scholarly journals Development and Evaluation of Lyophilized Methotrexate Nanosuspension using Quality by Design Approach

2021 ◽  
Vol 68 (4) ◽  
pp. 861-881
Author(s):  
Trupti Powar ◽  
Ashok Hajare ◽  
Ravindra Jarag ◽  
Sopan Nangare

With the application of the quality by design (QbD) approach, a high-pressure homogenizer (HPH) methodology was employed to develop methotrexate nanosuspension (MTX-NS) to boost bioavailability. The Ishikawa diagram was used to analyze potential risk factors in formulation development. To screen and study the impact of various formulation and process factors on the critical quality attributes (CQA), the Placket–Burman design and central composite design were utilized. The number of HPH cycles, poloxamer 188 concentration, and tween 80 concentration were shown to be significant parameters (P<0.05), that were further optimized using Central Composite Design. The zeta potential of optimized lyophilized MTX-NS was determined to be –11.6 ± 7.52 mV and the average particle size was 260 ± 0.25 nm. In vitro cytotoxicity experiments revealed a greater than 80% inhibition, with apoptotic cells shrinking, fragmentation, and cell death. Furthermore, the Cmax and AUC0-t were increased by 2.53 and 8.83 folds, respectively. The relative bioavailability of MTX-NS was found to be 8.83 times higher than that of MTX-aqueous dispersion. As a result, the QbD method resulted in the development of a lyophilized MTX-NS with process understanding and control based on quality risk management.

2019 ◽  
Vol 9 (2) ◽  
pp. 148-159 ◽  
Author(s):  
Anupam Sarma ◽  
Malay K. Das

The objective of the present investigation was to optimize and develop Tenofovir Disoproxil Fumarate (TDF) loaded Nanostrucrured Lipid Carriers (NLCs) with Compritol 888 ATO as solid lipid and oleic acid as liquid lipid by modified emulsion solvent diffusion method using Central Composite design (CCD). Three independent variables viz., Lipid to Drug ratio (A), Aqueous phase pH (B) and Sonication time (min) (C) were taken to investigate their effect on dependent variables viz., particle size (nm) (R1), PDI (R2) and % Entrapment Efficiency (%EE) (R3). Optimized formula of NLC was selected from the design space which was further optimized by changing the surfactants quantity. NLCs were evaluated for physicochemical, morphological, solid state characterization, and in-vitro dissolution in PBS pH 6.4, PBS 7.4 and ACSF. The average particle size was found to be 94.7 ± 15.70 nm with PDI of 0.380 ± 0.024 and 134.3 ± 9.71 nm with PDI of 0.358 ± 0.038 respectively for T4 and T5 NLC formulation. The zeta potential value of -17. ± 3.87 mV and -17.17 ± 1.05 mV and %EE of 35.5 ± 1.04 % and 34.2 ± 2.78 %. Overall, the above finding shows promising results in the area of developing non-invasive intranasal route as an alternative to oral route for brain delivery.  Keywords: Central composite design, Intranasal, Neuro-AIDS, CNS targeting.


Nanomaterials ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 808
Author(s):  
Ahmed Al Saqr ◽  
El-Sayed Khafagy ◽  
Ahmed Alalaiwe ◽  
Mohammed F. Aldawsari ◽  
Saad M. Alshahrani ◽  
...  

Green synthesis of gold nanoparticles (GNPs) with plant extracts has gained considerable interest in the field of biomedicine. Recently, the bioreduction nature of herbal extracts has helped to synthesize spherical GNPs of different potential from gold salt. In this study, a fast ecofriendly method was adopted for the synthesis of GNPs using fresh peel (aqueous) extracts of Benincasa hispida, which acted as reducing and stabilizing agents. The biosynthesized GNPs were characterized by UV–VIS and Fourier transform infrared spectroscopy, transmission electron microscopy (TEM), and dynamic light scattering. In addition, the in vitro antibacterial and anticancer activities of synthesized GNPs were investigated. The formation of gold nanoparticles was confirmed by the existence of a sharp absorption peak at 520 nm, corresponding to the surface plasmon resonance (SPR) band of the GNPs. TEM analysis revealed that the prepared GNPs were spherical in shape and had an average particle size of 22.18 ± 2 nm. Most importantly, the synthesized GNPs exhibited considerable antibacterial activity against different Gram-positive and Gram-negative bacteria. Furthermore, the biosynthesized GNPs exerted remarkable in vitro cytotoxicity against human cervical cancer cell line, while sparing normal human primary osteoblast cells. Such cytotoxic effect was attributed to the increased production of reactive oxygen species (ROS) that contributed to the damage of HeLa cells. Collectively, peel extracts of B. hispida can be efficiently used for the synthesis of GNPs, which can be adopted as a natural source of antimicrobial and anticancer agent.


