Microencapsulation of Ketoprofen in Blends of Acrylic Resins by Spray Drying

Microparticles of ketoprofen entrapped in blends of acrylic resins (Eudragit RL 30D and RS 30D) were successfully produced by spray drying. The effects of the proportion ketoprofen : polymer (1:1 and 1:3) and of spray-drying parameters (drying gas inlet temperatures of 80 and 100°C; microencapsulating composition feed flow rates of 4 and 6 g/min) on the microparticles properties (drug content, encapsulation efficiency, mean particle size, moisture content, and dissolution behavior) were evaluated. Differential scanning calorimetry (DSC) thermograms and X-ray diffractograms of the spray-dried product, the free drug, and the physical mixture between the free drug and spray-dried composition (blank) were carried out. Microparticles obtained at inlet temperature of 80°C, feed flow rate of 4 g/min, and ketoprofen : acrylic resin ratio of 1:3 presented an encapsulation efficiency of 88.1%, moisture content of 5.8%, production yield around 50%, and a higher reduction in dissolution rate of the entrapped ketoprofen. Sigmoidal shape dissolution profiles were presented by the spray-dried microparticles. The dissolution profiles were relatively well described by the Weibull model, a showing high coefficient of determination, R ², and a mean absolute error between experimental and estimated values of between 4.6 and 10.1%.     

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.     

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.     

Microparticulated Hydrochlorothiazide Solid Dispersion: Enhancing Dissolution Properties via Spray Drying

The aim of the present study was to obtain microparticles of hydrochlorothiazide, a diuretic drug that practically insoluble in water, by spray drying and to investigate the influence of process parameters using a three-level, three-factor Box-Behnken design. Process yields, moisture content, particle size, flowability, and solubility were used to evaluate the spray-dried microparticles. The data were analyzed by response surface methodology using analysis of variance. The independent variables studied were outlet temperature, atomization pressure, and drug content. The formulations were prepared using polyvinylpyrrolidone and colloidal silicon dioxide as the hydrophilic carrier and drying aid, respectively. The microparticle yield ranged from 18.15 to 59.02% and resulted in adequate flow (17 to 32°), moisture content between 2.52 to 6.18%, and mean particle size from 45 to 59 µm. The analysis of variance showed that the factors studied influenced the yields, moisture content, angle of repose, and solubility. Thermal analysis and X-ray diffractometry evidenced no drug interactions or chemical modifications. Photomicrographs obtained by scanning electron microscopy showed spherical particles. The solubility and dissolution rates of hydrochlorothiazide were remarkably improved when compared with pure drug. Therefore, the results confirmed the high potential of the spray-drying technique to obtain microparticulate hydrochlorothiazide with enhanced pharmaceutical and dissolution properties.     

Microstructured ternary solid dispersions to improve carbamazepine solubility

The aim of this study was to investigate the improvement of the aqueous solubility of carbamazepine by preparing microstructured ternary solid dispersions using polyoxylglycerides and colloidal silicon dioxide. Microstructured solid dispersions were obtained in a spray dryer. The influence of the spray drying conditions on the properties of the microparticles was investigated using a full 3² factorial design in which the factors studied were the silicon dioxide content and the air outlet temperature. The microparticles were thoroughly characterized in terms of yield, solubility, angle of repose, particle size, drug content, moisture content, sorption isotherms, morphology, thermal behavior, infrared spectroscopy and crystallinity. The dissolution rates of carbamazepine and of the microparticles in water were also determined. In general, the microstructured solid dispersions demonstrated good yield, adequate flow and moisture content (< 3%), drug recovery (91.98 to 100.22%) and particle size (< 142.90 μm). Thermal and infrared analysis showed that there was no drug interaction during the process. On the other hand, the results of X-ray diffraction evidenced a partial polymorphic modification of carbamazepine. The solubility and dissolution rates of carbamazepine were remarkably improved. Therefore, the results confirm the high potential of the spray drying technique to obtain microstructured ternary solid dispersions.     

