星点设计-效应面法优化冬凌草甲素聚乳酸纳米粒的制备工艺

目的：优化改良自乳化溶剂扩散法制备冬凌草甲素聚乳酸纳米粒的制备工艺。方法：采用星点设计-效应面法,以冬凌草甲素在有机相中的浓度、载体在有机相中的浓度和水相与有机相的比例为考察因素,以包封率、载药量及药物利用率为考察指标,根据星点设计原理进行实验安排,并用多元线性回归及二项式拟合建立指标与因素之间的数学模型,经效应面法预测最佳工艺条件。结果：优化的最佳因素范围为药物浓度X1：0．5—0．8mg／mL;载体浓度X2：1．6～2．6mg／mL;水油比X3：1～1．5。以优化条件制备的样品平均粒径为98．5nm,包封率为（28．86±0．93）％,载药量为（8．23±0．35）％。结论：星点设计-效应面法适用于冬凌草甲素聚乳酸纳米粒的工艺优化,所建立的数学模型预测性良好。     

Preparation and characterization of ibuprofen microspheres

Ibuprofen was microencapsulated with Eudragit RS using an o/w emulsion solvent evaporation technique. The effects of three formulation variables including the drug:polymer ratio, emulsifier (polyvinyl alcohol) concentration and organic solvent (chloroform) volume on the entrapment efficiency and microspheres size distribution were examined. The drug release rate from prepared microspheres and the release kinetics were also studied. The results demonstrated that microspheres with good range of particle size can be prepared, depending on the formulation components. The drug:polymer ratio had a considerable effect on the entrapment efficiency. However, particle size distribution of microspheres was more dependent on the volume of chloroform and polyvinyl alcohol concentration rather than the drug:polymer ratio. The drug release pattern showed a burst effect for all prepared microspheres due to the presence of uncovered drug crystals on the surface. It was shown that the release profiles of all formulations showed good correlation with the Higuchi model of release.     

Preparation and characterization of ibuprofen microspheres

Ibuprofen was microencapsulated with Eudragit RS using an o/w emulsion solvent evaporation technique. The effects of three formulation variables including the drug:polymer ratio, emulsifier (polyvinyl alcohol) concentration and organic solvent (chloroform) volume on the entrapment efficiency and microspheres size distribution were examined. The drug release rate from prepared microspheres and the release kinetics were also studied. The results demonstrated that microspheres with good range of particle size can be prepared, depending on the formulation components. The drug:polymer ratio had a considerable effect on the entrapment efficiency. However, particle size distribution of microspheres was more dependent on the volume of chloroform and polyvinyl alcohol concentration rather than the drug:polymer ratio. The drug release pattern showed a burst effect for all prepared microspheres due to the presence of uncovered drug crystals on the surface. It was shown that the release profiles of all formulations showed good correlation with the Higuchi model of release.     

Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride

In the present study, potential of polymeric microspheres for treatment of allergic conjunctivitis was investigated. Azelastine hydrochloride loaded Eudragit RL100 microspheres were prepared by solvent evaporation technique. The change in drug-polymer ratio on the particle size, zeta potential, entrapment efficiency and in?vitro drug release was investigated. As Eudragit concentration ranged from 40 to 80?mg/ml the size range obtained was 4.18-7.36?μm with positive zeta potential. With the increase in drug polymer ratio, the entrapment efficiency was increased with maximum 14.56%. In?vitro release studies demonstrated prolonged release of the drug over the period of 6?hr. Scanning electron micrographs showed that microspheres were spherical with distinct solid dense structure. Fourier transform infrared and differential scanning calorimetry studies concluded slight change in peak intensities of drug in microspheres. In?vivo studies in rat model indicated that reduction in eosinophil count number was more pronounced in azelastine hydrochloride microspheres than marketed formulation, Azelast?.     

阿托伐他汀钙纳米粒的制备与质量评价

目的:制备阿托伐他汀钙纳米粒新剂型,对其性质进行研究,优选最佳工艺条件。方法:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒溶液,通过对处方优化,以载体材料用量(X₁)、有机溶剂用量(X₂)、表面活性剂用量(X₃)为自变量,利用Box Behnken设计响应面法以纳米粒粒径(Y)为响应值,优化了阿托伐他汀钙纳米粒的处方。用Malvern激光粒度分析仪测定了粒径分布和纳米粒的Zeta电位,扫描电镜分析了其形态,用高速冷冻离心法和紫外分光光度法测定了包封率和载药量。结果:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒溶液是适合的。响应面优化最优值为阿托伐他汀钙20 mg、卵磷脂178 mg、乙酸乙酯15 mL、聚山梨酯80774 mg,所制备的阿托伐他汀钙纳米粒呈类球形,其平均粒径(71.99±13.62) nm,Zeta电位为(-31.48±2.46) mV,包封率为(91.27±1.7)%,载药量(9.58±0.22)%。结论:采用乳化-溶剂挥发法制备阿托伐他汀钙纳米粒处方及工艺适合,相关性质检测方法可行。     

