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  • 1.

    【2hr】Influence of Process Parameters on Tablet Bed Microenvironmental Factors During Pan Coating

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    机译 锅包衣过程中工艺参数对平板床微环境因素的影响
    摘要：Recent studies have shown the importance of monitoring microenvironmental conditions (temperature, relative humidity) experienced by the tablet bed during a pan coating process, thereby necessitating the need to understand how various process parameters influence these microenvironmental conditions. The process parameters studied in this work include exhaust air temperature, spray rate, inlet airflow rate, gun-to-bed distance, coating suspension percent solids, and atomization and pattern air pressure. Each of these process parameters was found to have an impact on the tablet bed relative humidity (RH), as measured using PyroButton data logging devices. A higher tablet bed RH was obtained with an increase in spray rate and atomization air pressure and with a decrease in exhaust air temperature, inlet airflow rate, gun-to-bed distance, suspension percent solids, and pattern air pressure. Based on this work, it can be concluded that the tablet bed thermodynamic conditions are a cumulative effect of the various process conditions. A strong correlation between the tablet bed RH and the frequency of tablet coating defect (logo bridging) was established, with increasing RH resulting in a higher percent of logo bridging events.
  • 2.

    【2hr】Influence of Starting Material Particle Size on Pellet Surface Roughness

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    机译 原料粒度对颗粒表面粗糙度的影响
    摘要：The purpose of this study was to investigate the effect of pelletization aids, i.e., microcrystalline cellulose (MCC) and cross-linked polyvinyl pyrrolidone (XPVP), and filler, i.e., lactose, particle size on the surface roughness of pellets. Pellets were prepared from powder blends containing pelletization aid/lactose in 1:3 ratio by extrusion–spheronization. Surface roughness of pellets was assessed quantitatively and qualitatively using optical interferometry and scanning electron microscopy, respectively. Both quantitative and qualitative surface studies showed that surface roughness of pellets depended on the particle size of XPVP and lactose used in the formulation. Increase in XPVP or lactose particle size resulted in rougher pellets. Formulations containing MCC produced pellets with smoother surfaces than those containing XPVP. Furthermore, surface roughness of the resultant pellets did not appear to depend on MCC particle size. Starting material particle size was found to be a critical factor for determining the surface roughness of pellets produced by extrusion–spheronization. Smaller particles can pack well with lower peaks and valleys, resulting in pellets with smoother surfaces. Similar surface roughness of pellets containing different MCC grades could be due to the deaggregation of MCC particles into smaller subunits with more or less similar sizes during wet processing. Hence, for starting materials that deaggregate during the wet processing, pellet surface roughness is influenced by the particle size of the material upon deaggregation.
  • 3.

    【2hr】Physicochemical Properties and Anti-Propionibacterium acnes Activity of Film-Forming Solutions Containing Alpha-Mangostin-Rich Extract

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    机译 富含α-Mangostin提取物的成膜溶液的理化性质和痤疮丙酸杆菌活性
    摘要：The objective of this study was to study the effect of formulation compositions on physicochemical properties and anti-Propionibacterium acnes activity of film-forming solutions containing alpha-mangostin-rich extract (AM). Film-forming solution bases and film-forming solutions containing AM were prepared by using Eudragit RL PO or Klucel LF or combinations of them as film-forming polymers. Rheological properties, pH values of the solutions, and mechanical properties of the dry films were investigated. An optimized formulation was selected and evaluated for the film surface, in vitro AM release, an anti-P. acnes activity, and potential for being a skin irritant. It was found that mechanical properties of the dry films were affected by total polymer contents, ratios of Klucel LF/Eudragit RL PO, AM, and contents of triethyl citrate. The film-forming solutions containing AM had pH values around 7.0. Their flow curves exhibited Newtonian flow behaviors. The optimized formulation provided films possessing smooth and nonporous surfaces. These films showed greater anti-P. acnes activity than their base films without toxicity to skin fibroblasts. Furthermore, AM released from the film matrix obeyed Higuchi's equation. In conclusion, the film-forming solutions containing AM had potential for treatment of acne vulgaris caused by P. acnes. However, further in vivo study is necessary to determine their efficacy and safety for using in patients suffering from acne vulgaris.
  • 4.

