Stabilizers used in nanocrystal based drug delivery systems

  • Ganesh Shete
  • Hemant Jain
  • Deeksha Punj
  • Hitesh Prajapat
  • Priya Akotiya
  • Arvind Kumar Bansal National Institute of Pharmaceutical Education and Research (NIPER), India

Abstract

Nanocrystals have emerged as a viable tool to enhance oral bioavailability of poorly water soluble drugs. They also enable parenteral administration of these drugs as nanosuspensions. The high surface free energy due to the large surface area to volume ratio of nanocrystals, makes them prone to aggregation, that can lead to physical instability and loss of solubility/dissolution advantage. Stabilizers are incorporated into nanocrystalline formulations to prevent aggregation and these include excipients such as polymers and surfactants. They achieve stabilization by electrostatic repulsion and/or steric hindrance. This article focuses on phenomenon of aggregation in nanocrystal based formulations, stabilizers for inhibition of aggregation, classification of stabilizers, properties of stabilizers and the mechanisms involved in stabilization. A compilation of stabilizers, drugs stabilized, formulation types and techniques used for generation of nanocrystals have been presented. Current challenges and future trends in the field of stabilizers have also been highlighted.

Author Biography

Arvind Kumar Bansal, National Institute of Pharmaceutical Education and Research (NIPER), India
RESUME

ARVIND K BANSAL

Educational Qualifications

April 1994 Doctor of Philosophy in Pharmacy from Delhi University on thesis entitled “Development of an Improved Drug Delivery System using Prodrug Approach

July 1988 Master of Pharmacy (Pharmaceutics) from Delhi University with 71.2 % marks

July 1986 Bachelor of Pharmacy from Delhi University with 71.0 % marks

Additional Qualification

July 2001 One and a half month certificate course in “Introduction to Intellectual Property” conducted by World Intellectual Property Organization (WIPO) Academy, Geneva, Switzerland

Professional profile

Positions held

May, 2008 onwards

Professor and Head, Department of Pharmaceutics, NIPER

June 2003 – April 2008

Associate Professor, Department of Pharmaceutical Technology (Formulations), NIPER

August 2000 – May 2003

Assistant Professor, Department of Pharmaceutical Technology (Formulations), NIPER

August 1995 to August 2000 (5 years)

Group Leader at Ranbaxy Research Labs, Gurgaon, Haryana, India

April 1993 to July 1995 (2 years and 4 months)

Research Scientist at JK Pharmaceuticals Shripati Singhania R & D Centre at Faridabad , Haryana.

February 1989 to January 1993

UGC Senior Research Fellow at College of Pharmacy (Delhi University), New Delhi.

Areas of Interest

Pre-formulation Profiling

Biopharmaceutical mapping of salt forms

Solid state characterization

Permeability profiling using Caco 2 cell lines and animal models

Molecular behaviour of powders during compaction

Enhancement of aqueous solubility

Molecular understanding of ‘stabilized’ amorphous forms

Nano-crystalline solid dispersions

Improvement of oral bioavailability - using formulation interventions like lipidic systems, nanoparticles, inclusion complexes etc.

Protein formulations

Interaction with preservatives

Stabilization during lyophilization

Scientific Publications and Presentations

Patent granted / applications – 26

Research papers – 60

Review articles – 16

General articles – 18

Book Chapters – 4

Conference presentations – 36

Selected Publications

1. Srivastava A, Mishra S, Tandon P, Patel S, Ayala AP , Bansal AK and Siesler HW. Moleculat structure and vibrational spectroscopic analysis of an antiplatelet drug; clopidogrel hydrogen sulphate (form 2) – A combined experimental and quantum chemical approach. Journal of Molecular Structure, 2010, 964, 88-96

2. Alam S, Patel S and Bansal AK. Effect of Sample Preparation Method on Quantification of Polymorphs using PXRD. Pharmaceutical Development and Technology, 2010

3. Bora P, Puri V and Bansal AK. Physicochemical Properties and Excipient Compatibility Studies of Probiotic Bacillus coagulans Spores. Scientia Pharmaceutica, 2009, 77(3) 625–637

4. Chawla G, Bansal AK. Molecular Mobility and Physical Stability of Amorphous Irbesartan. Scientia Pharmaceutica, 2009, 77(3) 695–709

5. Sharma SS, Srinivasan SK, Krishnamoorthy S, Kaushal AM and Bansal AK. Preclinical safety Pharmacology studies on the amorphous formulation of celecoxib. Arznemittelforschung, 2009, 59(5), 254-262.

