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

Pharmaceutics ◽  
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.

scholarly journals Chitosan Nanocarrier Entrapping Hydrophilic Drugs as Advanced Polymeric System for Dual Pharmaceutical and Cosmeceutical Application: A Comprehensive Analysis Using Box-Behnken Design

Polymers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 677
Author(s):  
Sara A. Abosabaa ◽  
Aliaa N. ElMeshad ◽  
Mona G. Arafa
Keyword(s):  
Particle Size ◽  
Sodium Tripolyphosphate ◽  
Chitosan Nanoparticles ◽  
Optimization Procedure ◽  
Entrapment Efficiency ◽  
Chitosan Solution ◽  
Polydispersity Index ◽  
Successful Implementation ◽  
Solution Ph ◽  
Box Behnken Design

The objective of the present research is to propose chitosan as a nanocarrier for caffeine—a commonly used drug in combating cellulite. Being a hydrophilic drug, caffeine suffers from insufficient topical penetration upon application on the skin. Chitosan nanoparticles loaded with caffeine were prepared via the ionic gelation technique and optimized according to a Box–Behnken design. The effect of (A) chitosan concentration, (B) chitosan solution pH, and (C) chitosan to sodium tripolyphosphate mass ratio on (Y1) entrapment efficiency percent, (Y2) particle size, (Y3) polydispersity index, and (Y4) zeta potential were studied. Subsequently, the desired constraints on responses were applied, and validation of the optimization procedure was confirmed by the parameters exhibited by the optimal formulation. A caffeine entrapment efficiency percent of 17.25 ± 1.48%, a particle size of 173.03 ± 4.32 nm, a polydispersity index of 0.278 ± 0.01, and a surface charge of 41.7 ± 3.0 mV were attained. Microscopical evaluation using transmission electron microscope revealed a typical spherical nature of the nanoparticles arranged in a network with a further confirmation of the formation of particles in the nano range. The results proved the successful implementation of the Box–Behnken design for optimization of chitosan-based nanoparticles in the field of advanced polymeric systems for pharmaceutical and cosmeceutical applications.

scholarly journals Translating the fabrication of protein-loaded poly(lactic-co-glycolic acid) nanoparticles from bench to scale-independent production using microfluidics

2020 ◽  
Vol 10 (3) ◽  
pp. 582-593 ◽  
Author(s):  
Carla B. Roces ◽  
Dennis Christensen ◽  
Yvonne Perrie
Keyword(s):  
Particle Size ◽  
Glycolic Acid ◽  
Polymeric Nanoparticles ◽  
Physicochemical Characteristics ◽  
European Medicines Agency ◽  
Protein Encapsulation ◽  
Human Use ◽  
Rate Ratios ◽  
The Impact ◽  
Process Controls

AbstractIn the formulation of nanoparticles, poly(lactic-co-glycolic acid) (PLGA) is commonly employed due to its Food and Drug Administration and European Medicines Agency approval for human use, its ability to encapsulate a variety of moieties, its biocompatibility and biodegradability and its ability to offer a range of controlled release profiles. Common methods for the production of PLGA particles often adopt harsh solvents, surfactants/stabilisers and in general are multi-step and time-consuming processes. This limits the translation of these drug delivery systems from bench to bedside. To address this, we have applied microfluidic processes to develop a scale-independent platform for the manufacture, purification and monitoring of nanoparticles. Thereby, the influence of various microfluidic parameters on the physicochemical characteristics of the empty and the protein-loaded PLGA particles was evaluated in combination with the copolymer employed (PLGA 85:15, 75:25 or 50:50) and the type of protein loaded. Using this rapid production process, emulsifying/stabilising agents (such as polyvinyl alcohol) are not required. We also incorporate in-line purification systems and at-line particle size monitoring. Our results demonstrate the microfluidic control parameters that can be adopted to control particle size and the impact of PLGA copolymer type on the characteristics of the produced particles. With these nanoparticles, protein encapsulation efficiency varies from 8 to 50% and is controlled by the copolymer of choice and the production parameters employed; higher flow rates, combined with medium flow rate ratios (3:1), should be adopted to promote higher protein loading (% wt/wt). In conclusion, herein, we outline the process controls for the fabrication of PLGA polymeric nanoparticles incorporating proteins in a rapid and scalable manufacturing process.