Fabrication of composite microparticles of artemisinin for dissolution enhancement

The main aim of this study is to enhance the dissolution of a poorly water soluble antimalarial drug, artemisinin (ART) by fabricating its microparticles and composites with selected hydrophilic polymers using a spray drier with a modified multi-fluid nozzle. We investigated the spray drying of ART with polyvinylpyrrolidone (PVP) considering the effect of feed ratio (ART:PVP) on the physical properties and dissolution of spray dried ART. Other hydrophilic carriers such as polyethylene glycol (PEG) were selected for comparing the dissolution with that of spray dried ART with PVP. The drug and polymer solutions were supplied through different liquid passages of the modified four-fluid nozzle to fabricate ART and composite microparticles. Characterization of the original ART powder, spray dried ART microparticles and ART-polymer composite microparticles was carried out by scanning electron microscopy (SEM), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and dissolution tester. The DSC and XRD studies suggested that the crystallinity of ART decreased after spray drying and depended on the weight ratio of drug to polymer. Percent dissolution efficiency (%DE); relative dissolution (RD); mean dissolution time (MDT); difference factor (f₁) and similarity factor (f₂) were calculated for the statistical analysis. The dissolution of ART from the spray dried ART-PVP composite microparticles was more rapid than that from their respective physical mixture, spray dried ART-PEG composite microparticles and original ART powder. In the mathematical modeling, the Weibull and Korsmeyer-Peppas model were found to best fit to the in vitro dissolution data and the drug release kinetics could be recognized as Fickian diffusion. This study demonstrated that the modified multi-fluid spray drier can be used for the preparation of drug microparticles to improve the dissolution ability of poorly water soluble drugs and overcome the problem of finding a common solvent for drugs and carriers.     

Formulation of metformin hydrochloride nanoparticles by using spray drying technique and in vitro evaluation of sustained release with 32-level factorial design approach

The aim of this study was to investigate the combined influence of two independent variables in the preparation of sustained release metformin hydrochloride (MH) nanoparticles by 32-factorial design using a spray drying method. Polymer concentration and amount of organic solvent are selected as independent variables while drug loading and drug release were considered as dependent variables. The nanoparticles were characterized using particle size analyzer, which is obtained in the range of 400–700?nm, Fourier transform infrared spectroscopy, and X-ray diffraction. The kinetics of the dissolution process was studied by analyzing the dissolution data. The results suggested that MH nanoparticles are suitable for sustained release of drug.     

Solvent evaporation and spray drying technique for micro- and nanospheres/particles preparation: A review

This article presents a comprehensive review of research relating to the preparation of biodegradable and biocompatible controlled/sustained release of micro and nanoparticles. It covers recent developments in the area of technology through solvent evaporation followed by lyophilization and spray drying. The last decade seen a shift from empirical formulation efforts to a technological approach based on better understanding of micro and nanoparticle formation in the solvent evaporation and spray drying technique. This review provides concepts and a theoretical framework for the preparation of micro and nanoparticle formation. Encapsulation of pharmaceutical materials has received much attention due to enhanced effectiveness, bioavailability, and the dissolution rates that can be achieved. Polymeric micro and nanoparticles can be used to transport drug in a rate-controlled and sometimes targeted manner. Initially, laboratory-scale experiments are performed, but for industrial scale-up, experiments are required using sophisticated technologies. The objective of this review article is to summarize the solvent evaporation and spray drying techniques for the preparation of biodegradable and biocompatible controlled/sustained release of micro and nanospheres/particles with focus on the steps involved in its preparation, materials used, and the technique of microencapsulation. The review also summarizes recent research on solvent evaporation and spray drying.     

Production of aceclofenac-loaded sustained release micro/nanoparticles using pressure homogenization and spray drying

The aim of the present study was to characterize polymeric micro/nanoparticles of aceclofenac produced using a high-pressure homogenizer and a spray dryer. The micro/nanoparticles were characterized in terms of their encapsulation efficiency (E.E.), particle size, morphology, and in vitro drug release performance. Interaction between the drug and the polymer (Eudragit RS 100 and ethylcellulose) was evaluated using Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffractometry. Analysis of the results showed that speed and operating pressure have significant negative effect on E.E. of the micro/nanoparticles. The nanoparticles (970–197?nm) had E.E. of 74.09?±?1.17 to 83.66?±?1.63% while microparticles displayed EE. of 72.15?±?2.5%. The micro/nanoparticles were observed to be discrete and spherical. The FTIR analysis confirmed compatibility of aceclofenac with Eudragit RS 100 as well as ethylcellulose. In vitro study showed sustained drug release of 65 and 90% over a period of 12?h, thus prolonging the drug activity to treat the musculoskeletal disorder.     

