Effects of fabrication conditions on the characteristics of etanidazole spray-dried microspheres

Etanidazole, a hypoxic radiosensitizer, has potential applications in radiotherapy. Due to its high solubility in water, common methods to encapsulate etanidazole into microspheres are not feasible. In this study, a spray-drying technique was employed to encapsulate etanidazole into the biodegradable polymer, PLGA65:35. Different fabrication conditions, such as polymer concentration, inlet temperature, feed rate, compressed air flow rate, aspirator ratio, as well as drug-loading were investigated to understand their effects on the particle size and distribution, encapsulation efficiency, and release behaviour. The effect on the morphologies of microspheres were also observed by scanning electron microscopy (SEM) and atomic force microscopy (AFM). It was demonstrated that most of these fabrication conditions influence either the droplet formation process or its subsequent evaporation and particle shrinking process, thereby determining the properties of the microspheres obtained. In many cases, temperature seems to be more important among all the factors considered. The present study demonstrates good fabrication conditions for producing the etanidazole-PLGA65:35-microspheres by using DCM as a solvent. The release of etanidazole from the spray dried PLGA65:35 microspheres was very fast, with an initial burst of 47% within the first 30 min and a cumulative release of over 80% within the first 5.5 h. The encapsulation efficiency of the drug in the microspheres varied with operating conditions from 69-96%.     

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15,000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15,000, 20,000 and 30,000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30,000 microspheres to 3.97% of PLGA 15,000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.     

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by UV/VIS spectrophotometry. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15 000 microspheres possessed a smooth and round appearance with average particle size of 50 microm or so. The encapsulation percentages of microspheres prepared from PLGA 15 000, 20 000 and 30 000 were 62.75, 27.52 and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30 000 microspheres to 3.97% of PLGA 15 000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increase in oil phase and PVA concentration decreased in aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30 degrees C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.     

Formulation, characterization, and evaluation of ketorolac tromethamine-loaded biodegradable microspheres

Ketorolac tromethamine has to be given every 6 hr intramuscularly in patients for acute pain, so to avoid frequent dosing and patient inconvenience we found it to be a suitable candidate for parenteral controlled delivery by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers: polycaprolactone, poly lactic-co-glycolic acid (PLGA 65/35), and poly lactic-co-glycolic acid (PLGA 85/15). To tailor the release profile of drug for several days, blends of PLGA 65/35 and PLGA 85/15 were prepared with polycaprolactone (PCL) in different ratios. The results revealed that microspheres made with 1:3 (PLGA65/35: PCL) blend released 97% of the drug in 5 days as compared with 97% in 30 days in with pure PLGA65/35 microspheres. Microspheres made with 1:1 (PLGA65/35:PCL) and 3:1 (PLGA65/35:PCL released 98% of the drug in 30 days. In microspheres made with 1:3 (PLGA85/15:PCL), almost the entire drug was released in a week whereas in batches made with pure PLGA85/15 and 3:1 (PLGA 85/15:PCL) more than 80% of the drug was released in 60 days as compared with 96% in 60 days in 1:1 (PLGA85/15:PCL). Higher encapsulation efficiency was obtained with microspheres made with pure PLGA 65/35. These formulations were characterized for particle size analysis by Malvern mastersizer that revealed particle size in range of 12-15 micron and 12-22 micron for microspheres made with polymer blends of PLGA 65/35:PCL and PLGA85/15:PCL, respectively. In with pure PLGA65/35 and PLGA85/15, particle size was 28 micron and 8 micron, respectively. Surface topography was studied by scanning electron microscopy that revealed a spherical shape of microspheres. From our study it we concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.     

Effects of formulation factors on encapsulation efficiency and release behaviour in vitro of huperzine A-PLGA microspheres

