Optimization of an herbicide release from ethylcellulose microspheres

Summary The herbicide 2,4-D was microencapsulated using ethyl cellulose to develop controlled release formulations that protect it from photodegradation and evaporation and to reduce the environment pollution. Ethyl cellulose microspheres loaded with 2,4-D were prepared by the emulsion solvent-evaporation technique. We have obtained the desired microspheres with higher drug entrapment and encapsulation yield by varying certain conditions as stirring speed, polymer-solvent ratio, drug-polymer ratio, pH of continuous phase and organic phase solvent. The shape and size of microspheres were analysed by scanning electron microscopy. The herbicide release was studied at 25 °C and the release data were analysed according to Fick’s Law. The results demonstrate that we can control the release rate by modifying the process parameters.     

5-FU-PLGA复乳微球的制备及体外释放

采用乳化溶剂挥发法制备W/O/W型5-FU-PLGA复乳微球,采用单因素设计考察了第一相体积比(内水相与油相)、第二相体积比(初乳与外水相)对复乳稳定性的影响,采用正交设计考察了搅拌温度、搅拌时间、辅料浓度和有机相中载体材料浓度对微球质量的影响,并对制备条件进行优化。最适宜制备条件为:第一相体积比为1:2,第二相体积比为1:1,搅拌温度为10 ℃、搅拌时间为6 h、辅料浓度为0.5%、有机相中载体材料浓度为15%。依据最适宜条件制备的微球圆整度良好、粒径范围窄,平均粒径5.20 μm,载药量为5.34%,包封率为77.22%。体外释放试验表明微球具有明显的缓释效果,释放行为符合Higuchi模型。     

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.     

Effect of Basic Factors of Preparation on Characteristics,Hydrolytic Degradation,and Drug Release From Poly(ester-anhydride) Microspheres

Functional poly(ester-anhydride) microspheres were prepared using emulsion solvent evaporation (ESE) and phase inversion methods (PIM). The poly(ester-anhydride)s were obtained by polycondensation of sebacic acid (SBA) and oligo(3-allyloxy-1,2-propylene succinate) terminated with carboxyl groups (OSAGE). The effects of various parameters, including: polymer and emulsifier concentrations, stirring speed and molecular weight of polyvinyl alcohol (PVA) used as emulsifier on size, size distribution and morphology of microspheres obtained by ESE technique were examined. The size of microspheres obtained was in the range 2–30 µm and depended mainly on the stirring rate in emulsion formulation process, as well as concentration of polymer solution used. Molecular weight of PVA, and its concentration in aqueous phase, significantly influenced tendency to agglomeration of microparticles formed, but only slightly changed the size of microspheres. The present study demonstrated that the ESE method can be useful to formulate, from functional poly(ester-anhydride)s, small (2–3 µm) or large (20–30 µm) microspheres with relatively narrow size distribution. Such microspheres were loaded with three model compounds (rhodamine B, p-nitroaniline, and piroxicam) with different water solubility and their release characteristics were examined. In the present study microparticles were also obtained by alternative phase inversion method to compare mainly stability of polymers during formulation of microspheres by both techniques.     

Preparation,characterization, and salicylic acid release behavior of chitosan/poly(vinyl alcohol) blend microspheres

Blend microspheres of chitosan (CS) with poly(vinyl alcohol) (PVA) were prepared as candidates for oral delivery system. CS/PVA microspheres containing salicylic acid (SA), as a model drug, were obtained using the coacervation‐phase separation method, induced by addition of a nonsolvent (sodium hydroxide solution) and then crosslinked with glutaraldehyde (GA) as a crosslinking agent. The microspheres were characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy. Percentage entrapment efficiency, particle size, and equilibrium swelling degree of the microsphere formulations were determined. The results indicated that these parameters were changed by preparation conditions of the microspheres. Effects of variables such as CS/PVA ratio, pH, crosslinker concentration, and drug/polymer (d/p) ratio on the release of SA were studied at three different pH values (1.2, 6.8, and 7.4) at 37°C. It was observed that SA release from the microspheres increased with decreasing CS/PVA ratio and d/p ratio whereas it decreased with the increase in the extent of crosslinking. It may also be noted that drug release was much higher at pH 1.2 than that of at pH 6.8 and 7.4. The highest SA release percentage was obtained as 100% for the microspheres prepared with PVA/CS ratio of 1/2, d/p ratio of 1/2, exposure time to GA of 5 min, and concentration of GA 1.5% at the end of 6 h. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Preparation and optimization of 2,4‐D loaded cellulose derivatives microspheres by solvent evaporation technique

