OPTIMIZATION OF PCL-PEG-PCL TRIBLOCK COPOLYMER MICELLES AS HYDROPHOBIC DRUG CARRIER WITH A 22 FULL FACTORIAL DESIGN

Objective: This study aims to optimize PCL-PEG-PCL (PCEC) triblock copolymer micelles as a hydrophobic drug carrier, simvastatin (SV). Methods: PCEC triblock copolymer was prepared by the ring-opening polymerization method (ROP) with different ɛCL/PEG ratio (2 and 5). SV was incorporated into the PCEC triblock copolymer micelles with a concentration of 2.5 and 10 % w/w by the solvent evaporation method (film formation). The influence of the ɛCL/PEG ratio and concentration of SV effect on the responses particle size (PS), polydispersity index (PI) and entrapment efficiency (EE) was assessed using 22 full factorial design method. The test results were analyzed using Design-Expert software to obtain the optimum formula. Result: The selection of the optimum formula is based on the desirability value, the formula with the largest desirability value is chosen as the optimum formula. The results showed the optimum formula chosen had a desirability value of 0.860 consisting of a ɛCL/PEG ratio of 5 and SV concentration of 10 % w/w, with the PS, PI dan EE value was 322.1±3.51 nm, 0.471±0.09 and 87.08±1.17 %, respectively. Conclusion: The 22 full factorial design has been proven to be used as an optimization method to determine the optimum formula of SV-loaded PCEC triblock copolymer micelles with a good result of the PS, PI and EE responses.

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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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SYNTHESIS, CHARACTERIZATION, AND OPTIMIZATION OF BIODEGRADABLE PCL-PEG-PCL TRIBLOCK COPOLIMERIC MICELLES AS NANOCARRIERS FOR HYDROPHOBIC DRUG SOLUBILITY ENHANCER

International Journal of Current Pharmaceutical Research ◽

10.22159/ijcpr.2020v12i2.37478 ◽

2020 ◽

pp. 6-10

Author(s):

JEFRI PRASETYO ◽

TEUKU NANDA SAIFULLAH SULAIMAN ◽

ENDANG LUKITANINGSIH

Keyword(s):

Particle Size ◽

Factorial Design ◽

Design Method ◽

Triblock Copolymers ◽

Entrapment Efficiency ◽

Optimization Method ◽

Polydispersity Index ◽

Drug Solubility ◽

Hydrophobic Drug ◽

Optimum Formula

Objective: This study aims to synthesize, characterize, and optimize biodegradable polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolimeric micelles as a nanocarrier for hydrophobic drug solubility enhancer of ketoprofen (K). Methods: PCL-PEG-PCL (PCEC) triblock copolymers was obtained from the synthesis of ɛ-caprolactone (ɛ-CL) and PEG by ring opening polymerization (ROP) method at different PCL: PEG ratio (2-5:1). The K-loaded PCEC triblock copolymeric micelles was obtained by solvent evaporation method. Optimization of PCEC triblock copolymers and analysis of the effect of PCL: PEG ratio factors on the responses toward particle size (PS), polydispersity index (PdI), and entrapment efficiency (EE), were carried out through the design of experiments (DoE) approach of the 22 full factorial design method using the Design-Expert software to obtain the optimum formula. Results: The higher the PCL: PEG ratio, the ZP value tends to be smaller while the PS, PdI, EE, and drug solubility may be increased, but the addition of hydrophobic blocks to some extent does not affect the EE and drug solubility. The optimum K-loaded PCEC triblock copolymeric micelles with a PCL: PEG 2.0:1 ratio has a zeta potential (ZP) of-24.07±0.35 mV, the particle size of 235.70±6.03 nm, polydispersity index of 0.30±0.06, entrapment efficiency of 87.08±0.06%, and the solubility of the K increases by 10.60 times. Conclusion: The 22full factorial design has been proven to be the suitable optimization method to determine the optimum condition that yields to the optimum results of the PS, PdI, and EE of the of the K-loaded PCEC triblock copolymer micelles.