2022 ◽  
Vol 8 ◽  
Author(s):  
Ao Li ◽  
Aixia Zhu ◽  
Di Kong ◽  
Chunwei Wang ◽  
Shiping Liu ◽  
...  

For improving solubility and bioaccessibility of phytosterols (PS), phytosterol nanoparticles (PNPs) were prepared by emulsification–evaporation combined high-pressure homogenization method. The organic phase was formed with the dissolved PS and soybean lecithin (SL) in anhydrous ethanol, then mixed with soy protein isolate (SPI) solution, and homogenized into nanoparticles, followed by the evaporation of ethanol. The optimum fabrication conditions were determined as PS (1%, w/v): SL of 1:4, SPI content of 0.75% (w/v), and ethanol volume of 16 ml. PNPs were characterized to have average particle size 93.35 nm, polydispersity index (PDI) 0.179, zeta potential −29.3 mV, and encapsulation efficiency (EE) 97.3%. The impact of temperature, pH, and ionic strength on the stability of fabricated PNPs was determined. After 3-h in vitro digestion, the bioaccessibility of PS in nanoparticles reached 70.8%, significantly higher than the 18.2% of raw PS. Upon freeze-drying, the particle size of PNPs increased to 199.1 nm, resulting in a bimodal distribution. The solubility of PS in water could reach up to 2.122 mg/ml, ~155 times higher than that of raw PS. Therefore, this study contributes to the development of functional PS-food ingredients.


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Susanne R. Youngren ◽  
Rakesh K. Tekade ◽  
Brianne Gustilo ◽  
Peter R. Hoffmann ◽  
Mahavir B. Chougule

The clinical utility of siRNA therapy has been hampered due to poor cell penetration, nonspecific effects, rapid degradation, and short half-life. We herewith proposed the formulation development of STAT6 siRNA (S6S) nanotherapeutic agent by encapsulating them within gelatin nanocarriers (GNC). The prepared nanoformulation was characterized for size, charge, loading efficiency, release kinetics, stability, cytotoxicity, and gene silencing assay. The stability of S6S-GNC was also assessed under conditions of varying pH, serum level, and using electrophoretic assays.In vitrocytotoxicity performance was evaluated in human adenocarcinoma A549 cells following MTT assay. The developed formulation resulted in an average particle size, surface charge, and encapsulation efficiency as70±6.5 nm,+10±1.5 mV, and85±4.0%, respectively. S6S-GNC showed an insignificant (P<0.05) change in the size and charge in the presence of buffer solutions (pH 6.4 to 8.4) and FBS (10% v/v). A549 cells were treated with native S6S, S6S-lipofectamine, placebo-GNC, and S6S-GNC using untreated cells as a control. It was observed that cell viability was decreased significantly with S6S-GNC by55±4.1%(P<0.001) compared to native S6S (2.0±0.55%) and S6S-lipofectamine complex (40±3.1%). This investigation infers that gelatin polymer-based nanocarriers are a robust, stable, and biocompatible strategy for the delivery of siRNA.


