APPLICATION OF QUALITY by DESIGN (CCD TECHNIQUE) FOR SIMULTANEOUS ESTIMATION OF CEFIXIME AND OFLOXACIN BY HPTLC METHOD
Keywords:Cefixime, ofloxacin, Central Composite Design, High performance thin layer chromatography, Validation, optimisation
Objective: The present manuscript describes about simultaneous multiple response optimizations using the Derringer's desirability function for the estimation of cefixime and ofloxacin in bulk and pharmaceutical dosage form by using HPTLC method.
Methods: Central composite design (CCD) was used for the optimization of chromatographic conditions in HPTLC. The independent variables used for the optimization were n-butanol content in the mobile phase, chamber saturation time and distance travel. HPTLC separation was performed on aluminum plates pre-coated with silica gel 60 F 254 as the stationary phase using n-butanol: Ammonia: water (8:3:1 % v/v/v) as the mobile phase. Quantification was achieved by densitometric analysis of cefixime and ofloxacin over the concentration range of 20-120ng/band at 297 nm.
Results: The method gave compact and well-resolved band at Rf of 0.43Â±0.02 and 0.73Â±0.02 respectively for cefixime trihydrate and ofloxacin hydrochloride. The linear regression analysis for the calibration plots showed r2 = 0.99985 and r2 = 0.9989 for cefixime and ofloxacin respectively. The optimized method complies validation parameters like precision, accuracy, robustness, specificity, limit of detection and limit of quantification as per ICH guidelines.
Conclusion: The mobile phase composition, chamber saturation time and solvent front factors are evaluated in the robustness test. The selected factors were found to have a significant effect on the Rf value of both drugs. The optimized method contains 7 ml of n-butanol, 75 mm solvent front and 33 min of saturation time was used. So the optimization process reduces the solvent usage and increases separation sensitivity for both drugs. The results indicate the CCD method is suitable for the routine quality control testing of marketed tablet formulation and bulk drugs.
Keywords: Cefixime, Ofloxacin, Central Composite Design (CCD), High-performance thin layer chromatography (HPTLC), Validation, Optimization
http://www.drugbank.ca/drugs/DB00671. [Last accessed on 10 Jan 2016].
https://en.wikipedia.org/wiki/Cefixime. [Last accessed on 10 Jan 2016].
https://en.wikipedia.org/wiki/Ofloxacin. [Last accessed on 10 Jan 2016].
Indian Pharmacopoeia: Ministry of Health and Family Welfare, Indian Pharmacopoeial commission, Ghaziabad; 2014. p. 254, 856.
ICH Topic Q8 (R2); ICH harmonised tripartite guideline,â€ in Proceedings of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH â€™09): Pharmaceutical Development; 2009.
ICH Topic Q2 (R1); ICH harmonised tripartite guideline,â€ in Proceedings of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH â€™94): Validation of Analytical Procedures; 1994.
ICH Topic Q9;ICH harmonised tripartite guideline,â€ in Proceedings of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH â€™94) Quality Risk Management; 2005.
Attimarad M. Simultaneous determination of ofloxacin and flavoxate hydrochloride by first and ratio first derivative UV spectrophotometry. J Iranian Chem Soc 2012;9:1â€“7.
Gonzalez-Hernandez R, Nuevas-Paz L, Soto-Mulet L, Lopez-Lopez M, Hoogmartens J. Reversed-phase high-performance liquid chromatographic determination of cefixime in bulk drugs. J Liq Chromatogr Relat Technol 2001;24:2315â€“24.
Pawar SJ, Kale AP, Amrutkar MP, Jagade JJ, Pore NS, Bhosale AV. HPTLC estimation of cefixime and cloxacillin in tablet dosage form. Asian J Res Chem 2010;3:299â€“301.
Chaitanya Krishna A, Vignesh R, Chelladurai R, Rajaram S Patil. A highly specific, sensitive and high-throughput method for the determination of ofloxacin in human plasma by liquid chromatography coupled with tandem mass. Asian J Pharm Clin Res 2012;5:174-9.
