Understanding the Impact of Multi-factorial Composition on Efficient Loading of the Stable Ketoprofen Nanoparticles on Orodispersible Films using Box-Behnken Design

Background: The present study deals with the formulation and optimization of piroxicam fast dissolving tablets and analyzes the impact of an independent variable while selecting the optimized formulation utilizing Quality by Design (QbD) and Box-Behnken Design (BBD). Methods: Seventeen formulations were prepared by direct compression technique by altering the proportion of cross carmellose sodium, spray dried lactose and hydro propyl methyl cellulose (HPMC K4M). The BBD statistical technique was used to optimize formulations and correlate the relationship among all the variables. Also, the powder mixture characteristics and tablet physiochemical properties such as hardness, friability, drug content, Disintegration Time (DT) and dissolution test were determined using 900 ml of 0.1N HCl (pH-1.2) at 37 ± 0.5°C. Results: Significant quadratic model and second order polynomial equations were established using BBD. To find out the relationship between variables and responses, 3D response surface and 2D contour plot was plotted. A perturbation graph was also plotted to identify the deviation of the variables from the mean point. An optimized formula was prepared based on the predicted response and the resulting responses were observed to be close with the predicted value. Conclusion: The optimized formulation with the desired parameter and formulation with variables and responses can be obtained by BBD and could be used in the large experiment with the involvement of a large number of variables and responses.

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Optimization and development of orodispersible films for ledipasvir and sofosbuvir through solid dispersion using Box-Behnken design

Research Journal of Pharmaceutical Dosage Forms and Technology ◽

10.52711/0975-4377.2021.00036 ◽

2021 ◽

pp. 201-208

Author(s):

Uday Kumar Thummala ◽

Eswar Guptha Maddi ◽

Prameela Rani Avula

Keyword(s):

Solid Dispersions ◽

Methyl Cellulose ◽

Fixed Dose ◽

Polyethylene Glycol 400 ◽

Disintegration Time ◽

Box Behnken Design ◽

Orodispersible Films ◽

Low Viscosity ◽

Dose Combination ◽

Formulation Parameters

The fixed dose combination of ledipasvir (LDV) and sofosbuvir (SBV) is approved by USFDA in 2014 for the treatment of Hepatitis C virus infection and is available in the form of tablets. In the present work, the principal aim is to explore orodispersible films type dosage form to impart its characteristic advantages to these poorly soluble drugs so as to improve their bioavailability and ease of administration. Solid dispersions with low viscosity grade methyl cellulose A 15-LV (MC A 15-LV) at different ratios with LDV and SBV were prepared and evaluated to check their ability in improving the solubility of the drugs. The best drug to polymer ratio was selected to develop the films, using other excipients including plasticizer and superdisintegrant. Solvent casting method was used to develop the films. Three formulation parameters were selected as independent factors viz. thickness of the film (50-150 µm), concentration of superdisintegrant (sodium starch glycolate 6-10%) and concentration of plasticizer (polyethylene glycol 400, 10-20%). Disintegration time (DT), time for 90% dissolution (T90%) of LDV and time for 90% dissolution of SBV were taken as the response variables. The experiment was designed using Box-Behnken design. Among the polymers, MC A 15-LV produced maximum solubility at 1:2 ratio. The films obtained were found to have good tensile strength and % elongation with disintegration times in the range of 43-162 sec. The T90% values for LDV and SDV were found to be in the range of 8.4-21.2 min and 7.2-18.4 respectively. All the three formulation factors were found to have significant effect on the three responses. The optimum formulation was identified at 100 µm thickness, 10% superdisintegrant and 20% plasticizer which showed DT of 89 sec with T90% values of 8.4 min and 7.2 min for LDV and SBV respectively. The rapid disintegration and dissolution of the films signified that the set objective was achieved.