To develop a long-acting injectable huperzine A-PLGA microsphere for the chronic therapy of Alzheimer's disease, the microsphere was prepared by using an o/w emulsion solvent extraction evaporation method based on a series of formulation design of the emulsion. The dialysis method was used for release analysis. The encapsulation efficiency and release amount of the microspheres were determined by a UV/VIS spectrophotometer. The morphology of the microspheres was observed by scanning electron microscopy. The distribution of the drug within microspheres was observed by a confocal laser scanning microscope. The results indicated that the PLGA 15?000 microspheres possessed a smooth and round appearance with average particle size of 50?µm or so. The encapsulation percentages of microspheres prepared from PLGA 15?000, 20?000 and 30?000 were 62.75%, 27.52% and 16.63%, respectively. The drug release percentage during the first day decreased from 22.52% of PLGA 30?000 microspheres to 3.97% of PLGA 15?000 microspheres, the complete release could be prolonged to 3 weeks. The initial burst release of microspheres with higher molecular weight PLGA could be explained by the inhomogeneous distribution of drug within microspheres. The encapsulation efficiency of the microspheres improved as the polymer concentration increased in the oil phase and PVA concentration decreased in the aqueous phase. The burst release could be controlled by reducing the polymer concentration. Evaporation temperature had a large effect on the drug release profiles. It had better be controlled under 30°C. Within a certain range of particle size, encapsulation efficiency decreased and drug release rate increased with the reducing of the particle size.     

Formulation,Characterization, and Evaluation of Ketorolac Tromethamine-Loaded Biodegradable Microspheres

Ketorolac tromethamine has to be given every 6 hr intramuscularly in patients for acute pain, so to avoid frequent dosing and patient inconvenience we found it to be a suitable candidate for parenteral controlled delivery by biodegradable microspheres for the present study. Ketorolac tromethamine-loaded microspheres were prepared by o/w emulsion solvent evaporation technique using different polymers: polycaprolactone, poly lactic-co-glycolic acid (PLGA 65/35), and poly lactic-co-glycolic acid (PLGA 85/15). To tailor the release profile of drug for several days, blends of PLGA 65/35 andPLGA85/15 were prepared with polycaprolactone (PCL) in different ratios. The results revealed that microspheres made with 1:3 (PLGA65/35: PCL) blend released 97% of the drug in 5 days as compared with 97% in 30 days in with pure PLGA65/35 microspheres. Microspheres made with 1:1 (PLGA65/35:PCL) and 3:1 (PLGA65/35:PCL released 98% of the drug in 30 days. In microspheres made with 1:3 (PLGA85/15:PCL), almost the entire drug was released in a week whereas in batches made with pure PLGA85/15 and 3:1 (PLGA 85/15:PCL) more than 80% of the drug was released in 60 days as compared with 96% in 60 days in 1:1 (PLGA85/15:PCL). Higher encapsulation efficiency was obtained with microspheres made with pure PLGA 65/35. These formulations were characterized for particle size analysis by Malvern mastersizer that revealed particle size in range of 12–15 micron and 12–22 micron for microspheres made with polymer blends of PLGA 65/35:PCL and PLGA85/15:PCL, respectively. In with pure PLGA65/35 and PLGA85/15, particle size was 28 micron and 8 micron, respectively. Surface topography was studied by scanning electron microscopy that revealed a spherical shape of microspheres. From our study it we concluded that with careful selection of different polymers and their combinations, we can tailor the release of ketorolac tromethamine for long periods.     

丙氨瑞林微球制备工艺优化和体外释放研究

目的:制备包封率高、可持续释药35 d的丙氨瑞林微球.方法:以生物可降解聚合物聚乳酸-聚羟基乙酸(PLGA)为载体,采用W/O/W复乳溶剂挥发法制备缓释丙氨瑞林微球,以包封率为观察指标,用正交设计L9(34)对微球制备工艺进行优化.在pH=7.0的磷酸盐缓冲溶液中考察微球的体外释放.结果:经优化工艺制备的丙氨瑞林微球包封率为(93.2±1.6)％,90％的微球粒径分布范围为55～65 μm.在选择的释放条件下,至35 d时,药物累积释放92.3％,突释为9.7％.结论:该制备工艺简单、稳定.优化条件下制备的丙氨瑞林微球包封率高、粒径适宜、突释少.     

Formulation and evaluation of sustained release microspheres of poly-lactide-co-glycolide containing tamoxifen citrate

Tamoxifen citrate, a non-steroidal anti-oestrogen has potential applications in treatment of breast cancer. Biodegradable microspheres of' PLGA 65:35 were prepared by o/w emulsification solvent evaporation method. In this study, different batches of varying concentration of drug, polymer, polyvinyl alcohol and solvent were prepared. All the batches prepared were characterized by particle size distribution, encapsulation efficiency and in vitro release behaviour. Drug, polymer and PVA concentrations were varied to obtain optimum release profile for sustaining the action of drug.     