scholarly journals FORMULATION, OPTIMIZATION AND IN VITRO EVALUATION OF 5-FLUOROURACIL LOADED LIQUORICE CRUDE PROTEIN NANOPARTICLES FOR SUSTAINED DRUG DELIVERY USING BOX-BEHNKEN DESIGN

2021 ◽  
pp. 216-226
Author(s):  
GEETHA V. S. ◽  
MALARKODI VELRAJ
Keyword(s):  
Drug Delivery ◽  
Particle Size ◽  
Drug Release ◽  
Crude Protein ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Box Behnken Design ◽  
Sustained Drug Delivery ◽  
Drug Loading Efficiency

Objective: To formulate, optimize and evaluate 5-fluorouracil loaded liquorice crude protein nanoparticles for sustained drug delivery using Box-Behnken design. Methods: 5-fluorouracil (5-FU) loaded liquorice crude protein (LCP) nanoparticles were prepared by desolvation method using ethanol-water (1:2 ratio), Tween-80 (2%v/v) as stabilizing agent and gluteraldehyde (8% v/v) as cross linking agent. The optimization of prepared nanoparticles was carried out using Box-Behnken design with 3 factors 2 levels and 3 responses. The independent variables were A)5-FU concentration B)LCP concentration and C) sonication time while the responses were R1) Drug entrapment efficiency R2) Drug loading efficiency and R3) Particle size. The correlation between factors and responses were studied through response surface plots and mathematical equations. The nanoparticles were evaluated for FTIR, physicochemical properties like particle size and zeta potential by Photon correlation spectroscopy (PCS) and surface morphology by TEM. The entrapment efficiency, drug loading efficiency and in vitro drug release studies in PBS pH 7.4 (24 h) were carried out. The observed values were found to be in close agreement with the predicted value obtained from the optimization process. Results: 5-fluorouracil loaded LCP nanoparticles were prepared by desolvation method, the optimization was carried out by Box-Behnken design and the final formulation was evaluated for particle size (301.1 nm), zeta-potential (-25.8mV), PDI(0.226), with entrapment efficiency (64.07%), drug loading efficiency (28.54%), in vitro drug release (65.2% in 24 h) respectively. The formulated nanoparticles show Higuchi model drug release kinetics with sustained drug delivery for 24 h in pH7.4 buffer. Conclusion: The results were proved to be the most valuable for the sustained delivery of 5-Fluorouracil using liquorice crude protein as carrier. 5-FU–LCP nanoparticles were prepared using Tween-80 as stabilizing agent and gluteraldehyde as cross-linking agent to possess ideal sustained drug release characteristics.

scholarly journals Development of NIPAAm-PEG acrylate polymeric nanoparticles for co-delivery of paclitaxel with ellagic acid for the treatment of breast cancer

2019 ◽  
Vol 39 (3) ◽  
pp. 271-278 ◽  
Author(s):  
Suruchi Suri ◽  
Mohd. Aamir Mirza ◽  
Md. Khalid Anwer ◽  
Abdullah S. Alshetaili ◽  
Saad M. Alshahrani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Particle Size ◽  
Ellagic Acid ◽  
Oral Delivery ◽  
Polymeric Nanoparticles ◽  
Entrapment Efficiency ◽  
Shell Nanoparticles ◽  
Transmission Electron ◽  
Core Shell Nanoparticles

Abstract The aim of the current study was to develop a dual-loaded core shell nanoparticles encapsulating paclitaxel (PTX) and ellagic acid (EA) by membrane dialysis method. Based on particle size, polydispersity index (PDI), and entrapment efficiency, the dual drug-loaded nanoparticles (F2) was optimized. The optimized nanoparticles (F2) showed a particle size of 140±2 nm and a PDI of 0.23±3. The size and the morphology were confirmed by transmission electron microscopy (TEM) and found agreement with the results of dynamic light scattering. The entrapment efficiencies of total drug (PTX and EA), PTX, and EA in the nanoparticles (F2) were measured as 80%, 62.3%, and 37.7%, respectively. The in vitro release profile showed a controlled release pattern for 48 h. A higher cytotoxicity was observed with nanoparticles (F2) in comparison to free PTX. The results revealed that co-delivery of PTX and EA could be used for its oral delivery for the effective treatment of breast cancer.