    【2hr】Eudragit L/HPMCAS Blend Enteric-Coated Lansoprazole Pellets: Enhanced Drug Stability and Oral Bioavailability

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    机译 Eudragit L / HPMCAS混合肠溶兰索拉唑小丸：增强的药物稳定性和口服生物利用度
    摘要：The objectives of the present work were to use blends of Eudragit L and hydroxypropyl methylcellulose acetate succinate (HPMCAS) as enteric film coatings for lansoprazole (LSP) pellets. The enteric-coated pellets were prepared with a fluid-bed coater. The influence of the blend ratio, type of plasticizer, plasticizer level, coating level, and curing conditions on gastric stability in vitro drug release and drug stability was evaluated. Furthermore, the bioavailability of the blend-coated pellets in beagle dogs was also performed. The blend-coated pellets exhibited significant improvement of gastric stability and drug stability compared to the pure polymer-coated pellets. Moreover, the AUC values of blend-coated pellets were greater than that of the pure polymer-coated pellets. It was concluded that the using blends of Eudragit L and HPMCAS as enteric film coatings for LSP pellets improved the drug stability and oral bioavailability.Electronic supplementary materialThe online version of this article (doi:10.1208/s12249-013-0035-1) contains supplementary material, which is available to authorized users.
  • 5.

    【2hr】Quality-by-Design: Are We There Yet?

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    机译 按设计质量：我们还在那里吗？
    摘要：In 2012, the Quality-by-Design and Product Performance Focus Group of AAPS conducted a survey to assess the state of adoption and perception of Quality-by-Design (QbD). Responses from 149 anonymous individuals from industry—including consultants—(88%), academia (7%), and regulatory body (4%), were collected. A majority of respondents (54% to 76%) reported high frequency of utilization of several tools and most QbD elements outlined by International Conference on Harmonization Q8, with design of experiments, risk assessment, and the quality target product profile ranked as the top three. Over two thirds of respondents agreed that the benefits of QbD included both the positive impact it can have on the patient (78%), as well as on internal processes such as knowledge management (85%), decision making (79%), and lean manufacture (71%). However, more than 50% from industry were neutral about or disagreed with QbD leading to a better return on investment. This suggests that, despite the recognized scientific, manufacture, and patient-related benefits, there is not yet a clearly articulated business case for QbD available. There was a difference of opinion between industry and regulatory agency respondents as to whether a QbD-based submission resulted in increased efficiency of review. These contrasting views reinforce the idea that QbD implementation can benefit from further dialog between industry and regulatory authorities. A majority of respondents from academia indicated that QbD has influenced their research. In total, the results indicate the broad adoption of QbD but also suggest we are yet in a journey and that the process of gathering all experience and metrics required for connecting and demonstrating QbD benefits to all stakeholders is still in progress.
  • 6.

    【2hr】Chitosan Nanoparticle Encapsulated Hemagglutinin-Split Influenza Virus Mucosal Vaccine

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    机译 壳聚糖纳米颗粒包封的血凝素分裂流感病毒粘膜疫苗
    摘要：Subunit/split influenza vaccines are less reactogenic compared with the whole virus vaccines. However, their immunogenicity is relatively low and thus required proper adjuvant and/or delivery vehicle for immunogenicity enhancement. Influenza vaccines administered intramuscularly induce minimum, if any, mucosal immunity at the respiratory mucosa which is the prime site of the infection. In this study, chitosan (CS) nanoparticles were prepared by ionic cross-linking of the CS with sodium tripolyphosphate (TPP) at the CS/TPP ratio of 1:0.6 using 2 h mixing time. The CS/TPP nanoparticles were used as delivery vehicle of an intranasal influenza vaccine made of hemagglutinin (HA)-split influenza virus product. Innocuousness, immunogenicity, and protective efficacy of the CS/TPP-HA vaccine were tested in influenza mouse model in comparison with the antigen alone vaccine. The CS/TPP-HA nanoparticles had required characteristics including nano-sizes, positive charges, and high antigen encapsulation efficiency. Mice that received two doses of the CS/TPP-HA vaccine intranasally showed no adverse symptoms indicating the vaccine innocuousness. The animals developed higher systemic and mucosal antibody responses than vaccine made of the HA-split influenza virus alone. The CS/TPP-HA vaccine could induce also a cell-mediated immune response shown as high numbers of IFN-γ-secreting cells in spleens while the HA vaccine alone could not. Besides, the CS nanoparticle encapsulated HA-split vaccine reduced markedly the influenza morbidity and also conferred 100% protective rate to the vaccinated mice against lethal influenza virus challenge. Overall results indicated that the CS nanoparticles invented in this study is an effective and safe delivery vehicle/adjuvant for the influenza vaccine.
  • 7.