Controlled release herbicide formulations were prepared by microencapsulation using solvent evaporation technique. 2,4‐D was chosen as core material, which was microencapsulated in two cellulose derivatives as matrices: cellulose acetate butyrate butyryl (CAB) and ethylcellulose (EC). The work is intended to produce systems containing the herbicide to reduce its risks by dermal contact, evaporation, or degradation and to control the release of the active agent. The microspheres loaded by 2,4‐D were characterized by scanning electron microscopy and infrared spectroscopy. We have obtained microparticles in the range of D₃₂ of 42–277 μm with CAB and 88–744 μm with EC by varying the process parameters. The drug entrapment was improved by controlling certain factors such as polymer/solvent ratio, pH of continuous phase, and organic phase solvent. The drug release was established in deionized water at pH = 5.5 and 25°C and the 2,4‐D concentrations were estimated by UV analysis. The release data were analyzed according to Fick's law and the results demonstrate that the release rate can be controlled by modifying the process parameters. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 2742–2751, 2007     

泡沫相相分离制备多孔聚合物微球连续化工艺

采用在泡沫相进行溶剂挥发的方法，连续、高效制备聚甲基丙烯酸甲酯-丙烯酸丁酯[P(MMA-BA)]共聚物多孔微球。采用自制的连续化反应装置，在一定搅拌速率和反应温度下，向反应器连续加料，在出口处连续收集溢出的泡沫并进行消泡、分散，再经洗涤、过滤、干燥得到多孔聚合物微球。重点研究了油相进料速率、反应温度、搅拌速率、聚乙烯醇用量(PVA浓度)对平均泡沫溢出速率、微球收率、微球粒径以及多孔形态的影响规律。结果表明：在反应温度为45℃，搅拌速率为500 r/min，油相溶液进料速率为30 g/min，PVA浓度为1.0%(质量)，油相溶液中P(MMA-BA)∶二氯甲烷(DCM)∶正庚烷(HT)=10∶53∶6(质量比)的工艺条件下，聚合物微球的收率高达92%，平均粒径为130 μm，P(MMA-BA)微球球形饱满，呈多孔结构。     

CTX/淀粉接枝PLA共聚物微球的制备及药物释放行为

采用乳化-溶剂挥发法,以头孢噻肟钠(CTX)为模型药物,以自制两亲性聚合物淀粉聚乳酸接枝共聚物(ST-g-PLA)为药物载体,制备了CTX/ST-g-PLA载药微球。考察了乳化剂PVA浓度、油水体积比、ST-g-PLA浓度及搅拌速度对微球粒径、载药量及包裹率的影响,采用IR,DSC和SEM等技术对微球结构进行了表征,研究了微球在4种不同介质中的降解性及体外释药性能。结果表明,当PVA浓度为2%,Vo/Vw=1∶6,共聚物浓度为30%时,制备的微球外型规则,分散性好,载药率为8.2%,包载率为49.2%;微球在不同环境中降解速率不同:肠液>碱液>PBS>酸液;较PLA微球,CTX/ST-g-PLA微球有良好的缓释性。     

Development of tunable biodegradable polyhydroxyalkanoates microspheres for controlled delivery of tetracycline for treating periodontal disease

This article was aimed at preparation and characterization of drug delivery carriers made from biodegradable polyhydroxyalkanoates (PHAs) for slow release of tetracycline (TC) for periodontal treatment. Four PHA variants; polyhydroxybutyrate (PHB), poly(hydroxybutyrate‐co‐hydroxyvalerate) with 5, 12, and 50% hydroxyvalerate were used to formulate TC‐loaded PHA microspheres by double emulsion‐solvent evaporation method. We also compared the effect of different molecular weight (M_w) of polyvinyl alcohol (PVA) acting as surface stabilizer on particle size, drug loading, encapsulation efficiency, and drug release profile. The TC‐loaded PHA microspheres exhibited microscale and nanoscale spherical morphology under scanning electron microscopy. Among formulations, TC‐loaded PHB:low M_w PVA demonstrated the highest TC loading with slow release behavior. Our results showed that the release rate from PHA microspheres was influenced by both the type of PHA and M_w of PVA stabilizer. Lastly, TC‐loaded PHB microspheres showed efficient killing activity against periodontitis‐causing bacteria, suggesting its potential application for treating periodontal disease. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44128.     