Author(s):  
VIKAS BANSAL ◽  
ANJOO KAMBOJ ◽  
JITENDER MADAN

Objective: 5-Fluorouracil (5-FU) and celecoxib (Cel) combination offered additive effect in the treatment of colon cancer. However, physicochemical and biopharmaceutical attributes of both drugs deliver suboptimal concentration at the site of action. The objective of the current study is the development of a microparticulate drug delivery system loaded with a combination of 5-FU and Cel to achieve prolonged drug delivery in colon cancer. Methods: 5-FU and Cel combination were loaded in Eudragit coated chitosan (CH) microspheres (MSs) and characterized. Results: The average particle size of the MSs was in the range of 2.7±0.9μm to 4.8±1.1μm. A substantial drug encapsulation efficiency of 71.30±2.3% as obtained for 5-FU as compared to 35.20±1.9% of Cel in the tailored microparticles. The drug loading capacity of 6.5 mg/10 mg and 2.3 mg/10 mg was obtained for 5-FU and Cel, respectively. By Eudragit S 100 (Ed) coating, significant pH-dependent release profile was achieved, and no drug release was observed in simulated gastric and intestinal fluids. The developed MSs exhibited the release of 92.1±2.9% of 5-FU in 8h whereas 18.9±0.7% Cel was found to be released from the developed MSs. The drug-loaded MSs exhibited appreciable potency against HT-29 cells with an IC50 value of 35.9 μM. Conclusion: The results indicated that these microparticles are a promising vehicle for selectively targeting drugs to the colon in the chemotherapy of colon cancer.


Author(s):  
И.В. Бачериков ◽  
Б.М. Локштанов

При проектировании открытых и закрытых хранилищ измельченных сыпучих материалов древесных материалов, таких как щепа и опилки, большое значение имеет угол естественного откоса (статический и динамический) этих материалов. В технической литературе приводятся противоречивые сведения о величине этих углов, что приводит к ошибкам при проектировании складов. В справочных данных не учитываются условия, в которых эксплуатируются емкости для хранения сыпучих материалов, свойства и состояние этих сыпучих материалов. В свою очередь, ошибки при проектировании приводят к проблемам (зависание, сводообразование, «затопление» и т. д.) и авариям при эксплуатации бункеров и силосов на производстве. В статье представлены сведения, посвященные влиянию влажности и температуры на угол естественного откоса сыпучих материалов. На основании лабораторных и натурных экспериментов, проведенных с помощью специально разработанных методик и установок, была скорректирована формула для определения углов естественного откоса (статического и динамического) для измельченных древесных материалов в зависимости от их фракционного и породного состава, влажности (абсолютной и относительной) и температуры. При помощи скорректированной формулы можно определить угол естественного откоса древесных сыпучих материалов со среднегеометрическим размером частицы от 0,5 мм до 15 мм (от древесной пыли до технологической щепы) в различных производственных условиях. Статья может быть полезна проектировщикам при расчете угла наклона граней выпускающей воронки бункеров и силосов предприятий лесной отрасли и целлюлозо-бумажной промышленности. In the design of open and closed storage warehouses chopped wood materials for bulk materials such as wood chips and sawdust, great importance has an angle of repose (static and dynamic) of these materials. In the technical literature are conflicting reports about the magnitude of these angles, which leads to errors in the design of warehouses. In the referencesdoes not take into account the conditions under which operated capacities for storage of bulk materials, and properties and condition of the bulk material. The design errors lead to problems (hanging, arching, «flooding», etc.) and accidents in the operation of hoppers and silos at the mills. The article provides information on the impact of humidity and temperature on the angle of repose of granular materials. On the basis of laboratory and field experiments, conducted with the help of specially developed techniques and facilities has been adjusted formula for determining the angle of repose (static and dynamic) for the shredded wood materials depending on their fractional and species composition, humidity (absolute and relative) and temperature. It is possible, by using the corrected formula, to determine the angle of repose of loose wood materials with average particle size of from 0.5 mm to 15 mm (wood dust to pulpchips) in various operating conditions. The article can be helpful to designers in the calculation of the angle of inclination of the funnel faces produces bunkers and silos forest industries and pulp and paper industry.