亲水性小分子药物缓释微球制备方法的研究进展

缓释微球可以延长药物的作用时间,从而能够解决亲水性小分子药物由于半衰期较短需要长期频繁给药的问题。本文综述了亲水性小分子药物缓释微球制备方法的研究现状和发展方向,分别从使用非水溶性载体材料和水溶性载体材料两个方面介绍了亲水性小分子微球制备方法的优缺点。使用非水溶性载体材料方面,重点阐述了乳化溶剂挥发法和相分离法;使用水溶性载体材料方面,重点阐述了乳化交联法和喷雾干燥法。并着重分析了层层自组装法以及结合磁性粒子的溶剂挥发法的技术原理和制备过程。最后指出亲水性小分子药物缓释微球的制备方法将朝着操作简单、安全有效和智能靶向的方向发展。     

Spray dried solid dispersions of piroxicam in carboxymethyl sago cellulose using aqueous solvents: A simple,novel and green approach to produce enteric microparticles with enhanced dissolution

Piroxicam-CMSC solid dispersions were produced by spray drying from aqueous solvents. Depending on the drug-polymer ratio, loading and entrapment efficiency of CMSC microparticles were 6.8–46.75 and 40.79–60.35% w/w, respectively. Scanning electron microscopy revealed non-spherical geometry and agglomeration of the spray-dried particles. The average size of the particles ranged from 7 to 170?µm. Infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction confirmed intact crystalline piroxicam in the microparticles. In gastric pH, microparticles and native piroxicam have shown less than 25% and more than 45% of drug dissolution, respectively in 2?h. In contrast, at pH 7.4, microparticles have shown 80% of drug dissolution; whereas native piroxicam achieved only 30% of dissolution by 30?min. The spray-dried CMSC particles are efficient in restricting drug release in gastric pH and enhance drug dissolution in intestinal pH. The method is eco-friendly as it uses aqueous solvents and non-toxic materials.     

Preparation and characterization of lovastatin polymeric microparticles by coacervation‐phase separation method for dissolution enhancement

Dissolution rate of lovastatin is slow, only 30% of the oral dose is absorbed, and it undergoes extensive first‐pass extraction resulting in low and variable bioavailability. The objective of this research was to enhance the dissolution rate through preparing polymeric microparticles. Coacervation‐phase separation method through the addition of a non‐solvent was used to prepare polymeric microparticles. The method was optimized through studying effects of the type of solvent, the type of polymer, drug : polymer ratio and concentration of surfactant on particle size, particle size distribution, and in‐vitro drug release. Optimized polymeric microparticles and unprocessed drug were characterized using different techniques (SEM, FTIR, DSC, and PXRD) and their flow properties were evaluated. The optimum microparticles were prepared using ethanol as a solvent, Eudragit^® L 100 as a polymer in a drug:polymer ratio of 1:2 and SDS in a concentration of 0.25%. Characterization techniques indicated a change from the crystalline form to an amorphous form that was molecularly dispersed into the polymer. Flow properties of these microparticles were improved as compared to unprocessed drug. Drug release was enhanced 4‐ to 5‐folds probably due to precipitation of the drug in an amorphous form; wetting enhancement; size reduction and stabilization by polymers and surfactants. In conclusion the selection of proper process parameters enhanced drug release 5 folds. The use of DMSO as a solvent and the preparation of physical mixtures in this research provided a means for controlled or prolonged release. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 43277.     

不同干燥方式制备白果粉的性能比较

天然产物白果会因干燥方式的不同,而使得干燥白果粉性能有所差别。本研究分别采用喷雾干燥(SP)与真空冷冻干燥(FD)对白果浆进行干燥处理。然后对两种干燥白果粉的性能(含水量、颗粒度、色泽、蛋白质质量分数)进行对比来比较各自的优越性。喷雾干燥采用参数:风量120 m³/h,进料浓度8%(质量分数),进气温度205℃,出气温度100℃,雾化器转速32000 r/min。真空冷冻干燥先在-40℃下预冻4h后,再在真空度300 Pa下-50℃低温干燥48 h。结果发现含水量SP相似文献   

A new blend of polymeric encapsulation of azithromycin by spray-drying with a pH responsive in drug release