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.     

Controlled Delivery of Gentamicin Using Poly(3-hydroxybutyrate) Microspheres

Poly(3-hydroxybutyrate), P(3HB), produced from Bacillus cereus SPV using a simple glucose feeding strategy was used to fabricate P(3HB) microspheres using a solid-in-oil-water (s/o/w) technique. For this study, several parameters such as polymer concentration, surfactant and stirring rates were varied in order to determine their effect on microsphere characteristics. The average size of the microspheres was in the range of 2 μm to 1.54 μm with specific surface areas varying between 9.60 m(2)/g and 6.05 m(2)/g. Low stirring speed of 300 rpm produced slightly larger microspheres when compared to the smaller microspheres produced when the stirring velocity was increased to 800 rpm. The surface morphology of the microspheres after solvent evaporation appeared smooth when observed under SEM. Gentamicin was encapsulated within these P(3HB) microspheres and the release kinetics from the microspheres exhibiting the highest encapsulation efficiency, which was 48%, was investigated. The in vitro release of gentamicin was bimodal, an initial burst release was observed followed by a diffusion mediated sustained release. Biodegradable P(3HB) microspheres developed in this research has shown high potential to be used in various biomedical applications.     

Synthesis of multihollow polyester particles in supra‐ and infra‐millimeter size ranges by double emulsion process

Multivesiculated particles (MVPs) are obtained from a double emulsion system, being currently used as opacifying agents by waterborne paint industry. They have high mechanical resistance and low density as a result of a rigid multialveolar structure formed by cross‐linked polyester. Depending on the particle sizes, different novel applications can be envisaged. This work studies how the conventional one‐step batch emulsification approach can be adapted for producing MVPs with average diameters ranging from tens of microns to a few millimeters. The Taguchi method was employed to identify the level of influence of several process variables on the final yield of small (<100 µm) or large (>1 mm) particles. Poly(vinyl alcohol) (PVA) concentration and molecular weight proved to be the most significant factors to obtain small particles. For large particles, the most significant factors were the PVA molecular weight and the stirring rate during the curing phase. Uniform vesiculation and low particle density could only be obtained by adjusting the stirring conditions during dispersion of the organic phase, due to limitations in water diffusion rate into large organic droplets. Large particles exhibited tendency to fracture due to residual stresses, but this problem was solved by using an organic‐soluble cure initiator. POLYM. ENG. SCI., 56:590–597, 2016. © 2016 Society of Plastics Engineers     

Precipitation and encapsulation of β-carotene in PHBV using carbon dioxide as anti-solvent

The main objective of this work was to investigate the application of supercritical carbon dioxide as anti-solvent for the encapsulation of β-carotene in poly(hydroxybutirate-co-hydroxyvalerate) (PHBV) with dichloromethane as organic solvent using the Solution Enhanced Dispersion by Supercritical fluids (SEDS) technique. For the precipitation experiments with pure compounds the parameters investigated were the concentration of β-carotene (4 and 8 mg mL⁻¹) and PHBV (30 mg mL⁻¹) in the organic solution, pressure (from 80 to 200 bar), solution flow rate fixed at 1 mL min⁻¹, anti-solvent flow rate at 40 mL min⁻¹ and constant temperature of 313 K. Pure β-carotene precipitation indicates that an increase in pressure led in most cases to particles with larger sizes, while the opposite trend was verified for pure PHBV precipitation. The morphology of precipitated PHBV particles was spherical and was not influenced by increasing pressure. The morphology of β-carotene microparticles changed from plate-like to leaf-like particles when raising operational pressure, but was not influenced by its concentration in the organic solution as verified by micrographs of scanning electronic microscopy (SEM). For the co-precipitation experiments it was evaluated the effect of β-carotene concentration (2-30 mg mL⁻¹) in the organic solution, at fixed parameters: PHBV concentration (30 mg mL⁻¹) in organic solution, temperature at 313 K, pressure at 80 bar, solution flow rate at 1 mL min⁻¹ and anti-solvent flow rate at 40 mL min⁻¹. The encapsulation data showed that increasing the concentration of β-carotene, keeping fixed the PHBV content, results in higher percentage of solute encapsulated, increasing the encapsulation efficiency.     