    【2hr】Influence of Processing Parameters and Formulation Factors on the Bioadhesive, Temperature Stability and Drug Release Properties of Hot-Melt Extruded Films Containing Miconazole

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    机译 加工参数和配方因素对含咪康唑的热熔挤出薄膜的生物粘附性，温度稳定性和释药性能的影响
    摘要：This study investigated the processing parameters and formulation factors on the bioadhesive properties, temperature stability properties, and drug release properties of miconazole in PolyOx® and Klucel® matrix systems produced by Hot-melt Extrusion (HME) technology. Miconazole incorporated into these matrix systems were found to be stable for 8 months by X-ray diffraction (XRD). The addition of miconazole increased area under the curve (AUC) at contact time intervals of 30 and 60 sec, while the bioadhesion decreased with an increase in processing temperatures. The release profiles suggest that a sustained release of miconazole was observed from all of the tested HME film formulations for approximately 10 h. The release from the optimal HME film extruded at 205°C was found to be significantly different than that extruded at 190°C. Therefore, this matrix system may address the present shortcomings of currently available therapy for oral and pharyngeal candidiasis.
  • 8.

    【2hr】Investigation of Critical Core Formulation and Process Parameters for Osmotic Pump Oral Drug Delivery

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    机译 渗透泵口服药物输送的关键核心配方和工艺参数的研究
    摘要：Push–pull osmotic pump (PPOP) tablets of a practically insoluble model drug were developed and the effect of various formulation and process parameters on tablet performance was evaluated in order to identify critical factors. The formulation factors such as the viscosity grade of polyethylene oxide as the primary polymer as well as the level and location of osmogen within the bilayer tablets led to a difference in performance of osmotic tablets and hence should be critically evaluated in the design of such dosage forms. Modification of granulation process, i.e., the granulating liquid composition or drying method of granules, did not impact the drug release from the osmotic tablets at the evaluated scale of this study. The influence of varying dose and aqueous solubility of other model drugs (i.e., theophylline, acetaminophen, and verapamil HCl) on the developed PPOP template was also investigated. Results showed that irrespective of the perceived complexity of development and manufacturing of osmotic pumps, the osmotic tablets in this study demonstrated a robust and yet flexible platform in accommodating different types of drug candidates, regardless of solubility, for the dose levels below 25% w/w of the pull layer formulation.
  • 9.

    【2hr】A Prospective Analysis of Co-Processed Non-Ionic Surfactants in Enhancing Permeability of a Model Hydrophilic Drug

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    机译 共处理非离子表面活性剂提高模型亲水性药物渗透性的前瞻性分析
    摘要：Paracellular route is a natural pathway for the transport of many hydrophilic drugs and macromolecules. The purpose of this study was to prospectively evaluate the ability of novel co-processed non-ionic surfactants to enhance the paracellular permeability of a model hydrophilic drug metformin using Caco-2 (human colonic adenocarcinoma) cell model. A three-tier screen was undertaken to evaluate the co-processed blends based on cytotoxicity, cellular integrity, and permeability coefficient. The relative contribution of the paracellular and the transcellular route in overall transport of metformin by co-processed blends was determined. Immunocytochemistry was conducted to determine the distribution of tight-junction protein claudin-1 after incubation with the co-processed blends. It was found that novel blends of Labrasol and Transcutol-P enhanced metformin permeability by approximately twofold with transient reduction in the transepithelia electrical resistance (TEER) and minimal cytotoxicity compared with the control, with the paracellular pathway as the major route of metformin transport. Maximum permeability of metformin (∼10-fold) was mediated by Tween-20 blends along with >75% reduction in the TEER which was irreversible over 24-h period. A shift in metformin transport from the paracellular to the transcellular route was observed with some Tween-20 blends. Immunocytochemical analysis revealed rearrangement of the cellular borders and fragmentation on treatment with Tween-20 blends. In conclusion, cytotoxicity, cellular integrity, and permeability of the hydrophilic drugs can be greatly influenced by the polyoxyethylene residues and medium chain fatty acids in the non-ionic surfactants at clinically relevant concentrations and therefore should be thoroughly investigated prior to their inclusion in formulations.
  • 10.

