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

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.

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

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.

scholarly journals FORMULATION, OPTIMIZATIONANDEVALUATION OF SUBLINGUAL FILM OF ENALAPRILMALEATE USING 32 FULL FACTORIAL DESIGN

2021 ◽  
pp. 178-186
Author(s):  
SATYAJIT SAHOO ◽  
KIRTI MALVIYA ◽  
AMI MAKWANA ◽  
PRASANTA KUMAR MOHAPATRA ◽  
ASITRANJAN SAHU
Keyword(s):  
Tensile Strength ◽  
Drug Release ◽  
Factorial Design ◽  
Full Factorial Design ◽  
Disintegration Time ◽  
Surface Ph ◽  
Independent Variables ◽  
Folding Endurance ◽  
Full Factorial ◽  
32 Full Factorial Design

Objective: The purpose of this investigation was to formulate, optimize and evaluate sublingual film of Enalapril maleate for rapid management of Hypertension. Methods: Sublingual films were prepared by solvent casting method. Present investigation were formulated by using HPMC E 15 (X1) as polymer and Polyethylene glycol (X2) as plasticizer were chosen as independent variables in 32 full factorial design while Tensile strength (TS), Disintegration time (DT) and % Cumulative drug release at 10 min. (% CDR) were taken as dependent variables. The various physical parameters were evaluated for sublingual films such as thickness, tensile strength, folding endurance, disintegration time, surface pH and % CDR. Results: From the experimental study, it was concluded that the optimized batch F8 showed 98.6 %, the highest release of the drug. Stability study was performed by taking an optimized formulation and it was observed stable. The sublingual films showed acceptable results in all studies such as thickness, tensile strength, folding endurance, disintegration time, surface pH and % CDR at 10 min. R2 values for Tensile Strength (Y1), Disintegration time (Y2) and % cumulative drug release at 10 min. of Enalaprilmaleate(Y3) found to be 0.9852, 0.9829 and 0.9641 respectively. Thus, a good correlation between dependent and independent variables was developed. Conclusion: 32 full factorial design was successfully applied during preparation, optimization and evaluation of sublingual films of Enalapril maleate. The present investigation showed quick disintegration and fast release of the drug for rapid management of Hypertension.

scholarly journals IMPLEMENTATION OF QUALITY BY DESIGN (QBD) APPROACH IN FORMULATION AND DEVELOPMENT OF RITONAVIR PELLETS USING EXTRUSION SPHERONIZATION METHOD

2019 ◽  
pp. 139-146
Author(s):  
SATISH K. MANDLIK ◽  
PAYAL P. AGARWAL ◽  
HARSHAL P. DANDGAVHAL
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Factorial Design ◽  
Quality By Design ◽  
Research Work ◽  
Full Factorial Design ◽  
Extrusion Speed ◽  
Full Factorial ◽  
Extrusion Spheronization

Objective: Ritonavir is an antiretroviral drug used for HIV-AIDS treatment. The purpose of this research work was to implement the quality by design (QbD) approach in formulation of ritonavir sustained-release pellets by industrially applied extrusion spheronization technique. Methods: Pellets were prepared by extrusion spheronization method and evaluated for their physicochemical properties. Initially, on the basis of prior knowledge Quality Target Product Profile (QTTP) element was identified and further Critical Quality Attributes (CQA) elements were defined. Risk assessment (RA) was done by two tools as failure mode and effect analysis (FMEA) and fishbone diagram (Ishikawa plot). Placket Burman design was implemented as a screening design using seven high-risk factors (spheronization speed, spheronization time, extrusion speed, drying method, PVP K 30, cross povidone, and solvent). Optimization study was done by 23 full factorial design with three critical factors as (spheronization speed, extrusion speed and PVP K 30). The in vitro drug release was studied in both gastric and intestinal fluids for 12 h using USP Ι apparatus. Control space was established for the sustained release pellets. Results: Among all batches obtained in 23 full factorial design, batch R7 was found to be effective with carr’s index value of 5.281, percentage yield of 69.6%, time required to release 50% drug was 8 h and percent drug release after 12 h was found 83.132 %, R7 batch was selected as optimized batch. Statistical analysis showed model terms were significant. Conclusion: We can conclude that; sustained-release pellets of ritonavir were successfully designed using QbD approach.

