PREPARATION, PHYSICAL CHARACTERIZATION, AND PHARMACOKINETIC STUDY OF DOCETAXEL NANOCRYSTALS

  • ARVIND GANNIMITTA Aurobindo Pharma Pvt., Ltd., Hyderabad, Telangana, India.
  • PRATHIMA SRINIVAS Shantha Biotechnics Private Limited, Hyderabad, Telangana, India.
  • VENKATESHWAR REDDY A Anwarul Uloom College of Pharmacy, Hyderabad, Telangana, India.
  • PEDIREDDI SOBHITA RANI Vijaya College of Pharmacy, Munaganur, Hayathnagar, Hyderabad, Telangana, India.

Abstract

Objective: The main objective of this study was to prepare and evaluate the nanocrystal formulation of docetaxel.


Methods: Docetaxel nanocrystals were formulated to improve the water solubility. Docetaxel nanocrystals were prepared by nanoprecipitation method using Tween 80, egg lecithin, and povidone C-12 as stabilizers and poly(lactic-co-glycolic acid) (PLGA) as polymer in acceptable limits. A total of 16 formulations were prepared by changing stabilizer and polymer ratios. The prepared nanocrystals were characterized by particle size, zeta potential, crystalline structure, surface morphology, assay, saturation solubility, and in vitro drug release.


Results: Based on particle size, polydispersity index, and zeta potential data, four formulations were optimized. The formulation containing Tween 80 as stabilizer has shown lowest particle size and better drug release than the formulations containing egg lecithin and povidone C-12 as stabilizers. The formulation containing Tween 80 and PLGA has shown still lower sized particles than the Tween 80 alone and exhibited prolonged sustained drug release. The release kinetics of formulations containing Tween 80 and PLGA followed zero-order release kinetics and formulations containing egg lecithin and povidone C-12 followed Higuchi diffusion (non-Fickian).


Conclusion: From the study, we concluded that as the type and concentration of stabilizer changed the size and shape of the crystals were also changed and the formulations showed sustained drug release with non-Fickian diffusion.

Keywords: Docetaxel, Nanocrystals,, Tween 80, Egg lecithin,, Povidone C-12,, Poly(lactic-co-glycolic acid).

Author Biographies

PRATHIMA SRINIVAS, Shantha Biotechnics Private Limited, Hyderabad, Telangana, India.

Shantha Biotechnics Private Limited, Hyderabad, Telangana, India

VENKATESHWAR REDDY A, Anwarul Uloom College of Pharmacy, Hyderabad, Telangana, India.

Anwarul Uloom college of Pharmacy, Hyderabad, Telangana, India

PEDIREDDI SOBHITA RANI, Vijaya College of Pharmacy, Munaganur, Hayathnagar, Hyderabad, Telangana, India.

Vijaya College of Pharmacy, Munaganur, Hayathnagar, Hyderabad, Telangana, India.

