Quality by Design-based Optimization of Formulation and Process Variables for Controlling Particle Size and Zeta Potential of Spray Dried Incinerated Copper Nanosuspension

Author(s): Saurabh Singh, Sachin Kumar Singh*, Malti G. Chauhan, Bimlesh Kumar, Narendra Kumar Pandey, Barinder Kaur, Arun Kumar, Souvik Mohanta, Monica Gulati, Sheetu Wadhwa, Ankit Kumar Yadav, Pankaj Kumar Singh, Yogita Kumari, Gurmandeep Kaur, Rubiya Khursheed, A. Clarrisse

Journal Name: Recent Innovations in Chemical Engineering
Formerly Recent Patents on Chemical Engineering

Volume 12 , Issue 3 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: In the present study copper nanosuspension was prepared from Incinerated Copper Powder (ICP) by top down media milling. Glycyrrhiza glabra (GG) and Gum Acacia (GA) were used as stabilizers in the formulation.

Methods: Box Behnken Design was used to investigate the effect of formulation and process variables on particle size and zeta potential and optimize their ratio to get target product profile. The ratio of GA and GG to ICP was varied along with milling time and its speed. Further the prepared nanosuspensions were solidified using spray drying.

Results: The particle size was found to be decreased with the increase in GG to ICP ratio, milling time and milling speed, whereas, reverse effect on particle size was observed with an increase in GA to ICP ratio. The zeta potential was found to be increased with the increase in GG to CB ratio and milling speed and it decreased with the increase in GA to ICP ratio and milling time. The obtained value for particle size was 117.9 nm and zeta potential were -9.46 mV which was in close agreement with the predicted values by the design which was, 121.86 nm for particle size and -8.07 mV for zeta potential respectively. This indicated the reliability of optimization procedure. The percentage drug loading of copper in the nanosuspension was 88.26%. The micromeritic evaluation of obtained spray dried nanoparticles revealed that the particles were having good flow and compactibility.

Conclusion: It can be concluded that application of media milling, design of experiment and spray drying have offered very good copper nanosuspension that has the potential to be scaled up on industrial scale.

Keywords: Incinerated Copper Powder (ICP), Nanosuspension (NS), Media milling, Zeta potential, Particle size, Spray Drying (SD).

