Full-factorial design for statistical planning of attritor milling parameters and evaluation of effects on particle size and structure of sodium-montmorillonite

The main aim of the present study is to improve the dissolution rate of Raloxifene Hydrochloride by formulating nanostructured lipid carriers (NLC) using Quality by Design (QbD) approach. The formulations of NLC-RH were prepared by the ultrasonication method using stearic acid as solid lipid, medium-chain triglyceride as the liquid lipid and polysorbate 80 as the surface-active agent. Two most critical quality attributes (CQAs) for NLC-RH were particle size and entrapment efficiency. The other attributes of medium influence identified includes dissolution rate, zeta potential and particle size didtribution. The Critical Material Attributes (CMAs) identified were solid lipid/liquid lipid ratio and surfactant concentration. The time required for ultrasonication was selected as a Critical Process Parameter (CPP). The 23 full factorial design was used to evaluate the relationship between the CMAs and CPPs variable. Based on the experiments, the composition of the optimal formulation is achieved with solid lipid/liquid lipid ratio of 7:3 and 7 % of surfactant concentration with 15 min of ultrasonication time. The optimized formulation of NLC-RH was found to be with a mean particle size of 146 nm with narrow particle size distributions. From the above results, it is concluded that a promising Raloxifene HCl loaded NLC could give a novel and potential therapy for osteoporosis.

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OPTIMIZATION AND CHARACTERIZATION OF PEG-PCL-PEG TRIBLOCK COPOLYMER AS CARRIER OF DRUG USING FULL FACTORIAL DESIGN

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2019v11i5.35706 ◽

2019 ◽

pp. 65-71 ◽

Cited By ~ 1

Author(s):

ZYNOPSICHA ARMATAZAKA ◽

T. N. SAIFULLAH SULAIMAN ◽

ABDUL KARIM ZULKARNAIN

Keyword(s):

Particle Size ◽

Ethylene Glycol ◽

Factorial Design ◽

Triblock Copolymer ◽

Full Factorial Design ◽

Drug Solubility ◽

Poly Ethylene Glycol ◽

Poly Ethylene ◽

Optimum Formula ◽

Full Factorial

Objective: Triblock copolymer of poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) was applicated as hydrophobic drug. This study aims to optimization and characterization of PECE triblock copolymer as carriers of hydrophobic drug (ketoprofen). Methods: Triblock copolymer of PECE was prepared with varying composition ratio of PEG and PCL by ring-opening and coupling reaction. The characteristics of triblock copolymer were characterized using FTIR and DSC. Variation composition ratio of poly(ɛ-caprolactone) (PCL)/poly(ethylene glycol) (PEG) and ratio PECE/drug as factors for optimization using full factorial design. Ketoprofen was loaded into PECE triblock copolymer micelles by emulsification and solvent evaporation method. Responses were measured particle size, entrapment efficiency (EE) and drug solubility. Results: The result of this study showed that a higher ratio of PCL/PEG and ratio of PECE/drug, reducing particle size, increasing EE and improving drug solubility. The optimum formula obtained by ratio of PCL/PEG is 2:1 and ratio of PECE/drug is 40:1 with particle size is 356,967±9,142 nm, EE is 57,751±0,437%, drug solubility is 32,648±0,200 µg/ml and zeta potential-18,867±2,578 mV. A full factorial design was applied to determine the optimum formula for the PECE triblock copolymer as drug carriers. Conclusion: The PECE triblock copolymer was preparated using ring-opening polymerization method with Sn(Oct)2 as a catalyst and then continued the reaction with HMDI as coupling agent. Ketoprofen was loaded into PECE triblock copolymer using methods emulsification and solvent evaporation.