scholarly journals FORMULATION AND EVALUATION OF ETHAMBUTOL POLYMERIC NANOPARTICLES

2020 ◽  
pp. 207-217
Author(s):  
MONOWAR HUSSAIN ◽  
ANUPAM SARMA ◽  
SHEIKH SOFIUR RAHMAN ◽  
ABDUL MATIN SIDDIQUE ◽  
TANUKU PAVANI EESWARI
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Zeta Potential ◽  
Polymeric Nanoparticles ◽  
Release Kinetics ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Compatibility Study ◽  
Bacterial Disease ◽  
Dose Frequency

Objective: Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis which most commonly affects the lungs. TB has the highest mortality rate than any other infectious disease occurs worldwide. The main objective of the present investigation was to develop polymeric nanoparticles based drug delivery system to sustain the ethambutol (ETB) release by reducing the dose frequency. Methods: The Preformulation studies of drug ETB were done by physical characterization, melting point determination, and UV spectrophotometric analysis. The ETB loaded nanoparticles were prepared by double-emulsion (W/O/W) solvent evaporation/diffusion technique. The prepared polymeric nanoparticles were evaluated for particle size, polydispersity index, zeta potential, drug entrapment efficiency, drug loading, drug-polymer compatibility study, surface morphology, in vitro drug release, and release kinetics. Results: Based on the result obtained from the prepared formulations, F11 showed the best result and was selected as the optimized formulation. Optimized batch (F11) showed better entrapment efficiency (73.3%), good drug loading capacity (13.21%), optimum particle size (136.1 nm), and zeta potential (25.2 mV) with % cumulative drug release of 79.08% at the end of 24 h. Conclusion: These results attributed that developed polymeric nanoparticles could be effective in sustaining the ETB release over 24 h. Moreover, the developed nanoparticles could be an alternate method for ETB delivery with a prolonged drug release profile and a better therapeutic effect can be achieved for the treatment of tuberculosis.

scholarly journals ENHANCEMENT OF THERAPEUTIC WINDOW OF METFORMIN HYDROCHLORIDE BY FABRICATION OF MICROSPHERES COMPRISING POLYMERIC INCULCATION WITH SEMI-SYNTHETIC AND SYNTHETIC POLYMERS BY IMPLEMENTATION OF BOX-BEHNKEN DESIGN

2021 ◽  
pp. 257-264
Author(s):  
MD AAMER QUAZI ◽  
NAZIA KHANAM
Keyword(s):  
Particle Size ◽  
Controlled Release ◽  
Ex Vivo ◽  
Hydroxypropyl Methylcellulose ◽  
Entrapment Efficiency ◽  
Synthetic Polymers ◽  
Therapeutic Window ◽  
Metformin Hydrochloride ◽  
Box Behnken Design ◽  
Mean Particle Size

Objective: Innovative enhancement of therapeutic window of Metformin hydrochloride (MFH) and bioavailability through mucoadhesive microspheres by polymeric inculcation of hydroxypropyl methylcellulose K4M grade (HPMC K4M), hydroxypropyl methylcellulose K100M grade (HPMC K100M) and Kollidon SR grade (KS). Methods: Controlled release system was developed by incorporating semi-synthetic and synthetic polymers by modified solvent evaporation technique. Fabrication of mucoadhesive microspheres was designed by the implementation of experimental designs to obtain most optimum concentration of selected factors. The method was optimized by Box Behnken design (BBD) with selected factors as concentrations of semi-synthetic and synthetic polymer with stirring speed influence for the obtained responses that were mean particle size (Y1) entrapment efficiency of drug (Y2) and percent mucoadhesion (Y3). Microspheres were characterized for particle size, entrapment efficiency of drug, ex-vivo mucoadhesion study, in vitro study, Fourier transform infrared spectroscopy (FTIR), x-ray diffraction (XRD) detection and H1 Nuclear magnetic resonance (NMR) quantification for optimized formulation. Results: Implementation of response surface method software for BBD yielded stable microspheres with mean particle size 274 µm, entrapment efficiency of drug 85.07% and percent mucoadhesion 67.03% for optimized formulation F5. Conclusion: Bridging of MFH with the highly innovative combination of semi-synthetic and synthetic polymers yielded stable, cost-effective microspheres with improved bioavailability with controlled-release effect as till date no literature is available that provide information with selected polymeric combination and analytical characterization.