Formulation and evaluation of sustained release microspheres of poly-lactide-co-glycolide containing tamoxifen citrate

Tamoxifen citrate, a non-steroidal anti-oestrogen has potential applications in treatment of breast cancer. Biodegradable microspheres of' PLGA 65:35 were prepared by o/w emulsification solvent evaporation method. In this study, different batches of varying concentration of drug, polymer, polyvinyl alcohol and solvent were prepared. All the batches prepared were characterized by particle size distribution, encapsulation efficiency and in vitro release behaviour. Drug, polymer and PVA concentrations were varied to obtain optimum release profile for sustaining the action of drug.     

PLGA微球的制备及其用于脉冲给药的初步研究

目的：制备聚乳酸-羟基乙酸共聚物（PLGA）微球,并考察其用于脉冲式释药系统的可行性。方法：以牛血清白蛋白（BSA）为模型药物,用S/O/W（Solid-in-oil-in-water）法和S/O/O（Solid-in-oil-in-oil）法制备PLGA（75：25）和PLGA（50：50）微球,比较2种方法制备的微球的表面形态、包封率及载药量等,并考察2种微球的体外释放行为。结果：S/O/W法和S/O/O法制备的微球均圆整、无粘连、形态良好,但S/O/W法制备的微球表面较为平整,而S/O/O法表面均匀分布有较大的凹陷。S/O/W法制备的PLGA（75：25）和PLGA（50：50）微球包封率分别为（60.15±5.95）%、（49.50±3.69）%,载药量分别为（2.56±0.25）%、（2.10±0.16）%,10h内药物释放均为10%左右,而后随着聚合物的降解药物的释放量突然增加;S/O/O法所制微球包封率分别为（84.36±1.11）%、（77.94±1.42）%,载药量分别为（3.58±0.05）%、（3.31±0.06）%,24h内药物释放均可达50%左右,而后呈现较为平稳的释放行为。S/O/O法制备的微球包封率及载药量均较S/O/W法高;S/O/W法制备的PLGA微球药物释放呈现一定的脉冲行为,其中PLGA（75：25）微球体外释放行为受微球粒径的影响较大。结论：S/O/W法制备的PLGA微球具有一定的脉冲式释药效果,微球的粒径最好控制在120μm以下。     

β-methasone-containing biodegradable poly(lactide-co-glycolide) acid microspheres for intraarticular injection: effect of formulation parameters on characteristics and in vitro release

A sustained drug release system based on the injectable poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with β-methasone was prepared for localized treatment of rheumatic arthritis. The microscopy and structure of microspheres were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR). The effects of various formulation parameters on the properties of microspheres and in vitro release pattern of β-methasone were also investigated. The results demonstrated that increase in drug/polymer ratio led to increased particle size as well as drug release rate. Increase in PLGA concentration led to increased particle size, but decreased burst release. The drug encapsulation efficiency increased sharply by increasing polyvinyl alcohol (PVA) concentration in the aqueous phase from 1.5 to 2.0%. β-methasone release rate decreased considerately with decreasing OP (organic phase)/AP (aqueous phase) volume ratio. Stirring rate had significantly influence on the particle size and encapsulation efficiency. Independent of formulation parameters, β-methasone was slowly released from the PLGA microspheres over 11 days. The drug release profile of high drug loaded microspheres agree with Higuchi equation with a release mechanism of diffusion and erosion, that of middle drug loaded microspheres best agreed with Hixcon-Crowell equation and controlled by diffusion and erosion as well. The low drug loaded microspheres well fitted to logarithm normal distribution equation with mechanism of purely Fickian diffusion.     