    【2hr】A Short Term Quality Control Tool for Biodegradable Microspheres

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    机译 可生物降解微球的短期质量控制工具
    摘要：Accelerated in vitro release testing methodology has been developed as an indicator of product performance to be used as a discriminatory quality control (QC) technique for the release of clinical and commercial batches of biodegradable microspheres. While product performance of biodegradable microspheres can be verified by in vivo and/or in vitro experiments, such evaluation can be particularly challenging because of slow polymer degradation, resulting in extended study times, labor, and expense. Three batches of Leuprolide poly(lactic-co-glycolic acid) (PLGA) microspheres having varying morphology (process variants having different particle size and specific surface area) were manufactured by the solvent extraction/evaporation technique. Tests involving in vitro release, polymer degradation and hydration of the microspheres were performed on the three batches at 55°C. In vitro peptide release at 55°C was analyzed using a previously derived modification of the Weibull function termed the modified Weibull equation (MWE). Experimental observations and data analysis confirm excellent reproducibility studies within and between batches of the microsphere formulations demonstrating the predictability of the accelerated experiments at 55°C. The accelerated test method was also successfully able to distinguish the in vitro product performance between the three batches having varying morphology (process variants), indicating that it is a suitable QC tool to discriminate product or process variants in clinical or commercial batches of microspheres. Additionally, data analysis utilized the MWE to further quantify the differences obtained from the accelerated in vitro product performance test between process variants, thereby enhancing the discriminatory power of the accelerated methodology at 55°C.
  • 11.

    【2hr】Formulation and Optimization of Nonionic Surfactants Emulsified Nimesulide-Loaded PLGA-Based Nanoparticles by Design of Experiments

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    机译 实验设计的非离子表面活性剂乳化的负载尼美舒利的PLGA纳米粒子的配方与优化
    摘要：This investigation aimed to develop nimesulide (NMS)-loaded poly(lactic-co-glycolic acid) (PLGA)-based nanoparticulate formulations as a biodegradable polymeric drug carrier to treat rheumatoid arthritis. Polymeric nanoparticles (NPs) were prepared with two different nonionic surfactants, vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) and poly(vinyl alcohol) (PVA), using an ultrasonication solvent evaporation technique. Nine batches were formulated for each surfactant using a 32 factorial design for optimal concentration of the emulsifying agents, 0.03–0.09% for vitamin E TPGS and 2–4% for PVA. The surfactant percentage and the drug/polymer ratio (1:10, 1:15, 1:20) of the NMS-loaded NPs were investigated based on four responses: encapsulation efficiency, particle size, the polydispersity index, and the surface charge. The response surface plots and linearity curves indicated a relationship between the experiment’s responses and a set of independent variables. The NPs produced with both surfactants exhibited a negative surface charge, and scanning electron micrographs revealed that all of the NPs were spherical in shape. A narrower size distribution and higher drug loadings were achieved in PVA-emulsified PLGA NPs than in the vitamin E TPGS emulsified. Decreasing amounts of both nonionic surfactants resulted in a reduction in the emulsion’s viscosity, which led to a decrease in the particle size of NPs. According to the ANOVA results obtained in this present research, vitamin E TPGS exhibited the best correlation between the independent variables, namely drug/polymer ratio and the surfactant percentage, and the dependent variables (encapsulation efficiency R2 = 0.9603, particle size R2 = 0.9965, size distribution R2 = 0.9899, and surface charge R2 = 0.8969) compared with PVA.
  • 12.

    【2hr】Effect of Hydrocarbon Chain Length in 1,2-Alkanediols on Percutaneous Absorption of Metronidazole: Toward Development of a General Vehicle for Controlled Release