6. Kaushal A, Chakraborti AK and Bansal AK, FTIR Studies on differential intermolecular association in crystalline and amorphous states of structurally related non-steroidal anti-inflammatory drugs, Molecular Pharmaceutics, 2008, 5 (6), 937–945.

7. Bansal SS, Kaushal A and Bansal AK, Co-relationship of Physical stability of amorphous dispersions with enthalpy relaxation. Die Pharmazie, 2008, 63(11), 812-814.

8. Mohammaed GA, Puri V and Bansal AK, Co-processing of nevirapine and stavudine by spray drying. Pharmaceutical Development and Technology, 2008, 13(4), 299-310.

9. Kaushal A and Bansal AK, Thermodynamic behavior of glassy state of structurally related compounds. European Journal of Pharmaceutics and Biopharmaceutics, 2008, 69(3), 1067-1076.

10. Kumar S, Chawla G and Bansal AK. Characterization of solid-state forms of mebendazole. Die Pharmazie, 2008;63(2):136-43.

11. Patel S, Kaushal AM, and Bansal AK, Compaction behavior of roller compacted ibuprofen. Eur J Pharm Biopharm, 2008, 69, 743-749.

12. Patel S, Kaushal AM, and Bansal AK, Lubrication potential of magnesium stearate studied on instrumented rotary tablet press. AAPS PharmSciTech 2007, 8(4), Article 89, E1-E8.

13. Chawla G, and Bansal AK, A comparative assessment of solubility advantage from glassy and crystalline forms of a water-insoluble drug. Eur J Pharm Sci 2007, 32, 45-57.

14. Tiwari M, Chawla G, and Bansal AK, Quantification of olanzapine polymorphs using powder X-ray diffraction technique. J Pharm Biomed Anal 2007, 43 (3), 865-872.

15. Patel S, Kaushal AM, Bansal AK, Effect of particle size and compression force on compaction behavior and derived mathematical parameters of compressibility. Pharm Res 2007, 24(1), 111-124.

16. Banga S, Chawla G, Varandani D, Mehta BR, Bansal AK, Modification of the crystal habit of celecoxib for improved processability. J Pharm Pharmacol 2007, 59(1), 29-39.

17. Rao KP, Chawla G, Kaushal AM, Bansal AK. Impact of solid-state properties on lubrication efficacy of magnesium stearate. Pharm Dev Technol 2005, 10(3), 423-437.

18. Gupta P, Kakumanu VK, Bansal AK. Stability and solubility of celecoxib–PVP amorphous dispersions: a molecular perspective. Pharm Res 2004, 21(10), 1762-1769.

19. Gupta P, Chawla G, Bansal AK. Physical stability and solubility advantage from amorphous celecoxib: The role of thermodynamic quantities and molecular mobility. Mol Pharm 2004, 1(6), 406-413.

20. Chawla G, Gupta P, Thilagavathi R, Chakraborti AK, Bansal AK. Characterization of solid–state forms of celecoxib. Eur J Pharm Sci 2003, 20(3), 305–317.

Industrial Consultancy Projects

More than 125 projects completed with overseas and Indian pharmaceutical companies.

Awards and Honors

AAiPS Distinguished Educator and Researcher Award for the Year 2008

This award is given to a faculty member from a recognized Indian Pharmacy education and research center. The mission of American Association of Indian Pharmaceutical Scientists (AAiPS) is to provide a forum for discussion, continuing education, and exchange of ideas on advances in pharmaceutical sciences and technology.

Innocentive award, in the area of formulation development - April 2005, May 2006 and June 2007.

Innocentive (www.innocentive.com) is a web-based community, managed by a sister concern of Eli Lilly,USA and facilitates pharmaceutical scientists to address challenges faced by chemical and pharmaceutical companies, from around the globe.

OPPI (Organization of Pharmaceutical Producers of India (OPPI) Scientist Award 2006

This award was conferred in September 2006, for outstanding contribution in the area of Pharmaceutics. The OPPI, established in 1965, is a premier organization of pharmaceutical manufacturers in India. Its membership consists of companies with international collaboration and large Indian companies. It represents primarily research based companies in India. OPPI is not only an industry association but also a scientific and professional body.

E Mail Address

akbansal@niper.ac.in

 

Published
2014-12-19
How to Cite
SHETE, Ganesh et al. Stabilizers used in nanocrystal based drug delivery systems. Journal of Excipients and Food Chemicals, [S.l.], v. 5, n. 4, p. 184-209, dec. 2014. ISSN 21502668. Available at: <https://ojs.abo.fi/ojs/index.php/jefc/article/view/883>. Date accessed: 20 sep. 2019.
Section
Reviews

Keywords

Nanocrystal; Aggregation; Physical stabilization; DLVO theory; Stabilizer excipients