The microencapsulation of macrolides with polymers has been reported to retard the release of the drug in oral cavity. However, these methods are unable to control drug release in gastrointestinal tract. The aim of the present study was to investigate the effect of formulation of a new polymeric encapsulation of azithromycin which is suitable for both masking and sustained release usage. Eudragit E100 and polyethylene glycol (PEG) 4000 were chosen as the barrier coatings. The spray drying technique was used to obtain the microcapsules containing azithromycin. To obtain the initial results, the effects of several parameters were evaluated. A 3:2:1 ratio of E100:PEG 4000:azithromycin at pH 6 gave the best coating condition. Thermogravimetric analysis and IR analysis data confirmed the encapsulation of azithromycin inside polymers. The encapsulated drug was released in different rates from the particles by changing the pH (1.7 and 7.4). An analysis of the kinetic release properties indicates that the release of the drug is a combination of swelling and diffusion mechanism. The synergistic cooperation between polymers and drug due to the existence of several hydrogen bonding is supposed to influence the pH-responsive property of the encapsulated drug. Moreover, the use of mixtures of E100 and PEG 4000 appears to offer a good balance between cost and efficiency.     

A Comparative Study Between Spray-Drying and Fluidized Bed Coating Processes for the Preparation of Pramipexole Controlled-Release Microparticles for Orally Disintegrating Tablets

In the present study, controlled-release microparticles for orally disintegrating tablets (ODT) were prepared using two different processes, spray drying and fluidized bed coating processes. Pramipexole dihydrochloride monohydrate (PRM), an anti-Parkinson's disease agent, was selected as a model drug. The in vitro release rate and morphology of microparticles were evaluated and compared. The size of microparticles prepared by spray drying (SD microparticles) and fluidized bed coating (FC microparticles) was around 10 and 200 µm, respectively. The latter size was defined by the size of an inert core bead. The release behavior of SD microparticles was characterized by a large initial burst release prior to slow release. In the case of FC microparticles, the initial burst release was smaller than that of SD microparticles and the compression process damaged the release-controlling layer, which led to a change in release rate. The results indicated the importance of carefully considering the manufacturing process for microparticles during the design of controlled-release ODT.     

A comparison of spherical and cylindrical microparticles composed of nanoparticles for pulmonary application

Nano-embedded microparticles represent promising carrier systems to tackle the challenges of nanoparticle delivery into the lungs by inhalation. While spray drying is widely used for the incorporation of nanoparticles into microparticles, the template-assisted technique is a novel method to prepare aspherical, cylindrical microparticles composed of nanoparticles. In this work, both techniques were applied to produce both spherical and cylindrical nano-embedded microparticles. For both geometries particles consisting of gelatin nanoparticles, mannitol and leucine were prepared in three different sizes each. Cylindrical microparticles could be prepared with defined dimensions and narrow size distributions, allowing to target a wide range of aerodynamic diameters. The size of spherical microparticles was influenced by the spraying feed concentration, yielding only small differences in geometric and aerodynamic diameters and broad particle size distributions. Regarding the redispersibility of the nano-embedded microparticles, spherical particles showed better disintegration behavior and higher nanoparticle release in comparison to cylindrical particles upon contact with water. The template-assisted technique yielded higher nanoparticle content in contrast to spray drying. In summary, cylindrical particles represent a promising drug delivery system with high potential for later application. However, further improvements in the preparation method are required to enable higher yields and a possible later scale-up.

Copyright © 2018 American Association for Aerosol Research     

Development and evaluation of a novel dosage form of diltiazem HCl using ethylene vinyl acetate copolymer and sodium starch glycolate (in vitro/in vivo study)

The work aims at developing a CR formulation, with high encapsulation efficiency of diltiazem HCl, suitable for twice daily administration. Microparticles, using EVA copolymer, were prepared by coacervation‐phase separation technique, subjected to controlled extraction and vacuum freeze drying processes to generate and immobilize a non uniform initial drug concentration distribution, and evaluated in vitro and in animals. Effects of increasing initial drug concentration, varying polymer system, increasing porosity, and decreasing tortuosity, varying the size of the microparticles and the pH of the dissolution medium on the release rate were evaluated. The results indicated that the release rate from microparticles was constant (zero‐order) for an appreciable period of time but it was low for twice‐daily administration. It increased with increasing initial drug concentration, varying polymer system, increasing porosity, and decreasing tortuosity, and decreasing the size of the microparticles but the duration of constant release was shorter except for formulations containing 2.00 and 2.25% sodium starch glycolate. 10‐h duration of constant release was achieved and the zero‐order release rate was within the required rate to achieve the desired therapeutic level. The pH of the dissolution medium did not have any effect on the release rate. The results of the in vivo study indicated that in vitro dissolution correlated well with in vivo AUC_0‐10 and that there were no statistically significant differences in AUC_0‐10 and C_max between the new CR formulation and Cardizem® CD. Accordingly, a new CR formulation that delivers diltiazem HCl at a constant rate, suitable for twice daily administration was developed. © 2012 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2013     