Eudragit RL100 based microspheres for ocular administration of azelastine hydrochloride

In the present study, potential of polymeric microspheres for treatment of allergic conjunctivitis was investigated. Azelastine hydrochloride loaded Eudragit RL100 microspheres were prepared by solvent evaporation technique. The change in drug–polymer ratio on the particle size, zeta potential, entrapment efficiency and in vitro drug release was investigated. As Eudragit concentration ranged from 40 to 80?mg/ml the size range obtained was 4.18–7.36?µm with positive zeta potential. With the increase in drug polymer ratio, the entrapment efficiency was increased with maximum 14.56%. In vitro release studies demonstrated prolonged release of the drug over the period of 6?hr. Scanning electron micrographs showed that microspheres were spherical with distinct solid dense structure. Fourier transform infrared and differential scanning calorimetry studies concluded slight change in peak intensities of drug in microspheres. In vivo studies in rat model indicated that reduction in eosinophil count number was more pronounced in azelastine hydrochloride microspheres than marketed formulation, Azelast®.     

离子凝胶法制备水杨酸壳聚糖纳米粒

目的以壳聚糖为载体材料制备水杨酸壳聚糖纳米粒,并对其制备工艺及体系pH值对药物包封率的影响进行考察,初步探讨壳聚糖纳米粒的载药机制。方法以水杨酸为模型药物,采用离子凝胶法制备壳聚糖纳米粒,以包封率及粒径为指标,考察处方因素对纳米粒制备的影响。结果壳聚糖浓度、体系的pH值、药物质量浓度是影响制备工艺的主要因素;体系的pH值可显著提高壳聚糖纳米粒的包封率。结论药物与壳聚糖之间的离子相互作用较弱,并不是纳米粒载药的主要机制。     

改良自乳化-溶剂扩散法制备甲基莲心碱纳米粒的研究

目的制备甲基莲心碱纳米粒(NEF-NP),并采用正交试验设计对甲基莲心碱纳米粒制备工艺进行优化。方法以包封率和载药量为评价指标,采用聚乳酸-羟基乙酸共聚物(PLGA)为载体,丙酮-无水乙醇为有机溶剂,通过正交设计优化改良自乳化-溶剂扩散法制备载NEF的PLGA载药纳米粒的处方工艺。结果优化的最佳处方工艺为:PLGA的浓度为20 mg.mL-1,NEF的投药量为3.3 mg,PVA浓度为1.0%,水相与有机相的体积比为8∶1。最佳条件下制得的纳米粒平均包封率达(70.35±1.16)%,载药量(2.33±1.08)%,平均粒径为(213.5±2.7)nm。结论最佳处方工艺制备的NEF-PLGA纳米粒具有较高的包封率、载药量和较小的粒径。     

Development and characterization of HBsAg-loaded Eudragit nanoparticles for effective colonic immunization

The present study was undertaken with an aim to investigate the potential of targeting colonic mucosa following oral vaccine delivery to generate prophylactic humoral and mucosal immune response. In present study, response surface methodology (RSM) using the central composite design (CCD) was applied for optimization of process and composition to get uniform, stable reproducible eudragit nanoparticles suitable for targeting to colon. The optimized formulation had the composition of 173?μg HBsAg, 250?mg polymers concentration (4:1 combination of Eudragit S-100 and L-100) and 2% w/v Polyvinyl alcohol (PVA) along with adjuvant Monophosphoryl lipid A (MPLA). Mean particle size of optimized nanoparticles was found to be 730.4?nm, entrapment efficiency (58.38%) and polydispersity index of 0.185. Fluorescent spectroscopy, differential scanning calorimetry, and antigen integrity by SDS-PAGE established that antigen structure was preserved during and after formulation development. In-vitro release studies in different intestinal pH concluded antigen release at mild alkaline conditions. Real time fluorescence animal imaging confirmed the effective absorption and distribution of NPs at colon resulted in improved immune response. Present study concludes that Eudragit nanoparticles offers strong potential in colon targeting of vaccines through oral immunization.     

