmaceutics and biopharmaceutics》2008,70(3):828-838
Quality by design (QBD) refers to a holistic approach towards drug development. Important parts of QBD include definition of final product performance and understanding of formulation and process parameters. Inhalation of proteins for systemic distribution requires specific product characteristics and a manufacturing process which produces the desired product. The objective of this study was to understand the spray drying process of insulin intended for pulmonary administration. In particular, the effects of process and formulation parameters on particle characteristics and insulin integrity were investigated. Design of experiments (DOE) and multivariate data analysis were used to identify important process parameters and correlations between particle characteristics. The independent parameters included the process parameters nozzle, feed, and drying air flow rate and drying air temperature along with the insulin concentration as a formulation parameter. The dependent variables included droplet size, geometric particle size, aerodynamic particle size, yield, density, tap density, moisture content, outlet temperature, morphology, and physical and chemical integrity. Principal component analysis was performed to find correlations between dependent and independent variables. Prediction equations were obtained for all dependent variables including both interaction and quadratic terms. Overall, the insulin concentration was found to be the most important parameter, followed by inlet drying air temperature and the nozzle gas flow rate. The insulin concentration mainly affected the particle size, yield and tap density, while the inlet drying air temperature mainly affected the moisture content. No change was observed in physical and chemical integrity of the insulin molecule. 相似文献
4.
The effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation 总被引:7,自引:0,他引:7
Ståhl K Claesson M Lilliehorn P Lindén H Bäckström K 《International journal of pharmaceutics》2002,233(1-2):227-237
The aim of this study was to investigate the effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation. A 2(4) full factorial experimentally designed study was performed to investigate the influence of the following independent spray drying variables: feed flow rate, nozzle gas flow rate, inlet air temperature and aspirator capacity (drying gas flow rate). Human insulin (biosynthetic and Ph.Eur. quality) was dissolved in distilled water to concentrations of 5 mg/ml. The solutions were spray dried in a Mini Spray Dryer Büchi and the dry powders produced were characterized by high performance liquid chromatography, size exclusion chromatography, laser diffraction, thermo gravimetric analysis, scanning electron microscopy and weighing. The degradation of insulin was found to be affected mainly by the process variables that determine the outlet air temperature, i.e.: inlet air temperature, aspirator capacity and feed flow rate. The outlet air temperature should be kept below 120 degrees C to avoid degradation. A statistical optimization of the spray drying variables was performed, and found to recommend an experiment with an outlet air temperature of 61+/-4 degrees C. This experiment ought to generate a yield of 54+/-7% by weight of particles with a mass median diameter 2.9+/-0.4 microm, moisture content 3.9+/-0.5% by weight, content of high molecular weight proteins 0.3+/-0.1% by area, A-21 desamido insulin 0.3+/-0.05% by area and other insulin related compounds 0.3+/-0.1% by area. 相似文献
5.
Mishra M Mishra B 《Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan》2011,131(12):1813-1825
The local delivery of antibiotics in the treatment of infectious respiratory diseases is an attractive alternative to deliver high concentration of antimicrobials directly to the lungs and minimize systemic side effects. In this study, inhalable microparticles containing doxycycline hyclate, sodium carboxymethylcellulose, leucine and lactose were prepared by spray drying of aqueous ethanol formulations. Box-Behnken design was used to study the influence of various independent variables such as polymer concentration, leucine concentration, ethanol concentration and inlet temperature of the spray dryer on microparticle characteristics. The microparticles were characterized in terms of particle morphology, drug excipient interaction, yield, entrapment efficiency, Carr's index, moisture content, thermal properties, X-ray powder diffraction, aerosolization performance and in vitro drug release. The effect of independent variables on spray dryer outlet temperature was also studied. The overall shape of the particles was found to be spherical like doughnuts in the size range of 1.16-5.2 μm. The optimized formulation (sodium carboxymethylcellulose concentration 14% w/v, leucine concentration 33% w/v, ethanol concentration 36% v/v, inlet temperature of 140°C) exhibited the following properties: yield 56.69%, moisture content 3.86%, encapsulation efficiency 61.74%, theoretical aerodynamic diameter 3.11 μm and Carr's index 23.5% at an outlet temperature 77°C. The powders generated were of a suitable mass median aerodynamic diameter (4.89 μm) with 49.3% fine particle fraction and exhibited a sustained drug release profile in vitro. 相似文献
6.