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

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.

scholarly journals DESIGN AND OPTIMIZATION OF PEDIATRIC CEFUROXIME AXETIL DISPERSIBLE TABLET CONTAINING ION-EXCHANGE RESIN

2019 ◽  
pp. 325-332
Author(s):  
NISHANT OZA ◽  
SWATI SAGAR
Keyword(s):  
Ion Exchange ◽  
Drug Release ◽  
Factorial Design ◽  
Exchange Resin ◽  
Ion Exchange Resin ◽  
Cefuroxime Axetil ◽  
Full Factorial Design ◽  
Taste Masking ◽  
Dispersible Tablet ◽  
Full Factorial

Objective: The aim of present work was to develop of pediatric cefuroxime axetil 125 mg dispersible tablets by using ion exchange resin as a taste masking agent and quality target product profile was defined based on the properties of the cefuroxime axetil. Methods: Initially, cefuroxime axetil and various resin complexes (DRC) were prepared with different conditions and evaluated for taste masking and drug loading. Optimized DRC was used to formulate the dispersible tablet. A 32 full factorial design was employed to study the effect of mannitol (X1) and microcrystalline cellulose PH-101 (X2) on drug release at 10 min and time taken to 80% drug release. In the present study, the following constraints were arbitrarily used for the selection of an optimized batch: Q10>65% and T80%<30 min. Multiple linear regression analysis, ANOVA and graphical representation of the influence factor by 3D plots were performed by using Sigmaplot 11.0. Checkpoint batch was prepared to validate the evolved model. Results: Among the various drug resins complex DRC-9 was found with less bitter taste which was containing kyron T-114 and among the all factorial batch F7 showed highest drug release at 10 min (Q10) and lowest time taken to 80% drug release (T80) hence batch F7 was selected as an optimized batch and it’s found to be stable in the stability evaluation. Conclusion: The results of full factorial design indicate mannitol and MCC PH-101 have a significant effect on drug release.

scholarly journals FORMULATION AND CHARACTERIZATION OF SUSTAINED RELEASE MATRIX TABLETS OF IVABRADINE USING 32 FULL FACTORIAL DESIGN

2018 ◽  
Vol 10 (1) ◽  
pp. 59
Author(s):  
Olvishkumar M. Kothiya ◽  
Bhavana A. Patel ◽  
Kunal N. Patel ◽  
Madhubhai M. Patel
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Factorial Design ◽  
Xanthan Gum ◽  
Guar Gum ◽  
Full Factorial Design ◽  
Matrix Tablets ◽  
Independent Variables ◽  
Full Factorial ◽  
32 Full Factorial Design

Objective: Ivabradine (IB) is anti-Ischemic drug and used for the symptomatic management of stable angina pectoris. IB acts by reducing the heart rate in a mechanism different from beta blockers and calcium channel blockers, two commonly prescribed anti-anginal drugs. IB has a short biological half-life and the dose of 5/7.5 mg twice a day. In this present study, an attempt has been made to prepare sustained release tablet of IB to achieve the desired drug release.Methods: The sustained release polymers, hydroxypropyl methylcellulose K100M (HPMC K100M), guar gum (GG) and xanthan gum (XG) were taken for the preliminary trail from which guar gum and xanthan gum had shown better drug release. Initially, drug-excipients compatibility studies were carried out by using Fourier transformed infrared spectroscopy (FTIR) and Differential Scanning Calorimetry (DSC) which showed no interaction between drug and excipients. Tablets were prepared by wet granulation technique and evaluated for pre-compression and post-compression parameters.Results: 32 full factorial design was applied to achieve controlled drug release up to 24 h. The concentration of GG (X1) and XG (X2) were selected as independent variables and the % CDR at 2 h. (Y1) and 18 h. (Y2) were taken as dependent variables. In vitro drug release study revealed that as the amount of polymers increased, % CDR decreased.Conclusion: Contour as well as response surface plots were constructed to show the effect of X1 and X2 on % CDR and predicted at the concentration of independent variables X1 (10 mg) and X2 (10 mg) for a maximized response. The optimized batch (O1) was kept for stability study at 40±2 °C/75±5 %RH for a period of 6mo according to ICH guidelines and found to be stable.

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

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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