Formulation and optimization of rifampicin microparticles by Box-Behnken statistical design

The objective of the present study was to optimize and evaluate in vitro gastroretentive performance of rifampicin microparticles. Formulations were optimized using design of experiments by employing a 4-factor, 3-level Box-Behnken statistical design. Independent variables studied were the ratio of polymers (Eudragit RSPO: ethyl cellulose), inert drug dispersing agent (talc), surfactant (sodium dodecyl sulfate) and stirring speed. The dependent variables were particle size and entrapment efficiency. Response surface plots were drawn, statistical validity of the polynomials was validated and the optimized formulation was characterized by Fourier Transform-InfraRed spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Entrapment efficiency and particle size were determined. The designed microparticles have average particle size from 14.10 μm to 45.63 μm and entrapment efficiency from 38.14% to 94.81%. Optimized microparticles showed particle size and drug entrapment, 51.53 μm and 83.43%, respectively with sustained drug release behavior up to 12?h. In the present study, rifampicin microspheres were successfully prepared by a quasi-emulsion solvent diffusion technique for prolonged drug release. FT-IR and DSC studies did not reveal any significant drug interactions. The drug release was found to be controlled for more than 12?h by following zero order release pattern.     

Flurbiprofen loaded biodegradable nanoparticles for ophtalmic administration

Poly(lactic/glycolic) acid nanoparticles incorporating flurbiprofen (FB) were prepared by the solvent displacement technique using poloxamer 188 as a stabilizer to improve the availability of the drug for the prevention of the inflammation caused by ocular surgery. A 2(3) + star design was applied to investigate the influence of several factors such as the pH of the aqueous phase, the initial concentration of the stabilizer, and the drug used to prepare the nanoparticles (NPs) on the physicochemical properties (particle size analysis, zeta potential, and drug loading efficiency) of the colloidal system. The best formulations were those prepared at pH 3.5 with a concentration of 1.5 mg/mL of FB and 10 or 20 mg/mL of poloxamer 188. These formulations showed an appropriate average size for ophthalmic administration (232.8 and 277.6 nm, respectively) and a good yield of entrapment efficiency (94.60% and 93.55%, respectively). The release behavior of FB from the developed NPs was complete and exhibited a biphasic pattern. Formulations did not show toxicity on ocular tissues. In vivo anti-inflammatory efficacy was assessed in the rabbit eye after topical instillation of sodium arachidonate (SA). A higher decrease of the SA-induced inflammation was obtained for the NP formulations.     

Box-Behnken效应面法优化姜黄素正负离子固体脂质纳米粒的处方

目的 采用Box-Behnken效应面法筛选姜黄素正负离子固体脂质纳米粒的最优处方.方法 采用乳化蒸发-低温固化法制备姜黄素的固体脂质纳米粒,以固体脂质的质量、卵磷脂的质量和混合表面活性剂为考察对象,以包封率和脂质载药量为考察指标,利用3因素3水平Box-Behnken效应面设计法筛选姜黄素固体脂质纳米粒的最优处方.结果 按最优处方制备固体脂质纳米粒的包封率为94.20％ ±2.55％、脂质载药量为3.49％±0.11％,平均粒径为194.9 ±12.0 nm,Zeta电位为-28.15 ±2.72 mV.结论 采用Box-Behnken效应面法优化姜黄素正负固体脂质纳米粒的处方是有效、可行的.     

阿克他利固体脂质纳米粒的制备

目的以乳化蒸发一低温固化法制备阿克他利固体脂质纳米粒。方法在单因素考察的基础上以正交试验设计优化、筛选最佳处方和制备工艺。用透射电镜观察固体脂质纳米粒的形态，激光散射测定Zeta电位和粒度分布，高速离心法测定阿克他利固体脂质纳米粒的包封率。结果所制固体脂质纳米粒外观形态圆整，粒度分布为50～200am，平均粒径为120am，Zeta电位为一17．14mV，包封率为50．87％。结论阿克他利固体脂质纳米粒的制备，为开发阿克他利静脉注射被动靶向制剂奠定了试验基础。     

Formulation and optimization of rifampicin microparticles by Box-Behnken statistical design