Umamaheswari D, Jayakar B. Analytical method development, and validation for the simultaneous estimation of nimorazole and ofloxacin in pure and its pharmaceutical dosage form by RP-HPLC. Asian J Pharm Anal Med Chem 2014;2:268-75.
Prabhu S, Vijay Amirtharaj R, Senthilkumar N. Simultaneous RP-HPLC method development and validation of cefixime and ofloxacin in tablet dosage form. Asian J Res Chem 2010;3:367-9.
Khandagle KS, Gandhi SV, Deshpande PB, Kale AN, Deshmukh PR. High-performance liquid chromatographic determination of cefixime and ofloxacin in combined tablet dosage form. J Chem Pharm Res 2010;2:92-6.
Mahesh V Attimarad, Ahmed O Alnajjar. A conventional HPLC-MS method for the simultaneous determination of ofloxacin and cefixime in plasma development and validation. J Basic Clin Pharm 2013;4:36â€“41.
D Zendelovska, T Stafilov, P Milosevski. A highâ€performance liquid chromatographic method for determination of cefixime and cefotaxime in human plasma. Bull Chem Technol Maced 2003;22:39â€45.
Rao J. Validated HPTLC method for simultaneous quantitation of cefixime and ofloxacin in bulk drug and in a pharmaceutical formulation. Pharmacie Globale (IJCP) 2011;4:1-5.
Patel Satish A, Patel Natavarlal J. Development and validation of RP-HPLC method for simultaneous estimation of cefixime trihydrate and ofloxacin in tablets. Int J Pharm Res Biosci 2012;1:516-29.
Meng F, Chen X, Zeng Y, Zhong D. Sensitive liquid chromatography-tandem mass spectrometry method for the determination of cefixime in human plasma: application to a pharmacokinetic study. J Chromatogr B: Anal Technol Biomed Life Sci 2005;819:277-82.
Audumbar Digambar Mali, Ritesh Bathe, Ashpak Tamboli. Simultaneous determination of Cefixime trihydrate and Ofloxacin in pharmaceutical dosage form by second order derivative UV spectrophotometry. Int J Adv Pharm Anal 2015;(5 Suppl 2):42-6.
Ao Alnajjar. Simultaneous determination of ofloxacin and cefixime in tablet formulation using capillary electrophoresis. J Liq Chromatogr Relat Technol 2013;36:36-41.
P Borman, P Nethercote, M Chatfield. The application of quality by design to analytical methods. PharmTech; 2007.
MM Hendriks, JH De Boer, AK Smilde, DA Doornbos. Multicriteria decision making. Chemom Intell Lab Syst 1992;16:175-91.
T Sivakumar, R Manavalan, K Valliappan. Global optimization using derringerâ€™s desirability function: Enantioselective determination of ketoprofen in the formulation and in biological matrices. Acta Chromatogr 2007;19:29-47.
V Sree Janardhanan, R Manavalan, K Valliappan. Chemometric technique for the optimization of the chromatographic system. Simultaneous HPLC determination of Rosuvastatin, Telmisartan, Ezetimibe and Atorvastatin used in combined cardiovascular therapy. Arabian J Chem 2012;1-10. Doi:10.1016/J.Arabjc.2012.03.001. [Article in Press]
TB Solanki, PA Shah, KG Patel. Central composite design for validation of HPTLC method for simultaneous estimation of olmesartan medoxomil, amlodipine besylate and hydrochlorothiazide in tablets. Indian J Pharm Sci 2014;76:179-87.
JH Zar. Biostatical analysis: Pearson Education Inc. New Jersey; 2010.
G Kleinschmidt. In: Ermer J, Miller JHM. Eds. Method validation in pharmaceutical analysis. A Guide to Best Practice, Wiley-VCH Verlag GmbH and Co. KGaA, Weinheim; 2005.