微球的制备和表征

目的制备葡激酶突变体(K35R，DGR)的聚乳酸-羟基乙酸(PLGA)微球，使其在包封和释放过程中都能保持活性。方法使用复乳溶剂挥发法制备DGR的PLGA微球，研究了搅拌速度、PLGA浓度、内水相和外水相中的添加剂对蛋白包封率以及微球性质的影响，并进行了DGR微球的体外和体内释放试验。结果2%聚乙烯醇可以有效抑制超声乳化时DGR在水/二氯甲烷界面上的变性，将DGR的活性回收率从16%提高到几乎100%。在外水相中加入NaCl可以显著提高蛋白包封率，同时对微球的粒径分布和表面形态也产生了重要影响。DGR微球的体外释放呈现两个时相，15 d释放大约DGR总活性的50%。DGR微球在体内持续释放5 d。结论制备的PLGA微球，DGR包封率高，稳定性较好，是DGR的良好载药系统。     

The effect of different grades of PLGA on characteristics of microspheres encapsulated with cyclosporine A

The aim of this study was to evaluate the effect of different grades of poly D, L lactide-co-glycolide (PLGA) on the properties of microspheres encapsulated with Cyclosporine A (CyA). Microspheres were prepared by solvent evaporation method using three grades of PLGA. Various characteristics of microspheres such as morphology, size distribution, encapsulation efficiency and release profile were evaluated. Complementary studies were also carried out by Infrared (IR) spectroscopy and Differential scanning calorimetry (DSC) to evaluate possible drug-polymer interactions. Scanning electron microscopy (SEM) studies showed microspheres as spherical particles with CyA deposited as islands on the surface of spheres. Particle size range was 1-25 microm for microspheres made of PLGA (50:50) which showed the minimum size. Encapsulation efficiency was found to vary from 75% to 92% in various formulations. The profile of release was biphasic, showing an initial rapid phase followed by a continuous and slower rate thereafter. Microspheres made of grades 50:50 and 85:15 showed the highest and lowest amount of drug release, respectively. IR spectra for drug, polymer and microspheres did not indicate any chemical interaction between the components of microsphere and DSC thermograms revealed that CyA was present in its amorphous state within microspheres. In conclusion, the effect of polymer characteristics should be considered in microsphere formulations. In this study, suitable microspheres especially with PLGA (50:50) were prepared which allow the controlled release of CyA over a prolonged period of time.     

In vitro performance of carbamazepine loaded to various molecular weights of poly (D,L-lactide-co-glycolide)

The purpose of this study was to develop and assess the in vitro characteristics of carbamazepine-loaded microspheres. A solvent evaporation method was used to incorporate carbamazepine (CBZ) into poly (D,L-lactide-co-glycolide) (PLGA) with different molecular weights. The optimum conditions for CBZ-PLGA microspheres preparation were considered and the in vitro release of CBZ of PLGA microspheres were followed up to 24 hr in USP dissolution medium. The effect of using different ratios of PLGA microspheres, prepared with different molecular weights, for optimizing CBZ release also was investigated. CBZ encapsulation efficiency was 68 to 82% for all prepared formulations. Thermograms of CBZ-PLGA microspheres suggest that CBZ was totally entrapped with the PLGA polymer. The presence of Pluronic F-68 has improved the encapsulation of CBZ, resulted in better and smoother microspheres surfaces and enhanced its release pattern. CBZ release profiles were biphasic patterns; after an initial burst, a constant CBZ release rate was observed up to 24 hr. The release from these PLGA-based spherical matrices was consistent with the diffusion mechanism. CBZ dissolution T(50%) was significantly affected (> 3-fold) by increasing the lactide percent from 33.3 to 66.6% from different microspheres mixtures. The present study provides evidence that the encapsulation of CBZ to PLGA microspheres, either as a single polymer or mixture of two, was a successful attempt to control the release of CBZ.     

中药提取物葫芦素B-PLGA微球的制备及处方工艺优化

目的:制备中药提取物葫芦素(Cuc)B-乳酸-羟基乙酸共聚物(PLGA)微球。方法:应用改良的乳化溶剂挥发法制备微球;采用星点设计-效应面法优化制备工艺,以聚乙烯醇(PVA)浓度和投药比为自变量,微球的产率(Y1)、载药量(Y2)、包封率(Y3)、粒径(Y4)、24h累积释放量(Y5)为指标,进行多元线性回归和二次多项式拟合;改良的直接释药法考察微球的体外释放情况。结果:Y1、Y2、Y3、Y4、Y5二次多项式方程拟合效果较好,较优的工艺条件为PVA浓度0.014,投药比0.066 5。制得的微球形态圆整,Y1、Y2、Y3、Y4、Y5分别为79.9%、7.83%、80.5%、56.18μm、6.98%。体外释放35d的累积释放量为86.73%。结论:制备的CucB-PLGA微球满足了长效缓释的要求,所建立的模型预测性良好。     

