Formulation optimization and evaluation of Cefdinir nanosuspension using 23 Factorial design

Abstract

Poor water solubility and slow dissolution rate are the prime issues for the majority of upcoming and existing biologically active compounds. Cefdinir is a poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of the present investigation was to increase the solubility and dissolution rate of Cefdinir by preparation of its nanosuspension by solvent evaporation technique. The prepared formulation of nanosuspension was evaluated for its particle size, total drug content, entrapment efficiency, saturation solubility and in vitro dissolution. The optimized formulation was spray dried to obtain nanoparticles. The prepared nanoparticles were then evaluated for their particle size, saturation solubility and in-vitro drug release and the results were compared with the pure drug. A 23 factorial design was employed to study the effect of independent variables, amount of PVPK30 (X1), Poloxamer-188 (X2) and stirring rate (X3) on the dependent variables, particle size (nm,Y1) and in-vitro drug release (%, Y2). Validity of the developed mathematical equation was assayed by designing to check point. The results indicated the suitability of solvent evaporation method for Cefdinir with improved in vitro dissolution rate and thus perhaps enhance fast onset of action for the drug.

Keywords

• Cefdinir
• nanosuspension
• solvent evaporation
• factorial design
• spray dryer

References

1. [1] Mandal S, Phadtare S, Sastry M. Interfacing biology with nanoparticles. Curr Appl Phys. 2005; 5: 118-127.
2. [2] Muller RH, Gohla S, Keck CM. State of the art of nanocrystals - Special features, production, nanotoxicology aspects and intracellular delivery. Eur J Phar Biopharm. 2011; 78(1): 1-9.
3. [3] Kocbek P, Baumgartner S, Kristl J. Preparation and evaluation of nanosuspensions for enhancing the dissolution of poorly soluble drugs. Int J Pharm. 2006; 312(1-2): 179-186.
4. [4] Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: A promising drug delivery strategy. J Pharm Pharmacol. 2004; 56: 827-840.
5. [5] Liu Y, Xie P, Zhang D, Zhang Q. A mini review of nanosuspensions development. J Drug Target. 2012; 20(3): 209-223.
6. [6] Sastry SV, Nyshadham JR, Fix JA. Recent technological advances in oral drug delivery – a review. Pharm Sci Technol Today. 2000; 3(4): 138-145.
7. [7] Junyaprasert VB, Morakul B. Nanocrystals for enhancement of oral bioavailability of poorly water-soluble drugs. Asian J Pharm Sci. 2015; 10(1): 13-23.
8. [8] Mathur P, Saroha K, Syan N, Verma S, Kumar V. Floating drug delivery system: An innovative acceptable approach in gastroretentive drug delivery. Arch Appl Sci Res. 2010; 2(2): 257-270.

9. [9] Desai S, Bolton SA. A floating controlled release drug delivery system: In vitro-In vivo evaluation. Pharm Res. 1993; 10(9): 1321-1325.
10. [10] Oxford Handbook of Infectious Diseases and Microbiology. OUP Oxford; ISBN 9780191039621, 2009, pp. 56.
11. [11] Jadhav JB, Girawale NN, Chaudhari RA. Quality by Design (QBD) approach used in development of pharmaceuticals. Int J Pure App Biosci. 2014; 2(5): 214-223.
12. [12] Jacobs C, Kayser O, Müller RH. Nanosuspensions as a new approach for the formulation for the poorly soluble drug tarazepide. Int J Pharm. 2000; 196(2): 161-164.
13. [13] Singh V, Malik S. Formulation of alternative dosage form for Cephalosporin (Cefdinir). Asian J Biomed Pharm Sci. 2014; 4(33): 29-42.
14. [14] Bansal S, Aggarawal G, Chandel P, Harikumar SL. Design Development of cefdinir niosomes for oral delivery. J Pharm Bio Sci. 2013; 5(4): 318-325.
15. [15] Shid RL, Dhole SN, Kulkarni N, Shid SL. Formulation and evaluation of Nanosuspension delivery system for Simvastin. Int J Pharm Sci Nanotech. 2014; 7(2): 2459-2476.
16. [16] Shid RL, Dhole SN, Kulkarni N, Shid SL. Formulation and evaluation of Nanosuspension formulation for drug delivery system for Simvastin. Int J Pharm Sci Nanotech. 2014; 7(4): 2650-2665.
17. [17] Dandagi P, Kerur S, Mastiholimath V. Polymeric ocular nanosuspension for controlled release of acyclovir: In vitro release and ocular distribution. Iran J Pharm Res. 2009; 8(2): 79-86.
18. [18] Kalvakuntla S, Deshpande M, Attari Z, Koteshwara KB. Preparation and Characterization of Nanosuspension of Aprepitant by H96 Process. Adv Pharm Bull. 2016; 6(1): 83-90.
19. [19] Thota S, Syed MA, Bomma R, Veerabrahma K. Development and In vivo Evaluation of Cefdinir Nanosuspension for Improved Oral Bioavailability. Int J Pharm Sci Nanotech. 2014; 7(3): 2553-2560.
20. [20] Hussein FM, Ahmed NA, Hayder KA. Preparation and Evaluation of Ketoprofen Nanosuspension Using Solvent Evaporation Technique. Iraqi J Pharm Sci. 2017; 26(2): 41-55.
21. [21] Sahu BP, Das MK. Nanosuspension for enhancement of oral bioavailability of felodipine. App Nano Sci. 2014; 4: 189–197.
22. [22] Shetiya P, Vidyadhara S, Ramu A, Reddyvalam LS. Development and characterization of a novel nanosuspension based drug delivery system of valsartan: A poorly soluble drug. Asian J Pharm. 2015; 9: 29-34.
23. [23] Thakkar HP, Patel BV, Thakkar SP. Development and characterization of nanosuspension of olmisartan medoxomil for bioavailability. J Pharm Bioall Sci. 2011; 3(3): 426–434.