SYNTHESIS, CHARACTERIZATION AND QUANTITATION OF REGIOISOMERIC IMPURITY IN NIMODIPINE BULK AND FORMULATION

Authors

  • Gauri P. Jadhav Department of Quality Assurance Techniques, Sanjivani College of Pharmaceutical Education and Research, Kopargaon, Maharashtra, India, 423601
  • Veena S. Kasture Department of Quality Assurance Techniques, Sanjivani College of Pharmaceutical Education and Research, Kopargaon, Maharashtra,India, 423601
  • Sarita S. Pawar Department of Medicinal Chemistry, Sanjivani College of Pharmaceutical Education and Research, Kopargaon, Maharashtra, India, 423601
  • Ashish P. Lodha Department of Pharmaceutics, Sanjivani College of Pharmaceutical Education and Research, Kopargaon, Maharashtra, India, 423601
  • Anuja R. VADGAONKAR Department of Quality Assurance Techniques, Sanjivani College of Pharmaceutical Education and Research, Kopargaon, Maharashtra,India, 423601
  • Rohit K. Ajage Department of Quality Assurance Techniques, Sanjivani College of Pharmaceutical Education and Research, Kopargaon, Maharashtra, India, 423601
  • Shraddha G. Deshpande Department of Quality Assurance Techniques, Sanjivani College of Pharmaceutical Education and Research, Kopargaon, Maharashtra, India, 423601

Keywords:

NI, IR, NMR, GCMS, RP-HPLC, Validation

Abstract

Objective: The present research work was directed towards the synthesis characterization and quantitation of regioisomeric impurity of Nimodipine i.e. diethyl 1, 4-dihydro-2,6-dimethyl pyridine dicarboxylate in bulk and tablet formulation, by UV,IR,NMR and GC-MS techniques and a RP-HPLC method was developed as per ICH Q2B guidelines for quantitation of 1, 4-Dihydro-2, 6-Dimethyl-4-(p-nitro phenyl) pyridine-3,5 dicarboxylate (NI) from bulk and formulation.

Methods: The synthesis of NI was carried out by Hantzch pyridine synthesis, by using p-nitrobenzaldehyde, ethylacetoacetate, in presence of ammonia and methanol as a catalyst. The percentage yield was found to be 89.29%. Recrystallization and purification of NI was done. The preliminary evaluation was done on laboratory scale via melting point, elemental analysis and TLC.

Results: The melting point of impurity was found to be 156-1580C. The TLC of impurity was carried by using Chloroform: Methanol (9:1) and the Rf was found to be 0.79. The confirmation of structure of NI was carried out by using sophisticated techniques i.e., FT-IR, NMR (13C and 1H), GC-MS etc. The RP-HPLC method was developed to quantify the NI in Nimodipine bulk and formulation as per ICH Q2B guidelines. The method validation was done as per ICH guidelines.

Conclusion: The validated optimized method was found to be linear, précised, robust, rugged and accurate. Finally NI was quantified from bulk Nimodipine and its marketed tablet formulation. It was concluded that the amount of NI, present in tablet was found to be 0.1% and in the bulk 0.067% respectively. Thus it was revealed that the NI was found to be within the limit laid down ICH guidelines (Not more than 0.1 %).

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References

British Pharmacopoeia, Volume II, The Department of Health, British Pharmacopoeia Commission Office, 1st edition, (2011):1547-1548.

Ahuja S., Impurities Evaluation of Pharmaceuticals, 1st edition, India: Marcel Dekker, (2006): 85- 108.

Federal Register, International Conferences on Harmonization, Impurities Testing Guideline, Impurities in New Drug Substances, The European Agency for the Evaluation of Medicinal Products, Q3A, (1995):1-11.

Federal Register, International Conferences on Harmonization, Impurities in New Drug Substances U.S. Department of Health and Human Services Food and Drug Administration Centre for Drug Evaluation and Research (CDER), Centre for Biologics Evaluation and Research (CBER), Q3A, (2008):1-14.

Bari S.B., Kadam B.R., Jaiswal Y.S., Shirkhedkar A.A., Impurity Profile: Significance in Active Pharmaceutical Ingredients, Eurasian Journal of Analytical Chemistry, (2007); 2(1):32-53.

Shah R.S., Patel M.A., Naik M.V., Pradhan P.K., Recent Approaches of Impurity Profiling in Pharmaceutical Analysis: A Review, International Journal of Pharmaceutical Sciences and Research, (2012); 3(10):3603-3617.

Federal Register, International Conferences on Harmonization, Guidance for Industry: Impurities Residual Solvents, U.S. Department of Health and Human Services Food and Drug Administration, (CDER), Q3C, (1997):1-13.

Rao N.R., Mani Kiran S.S., Prasanthi N.L., Pharmaceutical Impurities: An Overview, Indian J.Pharm.Educ. Res., (2010); 44(3):301-310.

Tegeli V.S., Gajeli G.K., Chougule G.K., Thorat Y.S., Shivsharan U.S. , Kumbhar, S.T., Significance of Impurity Profiling: A review, International Journal of Drug Formulation and Research, (2011); 2(4):174-195.

Federal Register, International Conferences on Harmonization, Impurities in New Drug Products, European Medicines Agency, Q3B (R2), (2006):3-14.

Abiedalla YFH, Abdel-Hay K., DeRuiter J., Clark C.R., Synthesis and GC-MS Analysis of a Series of Homologs and Regioisomers of 3, 4-methylenedioxypyrovalerone (MDPV), Forensic Science International (2012); 223(1-3):189-197.

Belal T., Awad T., DeRuiter J., Clark C.R., GC–MS Studies on Acylated Derivatives of 3-methoxy-4-methyl- and 4-methoxy-3-methyl-phenethylamines: Regioisomers Related to 3, 4-MDMA, Forensic Science International, (2008); 178:61-82.

Skoog D.A., West D.M., Holler F.J., Crouch S.R., Fundamentals of Analytical Chemistry, 8th edition, Singapore, Thomson Brooks/cole, (2004):906-946.

Silverstein R. M., Webster F. X., Spectrometric Identification of Organic Compounds, Published by, John Wiley and Sons publications, 6th edition(2005):81-109.

David R., Synthesis and NMR Characterization of Six Regioisomeric Impurities of Mono-o-phosphates of octyl 2-acetamido-2-deoxy-4-o-(B-D-galactopyranosyl)-B-D-glucopyranoside,Edmonton,Alberta fall, University of Alberta, (2000):1-153.

Federal Register, International Conferences on Harmonization, Guidance for Industry, Validation of Analytical Procedures: Methodology U.S. Department of Health and Human Services Food and Drug Administration, (CDER), (CBER), Q2B, (1996):1-10.

Federal Register, International Conferences on Harmonization, Impurities in New Medicinal Products, 3AQ12a, (1996):95-105.5.

Published

01-07-2014

How to Cite

Jadhav, G. P., V. S. Kasture, S. S. Pawar, A. P. Lodha, A. R. VADGAONKAR, R. K. Ajage, and S. G. Deshpande. “SYNTHESIS, CHARACTERIZATION AND QUANTITATION OF REGIOISOMERIC IMPURITY IN NIMODIPINE BULK AND FORMULATION”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 7, July 2014, pp. 400-7, https://www.innovareacademics.in/journals/index.php/ijpps/article/view/1777.

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