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    机译 1,2-链烷二醇中烃链长度对甲硝唑经皮吸收的影响：趋向于控制释放的通用车辆的发展。
    摘要：The objective of the present study is to investigate the effect of hydrocarbon chain length in 1,2-alkanediols on percutaneous absorption of metronidazole (MTZ). Twelve formulations (1,2-propanediol, 1,2-butanediol, 1,2-pentanediol, 1,2-hexanediol in 4% concentration, 1,2-hexanediol, and 1,2-heptanediol in 1% concentration, in the absence and presence of 1,4-cyclohexanediol, respectively) were studied in an in vitro hairless mouse skin model using Franz diffusion cell. Based on the flux values and retardation ratios (RR), a penetration retardation effect on percutaneous absorption of MTZ was observed for the formulations containing 1,2-diols having six- to seven-carbon chain in the presence of 1,4-cyclohexanediol (1,2-hexanediol with chain length of six hydrocarbons, RRs are 0.69 and 0.76 in the concentration of 4% and 1%, respectively; 1,2-heptanediol with chain length of seven hydrocarbons, RR is 0.78 in the concentration of 1%). On the other hand, no retardation effect was observed in formulations containing short alkyl chains (RRs of 1,2-propanediol, 1,2-butanediol, and 1,2-pentanediol are 0.99, 1.61, and 0.96, respectively). Instead, a penetration enhancement effect was observed for 1,2-diols having four and five carbons. In other words, effect of 1,2-alkanediols on percutaneous absorption of MTZ can be systematically modulated by simply varying number of –CH2 groups in the hydrocarbon chain—from being a penetration enhancer to retardant. These observations shed light on mechanism of the penetration enhancement and retardation effect and provide insight into rational design of penetration enhancers and retardants. Furthermore, the combination of 1,2-alkanediols and 1,4-cyclohexanediol could become a general vehicle for controlled release of pharmaceutical and cosmetic active ingredients.

    Figureᅟ

  • 13.

    【2hr】Effect of Acetate and Carbonate Buffers on the Photolysis of Riboflavin in Aqueous Solution: A Kinetic Study

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    机译 乙酸和碳酸盐缓冲液对核黄素在水溶液中光解的影响：动力学研究
    摘要：The photolysis of riboflavin (RF) in the presence of acetate buffer (pH 3.8–5.6) and carbonate buffer (pH 9.2–10.8) has been studied using a multicomponent spectrophotometric method for the simultaneous assay of RF and its photoproducts. Acetate and carbonate buffers have been found to catalyze the photolysis reaction of RF. The apparent first-order rate constants for the acetate-catalyzed reaction range from 0.20 to 2.86 × 10−4 s−1 and for the carbonate-catalyzed reaction from 3.33 to 15.89 × 10−4 s−1. The second-order rate constants for the interaction of RF with the acetate and the carbonate ions range from 2.04 to 4.33 × 10−4 M−1 s−1 and from 3.71 to 11.80 × 10−4 M−1 s−1, respectively. The k-pH profile for the acetate-catalyzed reaction is bell shaped and for the carbonate-catalyzed reaction a steep curve. Both HCO3− and CO32 − ions are involved in the catalysis of the photolysis reaction in alkaline solution. The rate constants for the HCO3− and CO32 − ions catalyzed reactions are 0.72 and 1.38 × 10−3 M−1 s−1, respectively, indicating a major role of CO32 − ions in the catalysis reaction. The loss of RF fluorescence in acetate buffer suggests an interaction between RF and acetate ions to promote the photolysis reaction. The optimum stability of RF solutions is observed in the pH range 5–6, which is suitable for pharmaceutical preparations.
  • 14.

    【2hr】Hydrogels Composed of Cyclodextrin Inclusion Complexes with PLGA-PEG-PLGA Triblock Copolymers as Drug Delivery Systems

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    机译 水凝胶由环糊精包合物与PLGA-PEG-PLGA三嵌段共聚物作为药物输送系统组成。
    摘要：Although conventional pharmaceuticals have many drug dosage forms on the market, the development of new therapeutic molecules and the low efficacy of instant release formulations for the treatment of some chronic diseases and specific conditions encourage scientists to invent different delivery systems. To this purpose, a supramolecular hydrogel consisting of the tri-block copolymer PLGA-PEG-PLGA and α-cyclodextrin was fabricated for the first time and characterised in terms of rheological, morphological, and structural properties. Naltrexone hydrochloride and vitamin B12 were loaded, and their release profiles were determined.
  • 15.