scholarly journals CHITOSAN NANOPARTICLE AS A DELIVERY SYSTEM FOR POLYPHENOLS FROM MENIRAN EXTRACT (PHYLLANTHUS NIRURI L.): FORMULATION, OPTIMIZATION, AND IMMUNOMODULATORY ACTIVITY

2019 ◽  
pp. 50-58
Author(s):  
GALIH PRATIWI ◽  
RONNY MARTIEN ◽  
RETNO MURWANTI
Keyword(s):  
Particle Size ◽  
Phagocytic Activity ◽  
Polymeric Nanoparticles ◽  
Entrapment Efficiency ◽  
Assay Method ◽  
Immunomodulatory Activity ◽  
Lattice Design ◽  
Simplex Lattice ◽  
Phagocytosis Index ◽  
Optimum Formula

Objective: This study aims to formulate meniran extract into polymeric nanoparticles. Better stability of active substances in formulas compared to unformulated extracts is expected to increase immunomodulatory activity. Methods: Nanoparticles were formulated using ionic gelation method with chitosan and tripolyphosphate polymers. Optimize the mixture of nanoparticles using simplex lattice design (SLD) with the help of Design-Expert (DX) software. Evaluation of particle size and potential zeta using dynamic light scattering (DLS). Interactions between components were analyzed using Fourier transform infrared spectrophotometry-attenuated total reflectance (FTIR-ATR) and morphology of the lyophilization results observed using scanning electron microscopy (SEM). Immunomodulatory tests using the latex assay method. The parameters tested included phagocytosis index, phagocytic activity, and nitric oxide secretion. Results: The optimum mixture of the formulation process was obtained in the composition of chitosan 0.270 %, extract 0.626 %, and tripolyphosphate 0.074 % with desirability value of 0.841. Optimal response with particle size 434.7±3.90 d. nm, polydispersity index 0.285±0.03 and entrapment efficiency 62.98±0.65 %. The zeta potential value in the optimum formula is 11.9±0.1 mV with a positive charge. Phagocytosis index and phagocytic activity of nanoparticles differed significantly (p<0.05) compared with unformulated extracts. Conclusion: Meniran extract was successfully formulated into polymeric nanoparticles using chitosan-tripolyphosphate polymer. The developed nanoparticles have the immunomodulatory activity that is better than unformulated extract.

scholarly journals Formulation and Optimization of Butenafine-Loaded Topical Nano Lipid Carrier-Based Gel: Characterization, Irritation Study, and Anti-Fungal Activity

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1087
Author(s):  
Wael A. Mahdi ◽  
Sarah I. Bukhari ◽  
Syed Sarim Imam ◽  
Sultan Alshehri ◽  
Ameeduzzafar Zafar ◽  
...  
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Fungal Infection ◽  
Entrapment Efficiency ◽  
Tween 80 ◽  
Stability Study ◽  
Box Behnken Design ◽  
Compritol 888 Ato ◽  
High Entrapment Efficiency ◽  
Anti Fungal

The present study aims to prepare and optimize butenafine hydrochloride NLCs formulation using solid and liquid lipid. The optimized selected BF-NLCopt was further converted into Carbopol-based gel for topical application for the treatment of fungal infection. Box Behnken design was employed to optimize the nanostructure lipids carriers (NLCs) using the lipid content (A), Tween 80 (B), and homogenization cycle (C) as formulation factors at three levels. Their effects were observed on the particle size (Y1) and entrapment efficiency (Y2). The selected formulation was converted into gel and further assessed for gel characterization, drug release, anti-fungal study, irritation study, and stability study. The solid lipid (Compritol 888 ATO), liquid lipid (Labrasol), and surfactant (tween 80) were selected based on maximum solubility. The optimization result showed a particle size of 111 nm with high entrapment efficiency of 86.35% for BF-NLCopt. The optimized BF-NLCopt converted to gel (1% w/v, Carbopol 934) and showed ideal gel evaluation results (drug content 99.45 ± 2.11, pH 6.5 ± 0.2, viscosity 519 ± 1.43 CPs). The drug release study result depicted a prolonged drug release (65.09 ± 4.37%) with high drug permeation 641.37 ± 46.59 µg (32.07 ± 2.32%) than BF conventional gel. The low value of irritation score (0.17) exhibited negligible irritation on the skin after application. The anti-fungal result showed greater efficacy than the BF gel at both time points. The overall conclusion of the results revealed NLCs-based gel of BF as an ideal delivery system to treat the fungal infection.