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Effect of The Surfactant and Liquid Lipid Type in The Physico-chemical Characteristics of Beeswax-based Nanostructured Lipid Carrier (NLC) of Metformin

Pharmaceutical Nanotechnology ◽

10.2174/2211738509666210222143716 ◽

2021 ◽

Vol 09 ◽

Author(s):

Mona Qushawy

Keyword(s):

Drug Release ◽

Factorial Design ◽

Biological Membrane ◽

Entrapment Efficiency ◽

Tween 80 ◽

Full Factorial Design ◽

Nanostructured Lipid Carrier ◽

Class Iii ◽

Scanning Calorimetry ◽

Full Factorial

Background: Metformin (MF) is an antidiabetic drug that belongs to class III of the biopharmaceutical classification system (BCS) which is characterized by high solubility and low permeability. Objective: The study aimed to prepare metformin as nanostructured lipid carriers (MF-NLCs) to control the drug release and enhance its permeability through the biological membrane. Method: 22 full factorial design was used to make the design of MF-NLCs formulations. MF-NLCs were prepared by hot-melt homogenization-ultra sonication technique using beeswax as solid lipid in presence of liquid lipid (either capryol 90 or oleic acid) and surfactant (either poloxamer 188 or tween 80). Results: The entrapment efficiency (EE%) of MF-NLCs was ranged from 85.2±2.5 to 96.5±1.8%. The particle size was in the nanoscale (134.6±4.1 to 264.1±4.6 nm). The value of zeta potential has a negative value ranged from -25.6±1.1 to -39.4±0.9 mV. The PDI value was in the range of (0.253±0.01 to 0.496±0.02). The cumulative drug release was calculated for MF-NLCs and it was found that Q12h ranged from 90.5±1.7 % for MF-NLC1 to 99.3±2.8 for MF-NLC4. Infra-red (IR) spectroscopy and differential scanning calorimetry (DSC) studies revealed the compatibility of the drug with other ingredients. MF-NLC4 was found to the optimized formulation with the best responses. Conclusion: 22 full factorial design succeed to obtain an optimized formulation which controls the drug release and increases the drug penetration.

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DEVELOPMENT AND EVALUATION OF FLOATING TABLET CONTAINING NEVIRAPINE USING A 32 FULL FACTORIAL DESIGN OPTIMIZATION METHOD

International Research Journal of Pharmacy ◽

10.7897/2230-8407.1006200 ◽

2019 ◽

Vol 10 (6) ◽

pp. 37-42

Author(s):

Subhash V Deshmane ◽

Aijaz A Sheikh ◽

Om S Kharde ◽

Ravindra H Kale ◽

Kailash R Biyani

Keyword(s):

Design Optimization ◽

Factorial Design ◽

Optimization Method ◽

Full Factorial Design ◽

Floating Tablet ◽

Full Factorial ◽

32 Full Factorial Design

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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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Modeling and Optimizationof an Ultrasonic Setup Based on Combination of Finite Element Method and Mathematical Full Factorial Design

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.320.553 ◽

2011 ◽

Vol 320 ◽

pp. 553-558 ◽

Cited By ~ 1

Author(s):

Mohsen Ghahramani Nick ◽

J. Akbari ◽

Mohamad.R. Movahhedy ◽

S.Mehdi Hoseini

Keyword(s):

Mathematical Model ◽

Finite Element ◽

Objective Function ◽

Factorial Design ◽

Element Model ◽

Optimization Method ◽

Full Factorial Design ◽

High Frequency Oscillation ◽

Design Parameters ◽

Full Factorial

Ultrasonic assisted machining (UAM) is an efficient nontraditional machining operation for brittle, hard-to-cut and poor-machinability materials. In UAM, high frequency oscillation in ultrasonic range at low amplitude is imposed on the workpiece or cutting tool. In most cases, the equipments that generates and transfers the vibration, have a complicated structure, and requires significant effort to achieve their optimum function. In this work, a mathematical model is developed and an optimization method is employed for design process. This makes it possible to achieve proper setup and reduce the amount of calculation. For this purpose, the combination of a two level full factorial design is performed with data that are obtained from finite element model(FEM)are used. Based on the mathematical model, an objective function is defined with the objective of maximizing the vibration amplitude at longitudinal resonance frequency of 22 kHz. Genetic algorithm is used to optimize the design parameters according to the defined objective function. The obtained results are shown just an error about 0.03 percent between FEM modal analysis and mathematical model answer. The advantages of the proposed optimization method in ultrasonic setup design in case of complicated geometries is discussed. Therefore optimization methods via FEM data could be regarded as an efficient approach for design of complicated structures.

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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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