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Formulation and Optimization of Avanafil Biodegradable Polymeric Nanoparticles: A Single-Dose Clinical Pharmacokinetic Evaluation

Pharmaceutics ◽

10.3390/pharmaceutics12060596 ◽

2020 ◽

Vol 12 (6) ◽

pp. 596

Author(s):

Hibah M. Aldawsari ◽

Usama A. Fahmy ◽

Fathy Abd-Allah ◽

Osama A. A. Ahmed

Keyword(s):

Particle Size ◽

Polymeric Nanoparticles ◽

Pde5 Inhibitor ◽

Area Under The Curve ◽

Entrapment Efficiency ◽

Pharmacokinetic Data ◽

Box Behnken Design ◽

Fast Absorption ◽

The Impact ◽

Phosphodiesterase 5

Avanafil (AVA) is a second-generation phosphodiesterase-5 (PDE5) inhibitor. AVA shows high selectivity to penile tissues and fast absorption, but has a bioavailability of about 36%. The aim was to formulate and optimize AVA-biodegradable nanoparticles (NPs) to enhance AVA bioavailability. To assess the impact of variables, the Box–Behnken design was utilized to investigate and optimize the formulation process variables: the AVA:poly (lactic-co-glycolic acid) (PLGA) ratio (w/w, X1); sonication time (min, X2); and polyvinyl alcohol (PVA) concentration (%, X3). Particle size (nm, Y1) and EE% (%, Y2) were the responses. The optimized NPs were characterized for surface morphology and permeation. Furthermore, a single-oral dose (50 mg AVA) pharmacokinetic investigation on healthy volunteers was carried out. Statistical analysis revealed that all the investigated factors exhibited a significant effect on the particle size. Furthermore, the entrapment efficiency (Y2) was significantly affected by both the AVA:PLGA ratio (X1) and PVA concentration (X3). Pharmacokinetic data showed a significant increase in the area under the curve (1.68 folds) and plasma maximum concentration (1.3-fold) for the AVA NPs when compared with raw AVA. The optimization and formulation of AVA as biodegradable NPs prepared using solvent evaporation (SE) proves a successful way to enhance AVA bioavailability.

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PREPARATION OF ORAL CURCUMIN DELIVERY FROM 3D-NANO-CELLULOSE NETWORKS MATERIAL PRODUCED BY ACETOBACTER XYLINUM USING OPTIMIZATION TECHNIQUE

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2020v12i2.36627 ◽

2020 ◽

pp. 47-52

Author(s):

THANH XUAN NGUYEN ◽

HUONG LAN THI PHAM ◽

THUONG THI NGO ◽

PHONG XUAN ONG

Keyword(s):

Oral Delivery ◽

Positive Impact ◽

Optimization Technique ◽

Box Behnken Design ◽

Independent Variables ◽

3D Network ◽

Nano Cellulose ◽

Optimized Conditions ◽

The Impact

Objective: To prepare oral curcumin delivery and optimize curcumin loading of 3D-nano-cellulose networks material (3DCM) by looking into the impact of process variables on the response utilizing response surface methodology (RSM) and Box-Behnken design. Methods: Optimization of curcumin loading of 3DCM was conducted using RSM and Box-Behnken model. Impact of four independent variables, including, the concentration of curcumin (X1), temperature (X2), shaking speed (X3), and time of loading (X4), was studied on one dependent response, that is, an amount of loaded curcumin (Y). Characterization of optimized 3DCM including curcumin was examined by Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) analysis . Results: R2 value for Y was approximately 0.94. X1 possessed the biggest positive impact compared to X2, X3 and X4. Optimized conditions for curcumin loading of 3DCM were X1 at 3 mg/ml, X2 at 40 °C, X3 at 120 rpm and X4 at 120 min. SEM photograph of 3DCM surfaces were found including fibers creating a 3D network structure. FTIR spectra studies depicted that there was no interaction between curcumin and 3DCM. Conclusion: The data obtained in this study thus suggest that curcumin loaded 3DCM was successfully fabricated to give a potential oral delivery system of curcumin.

