To Study the Significance of Processing Variables Using Quality by Design for Optimization of Nanoparticulate System of Cilnidipine

This investigation aimed to prepare Cilnidipine Nanoparticles by nanoprecipitation ultrasonication method and to study the significance of processing variables by applying quality by design. Cilnidipine is fourth-generation dual L/N-type Ca2+ channel blocker used for the management of hypertension. It is BCS class-II drug exhibiting lower aqueous solubility, which tends to lower bioavailability. The combination of Poloxamer 188 and Tween 80 was used as a stabilizer. The design of the experiment is one of the tools of Quality by design. Plackett -Burman design was applied for the screening of processing variables, which are significant for the method. The processing variables screened were stirring speed, antisolvent ratio, drug concentration, polymer concentration, stabilizer concentration. The effect of each parameter evaluated by particle size, entrapment efficiency, and drug release at 10 minutes of prepared Nanoparticles of Cilnidipine. Analysis of variance and Pareto-plot of Plackett-Burman design were utilized to find the significance of the factor and extent of the effect. The surface morphology of Cilnidipine Nanoparticles was studied by SEM. The Pareto plot, as well as statistical analysis of design, had shown that the Concentration of drug, solvent: antisolvent ratio and concentration of poloxamer 188 were the significant parameters for the method. The stabilizer concentration, the stirring speed, and the antisolvent ratio had a negative effect of while the concentration of drug has a positive effect on the particle size of Nanoparticles and drug release at 10 minutes and positive effect of entrapment efficiency of Cilnidipine Nanoparticles. The Cilnidipine Nanoparticles were characterized by FTIR and DSC analysis.

[1]  S. Mir,et al.  POLYMERIC NANOPARTICLES FOR IMPROVED BIOAVAILABILITY OF CILNIDIPINE , 2017 .

[2]  J. Avari,et al.  Development and Characterization of Solid Self-emulsifying Drug Delivery System of Cilnidipine. , 2015, Chemical & pharmaceutical bulletin.

[3]  M. K. Das,et al.  Nanosuspension for enhancement of oral bioavailability of felodipine , 2014, Applied Nanoscience.

[4]  Judit Tóth,et al.  Preparation of protein loaded chitosan microparticles by combined precipitation and spherical agglomeration , 2013 .

[5]  I. Carvalho,et al.  Phenolics extraction from sweet potato peels: key factors screening through a placket-burman design , 2013 .

[6]  Kathiresan Krishnasamy,et al.  Application of Plackett-Burman Factorial Design in The Development of Curcumin Loaded Eudragit E 100 Nanoparticles , 2013 .

[7]  N. Sheth,et al.  Application of Plackett-Burman screening design for preparing glibenclamide nanoparticles for dissolution enhancement , 2013 .

[8]  Neha Singh,et al.  Improved antimicrobial compound production by a new isolate Streptomyces hygroscopicus MTCC 4003 using Plackett-Burman design and response Surface methodology , 2012, Bioinformation.

[9]  D. Awotwe-Otoo,et al.  Evaluation of Anticancer Drug-Loaded Nanoparticle Characteristics by Nondestructive Methodologies , 2012, AAPS PharmSciTech.

[10]  K. Raval,et al.  Preparation and evaluation of cilnidipine microemulsion , 2012, Journal of pharmacy & bioallied sciences.

[11]  Lin Li,et al.  Preparation of nanoparticles of poorly water-soluble antioxidant curcumin by antisolvent precipitation methods , 2012, Journal of Nanoparticle Research.

[12]  F. Cui,et al.  Preparation of stable nitrendipine nanosuspensions using the precipitation-ultrasonication method for enhancement of dissolution and oral bioavailability. , 2010, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[13]  Ziyaur Rahman,et al.  Understanding the quality of protein loaded PLGA nanoparticles variability by Plackett-Burman design. , 2010, International journal of pharmaceutics.

[14]  Jianfeng Chen,et al.  Nanonization of Megestrol Acetate by Liquid Precipitation , 2009 .

[15]  Yuan Le,et al.  Micronization of atorvastatin calcium by antisolvent precipitation process. , 2009, International journal of pharmaceutics.

[16]  M. Ali,et al.  Screening of Nutrient Parameters for Red Pigment Production by Monascus purpureus MTCC 369 Under Submerged Fermentation Using Plackett- Burman Design , 2007 .

[17]  Yuan Le,et al.  Preparation of ultrafine beclomethasone dipropionate drug powder by antisolvent precipitation , 2007 .

[18]  Raviraj M. Kulkarni,et al.  Nanosuspensions: a promising drug delivery strategy , 2004, The Journal of pharmacy and pharmacology.

[19]  K. Kanmatsuse,et al.  Effect of Morning and Bedtime Dosing with Cilnidipine on Blood Pressure, Heart Rate, and Sympathetic Nervous Activity in Essential Hypertensive Patients , 2004, Journal of cardiovascular pharmacology.

[20]  M. Morishita,et al.  Encapsulation of hydrophilic and lipophilic drugs in PLGA nanoparticles by the nanoprecipitation method. , 1999, Drug development and industrial pharmacy.

[21]  A. Sahu,et al.  Solubility Enhancement by Solid Dispersion and Effervescence Assisted Fusion Technique Using Cilnidipine as a Model Drug , 2018 .

[22]  M. K. Das,et al.  Nanoprecipitation with sonication for enhancement of oral bioavailability of furosemide. , 2014, Acta Poloniae Pharmaceutica - Drug Research.

[23]  C. Lipinski.  Poor aqueous solubility-an industry wide problem in drug discovery , 2002 .

[24]  D. Quintanar-Guerrero,et al.  Preparation techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers. , 1998, Drug development and industrial pharmacy.