scholarly journals FORMULATION AND EVALUATION OF PRONIOSOMAL GEL-BASED TRANSDERMAL DELIVERY OF ATORVASTATIN CALCIUM BY BOX–BEHNKEN DESIGN

2019 ◽  
pp. 335-343 ◽  
Author(s):  
SOUJANYA C ◽  
RAVI PRAKASH P
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Release Kinetics ◽  
Skin Permeation ◽  
Spherical Shape ◽  
Entrapment Efficiency ◽  
Transmission Electron Microscopy Analysis ◽  
Box Behnken Design ◽  
Atorvastatin Calcium ◽  
Span 60

Objective: The aim of this study was to investigate the combined influence of three independent variables in the preparation of atorvastatin proniosomes by coacervation-phase separation method. Methods: On the basis of the preliminary trials, a 3-factor, 3-level Box–Behnken design was employed to study the effect of cholesterol, soya lecithin, and Span 60 independent variable on dependent variables (particle size and % entrapment efficiency). Transmission electron microscopy analysis of optimized formulation has demonstrated the presence of individual proniosomes in spherical shape. Results: Atorvastatin optimized proniosomal formulation F2 shown better particle size and % entrapment efficiency, and also, the drug release was 99.72% within 24 h in slow and controlled manner when compared with control. Kinetic analysis of drug release profiles showed that the drug release was followed by zero-order manner with Korsmeyer–Peppas model, which implies super case II release kinetics. The particle size and zeta potential of the optimized atorvastatin proniosomal gel were found to be 65.72 and −10.5, respectively. The optimized batch of proniosomes was used for the preparation of atorvastatin-based proniosomal hydrogel by incorporating hydrated proniosomes to carbopol matrix to enhance the stability and viscosity of the system. Conclusion: The enhanced skin permeation, for a prolonged period of time, may lead to improved efficacy and better patient compliance. This study suggests that proniosomal gel-containing atorvastatin could perform therapeutically better effects than the conventional formulations.

scholarly journals Formulation and Evaluation of Miconazole Nitrate Loaded Nanoparticles for Topical Delivery

2021 ◽  
pp. 102-123
Author(s):  
Ashish Y. Pawar ◽  
Khanderao R. Jadhav ◽  
Komal D. Ahire ◽  
Tushar P. Mahajan
Keyword(s):  
Particle Size ◽  
Polymeric Nanoparticles ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Topical Delivery ◽  
Topical Administration ◽  
Hair Follicles ◽  
Systemic Delivery ◽  
Mean Particle Size ◽  
Miconazole Nitrate

The aim of the present work was to formulate and evaluate Miconazole nitrate (MN) polymeric nanoparticles (NPs) for systemic delivery of the active ingredient after topical administration. The Solvent evaporation approach was used to make nanoparticles for topical delivery of MN. Particle size, entrapment efficiency and SEM were all measured in MN-SLN. A consistent size distribution (PI 0.300) was used to generate aqueous NPs dispersions with a mean particle size less than 250 nm. After 3 months of storage, the produced semi-solid systems had a mean particle size of less than 250 nm and a PI of less than 0.500. The F5 formulation was been chosen as the model formulation from among the nine nanoparticle formulations developed (F1 to F9). The reason for this was that, according to the ICH stability guidelines, formulation F5 was judged to be optimal and stable. The F5 formulations of miconazole nanoparticles shows the highest entrapment efficiency (93.28%) and drug loading (86.64%). In conclusion, there are two major advantages of using miconazole nanoparticle drug delivery systems. i.e., they are topical preparations that assemble in the hair follicles and wrinkles to produce a systemic and local action. It is possible that nanoparticles will be the most effective treatment for fungal skin infections.

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