Author(s):  
Kumar Nishchaya ◽  
Swatantra K.S. Kushwaha ◽  
Awani Kumar Rai

Background: Present malignant cancer medicines has the advancement of magnetic nanoparticles as delivery carriers to magnetically accumulate anticancer medication in malignant growth tissue. Aim: In the present investigation, a silica nanoparticles (MSNs) stacked with hydroxyurea were combined and was optimized for dependent and independent variables. Method: In this study, microporous silica nanoparticle stacked with neoplastic medication had been prepared through emulsification followed with solvent evaporation method. Prepared MSNs were optimized for dependent and independent variables. Different formulations were prepared with varying ratio of polymer, lipid and surfactant which affects drug release and kinetics of drug release pattern. The obtained MSNs were identified by FTIR, SEM, drug entrapment, in-vitro drug release, drug release kinetics study, stability testing in order to investigate the nanoparticle characteristics. Results: The percentage drug entrapment of the drug for the formulations F1, F2, F3, was found to be 27.78%, 65.52% and 48.26%. The average particle size for F2 formulation was found to be 520 nm through SEM. The cumulative drug release for the formulations F1, F2, F3 was found to be 64.17%, 71.82% and 32.68%. The formulations were found to be stable which gives controlled drug delivery for 6 hours. Conclusion: From the stability studies data it can be culminated that formulations are most stable when stored at lower temperature or in refrigerator i.e. 5˚C ± 3˚C. It can be concluded that MSN’s loaded with hydroxyurea is a promising approach towards the management of cancer due to its sustained release and less side effects.


2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Giulia Tamborino ◽  
Marijke De Saint-Hubert ◽  
Lara Struelens ◽  
Dayana C. Seoane ◽  
Eline A. M. Ruigrok ◽  
...  

2019 ◽  
Vol 829 ◽  
pp. 263-269
Author(s):  
Denny Nurdin ◽  
Andri Hardiansyah ◽  
Elsy Rahimi Chaldun ◽  
Anti Khoerul Fikkriyah ◽  
Hendra Dian Adhita Dharsono ◽  
...  

Exploration of natural compound for the treatment of dental-related problems are gaining of interest for enhancing therapeutic efficacy of the drugs delivery system. In this study, we have prepared terpenoid, which have been isolated from Myrmecodia pendens Merr & Perry from Papua Island, Indonesia, to be encapsulated in Polylactic-co-glycolic acid (PLGA), as the most widely used biodegradable polymer for biomedical applications, through one step single-emulsion method followed by subsequent coating by poly (vinyl alcohol) (PVA). The resultant of terpenoid-loaded PLGA microparticles were characterized systematically through scanning electron microscope and Fourier-transform infrared spectroscopy. In vitro drug release test was evaluated through dialysis method. Antibacterial test was conducted against Enterococcus faecalis as a model for persistent bacteria that causes root canal infections. The results showed that terpenoid-loaded PLGA microparticles were developed in spherical morphology with an average particle size of around 1-2μm. Terpenoid released from PLGA compartment at pH 6.5 and temperature of 37°C through a controlled-release profile mechanism with enhanced prolonged release. The bacterial assay result showed that terpenoid-loaded PLGA microparticles could reduce Enterococcus faecalis, effectively. Eventually, these result show that terpenoid-loaded PLGA microparticles as unique natural product-based extract could be developed as a potential naturally-based drug for dental-related diseases applications.


2007 ◽  
Vol 121-123 ◽  
pp. 1451-1454
Author(s):  
Jian Feng Chen ◽  
Guo Quan Wang ◽  
Xiao Fei Zeng ◽  
Hong Ying Zhao

Nanocomposites of nanosized-CaCO3/polypropylene-ethylene copolymer (PPE) and nanosized CaCO3/ PPE/ styrene-butadiene-styrene (SBS) were prepared by using two-roll mill and single screw extruder. The average particle size of nanosized CaCO3 was determined to be about 30 nm. By adding nanosized CaCO3 into PPE matrix, the toughness of the matrix improves significantly. At nanosized CaCO3 content of 12 phr (parts per hundred PPE resin by weight), the impact strength of CaCO3/PPE at room temperature reaches 61.6 KJ/m2, which is 3.02 times that of unfilled PPE matrix. In addition, the synergistic toughening effect of nanosized CaCO3 and SBS particles on PPE matrix was investigated.


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