Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

Dermal Flurbiprofen Nanosuspensions: Optimization With Design Of Experiment Approach And In Vitro Evaluation

A. N. Oktay, A. Karakucuk, S. Ilbasmiş-Tamer, N. Celebi
Published 2018 · Materials Science, Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
Share
&NA; Flurbiprofen (FB) is the one of the non‐steroidal anti‐inflammatory drugs (NSAIDs) which has low water solubility and dissolution. Nanosuspensions are promising drug delivery systems consisting pure drug particles to overcome poor water solubility issues. Recently, design of experiment (DoE) approaches have often been used to develop new formulations include nanosuspensions. The main objective of this study was to prepare FB nanosuspensions in existence of Plantacare 2000 (PL) as stabilizer using DoE approach to evaluate the critical formulation attributes (CFAs) and critical process parameters (CPPs). Particle size, particle size distribution and zeta potential values were selected as dependent variables and FB%, FB: PL and homogenization cycles were independent variables. Both 23 and 33 factorial designs were used to achieve optimum nanosuspension formulation. The final nanosuspension was freeze‐dried and then crystalline state, morphological and thermal properties were investigated using X‐ray diffraction, scanning electron microscopy and differential scanning calorimetry, respectively. The saturation solubility studies of nanosuspensions were conducted in comparison with the coarse powder and the physical mixture. The in vitro permeation of nanosuspension and FB solution were determined through dialysis membrane and rat skin. The particle size, polydispersity index and zeta potential values were found to range 665 nm–700 nm, 0.200–0.300 and approximately −30 mV, respectively. Nanosuspensions were obtained with spherical shape and no polymorphic or crystalline state change were observed. The saturation solubility of FB was 5.3 fold increased in nanosuspension formulation. Permeability of FB nanosuspension was higher than FB solution in rat skin. It was concluded that the DoE approach is a useful tool to prepare FB nanosuspensions and nanosuspensions benefit to improve water solubility and dermal permeation of Biopharmaceutical Classification System (BCS) Class II drugs. Graphical abstract Figure. No caption available.
This paper references
10.1016/j.colsurfb.2017.11.012
The effect of diethylene glycol monoethyl ether on skin penetration ability of diclofenac acid nanosuspensions.
R. Pireddu (2018)
10.1016/J.CES.2015.03.020
Sub-100nm drug particle suspensions prepared via wet milling with low bead contamination through novel process intensification
M. Li (2015)
Nanocrystallization by evaporative
M.R.P. Rao (2010)
10.1016/j.ijpharm.2011.08.026
Lutein nanocrystals as antioxidant formulation for oral and dermal delivery.
Khalil Mitri (2011)
10.1016/j.ejpb.2012.01.005
Generation of wear during the production of drug nanosuspensions by wet media milling.
M. Juhnke (2012)
10.1016/j.colsurfb.2013.04.045
Flurbiprofen PLGA-PEG nanospheres: role of hydroxy-β-cyclodextrin on ex vivo human skin permeation and in vivo topical anti-inflammatory efficacy.
E. Vega (2013)
In situ determination
M. 02.006. Colombo (2017)
10.1016/j.jconrel.2010.11.015
Selective follicular targeting by modification of the particle sizes.
A. Patzelt (2011)
10.1159/000056385
Investigation of Follicular Penetration of Topically Applied Substances
J. Lademann (2001)
10.1016/j.ijpharm.2013.12.039
Quality by Design approach to spray drying processing of crystalline nanosuspensions.
S Kumar (2014)
10.1080/03639040500214613
Dissolution, Solubility, XRD, and DSC Studies on Flurbiprofen-Nicotinamide Solid Dispersions
M. Varma (2005)
10.1016/j.ijpharm.2009.05.006
Quality by design approach to understand the process of nanosuspension preparation.
S. Verma (2009)
10.1016/j.ejpb.2011.09.012
Twenty years of drug nanocrystals: where are we, and where do we go?
R. Mueller (2012)
Challenges and solutions for the delivery of biotech drugs
C. M. Keck (2004)
Resveratrol nanosuspensions for dermal application--production, characterization, and physical stability.
S. Kobierski (2009)
Resveratrol nanosus
S. ejpb.2005.05.009. Kobierski (2009)
10.1016/j.ijpharm.2008.12.030
Production and characterization of Hesperetin nanosuspensions for dermal delivery.
P. R. Mishra (2009)
10.1016/j.ijpharm.2017.03.082
Improved release of triamcinolone acetonide from medicated soft contact lenses loaded with drug nanosuspensions.
Eva García-Millán (2017)
10.1208/s12249-012-9860-x
Nanocrystallization by Evaporative Antisolvent Technique for Solubility and Bioavailability Enhancement of Telmisartan
A. Bajaj (2012)
10.1016/J.IJPHARM.2004.01.033
Factorial design, physicochemical characterisation and activity of ciprofloxacin-PLGA nanoparticles.