Asok A, Ghosh S, More PA, Chopade BA, Gandhi MN, Kulkarni AR. Surface defect rich ZnO quantum dots as antioxidants inhibiting a-amylase and a-glucosidase: A potential anti-diabetic nanomedicine. J Mater Chem B Mater Biol Med 2015; 3: 4597-606.
Ghosh S, More P, Nitnavare R, et al. Antidiabetic and antioxidant properties of copper nanoparticles synthesized by medicinal plant Dioscorea bulbifera. J Nanomed Nanotechnol 2015; S6: 1-9.
Li N, Zhao Y, Yang J. Effects of water-borne copper on digestive and metabolic enzymes of the giant freshwater prawn Macrobrachium rosenbergii. Arch Environ Contam Toxicol 2008; 55(1): 86-93.
[http://dx.doi.org/10.1007/s00244-007-9099-9] [PMID: 18175162]
Chan K. Some aspects of toxic contaminants in herbal medicines. Chemosphere 2003; 52(9): 1361-73.
[http://dx.doi.org/10.1016/S0045-6535(03)00471-5] [PMID: 12867165]
Kumar A, Nair AG, Reddy AV, Garg AN. Availability of essential elements in Bhasmas: Analysis of ayurvedic metallic preparations by INAA. J Radioanal Nucl Chem 2006; 270: 173-80.
Jagtap CY, Ashok BK, Patgiri BJ, Prajapati PK, Ravishankar B. Acute and subchronic toxicity study of tamra bhasma (incinerated copper) prepared from Ashodhita (Unpurified) and Shodhita (Purified) tamra in rats. Indian J Pharm Sci 2013; 75(3): 346-52.
[http://dx.doi.org/10.4103/0250-474X.117433] [PMID: 24082351]
Singare DS, Marella S, Gowthamrajan K, Kulkarni GT, Vooturi R, Rao PS. Optimization of formulation and process variable of nanosuspension: An industrial perspective. Int J Pharm 2010; 402(1-2): 213-20.
[http://dx.doi.org/10.1016/j.ijpharm.2010.09.041] [PMID: 20933066]
Singh SK, Srinivasan KK, Gowthamarajan K, Singare DS, Prakash D, Gaikwad NB. Investigation of preparation parameters of nanosuspension by top-down media milling to improve the dissolution of poorly water-soluble glyburide. Eur J Pharm Biopharm 2011; 78(3): 441-6.
[http://dx.doi.org/10.1016/j.ejpb.2011.03.014] [PMID: 21439378]
Müller RH, Jacobs C, Kayser O. Nanosuspensions as particulate drug formulations in therapy. Rationale for development and what we can expect for the future. Adv Drug Deliv Rev 2001; 47(1): 3-19.
[http://dx.doi.org/10.1016/S0169-409X(00)00118-6] [PMID: 11251242]
Mahesh KV, Singh SK, Gulati M. A comparative study of top-down and bottom-up approaches for the preparation of nanosuspensions of glipizide. Powder Technol 2014; 256: 436-49.
Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: A promising drug delivery strategy. J Pharm Pharmacol 2004; 56(7): 827-40.
[http://dx.doi.org/10.1211/0022357023691] [PMID: 15233860]
Singh SK, Vaidya Y, Gulati M, Bhattacharya S, Garg V, Pandey NK. Nanosuspensions: Principles, perspectives and practices. Curr Drug Deliv 2016; 13(8): 1222-46.
[http://dx.doi.org/10.2174/1567201813666160101120452] [PMID: 26721266]
Rabinow BE. Nanosuspensions in drug delivery. Nat Rev Drug Discov 2004; 3(9): 785-96.
[http://dx.doi.org/10.1038/nrd1494] [PMID: 15340388]
Date AA, Patravale VB. Current strategies for engineering drug nanoparticles. Curr Opin Colloid Interface Sci 2004; 9: 222-35.
Hüttenrauch R, Fricke S, Zielke P. Mechanical activation of pharmaceutical systems. Pharm Res 1985; 2(6): 302-6.
[http://dx.doi.org/10.1023/A:1016397719020] [PMID: 24271128]
Heng JYY, Thielmann F, Williams DR. The effects of milling on the surface properties of form I paracetamol crystals. Pharm Res 2006; 23(8): 1918-27.
[http://dx.doi.org/10.1007/s11095-006-9042-1] [PMID: 16850263]
Verma S, Gokhale R, Burgess DJ. A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions. Int J Pharm 2009; 380(1-2): 216-22.
[http://dx.doi.org/10.1016/j.ijpharm.2009.07.005] [PMID: 19596059]
Hajimohammadi R, Hosseini M, Amani H, Najafpour GD. Production of saponin biosurfactant from Glycyrrhiza glabra as an agent for upgrading heavy crude oil. J Surfactants Deterg 2016; 19: 1251-61.
Kumar B, Garg V, Singh S, et al. Impact of spray drying over conventional surface adsorption technique for improvement in micrometric and biopharmaceutical characteristics of self-nanoemulsifying powder loaded with two lipophilic as well as gastrointestinal labile drugs. Powder Technol 2018; 326: 42542.
Sood S, Jain K, Gowthamarajan K. Optimization of curcumin nanoemulsion for intranasal delivery using design of experiment and its toxicity assessment. Colloids Surf B Biointerfaces 2014; 113: 330-7.
[http://dx.doi.org/10.1016/j.colsurfb.2013.09.030] [PMID: 24121076]
Kaur P, Singh SK, Garg V, Gulati M, Vaidya Y. Optimization of spray drying process for formulation of solid dispersion containing polypeptide-k powder through quality by design approach. Powder Technol 2015; 284: 1-11.
Jyoti J, Anandhakrishnan NK, Singh SK, et al. A three-pronged formulation approach to improve oral bioavailability and therapeutic efficacy of two lipophilic drugs with gastric lability. Drug Deliv Transl Res 2019.
[http://dx.doi.org/10.1007/s13346-019-00635-0] [PMID: 30911996]
Verma S, Gokhale R, Burgess DJ. A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions. Int J Pharm 2009; 380(1-2): 216-22.
[http://dx.doi.org/10.1016/j.ijpharm.2009.07.005] [PMID: 19596059]
Elversson J, Millqvist-Fureby A. Particle size and density in spray drying-effects of carbohydrate properties. J Pharm Sci 2005; 94(9): 2049-60.
[http://dx.doi.org/10.1002/jps.20418] [PMID: 16052553]
Wang W, Duofour C, Zhou W. Impacts of spray-drying conditions on the physicochemical properties of soy sauce powders using maltodextrin as auxiliary drying carrier. CyTA -. J Funct Foods 2015; 13: 548-55.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 21 October, 2019
Page: [248 - 260]
Pages: 13
DOI: 10.2174/2405520412666190627144845
Price: $65

Article Metrics

PDF: 374