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The Impact of the Preparation Method on the Properties of Orodispersible Films with Aripiprazole: Electrospinning vs. Casting and 3D Printing Methods

Pharmaceutics ◽

10.3390/pharmaceutics13081122 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1122

Author(s):

Ewelina Łyszczarz ◽

Witold Brniak ◽

Joanna Szafraniec-Szczęsny ◽

Tomasz Mariusz Majka ◽

Dorota Majda ◽

...

Keyword(s):

Mechanical Properties ◽

3D Printing ◽

Microscopic Analysis ◽

Storage Condition ◽

Stability Studies ◽

Disintegration Time ◽

Manufacturing Method ◽

Orodispersible Films ◽

Swallowing Problems ◽

The Impact

Orodispersible films (ODFs) address the needs of pediatric and geriatric patients and people with swallowing difficulties due to fast disintegration in the mouth. Typically, they are obtained using the solvent casting method, but other techniques such as 3D printing and electrospinning have already been investigated. The decision on the manufacturing method is of crucial importance because it affects film properties. This study aimed to compare electrospun ODFs containing aripiprazole and polyvinyl alcohol with films prepared using casting and 3D printing methods. Characterization of films included DSC and XRD analysis, microscopic analysis, the assessment of mechanical parameters, disintegration, and dissolution tests. Simplified stability studies were performed after one month of storage. All prepared films met acceptance criteria for mechanical properties. Electrospun ODFs disintegrated in 1.0 s, which was much less than in the case of other films. Stability studies have shown the sensitivity of electrospun films to the storage condition resulting in partial recrystallization of ARP. These changes negatively affected the dissolution rate, but mechanical properties and disintegration time remained at a desirable level. The results demonstrated that electrospun fibers are promising solutions that can be used in the future for the treatment of patients with swallowing problems.

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Optimization of process parameters for the green synthesis of silver nanoparticles using Plackett-Burman and 3-level Box–Behnken Design

10.21203/rs.3.rs-72146/v1 ◽

2020 ◽

Author(s):

Halima R ◽

Archna Narula ◽

R.R Sivakiran

Keyword(s):

Silver Nanoparticles ◽

Green Synthesis ◽

Silver Nitrate ◽

Plant Extract ◽

Piper Betle ◽

Experimental Conditions ◽

Box Behnken Design ◽

Synthesis Of Nanoparticles ◽

Optimization Parameters ◽

The Impact

Abstract Background: The present work describes the synthesis of silver nanoparticles (AgNps) from leaf extracts of Piper betle and Jatropha curcas using a green approach. Green synthesis of nanoparticle is superior over other methods of synthesis as it is ecofriendly and cost effective. The phytochemical components in the leaf extract play a vital role in reducing the AgNO3 and hence synthesizing the silver nanoparticles. During this reduction activity, the several factors which affect the synthesis of nanoparticles were investigated and optimized according to the yield of nanoparticles. The experimental conditions investigated were pH, temperature, pressure, time of reaction, microwave radiation, UV radiation and concentration of plant extract, silver nitrate & sunlight. Satisfactory yields of silver nanoparticles synthesis from plant extract were obtained by using optimum conditions when compared to conventional synthesis of nanoparticles. The optimization parameter was later Result: A mathematical model was formulated to correlate the interactive influence of the parameters and the significant reduction. Plackett-Burman design (PBD) indicated that concentration of plant extract, concentration of silver nitrate and sunlight were the major parameters affecting the synthesis of silver nanoparticle. The mutual interactions of these variables are mapped in the design by 3 Box-Behnken design (BBD). The significant factors and their interactions in the green synthesis were examined by analysis of Variance (ANOVA). The result indicated that the BBD was a good predictive model for the experimental results. Though the plant extracts are different, the characterization of the synthesized nanoparticle after optimization of parameters showed uniform size and shape i.e. spherical shape and size of 41 nm. Conclusion: The silver nanoparticles were synthesized under different optimization parameters were uniformly shaped (spherical) and sized (41 nm) particles. The mathematical models Plackett-Burman and Box-Behnken helped in analyzing the impact of the optimization parameters.

