6.
7.
8. / ENCLOSURE-I
BRIEF RESUME OF THE INTENDED WORK:
6.1 GENERAL DISCUSSION:
Lacosamide [1, 2] is a functionalized amino acid specifically synthesized as an anticonvulsant drug. It is chemically (2R) - 2-(acetylamino) - N - benzyl - 3-methoxypropanamide. It selectively enhances slow inactivation of voltage-gated sodium channels, stabilizing hyperexcitable neuronal membranes and inhibiting neuronal firing.In addition to being approved for use as an adjunctive therapy in the treatment of partial-onset seizures it is being investigated as a treatment for diabetic neuropathic pain.
Molecular Structure :

Nomenclature :(2R)-2-(acetylamino)-N-benzyl-3-methoxypropanamide.
Molecular formula : C13H18N2O3.
Molecular weight : 250.294 g/mol.
Characteristics : white to slightly yellow crystalline powder.
Category : Antiepileptic.
Solubility : Sparingly soluble in water,Soluble in ethanol, Dimethyl
Sulfoxide and dimethyl formamide.
Functional groups : Carbonyl group, Methoxy group and Aliphatic secondary
Amines.
6.2. NEED FOR THE STUDY :
Modern analytical chemistry generally requires precise analytical measurements at very low concentrations, with a variety of instruments. Frequently, high-resolution separations have to be achieved with selective chromatographic methods for thequantitation. Therefore, the knowledge of instrumentation used in chemical analysis today is of paramount importance to assure future progress in various fields of scientific endeavor.
There is constant development and change in the techniques and methods of analytical chemistry. Better instrument design and a fuller understanding of the mechanics of analytical processes enable steady improvements to be made in sensitivity, precision, and accuracy. These same changes contribute to more economic analysis as they frequently lead to the elimination of time-consuming separation steps. The ultimate development in this direction is a non-destructive method, which not only saves time but leaves the sample unchanged for further examination or processing.
Upon extensive literature survey reveals that one analytical method have been reported for the estimation of Lacosamide by High Performance Layer Chromatography.
Hence there is a need for the development of newer, simple, sensitive, rapid, accurate and reproducible analytical methods for the routine estimation of Lacosamide in bulk and pharmaceutical dosage form.
6.3 REVIEW OF LITERATURE :
  1. Greenaway C, et al[3].,has developed a simple high-performance liquid chromatographic micromethod is described for the quantitation of the new antiepileptic drug lacosamide in serum of patients. Serum (100 ml) was first precipitated with 10 ml 60% perchloric acid and 10 ml supernatant injected directly into the high-performance liquid chromatograph. Chromatographic separation was achieved by use of a steel cartridge column (125 x 3 mm) packed with Hypersil BDS C-18, at 40 0C, and with a gradient elution system comprising methanol, formic acid and water. The eluent was monitored at 215 nm by diode array detection and the calibration curve was linear in the range of 10 to 250 ml/L. Recovery ranged from 99% to 106%.
6.4OBJECTIVES OF THE STUDY:
In view of the need for a suitable method for routine analysis ofLacosamide in formulations, attempts are being made to develop simple, precise and accurate analytical methods for estimation ofLacosamide and extend it for their formulation.
In the proposed work attempts shall be made to:
  1. To establish sensitive and accurate methods for the quantitative determination of Lacosamide in pure and dosage forms preferably by HPLC, HPTLC and UV/Visible Spectroscopy.
  2. To validate the newly developed methods in accordance with the analytical parameters mentioned in the ICH guidelines.[4,5,6]
  3. To apply the newly developed and validated analytical methods for the quantitation of pharmaceutical dosage forms.
ENCLOSURE-II
7.1.MATERIALS :
All the chemicals and reagents for the development of new analytical methods to estimateLacosamide will be of analytical grade. All the method development and validation will becarried out in our Department of Pharmaceutical Analysis, Bharathi College of Pharmacy, Bharathinagara by using UV-Visible Spectrophotometer (Shimadzu-1800), HPLC (Shimadzu LC-20 AT) and HPTLC (Lamag, Linomat-5). The pure sample of Lacosamide for the research work will be procured fromRanbaxy Pharma, Ahmedabad.
METHODS:
  1. The UV spectrophotometric methods will be developed and validated depends upon their solubility.[7]
  • Area under curve.
  • Derivative spectroscopy.
  • Difference spectrophotometry.
  1. The RP-HPLC[8,9] methods will be developed and validated for the estimation of Lacosamide with lesser retention time and run time by using defferent columns and solvent systems.
  2. The validation HPTLC[10] method will be made and the chromatographic conditions will be optimized.
  3. The Colorimetric methods[11,12] will be developed and validateddepending upon the chemical nature (functional groups, chromophore) of Lacosamide.
7.2.Source of Data:
  1. Library, Bharathi College of Pharmacy.
  2. E-library, Bharathi College of Pharmacy.
  3. Library IICT, Hyderabad.
  4. Library IISC, Bangalore.
  5. Library, RGUHS, Bangalore.
  6. Internet.
7.3.Method of Collection of Data:
DATA COLLLECTED FROM:
JOURNALS:
  1. Journal of Chromatography B.
  2. Therapeutic Drug Monitoring.
  3. E-Journal of Chemistry.
  4. Chromatographia.
  5. Asian Journal of Chemistry
RELATED LINKS:
7.4.DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS
NOT APPLICABLE
7.5. HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.4?
NOT APPLICABLE
ENCLOSURE-III
REFERENCES:
  1. URL:
  2. URL:
  3. Greenaway C, Ratnaraj Neville, Sander, JosemirW, Patsalos, Philip N.A High-Performance Liquid Chromatography Assay to Monitor the New Antiepileptic Drug Lacosamide in Patients with Epilepsy.Ther Drug Monit 2010;32(4):448-52.
  4. ICH, Q2A Text on Validation of Analytical Procedures; 1994.
  5. ICH, Q2B Validation of Analytical Methodology; 1996.
  6. ICH, Q2 (R1) Validation of Analytical Procedures: text and methodology; 2005.
  7. Gurudeep R. Chatwal, Sham K. Anand. Instrumental methods of chemical analysis. 5thed. Hyderabad: HPH; 2002. p. 149-184.
  8. Yuri Kazakevich, Rosaria Lobrutto. HPLC for Pharmaceutical scientists. New York: CBS; 2007. P. 139-161.
  9. Snyder LR, Kirkland JJ, Glajch JL. Practical HPLC method development. 2nd ed. New York: Wiley Inter Science; 1997. p. 1-50.
  10. Sethi PD. HPTLC: Quantitative analysis of pharmaceutical formulations. 1st ed. New Delhi: CBS; 1996. p. 53-57.
  11. Beckett AH, Stenlake JB. Pharmaceutical Chemistry. 4thed. Part-two. New Delhi: CBS; 1997. p. 302-304.
  12. Hobart H. Willard, Lynne L. Meritt, John A. Dean, Frank A. Settle. Instrumental method of analysis. 7thed. New Delhi: CBS; 1986. p. 159-177.