Y Gonnissen J P Remon C Vervaet 《European journal of pharmaceutics and biopharmaceutics》2007,67(1):220-226
Continuous production of directly compressible powders was achieved by coprocessing acetaminophen and carbohydrates via spray drying. Binary and ternary powder mixtures containing drug substance and carbohydrates were prepared by co-spray drying and evaluated on spray drying processibility, powder hygroscopicity, flowability, and compactability. The influence of process parameters during spray drying on the compaction behaviour of drug/excipient mixtures was investigated via Heckel analysis. Erythritol, lactose, maltodextrin, and mannitol were efficient in co-spray drying with acetaminophen. However, lactose mixtures showed poor flowability. Spray dried mixtures containing mannitol and erythritol were characterised as non-hygroscopic, highly dense, and good flowing powders. Mannitol increased tablet tensile strength in contrast with the poor compactability of erythritol. Maltodextrin was selected for further experiments because it provided excellent tablet tensile strength. The use of erythritol, maltodextrin and mannitol in binary drug/excipient mixtures resulted in high process yields. Compacts of erythritol, mannitol, and maltodextrin were characterised by higher tablet tensile strength at higher spray drying temperatures due to the increased particle fragmentation of erythritol and mannitol mixtures and to the increased plastic deformation of maltodextrin formulations. A combination of erythritol, maltodextrin, and mannitol was selected for further formulation and process optimisation of co-spray dried powders for direct compression. 相似文献
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8.
《Asian Journal of Pharmaceutical Sciences》2016,11(4):507-515
The conversion of aqueous dispersion of nanostructured lipid carriers (NLCs) into dry powder by spray drying could be a useful approach to render NLCs with better physical chemical stability than the aqueous dispersion. In this study, aqueous NLC dispersion containing fenofibrate was converted into dry, easily reconstitutable powder using spray drying. A central composite face centered design (CCFD) was used to investigate the influence of the ratio of lipid to protectant (mannitol and trehalose) and crystallinity of spray-dried powder on the particle size, yield and residual moisture content of the dried powder. A linear relationship (R2 = 0.9915) was established between the crystalline content of the spray-dried powders against the ratio of mannitol to trehalose from 3:7 to 10:0 (w/w). Spray drying of NLC aqueous dispersion using a mannitol and trehalose mixture resulted in an increase in particle size of the NLCs after reconstitution in water as compared to that in the initial aqueous dispersion. The decrease in crystallinity of the dry powder by reducing the ratio of mannitol to trehalose could improve the reconstitution of the NLCs in water. However the yield and residual moisture content of dry powder decreased with an increase in the ratio of mannitol to trehalose. Lipid nanoparticles were able to retain the drug incorporation and the prolonged drug release profile after spray drying. The experimental model was robust, and suggested that spray drying is a viable technique for the conversion of NLCs into dry powder. 相似文献
9.
The purpose of this study was to select the critical process parameters of the fluid bed processes impacting the quality attribute of a solid self-microemulsifying (SME) system of albendazole (ABZ). A fractional factorial design (2(4-1)) with four parameters (spray rate, inlet air temperature, inlet air flow, and atomization air pressure) was created by MINITAB software. Batches were manufactured in a laboratory top-spray fluid bed at 625-g scale. Loss on drying (LOD) samples were taken throughout each batch to build the entire moisture profiles. All dried granulation were sieved using mesh 20 and analyzed for particle size distribution (PSD), morphology, density, and flow. It was found that as spray rate increased, sauter-mean diameter (D(s)) also increased. The effect of inlet air temperature on the peak moisture which is directly related to the mean particle size was found to be significant. There were two-way interactions between studied process parameters. The main effects of inlet air flow rate and atomization air pressure could not be found as the data were inconclusive. The partial least square (PLS) regression model was found significant (P < 0.01) and predictive for optimization. This study established a design space for the parameters for solid SME manufacturing process. 相似文献
10.
目的 螺旋霉素原料药粉的粒径大、团聚现象严重,因此极大的限制了其临床应用;有研究报道超细粉制备技术可以很好地解决这些问题;方法 采用了两种代表性的方法制备螺旋霉素的超细粉:分别为喷雾干燥法和反溶剂法;并以粒径为指标,采用单因素实验优化得到最佳结果,对上述两种方法制备的粉体分别进行粒径、形貌特征和物化性质对比。结果 两种方法的最佳条件为:喷雾干燥法的进料速度为5 mL/min,雾化空气速度为800 L/h,进口温度为150℃,出口温度为85℃,平均粒径为(1638±10.99) nm。反溶剂法在25℃条件进行实验,溶剂与反溶剂的比例为1:5,最佳搅拌速度为1000 r/min,获得的平均粒径为(230±7.31)nm,以上结果经过扫描电子显微镜(SEM),动态光散射(DLS),傅立叶变换红外光谱(FTIR),差示扫描量热仪(DSC)和X射线衍射(XRD)进行表征;经气相色谱检测,两种方法中的溶剂残留均符合ICH最低标准(5000 ppm);结论 与喷雾干燥法相比,反溶剂法制备的螺旋霉素粒径更小、粉体分散性更佳,其溶解度更高。因此反溶剂法制备的螺旋酶素微粉更适用于制药业,为微粉技术提供技术... 相似文献
11.