    【2hr】Evaluation of Tadalafil Nanosuspensions and Their PEG Solid Dispersion Matrices for Enhancing Its Dissolution Properties

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    机译 他达拉非纳米悬浮液及其PEG固体分散体基质增强其溶解性能的评价
    摘要：The aim of this work was to prepare and evaluate Tadalafil nanosuspensions and their PEG 4000 solid dispersion matrices to enhance its dissolution rate. Nanosuspensions were prepared by precipitation/ultrasonication technique at 5°C where different stabilizers were screened for stabilization. Nanosuspensions were characterized in terms of particle size and charge. Screening process limited suitable stabilizers into structurally related surfactants composed of a mixture of Tween80 and Span80 at 1:1 ratio (in percent, weight/volume) in adjusted alkaline pH (named TDTSp-OH). The surfactant mixture aided the production of nanosuspensions with an average particle size of 193 ± 8 nm and with short-term stability sufficient for further processing. Solid dispersion matrices made of dried Tadalafil nanosuspensions or dried Tadalafil raw powder suspensions and PEG 4000 as a carrier were prepared by direct compression. Drying was performed via dry heat or via freeze dry. Drug release studies showed that, in general, tablet formulations made of freeze-dried product exhibited faster initial release rates than the corresponding tablets made of oven-dried products which could be attributed to possible larger crystal growth and larger crushing strengths of oven-dried formulations. At best, 60% of drug was released from solid dispersion matrices, while more than 90% of drug was released from TDTSp-OH nanosuspension within the first 5 min. In conclusion, Tadalafil nanosuspensions obtained using a mixed surfactant system provided rapid dissolution rates of Tadalafil that can theoretically enhance its bioavailability.
  • 16.

    【2hr】Application of Carrier and Plasticizer to Improve the Dissolution and Bioavailability of Poorly Water-Soluble Baicalein by Hot Melt Extrusion

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    机译 载体和增塑剂通过热熔挤出改善水溶性较差的黄ical素的溶解度和生物利用度的应用
    摘要：The objective of this study was to develop a suitable formulation for baicalein (a poorly water-soluble drug exhibiting high melting point) to prepare solid dispersions using hot melt extrusion (HME). Proper carriers and plasticizers were selected by calculating the Hansen solubility parameters, evaluating melting processing condition, and measuring the solubility of obtained melts. The characteristic of solid dispersions prepared by HME was evaluated. The dissolution performance of the extrudates was compared to the pure drug and the physical mixtures. Physicochemical properties of the extrudates were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR). Relative bioavailability after oral administration in beagle dogs was assessed. As a result, Kollidon VA64 and Eudragit EPO were selected as two carriers; Cremophor RH was used as the plasticizer. The dissolution of all the extrudates was significantly improved. DSC and PXRD results suggested that baicalein in the extrudates was amorphous. FTIR spectroscopy revealed the interaction between drug and polymers. After oral administration, the relative bioavailability of solid dispersions with VA64 and EPO was comparative, about 2.4- and 2.9-fold greater compared to the pure drug, respectively.

    Figureᅟ

  • 17.

    【2hr】Development and Validation of a Discriminative Dissolution Method for Atorvastatin Calcium Tablets using in vivo Data by LC and UV Methods

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    机译 LC和UV方法利用体内数据开发和鉴别阿托伐他汀钙片溶出度鉴别方法
    摘要：A dissolution method to analyze atorvastatin tablets using in vivo data for RP and test pilot (PB) was developed and validated. The appropriate conditions were determined after solubility tests using different media, and sink conditions were established. The conditions used were equipment paddle at 50 rpm and 900 mL of potassium phosphate buffer pH 6.0 as dissolution medium. In vivo release profiles were obtained from the bioequivalence study of RP and the generic candidate PB. The fraction of dose absorbed was calculated using the Loo–Riegelman method. It was necessary to use a scale factor of time similar to 6.0, to associate the values of absorbed fraction and dissolved fraction, obtaining an in vivo–in vitro correlation level A. The dissolution method to quantify the amount of drug dissolved was validated using high-performance liquid chromatography and ultraviolet spectrophotometry, and validated according to the USP protocol. The discriminative power of dissolution conditions was assessed using two different pilot batches of atorvastatin tablets (PA and PB) and RP. The dissolution test was validated and may be used as a discriminating method in quality control and in the development of the new formulations.
  • 18.