K. Dillen (2004)
10.1016/J.EJPB.2005.05.009
Drug nanocrystals of poorly soluble drugs produced by high pressure homogenisation.
C. Keck (2006)
10.1111/J.0022-202X.2004.22717.X
Penetration profile of microspheres in follicular targeting of terminal hair follicles.
R. Toll (2004)
10.1016/J.JCONREL.2004.03.028
Transdermal delivery of mixnoxidil with block copolymer nanoparticles.
Jongwon Shim (2004)
10.1016/j.ijpharm.2013.10.007
Nanosuspension improves tretinoin photostability and delivery to the skin.
F. Lai (2013)
Preserving hesperetin nanosuspensions for dermal application.
L. Al Shaal (2010)
10.1016/j.ijpharm.2017.08.108
Dermal miconazole nitrate nanocrystals - formulation development, increased antifungal efficacy & skin penetration.
S. M. Pyo (2017)
Preserving hesperetin nanosuspensions
L. Al Shaal (2010)
Advantages of celecoxib
A. 033. Dolenc (2009)
10.1016/j.ejpb.2011.12.015
Nanocrystals: comparison of the size reduction effectiveness of a novel combinative method with conventional top-down approaches.
J. Salazar (2012)
10.1016/j.ijpharm.2017.02.030
In situ determination of the saturation solubility of nanocrystals of poorly soluble drugs for dermal application.
M. Colombo (2017)
10.1016/j.ejps.2012.12.026
Preparation of apigenin nanocrystals using supercritical antisolvent process for dissolution and bioavailability enhancement.
J. Zhang (2013)
10.1016/S0169-409X(00)00118-6
Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future.
R. Mueller (2001)
Production and characterization
P. R. ijpharm.2011.03.050. Mishra (2009)
Lutein nanocrystals
R. Shegokar (2011)
10.1016/j.ijpharm.2008.07.023
Top-down production of drug nanocrystals: nanosuspension stabilization, miniaturization and transformation into solid products.
B. Van Eerdenbrugh (2008)
10.1016/J.JBIOTEC.2004.06.007
Challenges and solutions for the delivery of biotech drugs--a review of drug nanocrystal technology and lipid nanoparticles.
R. H. Muller (2004)
10.1016/j.colsurfb.2016.03.070
Stimuli-responsive lipid nanotubes in gel formulations for the delivery of doxorubicin.
S. Ilbasmiş-Tamer (2016)
Sub-100 nm drug
N. Yaragudi (2013)
Top-down production
G. Van den Mooter (2008)
10.1016/j.ijpharm.2009.04.038
Advantages of celecoxib nanosuspension formulation and transformation into tablets.
Andrej Dolenc (2009)
10.1016/j.ejpb.2011.01.007
State of the art of nanocrystals--special features, production, nanotoxicology aspects and intracellular delivery.
R. Mueller (2011)
Quality by design approach to spray drying
R. Gokhale (2014)
10.3109/03639045.2012.686509
Formulation, characterization and in vitro–in vivo evaluation of flurbiprofen-loaded nanostructured lipid carriers for transdermal delivery
J. Kawadkar (2013)
10.1016/j.ijpharm.2014.04.060
Nanocrystals of medium soluble actives--novel concept for improved dermal delivery and production strategy.
X. Zhai (2014)
10.1016/j.jcis.2016.09.003
A cost-effective method to prepare curcumin nanosuspensions with enhanced oral bioavailability.
Y. Wang (2017)
10.1016/j.ejpb.2015.02.031
Process parameter dependent growth phenomena of naproxen nanosuspension manufactured by wet media milling.
A. Bitterlich (2015)
Preparation of ritonavir nanosuspensions
N. Celebi (2016)
10.1016/j.ijpharm.2011.03.050
Nanosuspensions of poorly soluble drugs: preparation and development by wet milling.
Peng Liu (2011)
10.1007/S11051-008-9357-4
Drug nanocrystals for the formulation of poorly soluble drugs and its application as a potential drug delivery system
L. Gao (2008)
10.1016/j.ejps.2012.04.020
Application of spray granulation for conversion of a nanosuspension into a dry powder form.
S. Bose (2012)
10.1016/S0378-5173(02)00540-9
Effect of enhancers and retarders on percutaneous absorption of flurbiprofen from hydrogels.
Jia-You Fang (2003)
10.1016/j.ijpharm.2010.02.006
Evaluation of the transdermal permeation of different paraben combinations through a pig ear skin model.
Thiago Caon (2010)
10.1016/j.ejps.2015.06.006
Novel nanosized formulations of two diclofenac acid polymorphs to improve topical bioavailability.
R. Pireddu (2015)
10.1016/j.ijpharm.2014.10.044
Effects of stabilizing agents on the development of myricetin nanosuspension and its characterization: an in vitro and in vivo evaluation.