The objective of the present study was to optimize and evaluate in vitro gastroretentive performance of rifampicin microparticles. Formulations were optimized using design of experiments by employing a 4-factor, 3-level Box-Behnken statistical design. Independent variables studied were the ratio of polymers (Eudragit RSPO: ethyl cellulose), inert drug dispersing agent (talc), surfactant (sodium dodecyl sulfate) and stirring speed. The dependent variables were particle size and entrapment efficiency. Response surface plots were drawn, statistical validity of the polynomials was validated and the optimized formulation was characterized by Fourier Transform-InfraRed spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Entrapment efficiency and particle size were determined. The designed microparticles have average particle size from 14.10 μm to 45.63 μm and entrapment efficiency from 38.14% to 94.81%. Optimized microparticles showed particle size and drug entrapment, 51.53 μm and 83.43%, respectively with sustained drug release behavior up to 12?h. In the present study, rifampicin microspheres were successfully prepared by a quasi-emulsion solvent diffusion technique for prolonged drug release. FT-IR and DSC studies did not reveal any significant drug interactions. The drug release was found to be controlled for more than 12?h by following zero order release pattern.     

Lappaconitine-loaded microspheres for parenteral sustained release: effects of formulation variables and in vitro characterization

Lappaconitine instead of its hydrobromide salts has been encapsulated in poly (lactide-co-glycolide) acid (PLGA) microspheres by the simple o/w emulsion solvent evaporation technique. The effects of several variables including emulsifier (polyvinyl alcohol, PVA) concentration, stirring speed, PLGA concentration and drug/polymer mass ratios on quality of microspheres have been investigated. The particle size and size distribution can be controlled by PVA concentration, stirring speed and PLGA concentration. The entrapment efficiency and the burst release of lappaconitine from drug-loaded microspheres were dominantly affected by the drug/polymer mass ratio and PVA concentration. The best parameters of formulation were 1.5% PVA, the PLGA concentration of 50 g/L, and the stirring speed of 800 rpm and drug/polymer of 1:5. The optimized formulation has a mean particle size of 19.3 +/- 0.93 microm, mean entrapment efficiency of 70.77 +/- 3.23% and mean drug loading of 11.45 +/- 0.47%. Based on the optimized parameters of formulation, the effects of oil/aqueous solubility partition ratio of drug on entrapment efficiency of drug-loaded microspheres prepared by o/w emulsion solvent evaporation were further studied. A good linear relation existed between the partition ratio and entrapment efficiency. The optimized microspheres were characterized by SEM, FT-IR, DSC and XRD. SEM shows spherical and smooth surface and uniform size distribution. The results of DSC, FT-IR study reveal no interaction between drug and polymer. The results of the XRD study indicate lappaconitine trapped in microsphere exists in form of an amorphous or disordered crystalline status in polymer matrix. The in vitro release models were evaluated with two different groups of drug-loaded microspheres including microspheres washed with distilled water and 0.01N HCL, respectively. The drug release profile of lappaconitine-loaded microspheres washed with distilled water agreed with zero order equation and that of the latter better agreed with first order equation.     

Effect of process and formulation variables on the preparation of parenteral paclitaxel-loaded biodegradable polymeric nanoparticles: A co-surfactant study

The purpose of this study was to evaluate the effect of process (homogenization speed and evaporation time) and formulation (aqueous/organic phase ratio, surfactant concentration, polymer type and concentration, and drug amount) variables on the preparation of paclitaxel-loaded biodegradable polymeric nanoparticles using modified solvent evaporation technique. Thereafter, a formulation was selected and subjected to evaluation of inclusion of a co-surfactant for further reduction of particle size. Particle size, encapsulation efficiency and in-vitro drug release kinetics were evaluated. It was observed that the inclusion of vitamin E TPGS (0.01%), Poloxamer 188 (0.5%) or Tween 80 (0.25%) reduced the particle size of nanoparticles to 230, 244 or 301 nm from 438 nm, respectively. Encapsulation efficiency increased for both vitamin E TPGS and Poloxamer 188 up to concentration at 0.010% and 0.25%, respectively, while this was not the case for Tween 80. Comparison of drug release kinetics demonstrated that drug release accelerated from paclitaxel-loaded biodegradable nanoparticles prepared with the inclusion of Tween 80 but was delayed for Poloxamer 188 and vitamin E TPGS. Thus, it was concluded that the particle size of the nanoparticles could be reduced further and the paclitaxel release kinetics could easily be adjusted by taking advantage by the inclusion of a co-surfactant.     