    【2hr】Statistical Design for Formulation Optimization of Hydrocortisone Butyrate-Loaded PLGA Nanoparticles

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    机译 丁酸氢化可的松负载PLGA纳米粒配方优化的统计设计
    摘要：The aim of this investigation was to develop hydrocortisone butyrate (HB)-loaded poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NP) with ideal encapsulation efficiency (EE), particle size, and drug loading (DL) under emulsion solvent evaporation technique utilizing various experimental statistical design modules. Experimental designs were used to investigate specific effects of independent variables during preparation of HB-loaded PLGA NP and corresponding responses in optimizing the formulation. Plackett–Burman design for independent variables was first conducted to prescreen various formulation and process variables during the development of NP. Selected primary variables were further optimized by central composite design. This process leads to an optimum formulation with desired EE, particle size, and DL. Contour plots and response surface curves display visual diagrammatic relationships between the experimental responses and input variables. The concentration of PLGA, drug, and polyvinyl alcohol and sonication time were the critical factors influencing the responses analyzed. Optimized formulation showed EE of 90.6%, particle size of 164.3 nm, and DL of 64.35%. This study demonstrates that statistical experimental design methodology can optimize the formulation and process variables to achieve favorable responses for HB-loaded NP.
  • 19.

    【2hr】Novel Self-assembly Endows Human Serum Albumin Nanoparticles with an Enhanced Antitumor Efficacy

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    机译 新型的自组装赋予人类血清白蛋白纳米颗粒增强的抗肿瘤功效。
    摘要：Protein-based nanomedicine plays an important role in tumor chemotherapy due to their merits in bioavailability, biocompatibility, biodegradability, and low toxicity. In this study, we developed a novel method of preparing human serum albumin (HSA) nanoparticles for targeted delivery of paclitaxel (PTX) to tumors. HSA-PTX nanoparticles (NPs-PTX) were fabricated via unfolding of HSA in appropriate solution to expose more hydrophobic domains and consequent self-assembling into nanoparticles with added PTX. Via this self-assembly method, a desirable particle size (around 120 nm), a high drug loading (>20%), and a high encapsulation efficiency (near 100%) were obtained. PTX dispersed as an amorphous state in NPs-PTX and the secondary structures of HSA were maintained. In a cytotoxicity study, NPs-PTX displayed an enhanced cytotoxicity in MCF-7 and A549 cells. Confocal microscopy and flow cytometry revealed that the uptake of NPs-PTX was mediated by secreted protein acidic and rich in cysteine and “caveolar” transport. In H22 tumor-bearing mice, NPs-PTX displayed an increasing and everlasting tumor distribution, leading to slower tumor growth and longer mice survival than PTX. Therefore, this novel self-assembly method offers a much easier method to prepare PTX nanoparticles, provides better antitumor efficacy in vitro and in vivo, and more importantly, sets up a delivery platform for other hydrophobic drugs to improve their effectiveness in cancer therapy.Electronic supplementary materialThe online version of this article (doi:10.1208/s12249-013-0041-3) contains supplementary material, which is available to authorized users.
  • 20.

    【2hr】Dendrimer, Liposomes, Carbon Nanotubes and PLGA Nanoparticles: One Platform Assessment of Drug Delivery Potential

    包量

    机译 树枝状大分子，脂质体，碳纳米管和PLGA纳米颗粒：药物输送潜力的一种平台评估
    摘要：Liposomes (LIP), nanoparticles (NP), dendrimers (DEN), and carbon nanotubes (CNTs), represent eminent classes of drug delivery devices. A study was carried out herewith by employing docetaxel (DTX) as model drug to assess their comparative drug delivery potentials. Under optimized conditions, highest entrapment of DTX was observed in CNT-based formulation (DTX-CNTs, 74.70 ± 4.9%) followed by nanoparticles (DTX-NP, 62.34 ± 1.5%), liposome (49.2 ± 1.51%), and dendrimers (28.26 ± 1.74%). All the formulations were found to be of nanometric size. In vitro release studies were carried out in PBS (pH 7.0 and 4.0), wherein all the formulations showed biphasic release pattern. Cytotoxicity assay in human cervical cancer SiHa cells inferred lowest IC50 value of 1,235.09 ± 41.93 nM with DTX-CNTs, followed by DTX-DEN, DTX-LIP, DTX-NP with IC50 values of 1,571.22 ± 151.27, 1,653.98 ± 72.89, 1,922.75 ± 75.15 nM, respectively. Plain DTX showed higher hemolytic toxicity of 22.48 ± 0.94%, however loading of DTX inside nanocarriers drastically reduced its hemolytic toxicity (DTX-DEN, 17.22 ± 0.48%; DTX-LIP, 4.13 ± 0.19%; DTX-NP, 6.43 ± 0.44%; DTX-CNTs, 14.87 ± 1.69%).
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