C. Hong (2014)
Formulation, Optimization and characterization of Simvastatin Nanosuspension prepared by nanoprecipitation technique
P. VikramM. (2011)
Improved release
M. Quintáns-Carballo (2017)
10.1016/j.ejps.2016.05.010
Preparation of ritonavir nanosuspensions by microfluidization using polymeric stabilizers: I. A Design of Experiment approach.
A. Karakucuk (2016)



This paper is referenced by
10.35333/jrp.2019.65
Optimization and evaluation of cyclosporine A nanosuspension stabilized by combination stabilizers using high pressure homogenization method
Sıla Gülbağ Pinar (2019)
Design, Preparation, and Characterization of Dioscin NanosuspensionsandEvaluationofTheirProtectiveEffect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice
JU Hong-Ye (2019)
10.1208/s12249-020-01653-9
Development of Nanocrystal Ziprasidone Orally Disintegrating Tablets: Optimization by Using Design of Experiment and In Vitro Evaluation
Emine Taşhan (2020)
10.1016/j.molliq.2020.114924
Vicissitudes of liquid crystals for solubility enhancement of poorly soluble drugs
A. Shoaib (2021)
10.22270/JDDT.V9I2.2436
Nanosuspensions as a promising approach to enhance bioavailability of poorly soluble drugs : An update
Stanekzai Azimullah (2019)
10.2147/IJN.S178077
Microfluidization trends in the development of nanodelivery systems and applications in chronic disease treatments
P. Ganesan (2018)
10.1016/j.ijpharm.2020.119636
Nanosuspensions of a poorly soluble investigational molecule ODM-106: impact of milling bead diameter and stabilizer concentration.
Mayank Singhal (2020)
10.1016/j.ejps.2020.105654
Anti-inflammatory drug nanocrystals: state of art and regulatory perspective.
Luiza de O Macedo (2020)
10.1016/j.ejps.2020.105548
Preparation and In Vitro / In Vivo Evaluation of Flurbiprofen Nanosuspension-Based Gel for Dermal Application.
A. N. Oktay (2020)
10.1155/2019/3907915
Design, Preparation, and Characterization of Dioscin Nanosuspensions and Evaluation of Their Protective Effect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice
Hong-Ye Ju (2019)
10.1080/10717544.2019.1682721
Advanced modification of drug nanocrystals by using novel fabrication and downstream approaches for tailor-made drug delivery
T. Liu (2019)
10.1016/J.JDDST.2019.04.024
Optimization and in vitro evaluation of ziprasidone nanosuspensions produced by a top-down approach
Emine Taşhan (2019)
10.1080/10837450.2020.1805761
Preparation, characterization and antimicrobial activity evaluation of electrospun PCL nanofiber composites of resveratrol nanocrystals
A. Karakucuk (2020)
10.1016/j.mtchem.2020.100364
Formulation and molecular docking simulation study of luliconazole nanosuspension–based nanogel for transdermal drug delivery using modified polymer
Mohd Sayeed Shaikh (2020)
10.3390/pharmaceutics10040247
Flurbiprofen-Loaded Solid SNEDDS Preconcentrate for the Enhanced Solubility, In-Vitro Dissolution and Bioavailability in Rats
Rae Man Kim (2018)
10.1080/10837450.2019.1667384
The effect of critical process parameters of the high pressure homogenization technique on the critical quality attributes of flurbiprofen nanosuspensions
A. N. Oktay (2019)
10.1016/j.colsurfb.2020.111501
Dual response to pH and chiral microenvironments for the release of a flurbiprofen-loaded chiral self-assembled mesoporous silica drug delivery system.
Lulu Wu (2020)
10.3390/medicines6010007
Drug-Loaded Biocompatible Nanocarriers Embedded in Poloxamer 407 Hydrogels as Therapeutic Formulations
Elena Giuliano (2018)
10.1016/j.ijpharm.2019.04.016
Preparation of in situ hydrogels loaded with azelaic acid nanocrystals and their dermal application performance study
I. Tomić (2019)
10.1016/j.jddst.2020.101690
Screening of stabilizing agents to optimize flurbiprofen nanosuspensions using experimental design
A. N. Oktay (2020)
10.1007/s11095-020-02815-x
Investigation of Formulation and Process Parameters of Wet Media Milling to Develop Etodolac Nanosuspensions
A. Karakucuk (2020)
10.1208/s12249-020-01703-2
Correction to: Development of Nanocrystal Ziprasidone Orally Disintegrating Tablets: Optimization by Using Design of Experiment and In Vitro Evaluation
Emine Taşhan (2020)
10.1016/j.xphs.2020.07.015
Freeze-drying of pharmaceutical and nutraceutical nanoparticles: The effects of formulation and technique parameters on nanoparticles characteristics.
M. Mohammady (2020)
Semantic Scholar Logo Some data provided by SemanticScholar