快速膜乳化法制备尺寸均一PELA多孔微球及其孔径调控

采用快速膜乳化法,以二氯甲烷为油相,通过溶剂挥发制孔,在室温下制备了一系列聚乙二醇-聚乳酸共聚物(PELA)多孔微球. 结果表明,优化的制备条件为：搅拌速度250 r/min、油相中PELA浓度50 g/L、水/二氯甲烷/PVA水溶液体积比1:2.5:25及mPEG:PLA分子量比1:14,在该条件下可制备粒径均一、尺寸可控的PELA多孔微球,且孔径较大,孔径最大为15.0 nm,属介孔材料,可用于蛋白多肽类药物的吸附.     

Improved liquid phase separation processes for generating biodegradable microspheres loaded with high concentrations of drugs for tumor embolization

Drug-eluting microspheres are the most commonly used particulate embolic agents for transarterial chemoembolization of liver tumors. However, drug loading of degradable embolic particles is often insufficient. In the current study, microspheres prepared from poly(D,L-lactic-co-glycolic acid) were investigated as a biodegradable embolic agent for arterial embolization applications. Through modified solvent evaporation and liquid-induced phase separation, high drug loading (as high as 32%) and low solvent residue (as low as 0.03%) was achieved. Degradation performance, ¹H NMR, and the nonsolvent’s influence on solvent residue content were assessed. These drug-loading microspheres with biodegradability hold promise for embolization therapies.     

Optimization of spray-dried diclofenac sodium-loaded microspheres by screening design

The aim of the present study was to investigate the effect of formulation and operating parameters of the laboratory spray dryer on polymeric microspheres intended to be used for sustaining drug delivery of diclofenac sodium (DS). Four operating and four formulation parameters were investigated by Plackett–Burman design to enhance the encapsulation efficiency (EE). The independent variables were air inlet temperature, aspirator, feed flow rate, spray nozzle diameter, amount of drug, amount of polymers, and volume of organic solvent. The resultant microspheres were characterized for their EE. The microspheres having high EE were further characterized for particle size, morphology, and in vitro drug release. Interaction between the drug and the polymer were investigated by Fourier transform infrared (FTIR) spectroscopy and X-ray powder diffractometry (XRPD). The Pareto chart showed that amount of Eudragit® RS100, amount of ethylcellulose, and aspirator were identified as significant factors. The microspheres showed high EE (47.55?±?0.006% to 67.99?±?0.007%). The microspheres were found to be discrete, spherical with smooth surface. The FTIR analysis confirmed the compatibility of DS with the polymers without interaction. The XRPD revealed the dispersion of drug within microspheres formulation. The in vitro drug release from these DS-loaded microspheres showed sustained release of DS over a period of 12?h and followed the Korsmeyer–Peppas model [R²?=?0.9920 (Run 1) and 0.9957 (Run 13)] with a value of the slope (n)?≤?0.43. This n value, however, appears to indicate that Fickian release is the dominant mechanism of drug release with these formulations.     

Development of polylactide microspheres for protein encapsulation and delivery

The development of injectable microparticles for protein delivery is a major challenge. We demonstrated the possibility of entrapping human serum albumin (HSA) and thrombin (Thr) in poly(ethylene glycol) (PEG)‐coated, monodisperse, biodegradable microspheres with a mean diameter of about 10 μm. In our earlier studies, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) analysis was used to characterize the surface of PEG‐coated, taxol‐loaded poly(lactic acid) (PLA) microspheres. An analysis by DRIFTS revealed that PEG was incorporated well on the PLA microsphere surface. An emulsion of protein (in water) and PLA dissolved in an acetone–dichloromethane (or acetone–chloroform) mixture were poured into an aqueous solution of PEG [or poly(vinyl alcohol) (PVA)] with stirring with a high‐speed homogenizer for the formation of microparticles. HSA recovery in microspheres ranged from 13 to 40%, depending on the solvent and emulsification systems used for the preparation. PLA dissolved in a dichloromethane/acetone system and albumin loaded via a PEG emulsification solution (PLA–PEG–HSA) showed maximum drug recovery (39.5%) and drug content (9.9%). Scanning electron microscopy revealed that PEG‐coated microspheres had less surface micropores than PVA‐based preparations. The drug‐release behavior of microspheres suspended in phosphate‐buffered saline exhibited a biphasic pattern. An initial burst release (30%) followed by a constant slow release for 20 days was observed for HSA and Thr from PLA–PEG microspheres. PEG‐coated PLA microspheres show great potential for protein‐based drug delivery. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 86: 1285–1295, 2002     