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A 32 FULL FACTORIAL DESIGN FOR TOPICAL CONTROLLED RELEASETAZAROTENE MICROSPONGE USING HPMC GEL

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2019v11i5.34496 ◽

2019 ◽

pp. 12-18

Author(s):

NISHANT OZA ◽

SATYAJIT SAHOO ◽

SWATI SAGAR

Keyword(s):

Particle Size ◽

Regression Analysis ◽

Drug Release ◽

Factorial Design ◽

Full Factorial Design ◽

Diffusion Method ◽

Ft Ir ◽

Time Required ◽

Full Factorial ◽

32 Full Factorial Design

Objective: The aim of present work was to the development of control release 0.1% tazarotene microsponge and incorporated into a HPMC K-100M gel. Methods: Drug compatibility with polymer was evaluated by FT-IR spectrum. Tazarotene microsponge was prepared by quasi-emulsion solvent diffusion method. On the basis of preliminary results, 32 full factorial design was employed to study the effect of Eudragit RS-100 conc. (X1) and PVA conc. (X2) on as particle size (Y1), % drug entrapment (Y2) and time required to 80% drug release (Y3). Multiple linear regression analysis, ANOVA and graphical representation of the influence factor by 3D plots were performed by using Sigma plot 11.0. In this study, the following constraints were arbitrarily used for the selection of an optimized batch: particle size<200 µm, drug entrapment>70 %, and time required to 80% drug release>360 min. The optimized formulation was subjected to SEM study. Tazarotene microsponge incorporates in 3% HPMC K-100M gel evaluated for viscosity, pH, drug content, spreadability, In vitro diffusion study, release kinetic study and photostability study. Results: The FT-IR result showed that there was no chemical interaction and SEM photograph indicates that microsponges are spherical and pores. From the results of multiple regression analysis, it was found that all factors had a statistically significant influence on all dependent variables. Conclusion: The optimized formulation of gel release kinetics having good linearity (R2= 0.987) of zero-order kinetic and it was found to be stable in the stability evaluation.

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A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design

Polymers ◽

10.3390/polym12040772 ◽

2020 ◽

Vol 12 (4) ◽

pp. 772 ◽

Cited By ~ 2

Author(s):

Hazem Abdul Kader Sabbagh ◽

Samer Hasan Hussein-Al-Ali ◽

Mohd Zobir Hussein ◽

Zead Abudayeh ◽

Rami Ayoub ◽

...

Keyword(s):

Particle Size ◽

Zeta Potential ◽

Factorial Design ◽

Drug Loading ◽

Spherical Shape ◽

Full Factorial Design ◽

Gravimetric Analysis ◽

Loading Efficiency ◽

Full Factorial

The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (21 × 31 × 21) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl2) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl2 concentrations, whereas zeta potential depends only on the Alg and CaCl2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (−9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm−1, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model (R2 between 0.956–0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.

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RIZATRIPTAN BENZOATE LOADED NATURAL POLYSACCHARIDE BASED MICROSPHERES FOR NASAL DRUG DELIVERY SYSTEM

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2018v10i5.27877 ◽

2018 ◽

Vol 10 (5) ◽

pp. 261

Author(s):

Meenakshi Sharma ◽

Nitin Sharma ◽

Anjana Sharma

Keyword(s):

Drug Delivery ◽

Particle Size ◽

Factorial Design ◽

Entrapment Efficiency ◽

Full Factorial Design ◽

Nasal Drug Delivery ◽

Rizatriptan Benzoate ◽

Trigonella Foenum Graecum ◽

Full Factorial ◽

32 Full Factorial Design

Objective: The objective of this research was to formulate and evaluate the different grades of rizatriptan benzoate loaded polysaccharide based microspheres for the nasal drug delivery system.Methods: The polysaccharide was extracted from the seed of Trigonella foenum-graecum and microspheres were prepared by emulsification, followed by crosslinking using epichlorohydrin. A 32 full factorial design was employed in formulating the microspheres with polymer concentration (X1), and stirring rate (X2) as independent variables and particle size (Y1) and entrapment efficiency (Y2) were dependent variables.Results: The microspheres were discrete and free-flowing. The mean particle size (Y1) of microspheres ranged from 40.82+12 µm to 62.48+0.41 µm and the encapsulation efficiency (Y2) was found to be increased from 60.7+0.2% to 79.22+0.2% as the drug polysaccharide ratio increased. A 32 full factorial design confirmed that the X1 and X2 both effect on particle size whereas X1 alone effect on entrapment efficiency. SEM revealed the smooth spherical surface of microspheres whereas kinetic model revealed that drug release followed the case II transport. FTIR indicated good compatibility of the excipients with rizatriptan benzoate. Stability studies were carried out for formulation F7 at 4°C ambient, 25+2°C/60+5%, 40+2°C/75+5% relative humidity revealed that the physical drug appearance, entrapment efficiency were within the permissible limits.Conclusion: The result obtained in this research work indicate a promising potential of control release rizatriptan benzoate loaded microspheres whereas the Trigonella foenum-graecum polysaccharide used as rate controlling polymer for the effective treatment of migraine patients.