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A composite endpoint for acceptability evaluation of oral drug formulations in the pediatric population

10.1101/2021.08.20.21262333 ◽

2021 ◽

Author(s):

Manfred Wargenau ◽

Sibylle Reidemeister ◽

Ingrid Klingmann ◽

Viviane Klingmann

Keyword(s):

Assessment Tool ◽

Pediatric Population ◽

Age Groups ◽

Composite Endpoint ◽

Oral Drug ◽

Orodispersible Films ◽

Fda Guidance ◽

Oral Formulations ◽

Definition Of ◽

The Impact

Introduction: A medicine's acceptability is likely to have significant impact on pediatric compliance. EMA and FDA guidance on this topic ask for investigation of acceptability. Although palatability and deglutition are denoted as elements of acceptability, the impact of both on acceptability remains unclear as an unambiguous definition of acceptability is lacking. Actually, globally applied standards for acceptability definition, testing methodology and assessment criteria do not exist. A definition of acceptability establishing a composite endpoint that combines deglutition and palatability in different age groups is presented here. Methods: This composite acceptability endpoint is based on validated assessment methods for deglutition and palatability in children of different age groups with different galenic placebo formulations, in line with criteria EMA proposed for assessing acceptability in children from newborn to 18 years. Data from two studies investigating mini-tablets, oblong tablets, orodispersible films and syrup were used to investigate the validity, expediency and applicability of the suggested composite acceptability assessment tool. Results: The new composite endpoint is highly suitable and efficient to distinguish preferences of oral formulations: Mini-tablets and oblong tablets were significantly better accepted than syrup and orodispersible film. Conclusion: Since the suggested acceptability criterion takes both deglutition and palatability into account as composite endpoint, it is highly sensitive to detect acceptability differences between oral formulations. It is a well-defined, valid approach, which particularly meets regulatory requirements in an appropriate and comprehensive manner and may in future serve as an easy, standardized method to assess and compare acceptability of pediatric formulations with active substances.

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Dendritic cell-induced apoptosis of human cytomegalovirus-infected fibroblasts promotes cross-presentation of pp65 to CD8+ T cells

Journal of General Virology ◽

10.1099/vir.0.83278-0 ◽

2008 ◽

Vol 89 (1) ◽

pp. 78-86 ◽

Cited By ~ 19

Author(s):

Marie Mandron ◽

Hélène Martin ◽

Béatrice Bonjean ◽

Jacqueline Lulé ◽

Eric Tartour ◽

...

Keyword(s):

T Cells ◽

Human Cytomegalovirus ◽

Antigen Processing ◽

Early Stage ◽

Present Report ◽

Necrosis Factor Alpha ◽

Cross Presentation ◽

Induced Apoptosis ◽

Efficient Loading ◽

The Impact

An efficient host response to human cytomegalovirus (HCMV) infection may depend on rapid sensing of the infection by the innate immune response prior to deployment of viral immunosubversive functions. Control of HCMV dissemination could be ensured by apoptosis of cells immediately following infection. In the present report, it is demonstrated that changes in the ratio of c-FLIP to FLICE contributed to early sensitivity of HCMV-infected MRC5 fibroblasts to tumour necrosis factor alpha (TNF-α), providing an innate response to infection. Dendritic cells (DCs) co-cultured with HCMV-infected MRC5 cells acquired the ability to secrete TNF-α in an amount sufficient to kill infected fibroblasts. Blockage of TNF-α binding to its receptor on MRC5 cells with soluble TNF-R reduced the number of dead, HCMV-infected fibroblasts ingested by DCs, thus highlighting the impact of the apoptotic state of infected cells for efficient loading of DCs. Those DCs loaded with antigens available early in infection, such as input virion-associated pp65, could then engage antigen processing for cross-presentation to specific CD8+ T cells. Cross-presentation was impaired when MRC5 cells were treated with the pan-caspase inhibitor ZVAD before co-culture with DCs. Altogether, our data suggest that the innate killing capacity of DCs at the early stage of infection plays a role in the activation of anti-HCMV CD8+ T cells.