PYRENE ENCAPSULATED ALGINATE BEAD TYPE FOR SUSTAINED RELEASE IN BIODEGRADATION: PREPARATION AND CHARACTERISTICS

A novel method for preparation of pyrene encapsulated alginate beads for controlled release delivery of pyrene is reported in this study. Five different bead types that varied on the organic phase for pyrene delivery, presence or absence of polyvinyl alcohol (PVA) and boric acid treatment were prepared. Based on the pyrene release profile, silicone oil encapsulated in PVA-alginate bead was selected where encapsulation efficiency was more than 99% without any solvent leakage. Silicone oil encapsulation was further confirmed in microscopy observations. Pyrene release behavior from the beads was explained by a diffusion controlled first order release (R² > 0.96). Reusability of this bead was demonstrated, where pyrene was loaded from an external medium in a non-destructive way. Application of the system was finally established in a biodegradation study using Mycobacterium frederiksbergense, where simultaneous release and removal of pyrene along with appearance of pyrene metabolites was observed.     

Preparation and evaluation of cellulose acetate butyrate and poly(ethylene oxide) blend microspheres for gastroretentive floating delivery of repaglinide

In this study, hollow microspheres of cellulose acetate butyrate (CAB) and poly(ethylene oxide) (PEO) were prepared by emulsion–solvent evaporation method. Repaglinide was successfully encapsulated into floating microspheres. Various formulations were prepared by varying the ratio of CAB and PEO, drug loading and concentration of poly(vinyl alcohol) (PVA) solution. Encapsulation of the drug up to 95% was achieved. The microspheres tend to float over the simulated gastric media for more than 10 h. The micromeritic properties of microspheres reveal the excellent flow and good packing properties. The % buoyancy of microspheres was found to be up to 87. SEM showed that microspheres have many pores on their surfaces. Particle size ranges from 159 to 601 μm. DSC and X‐RD revealed the amorphous dispersion in the polymer matrix. In vitro release experiments were performed in simulated gastric fluid. In vitro release studies indicated the dependence of release rate on the extent of drug loading and the amount of PEO in the microspheres; slow release was extended up to 12 h. The release data were fitted to an empirical equation to compute the diffusional exponent (n), which indicated that the release mechanism followed the non‐Fickian trend. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 2007     

Preparation of sodium alginate/poly(vinyl alcohol) blend microspheres for controlled release applications

Sodium alginate (NaAlg)/poly (vinyl alcohol) (PVA) blend microspheres (MS) were prepared by water-in-oil (w/o) emulsion method. These polymer microspheres were crosslinked with glutaraldehyde and loaded with metformin hydrochloride (MHC). The microspheres were characterized by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and X-ray diffraction (XRD) analysis to confirm the molecular dispersion of the drug, thermal stability, morphological properties, and crystallinity of the polymer matrix before and after blending. SEM of the microspheres suggested the formation of microspheres in spherical structure. Drug release data were analyzed using an empirical equation to understand the nature of drug transport through polymeric matrices. The controlled release (CR) characteristics of the polymer matrices was investigated in pH 7.4 media and from the results it was obtained that the drug was released in controlled manner up to 10 h. The physico-chemical properties of the microspheres were studied by calculating drug entrapment efficiency and drug release kinetics. Percent of encapsulation efficiency (% EE) decreased with increase in crosslinking agent (GA) and PVA content in the microspheres. The optimum % EE (80%) was observed in case of MS containing 40% of PVA with 15% MHC. The release profiles indicate that the release of MHC decreases with increasing the PVA/NaAlg (w/w) and drug/polymer ratio. At the end of 10 h, the highest release of MHC was found to be 96% for MS containing PVA/NaAlg (40 : 60) and 15 wt % drug loaded. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012