References

1. Mousa SA, Bharali DJ. Nanotechnology-based detection and targeted therapy in cancer: Nano-bio paradigms and applications. Cancers (Basel) 2011;3:2888-903.
2. Shahira FE, Essam E, Adel AA, Ahmed AA. Enhancement of lornoxicam solubility by inclusion complexation with cyclodextrin: Preparation and characterization. Int J Pharm Pharm Sci 2017;9:132-8.
3. Bawa R. Nanoparticle-based therapeutics in humans: A survey. Nanotechnol Law Bus 2008;5:135-55.
4. Daraei B, Aghvami M, Pourahmad J, Dinarvand R. A comparison of hepatocyte cytotoxic mechanisms for docetaxel and PLGA-docetaxel nanoparticls. Iran J Pharm Res 2017;16:249-65.
5. Yared JA, Tkaczuk KH. Update on taxane development: New analogs and new formulations. Drug Des Devel Ther 2012;6:371-84.
6. Fauzee NJ. Taxanes: Promising anti-cancer drugs. Asian Pac J Cancer Prev 2011;12:837-51.
7. Velasco R, Bruna J. Taxane-induced peripheral neurotoxicity. Toxics 2015;3:152-69.
8. Matesanz R, Barasoain I, Yang CG, Wang L, Li X, de Inés C, et al. Optimization of taxane binding to microtubules: Binding affinity dissection and incremental construction of a high-affinity analog of paclitaxel. Chem Biol 2008;15:573-85.
9. Hart M, Acott S. Physical and chemical stability of taxotere (docetaxel) one-vial (20 mg/ml) infusion solution following refrigerated storage. Ecancermedicalscience 2010;4:202.
10. Qiu S, Liu Z, Hou L, Li Y, Wang J, Wang H, et al. Complement activation associated with polysorbate 80 in beagle dogs. Int Immunopharmacol 2013;15:144-9.
11. Varaporn BJ, Boontida M. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci 2015;10:13-23.
12. Li Q, Cai T, Huang Y, Xia X, Cole SPC, Cai Y, et al. A review of the structure, preparation, and application of NLCs, PNPs, and PLNs. Nanomaterials (Basel) 2017;7:122.
13. Savjani KT, Gajjar AK, Savjani JK. Drug solubility: Importance and enhancement techniques. ISRN Pharm 2012;2012:195727.
14. Deng J, Huang L, Liu F. Understanding the structure and stability of paclitaxel nanocrystals. Int J Pharm 2010;390:242-9.
15. Mosallaei N, Jaafari MR, Hanafi-Bojd MY, Golmohammadzadeh S, Malaekeh-Nikouei B. Docetaxel-loaded solid lipid nanoparticles: Preparation, characterization, in vitro, and in vivo evaluations. J Pharm Sci 2013;102:1994-2004.
16. Athul PV. Preparation and characterization of simvastatin nanosuspension By homogenization method. Int J Pharm Tech Res 2013;5:193-7.
17. Anita PP, Patel JK, Kishubu SP. A review on drug nanocrystal a carrier free drug delivery. Int J Res Ayurveda Pharm 2011;2:448-58.
18. Tuomela A, Hirvonen J, Peltonen L. Stabilizing agents for drug nanocrystals: Effect on bioavailability. Pharmaceutics 2016;8:E16.
19. Sun J, Wang F, Sui Y, She Z, Zhai W, Wang C, et al. Effect of particle size on solubility, dissolution rate, and oral bioavailability: Evaluation using coenzyme Q10 as naked nanocrystals. Int J Nanomedicine 2012;7:5733-44.
20. Hanafy A, Spahn-Langguth H, Vergnault G, Grenier P, Tubic Grozdanis M, Lenhardt T, et al. Pharmacokinetic evaluation of oral fenofibrate nanosuspensions and SLN in comparison to conventional suspensions of micronized drug. Adv Drug Deliv Rev 2007;59:419-26.
21. Gao L, Zhang D, Chen M, Duan C, Dai W, Jia L, et al. Studies on pharmacokinetics and tissue distribution of oridonin nanosuspensions. Int J Pharm 2008;355:321-7.
22. Ali HS, York P, Ali AM, Blagden N. Hydrocortisone nanosuspensions for ophthalmic delivery: A comparative study between microfluidic nanoprecipitation and wet milling. J Control Release 2011;149:175-81.
23. El-Gendy N, Pornputtapitak W, Berkland C. Nanoparticle agglomerates of fluticasone propionate in combination with albuterol sulfate as dry powder aerosols. Eur J Pharm Sci 2011;44:522-33.
24. Mitri K, Shegokar R, Gohla S, Anselmi C, Müller RH. Lutein nanocrystals as antioxidant formulation for oral and dermal delivery. Int J Pharm 2011;420:141-6.
25. Müller RH, Jacobs C. Buparvaquone mucoadhesive nanosuspension: Preparation, optimisation and long-term stability. Int J Pharm 2002;237:151-61.
26. Anju G, Rupa M, Kamla P. Formulation, optimization and characterization of ziprasidone nanocrystals prepared by media milling technique. Int J Pharm Pharm Sci 2015;7:146-50.
27. Vidyavathi M, Sandya P, Sarika B. Nanotechnology in development of drug delivery system. Int J Pharm Sci Res 2012;3:84-96.
28. Bosselmann S, Nagao M, Chow KT, Williams RO 3rd. Influence of formulation and processing variables on properties of itraconazole nanoparticles made by advanced evaporative precipitation into aqueous solution. AAPS PharmSciTech 2012;13:949-60.
29. Kakran M, Shegokar R, Sahoo NG, Gohla S, Li L, Müller RH, et al. Long-term stability of quercetin nanocrystals prepared by different methods. J Pharm Pharmacol 2012;64:1394-402.
30. Alessandra V, Jean J, Espitalier F, Mariaines R, Vicosa A. An innovative antisolvent precipitation process as a promising technique to prepare ultrafine rifampicin particles. J Cryst Growth 2012;342:80-7.
31. Basavaraj KN, Ganesh KD, Hiren MB, Veerendra KN, Manvi FV. Design and characterization of nanocrystals of lovastatin for solubility and dissolution enhancement. J Nanomed Nanotechnol 2011;2:1-7.
Statistics
204 Views | 80 Downloads
Citatons
How to Cite
ARVIND GANNIMITTA, PRATHIMA SRINIVAS, VENKATESHWAR REDDY A, and PEDIREDDI SOBHITA RANI. “PREPARATION, PHYSICAL CHARACTERIZATION, AND PHARMACOKINETIC STUDY OF DOCETAXEL NANOCRYSTALS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 6, Apr. 2019, pp. 238-44, doi:10.22159/ajpcr.2019.v12i6.32856.
Section
Original Article(s)