摘要:目的 螺旋霉素原料药粉的粒径大、团聚现象严重,因此极大的限制了其临床应用;有研究报道超细粉制备技术可
以很好地解决这些问题; 方法 采用了两种代表性的方法制备螺旋霉素的超细粉:分别为喷雾干燥法和反溶剂法;并以粒径为
指标,采用单因素实验优化得到最佳结果,对上述两种方法制备的粉体分别进行粒径、形貌特征和物化性质对比。结果 两种
方法的最佳条件为:喷雾干燥法的进料速度为5 mL/min,雾化空气速度为800 L/h,进口温度为150℃,出口温度为85℃,平均
粒径为(1638±10.99) nm。反溶剂法在25℃条件进行实验,溶剂与反溶剂的比例为1:5,最佳搅拌速度为1000 r/min,获得的平均
粒径为(230±7.31)nm,以上结果经过扫描电子显微镜(SEM),动态光散射(DLS),傅立叶变换红外光谱(FTIR),差示扫描量热仪
(DSC)和X射线衍射(XRD)进行表征;经气相色谱检测,两种方法中的溶剂残留均符合ICH最低标准(5000 ppm);结论 与喷雾干
燥法相比,反溶剂法制备的螺旋霉素粒径更小、粉体分散性更佳,其溶解度更高。因此反溶剂法制备的螺旋酶素微粉更适用于
制药业,为微粉技术提供技术思路。 相似文献
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13.
In this study the Nano Spray Dryer B-90 (BüCHI Labortechnik AG, Flawil, Switzerland) was evaluated with regard to the drying of proteins and the preparation of respirable powders in the size range of 1-5 μm. β-galactosidase was chosen as a model protein and trehalose was added as a stabilizer. The influence of inlet temperature, hole size of the spray cap membrane and ethanol concentration in the spray solution was studied using a 33 full factorial design. The investigated responses were enzyme activity, particle size, span, yield and shelf life. Furthermore, the particle morphology was examined. The inlet temperature as well as the interaction of inlet temperature and spray cap size significantly influenced the enzyme activity. Full activity was retained with the optimized process. The particle size was affected by the hole size of the spray cap membrane and the ethanol content. The smallest cap led to a monodisperse particle size distribution and the greatest yield of particles of respirable size. Higher product recovery was achieved with lower inlet temperatures, higher ethanol contents and smaller cap sizes. Particle morphology differed depending on the cap size. The protein exhibited higher storage stability when spray dried without ethanol and when a larger spray cap size was used. 相似文献
14.
《Pharmaceutical development and technology》2013,18(4):511-520
The purpose of this study was to select the critical process parameters of the fluid bed processes impacting the quality attribute of a solid self-microemulsifying (SME) system of albendazole (ABZ). A fractional factorial design (24–1) with four parameters (spray rate, inlet air temperature, inlet air flow, and atomization air pressure) was created by MINITAB? software. Batches were manufactured in a laboratory top-spray fluid bed at 625-g scale. Loss on drying (LOD) samples were taken throughout each batch to build the entire moisture profiles. All dried granulation were sieved using mesh 20 and analyzed for particle size distribution (PSD), morphology, density, and flow. It was found that as spray rate increased, sauter-mean diameter (Ds) also increased. The effect of inlet air temperature on the peak moisture which is directly related to the mean particle size was found to be significant. There were two-way interactions between studied process parameters. The main effects of inlet air flow rate and atomization air pressure could not be found as the data were inconclusive. The partial least square (PLS) regression model was found significant (P?<?0.01) and predictive for optimization. This study established a design space for the parameters for solid SME manufacturing process. 相似文献
15.