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Clay Ceramic Support Membrane Optimization Using Factorial Design Approach

Journal of Applied Membrane Science & Technology ◽

10.11113/amst.v25n3.208 ◽

2021 ◽

Vol 25 (3) ◽

pp. 1-15

Author(s):

M. Ait Baih ◽

N. Saffaj ◽

A. Bakka ◽

R. Mamouni ◽

N. El baraka ◽

...

Keyword(s):

Particle Size ◽

Mechanical Strength ◽

Factorial Design ◽

Heating Rate ◽

Sintering Temperature ◽

Full Factorial Design ◽

Ceramic Support ◽

Negative Effect ◽

Full Factorial ◽

Positive Effect

In the present study, the effect of Sintering temperature, Particle size and Heating rate of the ceramic support membrane Elaboration based on dry clay were evaluated using full factorial design and investigated by porosity and mechanical strength measures. The flat supports have been prepared from 5 g of the material with a two fraction 2 and 30 µm, the extrusion was performed using the uniaxial pressing in applicant a pressure of 12 tones, the supports sintered between 900° C and 1200°C with a different heating rate (1°C/min and 10°C/min). By using full factorial design 23, it was found that the sintering temperature is the main controlling factors of the physical properties of dry ceramic support membrane, and its increase had a positive effect on Mechanical strength and negative effect on porosity. The interactions between the factors were relatively less important, and they had different (antagonistic/synergetic) influence on the properties. The optimal factors to elaborate the support membrane include a particle size of 2 µm, sintering temperature of 950°C, Heating rate of 1°C predicting the porosity of 40, 8% and Mechanical strength of 12 MPa.

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Development and Optimization of Inhalable Levofloxacin Nanoparticles for The Treatment of Tuberculosis.

Current Drug Delivery ◽

10.2174/1567201817999201103194626 ◽

2020 ◽

Vol 17 ◽

Author(s):

Sunny Shah ◽

Rohit Ghetiya ◽

Moinuddin Soniwala ◽

Jayant Chavda

Keyword(s):

Particle Size ◽

Drug Release ◽

Factorial Design ◽

Full Factorial Design ◽

Pareto Chart ◽

Mean Particle Size ◽

Screening Design ◽

The Mean ◽

Full Factorial ◽

32 Full Factorial Design

Background:: Levofloxacin has been recommended by WHO for the treatment of pulmonary tuberculosis and inhalable delivery of levofloxacin can be advantageous over conventional delivery. Objective:: This study aimed to develop and optimize inhalable levofloxacin loaded chitosan nanoparticles (LCN). The objective was to achieve the mean particle size of LCN less than 300nm, sustain the drug release up to 24 h and achieve MMAD of LCN of less than 5μm. Methods:: LCN were prepared by ionic gelation of chitosan with sodium tripolyphosphate (STPP) and subsequent lyophilization. A Plackett Burman screening design, 32 full factorial design, and overlay plot were sequentially employed to optimize the formulation. The mean particle size, % entrapment efficiency, in vitro drug release, and Minimum inhibitory concentration were evaluated. Results:: The Pareto chart from Placket Burman screening design revealed that the concentration of chitosan and concentration of STPP were found to be significant (p < 0.05). Further analysis by 32 full factorial design revealed that F-ratio for each model generated was found to be greater than the theoretical value (p < 0.05), confirming the significance of each model. Conclusion:: The optimized formulation showed a mean particle size of 171.5 nm, sustained the drug release up to 24 h in simulated lung fluid, and revealed MMAD of 3.18 μm, which can confirm delivery of the drug to deep lung region. However, further in vivo studies are required to design suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery of the drug.