Spray Congealing of Pharmaceuticals: Study on Production of Solid Dispersions Using Box-Behnken Design

This work aimed at evaluating the spray congealing method for the production of microparticles of carbamazepine combined with a polyoxylglyceride carrier. In addition, the influence of the spray congealing conditions on the improvement of drug solubility was investigated using a three-factor, three-level Box-Behnken design. The factors studied were the cooling air flow rate, atomizing pressure, and molten dispersion feed rate. Dependent variables were the yield, solubility, encapsulation efficiency, particle size, water activity, and flow properties. Statistical analysis showed that only the yield was affected by the factors studied. The characteristics of the microparticles were evaluated using X-ray powder diffraction, scanning electron microscopy, differential scanning calorimetry, and hot-stage microscopy. The results showed a spherical morphology and changes in the crystalline state of the drug. The microparticles were obtained with good yields and encapsulation efficiencies, which ranged from 50 to 80% and 99.5 to 112%, respectively. The average size of the microparticles ranged from 17.7 to 39.4 µm, the water activities were always below 0.5, and flowability was good to moderate. Both the solubility and dissolution rate of carbamazepine from the spray congealed microparticles were remarkably improved. The carbamazepine solubility showed a threefold increase and dissolution profile showed a twofold increase after 60 min compared to the raw drug. The Box-Behnken fractional factorial design proved to be a powerful tool to identify the best conditions for the manufacture of solid dispersion microparticles by spray congealing.     

Engineering Active Pharmaceutical Ingredients by Spray Drying: Effects on Physical Properties and In Vitro Dissolution

Active pharmaceutical ingredients have very strict quality requirements; minor changes in the physical and chemical properties of pharmaceuticals can adversely affect the dissolution rate and therefore the bioavailability of a given drug. Accordingly, the aim of the present study was to investigate the effect of spray drying on the physical and in vitro dissolution properties of four different active pharmaceutical ingredients, namely carbamazepine, indomethacin, piroxicam, and nifedipine. Each drug was dispersed in a solution of ethanol and water (70:30) and subjected to single-step spray drying using similar operational conditions. A complete characterization of the spray-dried drugs was performed via differential scanning calorimetry (DSC), scanning electron microscopy (SEM), X-ray powder diffraction (XRPD), particle size distribution analysis, solubility analysis, and an in vitro dissolution study. The results from the thermal analysis and X-ray diffraction showed that, except for carbamazepine, no chemical modifications occurred as a result of spray drying. Moreover, the particle size distribution of all the spray-dried drugs significantly decreased. In addition, SEM images showed that most of the particles had an irregular shape. There was no significant improvement in the solubility of the spray-dried drugs compared with the unprocessed compounds; however, in general, the dissolution rates of the spray-dried drugs showed a remarkable improvement over their non-spray-dried counterparts. Therefore, the results from this study demonstrate that a single spray-drying step may lead to changes in the physical properties and dissolution characteristics of drugs and thus improve their therapeutic action.     

Spray Cooling Process Factors and Quality Interactions During the Preparation of Microparticles Containing an Active Pharmaceutical Ingredient

The current work studies the spray-cooling process factors and quality interactions during the production of microparticulated solid dispersions containing piroxicam, polyethylene glycol 4000, and poloxamer 407. The Box-Behnken factorial design was used to evaluate the influence of the temperature of the molten dispersion, the percentage of poloxamer 407 in the sample, and dispersion feed rate on the microparticles. The dependent variables studied by this design were particle size, flow properties, drug content, and solubility. Microparticle characterization was done through X-ray powder diffraction, thermogravimetry, differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and in vitro dissolution analysis. Statistical analysis showed that the factors studied in Box-Behnken factorial design significantly influenced (p < 0.05) the Carr index, the Hausner factor, and the solubility of these microparticles. The microparticles presented average diameter from 72 to 120 µm, moderate to excellent flowability, drug content between 77.5 to 99.2%, and an increase in solubility between 2.5- and 5.4-fold when compared to the solubility of the pure drug. In dissolution tests, more than 75.0% of the piroxicam present in the microparticles was released in just 2.5 minutes and the microparticles promoted a total release of the drug. In addition, microparticles increased both the release rate and the amount of drug released.