《Journal of pharmaceutical sciences》2022,111(9):2592-2605
A one-step spray drying based process was employed to generate ready-to-use nanocrystalline solid dispersion (NCSD) dry powder for inhalation (DPI) of voriconazole (VRC). The solid dispersion was prepared by spray drying VRC, MAN (mannitol) and soya lecithin (LEC) from mixture of methanol-water. Various formulation and process related parameters were screened, including LEC, inlet temperature, total solid content and feed flow rate to generate particles of geometric size ≤5 µm. Aerosil® 200 was explored as the quaternary excipient either during spray drying or by physically mixing with the optimized ternary NCSD. The powders were extensively characterized for solid form, primary particle size, assay, embedded nanocrystal size, morphology, porosity, density and moisture content. Aerodynamic properties were studied using next generation impactor (NGI), while surface elemental composition and topography were investigated using SEM-EDS (scanning electron microscopy- energy dispersive spectroscopy) and AFM (atomic force microscopy), respectively. At selected inlet temperature of 120 ?C, total solid content and feed flow rate significantly impacted the size of primary NCSD particles. Size of primary particles increased with increase in total solid content and feed flow rate of the solution. VRC nanocrystals were obtained in polymorphic Form B whereas the matrix of MAN consisted of mixture of polymorphic Forms α, β and δ. SEM-EDS analysis confirmed deposition of Aerosil® 200 on surface of spray dried particles. In addition to increased porosity and reduced density, increase in surface roughness of particles (evident from AFM topographic analysis) contributed to enhanced powder deposition at stages 3 and 4 in NGI. In comparison, physical blending of NCSD with Aerosil® 200 showed improvement in aerosolization due to flow enhancement property. 相似文献
16.
Using experimental design to optimize the process parameters in fluidized bed granulation on a semi-full scale 总被引:2,自引:0,他引:2
A face-centered central composite design was applied in order to optimize the granulation process on a semi-full scale (30-kg batch) for the geometric mean granule size. The granulation process variables investigated were: inlet air temperature, inlet airflow rate, spray rate and inlet air humidity. Based on the process variables, the theoretical powder bed moisture content after the spraying process and a measure for the droplet size were determined. Multiple regression modeling was used to develop two models for the granule size: an empirical model, based on the four process parameters, and a fundamental model, based on the balance between the granule growth affected by the theoretical powder bed moisture content and the droplet size and the breakage effect of the airflow rate. These regression models were used to optimize the granulation process to obtain a granule size between 300 and 500 μm. Additional experiments confirmed that these models were valid. Other granule properties, namely the geometric standard deviation, the Hausner index, the angle of repose and the moisture content, were evaluated at the optimal operation conditions. 相似文献
17.
There has been an increasing interest in the development of protein nanotherapeutics for diseases such as cancer, diabetes and asthma. Spray drying with prior micro mixing is commonly used to obtain these powders. However, the separation and collection of protein nanoparticles with conventional spray dryer setups has been known to be extremely challenging due to its typical low collection efficiency for fine particles less than 2μm. To date, there has been no feasible approach to produce these protein nanoparticles in a single step and with high yield (>70%). In this study, we explored the feasibility of the novel Nano Spray Dryer B-90 (equipped with a vibrating mesh spray technology and an electrostatic particle collector) for the production of bovine serum albumin (BSA) nanoparticles. A statistical experimental design method (Taguchi method based on three levels, five variables L(18) orthogonal array robust design) was implemented to study the effect of and optimize the experimental conditions of: (1) spray mesh size, (2) BSA solution concentration, (3) surfactant concentration, (4) drying air flow rate and (5) inlet temperature on: (1) size and (2) morphology (axial ratio). Particle size and morphology were predominantly influenced by the spray mesh size and surfactant concentration, respectively. The drying air flow rate and inlet temperature had minimal impact. Optimized production of smooth spherical nanoparticles (median size: 460±10nm, axial ratio: 1.03±0.00, span 1.03±0.03, yield: 72±4%) was achieved using the 4μm spray mesh at BSA concentration of 0.1% (w/v), surfactant concentration of 0.05% (w/v), drying flow rate of 150L/min and inlet temperature of 120°C. The Nano Spray Dryer B-90 thus offers a new, simple and alternative approach for the production of protein nanoparticles suited for a variety of drug delivery applications. 相似文献
18.
The use of a small-dimensioned cyclone separator to spray-dry an aqueous solution of lysozyme on a mini spray-dryer produces consistently higher protein inactivation at all drying-air outlet temperatures examined between 50°C and 105°C. Differences in drying air flow rate through the machines will influence droplet/particle residence times within the drying chamber, but these are considered too small to explain the result. It appears more likely that a higher separation and retention of fines within the small cyclone causes higher measured protein inactivation. By virtue of their small size the fines have a greater specific surface area and suffer therefore a greater degree of protein damage when passing through the spray dryer from nozzle to collecting vessel. Although the dry powder yield is higher with the small-dimensioned cyclone than that obtained with the standard cyclone, the profile of residual moisture versus T(outlet) is irregular in shape. A possible lack of equilibrium between the attributes of the protein particles and the exhaust air needs therefore to be considered. 相似文献
19.
20.
Zahra Shokri Mohammad Reza Fazeli Mehdi Ardjmand Seyyed Mohammad Mousavi Kambiz Gilani 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2015,23(1)