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Application of 32 Full Factorial Design and Desirability Function for Optimizing The Manufacturing Process for Directly Compressible Multi-Functional Co-Processed Excipient

Current Drug Delivery ◽

10.2174/1567201817666200508094743 ◽

2020 ◽

Vol 17 (6) ◽

pp. 523-539

Author(s):

Jalpa Patel ◽

Dhaval Mori

Keyword(s):

Factorial Design ◽

Spray Drying ◽

Desirability Function ◽

Full Factorial Design ◽

Angle Of Repose ◽

P Value ◽

Independent Variables ◽

Full Factorial ◽

32 Full Factorial Design ◽

Response Variables

Background: Developing a new excipient and obtaining its market approval is an expensive, time-consuming and complex process. Compared to that, the co-processing of already approved excipients has emerged as a more attractive option for bringing better characteristic excipients to the market. The application of the Design of Experiments (DoE) approach for developing co-processed excipient can make the entire process cost-effective and rapid. Objective: The aim of the present investigation was to demonstrate the applicability of the DoE approach, especially 32 full factorial design, to develop a multi-functional co-processed excipient for the direct compression of model drug - cefixime trihydrate using spray drying technique. Methods: The preliminary studies proved the significant effect of atomization pressure (X1) and polymer ratio (microcrystalline cellulose: mannitol - X2) on critical product characteristics, so they were selected as independent variables. The angle of repose, Carr’s index, Hausner’s ratio, tensile strength and Kuno’s constant were selected as response variables. Result: The statistical analysis proved a significant effect of both independent variables on all response variables with a significant p-value < 0.05. The desirability function available in Design Expert 11® software was used to prepare and select the optimized batch. The prepared co-processed excipient had better compressibility than individual excipients and their physical mixture and was able to accommodate more than 40 percent drug without compromising the flow property and compressibility. Conclusion: The present investigation successfully proved the applicability of 32 full factorial design as an effective tool for optimizing the spray drying process to prepare a multi-functional co-processed excipient.

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Formulation of Extended-Release Beads of Lamotrigine Based on Alginate and Cassia fistula Seed Gum by QbD Approach

Current Drug Delivery ◽

10.2174/1567201817666200317124022 ◽

2020 ◽

Vol 17 (5) ◽

pp. 422-437

Author(s):

Dixita Jain ◽

Akshay Sodani ◽

Swapnanil Ray ◽

Pranab Ghosh ◽

Gouranga Nandi

Keyword(s):

Drug Release ◽

Factorial Design ◽

Extended Release ◽

Polymer Concentration ◽

Green Manufacturing ◽

Full Factorial Design ◽

Cassia Fistula ◽

Negative Environmental Impact ◽

Seed Gum ◽

Full Factorial

Aim: This study was focused on the formulation of the multi-unit extended-release peroral delivery device of lamotrigine for better management of epilepsy. Background: The single-unit extended-release peroral preparations often suffer from all-or-none effect. A significant number of multi-unit delivery systems have been reported as a solution to this problem. But most of them are found to be composed of synthetic, semi-synthetic or their combination having physiological toxicity as well as negative environmental impact. Therefore, fabrication and formulation of multi-unit extended-release peroral preparations with natural, non-toxic, biodegradable polymers employing green manufacturing processes are being appreciated worldwide. Objective: Lamotrigine-loaded extended-release multi-unit beads have been fabricated with the incorporation of a natural polysaccharide Cassia fistula seed gum in calcium-cross-linked alginate matrix employing a simple green process and 23 full factorial design. Methods: The total polymer concentration, polymer ratio and [CaCl2] were considered as independent formulation variables with two different levels of each for the experiment-design. The extended-release beads were then prepared by the ionotropic gelation method using calcium chloride as the crosslinkerions provider. The beads were then evaluated for drug encapsulation efficiency and drug release. ANOVA of all the dependent variables such as DEE, cumulative % drug release at 2h, 5h, 12h, rate constant and dissolution similarity factor (f2) was done by 23 full factorial design using Design-Expert software along with numerical optimization of the independent variables in order to meet USP-reference release profile. Results: The optimized batch showed excellent outcomes with DEE of 84.7 ± 2.7 (%), CPR2h of 8.41± 2.96 (%), CPR5h of 36.8± 4.7 (%), CPR12h of 87.3 ± 3.64 (%) and f2 of 65.9. Conclusion: This approach of the development of multi-unit oral devices utilizing natural polysaccharides might be inspiring towards the world-wide effort for green manufacturing of sustained-release drug products by the QbD route.

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