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Applying Box–Behnken Design for Formulation and Optimization of PLGA-Coffee Nanoparticles and Detecting Enhanced Antioxidant and Anticancer Activities

Polymers ◽

10.3390/polym14010144 ◽

2021 ◽

Vol 14 (1) ◽

pp. 144

Author(s):

Nouran S. Sharaf ◽

Amro Shetta ◽

Jailan E. Elhalawani ◽

Wael Mamdouh

Keyword(s):

Particle Size ◽

In Vitro Release ◽

Physicochemical Characteristics ◽

Plga Nanoparticles ◽

Anticancer Activities ◽

Particle Size Reduction ◽

Box Behnken Design ◽

Surface Stability ◽

The Impact

In an attempt to prove biological activity enhancement upon particle size reduction to the nanoscale, coffee (Cf) was chosen to be formulated into poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) using the single emulsion-solvent evaporation (SE-SE) method via Box–Behnken Design (BBD) to study the impact of certain process and formulation parameters on the particle size and size homogeneity, surface stability and encapsulation efficiency (EE%). The coffee-loaded PLGA (PLGA-Cf) NPs were characterized by different methods to aid in selecting the optimum formulation conditions. The desirable physicochemical characteristics involved small particle sizes with an average of 318.60 ± 5.65 nm, uniformly distributed within a narrow range (PDI of 0.074 ± 0.015), with considerable stability (Zeta Potential of −20.50 ± 0.52 mV) and the highest EE% (85.92 ± 4.01%). The antioxidant and anticancer activities of plain PLGA NPs, pure Cf and the optimum PLGA-Cf NPs, were evaluated using 2,2-Diphenyl-1-picryl-hydrazyl (DPPH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. As a result of nano-encapsulation, antioxidant activity was enhanced by 26.5%. Encapsulated Cf showed higher anticancer potency than pure Cf against different cancerous cell lines with an increase of 86.78%, 78.17%, 85.84% and 84.84% against MCF-7, A-549, HeLa and HepG-2, respectively. The in vitro release followed the Weibull release model with slow and biphasic release profile in both tested pH media, 7.4 and 5.5.

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A Study that Optimizate Reactive Brilliant Orange X-GN of CuO-CeO2/γ-Al2O3 under Oxidizing Conditions Based on Response Surface Methodology

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.955-959.3 ◽

2014 ◽

Vol 955-959 ◽

pp. 3-6

Author(s):

Fu Chen Ban ◽

Ya Ling Jiang ◽

Xiao Tong Zhao ◽

Xue Han

Keyword(s):

Response Surface ◽

Ph Value ◽

Cell Voltage ◽

Operating Conditions ◽

Optimum Operating ◽

Optimization Analysis ◽

Box Behnken Design ◽

Decolorization Rate ◽

Response Surface Optimization ◽

The Impact

To determine the reactive brilliant orange X-GN by CuO-CeO2/γ-Al2O3 optimum operating conditions.Under oxidizing conditions by CuO-CeO2/γ-Al2O3 that based on Box-Behnken Design,s response surface optimization analysis and establish model.The optimum operating conditions for cell voltage is 17.84V, pH is 7.0 ,concentration of electrolyte dosing is 966mg/L.Under this condition, the decolorization rate up to 95.5%,the impact of various factors on the size of decolorization rate is cell voltage>pH > concentration of electrolyte dosing ;the impact of the interaction between the factors various factors on the size of decolorization rate is cell voltage & pH value> cell voltage & concentration of electrolyte dosing>pH value & concentration of electrolyte dosing .

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