Preparation and characterization of biodegradable urea-loaded microparticles as an approach for transdermal delivery

This work describes the formulation and characterization of urea-loaded microspheres prepared using various polymers such as ethyl cellulose (EC), cellulose acetate phthalate (CAP) and poly (D,L-lactic-co-glycolic acid) (PLGA), along with the utilization of a solvent evaporation technique. The effect of various formulation parameters (i.e. polymer type and concentration, vehicle type, polymer solution/vehicle volume ratio, drug/polymer ratio, homogenizer and stirrer speed, sonication time and speed, type of washing solution, drying and separation method) on the characteristics of microspheres was also evaluated. Results obtained indicated that, in the presence of urea, highest rate of EC microsphere production could be obtained at a drug/polymer ratio of 1:2 and a polymer solution/vehicle volume ratio of 1:50. In some cases, crystallization of urea was observed during the encapsulation process using cellulose derivative polymers. CAP microparticles showed a rough and tortuous surface while EC microparticles had a wider range of particle size. However, with the PLGA polymer, much better desired microparticles with a smaller size range of 1-3 microm were obtained. In general, PLGA microspheres were spherical in shape and possessed smooth surfaces with less pores in comparison with those obtained by the other polymers. The yield of particle production and the extent of urea encapsulation in PLGA particles were measured to be 68.87% +/- 5.3 and 40.5% +/- 3.4, respectively. The release study from PLGA microspheres revealed that up to 70% of the drug was released within a few days, through a four-stage release pattern.     

Sodium fusidate-poly(D,L-lactide-co-glycolide) microspheres: preparation, characterisation and in vivo evaluation of their effectiveness in the treatment of chronic osteomyelitis

PURPOSE: The aim of this study was to prepare poly(D,L-lactide-co-glycolide) (PLGA) microspheres containing sodium fusidate (SF) using a double emulsion solvent evaporation method with varying polymer:drug ratios (1:1, 2.5:1, 5:1) and to evaluate its efficiency for the local treatment of chronic osteomyelitis. METHODS: The particle size and distribution, morphological characteristics, thermal behaviour, drug content, encapsulation efficiency and in vitro release assessments of the formulations had been carried out. Sterilized SF-PLGA microspheres were implanted in the proximal tibia of rats with methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. After 3 weeks of treatment, bone samples were analysed with a microbiological assay. RESULTS: PLGA microspheres between the size ranges of 2.16-4.12 microm were obtained. Production yield of all formulations was found to be higher than 79% and encapsulation efficiencies of 19.8-34.3% were obtained. DSC thermogram showed that the SF was in an amorphous state in the microspheres and the glass transition temperature (T(g)) of PLGA was not influenced by the preparation procedure. In vitro drug release studies had indicated that these microspheres had significant burst release and their drug release rates were decreased upon increasing the polymer:drug ratio (p < 0.05). Based on the in vivo data, rats implanted with SF-PLGA microspheres and empty microspheres showed 1987 +/- 1196 and 55526 +/- 49086 colony forming unit of MRSA in 1 g bone samples (CFU/g), respectively (p < 0.01). CONCLUSION: The in vitro and in vivo studies had shown that the implanted SF loaded microspheres were found to be effective for the treatment of chronic osteomyelitis in an animal experimental model. Hence, these microspheres may be potentially useful in the clinical setting.     

Preparation and in vitro characterization of vascular endothelial growth factor (VEGF)-loaded poly(D,L-lactic-co-glycolic acid) microspheres using a double emulsion/solvent evaporation technique