Design,in vitro and in vivo evaluation of glipizide Eudragit microparticles

Glipizide microparticles made with Eudragit (RS 100 and RL 100), prepared by emulsion solvent evaporation technique were evaluated for various in-vitro properties viz. encapsulation efficiency, particle size and surface morphology, drug release pattern and in-vivo hypoglycaemic activity. The optimized formulation parameters were used to prepare smooth and spherical microparticles (2–32 µm) with higher entrapment efficiency (67–89%). Drug release patterns of glipizide microparticles of Eudragit RS 100 and Eudragit RL 100 with drug-to-polymer ratio of 1 : 4 (i.e. EGM14 and ELGM14) have shown gradual and extended release for 24 h with cumulative release of glipizide to the extent of 72.3% and 83.9%, respectively. However, EGM14 showed a significant in-vivo hypoglycaemic effect up to 12 h in rabbits while ELGM14 showed for 9 h. Hence, glipizide microparticles of Eudragit RS 100 (glipizide: polymer 1 : 4) is better suited for oral sustained release formulation.     

Brain targeted oral delivery of doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles against ketamine induced psychosis: behavioral,biochemical, neurochemical and histological alterations in mice

To develop statistically optimized brain targeted Tween 80 coated chitosan nanoparticulate formulation for oral delivery of doxycycline hydrochloride for the treatment of psychosis and to evaluate its protective effect on ketamine induced behavioral, biochemical, neurochemical and histological alterations in mice. 3² full factorial design was used to optimize the nanoparticulate formulation to minimize particle size and maximize entrapment efficiency, while independent variables chosen were concentration of chitosan and Tween 80. The optimized formulation was characterized by particle size, drug entrapment efficiency, Fourier transform infrared, Transmission electron microscopy analysis and drug release behavior. Pure doxycycline hydrochloride (25 and 50?mg/kg, p.o.) and optimized doxycycline hydrochloride encapsulated Tween 80 coated chitosan nanoparticles (DCNP_opt) (equivalent to 25?mg/kg doxycycline hydrochloride, p.o.) were explored against ketamine induced psychosis in mice. The experimental studies for DCNP_opt, with mean particle size 237?nm and entrapment efficiency 78.16%, elucidated that the formulation successfully passed through blood brain barrier and exhibited significant antipsychotic activity. The underlying mechanism of action was further confirmed by behavioral, biochemical, neurochemical estimations and histopathological study. Significantly enhanced GABA and GSH level and diminished MDA, TNF-α and dopamine levels were observed after administration of DCNP_opt at just half the dose of pure doxycycline hydrochloride, showing better penetration of doxycyline hydrochloride in the form of Tween 80 coated nanoparticles through blood brain barrier. This study demonstrates the hydrophilic drug doxycycline hydrochloride, loaded in Tween 80 coated chitosan nanoparticles, can be effectively brain targeted through oral delivery and therefore represents a suitable approach for the treatment of psychotic symptoms.     

正交试验优选羧甲基壳聚糖-醋甲唑胺纳米微球的制备方案

目的：制备羧甲基壳聚糖载药纳米微球,醋甲唑胺为模型药物,测量药物的包封率和纳米微球形态.方法：采用乳化交联法,在微乳液的基础上制备载药纳米微球,对可能影响药物包封率的处方因素进行优化设计,筛选出最优配方.结果：羧甲基壳聚糖溶液的浓度对包封率有显著性影响,三聚磷酸钠溶液浓度和醋甲唑胺药量对包封率未见影响.优化方案的载药纳米微球包封率为49.36％,其电镜下为较规整的球型纳米微球,平均粒径386.0 nm.结论：采用乳化交联法,可形成较高包封率的羧甲基壳聚糖-醋甲唑胺纳米微球.     

香叶木素固体脂质纳米粒的制备及质量评价

目的 制备香叶木素固体脂质纳米粒并对其进行质量评价。方法 采用溶剂注入法制备香叶木素固体脂质纳米粒,用 Box-Benhnken效应面法优化处方,并通过包封率、微观形态、粒径分布和Zeta电位对香叶木素固体脂质纳米粒的质量进行评价。 结果 香叶木素固体脂质纳米粒最优处方组成：表面活性剂浓度3.39%,棕榈酸浓度0.116%,脂药质比为21:100,制备的香叶木素 固体脂质纳米粒外观澄清透明,带淡蓝色乳光;平均粒径为(91.73±3.18)nm(n=3),PDI为0.228,电位为(-11.46±0.74)mV(n=3);包 封率为95.13%,载药量为9.04%;透射电镜照片显示纳米粒大小均一,呈球形或类球形。 结论 该处方可用于香叶木素固体脂 质纳米粒的制备,工艺简单,稳定可行。