Biodegradable Poly(lactic-co-glycolic acid; PLGA), microspheres encapsulating the angiogenic protein recombinant human vascular endothelial growth factor (rhVEGF) were formed to achieve VEGF release in a sustained manner. These microspheres are a promising delivery system which can be used for therapeutic angiogenesis. The PLGA microspheres incorporating two different initial loading amounts of rhVEGF have been prepared by a modified water-in-oil-in-water (w/o/w) double emulsion/solvent evaporation technique. The microspheres have been characterized by particle size distribution, environmental scanning electron microscopy (ESEM), light microscopy, encapsulation efficiency and their degradation was studied in?vitro. The rhVEGF released from microspheres was quantified by the competitive enzyme-linked immunosorbent assay (ELISA) and human umbilical vein endothelial cell (HUVEC) proliferation assay was used to assess biological activity of the released VEGF. The microspheres were spherical with diameters of 10-60?μm and the encapsulation efficiency was between 46% and 60%. The release kinetics of rhVEGF was studied for two different amounts: 5?μg VEGF (V5) and 50?μg VEGF (V50) per 500?mg starting polymer. The total protein (VEGF:BSA) release increased up to 4 weeks for two rhVEGF concentrations. The ELISA results showed that the burst release for V5 and V50 microspheres were 4 and 27?ng/mL, respectively. For V5, the microspheres showed an initial burst release, followed by a higher steady-state release until 14 days. VEGF release increased up to 2 weeks for V50 microsphere. HUVEC proliferation assay showed that endothelial cells responded to bioactive VEGF by proliferating and migrating.     

Effects of process and formulation parameters on characteristics and internal morphology of poly(d,l-lactide-co-glycolide) microspheres formed by the solvent evaporation method.

Taking ABT627 as a hydrophobic model drug, poly-(lactic-co-glycolic acid) (PLGA) microspheres were prepared by an emulsion solvent evaporation method. Various process parameters, such as continuous phase/dispersed phase (CP/DP) ratio, polymer concentration, initial drug loading, polyvinyl alcohol concentration and pH, on the characteristics of microspheres and in vitro drug release pattern of ABT627 were investigated. Internal morphology of the microspheres was observed with scanning electron microscopy by stereological method. CP/DP is a critical factor in preparing microspheres and drug loading increased significantly with increasing CP/DP ratios accompanied by a remarkably decreased burst release. At CP/DP ratio 20, microspheres with a core-shell structure were formed and the internal porosity of the microspheres decreased with increasing CP/DP ratio. Increase in PLGA concentration led to increased particle sizes and decreased drug release rates. ABT627 release rate increased considerably with increasing PVA concentrations in the continuous phase from 0.1% to 0.5%. The maximum solubility of ABT627 in PLGA was approximately 30%, under which ABT627 was dispersed in PLGA matrix in a molecular state. Increase in initial drug loading had no significant influence on particle size, drug encapsulation efficiency, burst release and internal morphology. However, drug release rate decreased at higher drug loading. Independent of process parameters, ABT627 was slowly released from the PLGA microspheres over 30 days, by a combination of diffusion and polymer degradation. During the first 13 days, ABT627 was mainly released by the mechanism of diffusion demonstrated by the unchanged internal morphology. In contrast, a core-shell structure of the microspheres was observed after being incubated in the release medium for 17 days, independent of drug loading, implying that the ABT627/PLGA microspheres degraded by autocatalytic effect, starting from inside of the matrix. In conclusion, hydrophobic drug release from the PLGA microspheres is mainly dependent on the internal morphology and drug distribution state in the microspheres.     

Reverse micelle-based microencapsulation of oxytetracycline hydrochloride into poly-d,l-lactide-co-glycolide microspheres

The objectives of this study were to solubilize oxytetracycline hydrochloride (HCl) in reverse micelles to prepare poly-d,l-lactide-co-glycolide (PLGA) microspheres and to explore parameters affecting its encapsulation efficiency. Oxytetracycline HCl was dissolved in the reverse micelles consisting of cetyltrimethylammonium bromide, water, and ethyl formate. A PLGA polymer was then dissolved in the reverse micellar solution, and a modified solvent quenching procedure was carried out to prepare PLGA microspheres. Encapsulation efficiencies of oxytetracycline HCl ranged from 2.3 ± 0.2 to 24.9 ± 4.6%, depending on experimental conditions. Important parameters affecting its encapsulation efficiency included the amounts of water used to prepare the reverse micelles and PLGA polymer. With regard to microsphere morphology, the reverse micellar process produced the microspheres with smooth and pore-free surfaces. In particular, their internal matrices did not possess hollow cavities that were frequently observed when a typical double emulsion technique was used to make microspheres. In summary, it was possible to encapsulate oxytetracycline HCl into PLGA microspheres via the ethyl formate-based reverse micellar technique. We also anticipate that the use of ethyl formate could avoid environmental and human toxicity issues associated with methylene chloride.