6.
7.
8. / ENCLOSURE-I
BRIEF RESUME OF THE INTENDED WORK:
6.1 GENERAL DISCUSSION:
Dorzolamide HCl [1] is a carbonic anhydrase inhibitor. It is an anti-glaucoma agent and topically applied in the form of eye drops. Dorzolamide HCl is used to lower increased intraocular pressure in open-angle glaucoma and ocular hypertension.
Structural formula :

Nomenclature : (4S, 6S)-4-(Ethylamino)-6-methyl-5, 6-dihydro-4H-thieno [2, 3- b] thiopyran-2-sulphonamide 7, 7-dioxide hydrochloride.
Molecular formula : C10H16N2O4S3.HCl
Molecular weight : 324.443 g / mol.
Characteristics : White or almost white, crystalline powder.
Category : Carbonic anhydrase inhibitor; treatment of glaucoma and ocular hypertension.
Solubility : Soluble in water, slightly soluble in methanol, very slightly
soluble in anhydrous ethanol.
Functional group : Secondary amine group, Sulphanamide group.
6.2. NEED FOR STUDY:
Progress in almost every field of science depends on the contributions made by systematic research; thus research is often viewed as the corner stone of scientific progress. Broadly defined, the purpose of research is to answer questions and acquire new knowledge. Research is the primary tool used in virtually all areas of science to expand the frontiers of knowledge.
Analytical method development should be performed to the extent that it is sufficient for its intended purpose and cost effective. Upon successful completion of method development, the proposed method will be validated to show the suitability for its intended use. Finally, the validated method will be transferred to the quality control laboratory in preparation for the launch of the drug substance or drug product.
Whether it may be a drug substance or a drug product or the final product will need to be analysed to assess its potency or strength. Dorzolamide HCl is selected in order to assess the potency in pure and formulation and is not official in Indian Pharmacopoeia. Extensive literature survey reveals that only few analytical methods have been reported for the estimation of Dorzolamide HCl and are UV-Derivative Spectrophotometry[2,3] ,HPLC[4,5,6] ,and LC-MS[7] methods. Apart from above no other spectroscopic methods such as UV/Vis spectroscopy, Difference spectrophotometric method, HPLC by using internal standard etc., were reported for this compound.
Hence there is a need for the development of newer, simple, sensitive, rapid, accurate and reproducible analytical methods for the routine estimation of Dorzolamide HCl in pure and pharmaceutical dosage form.
6.3. REVIEW OF LITERATURE:
1.  Nevin Erk, et al [2]., Studied on Simultaneous determination of Dorzolamide HCl and Timolol Maleate in eye drops by two Different Spectroscopic method.
2.  Lories IB, et al [3]., Studied on Application of TLC-densitometry, first-derivative UV- Spectrophotometry and Ratio Derivative Spectrophotometry for the determination of Dorzolamide Hydrochloride and Timolol Maleate.
3.  Nevin Erk, et al [4]., Studied on Rapid and sensitive HPLC method for the simultaneous determination of Dorzolamide Hydrochloride andTimolol Maleate in eye drops with diode-array and UV detection.
4.  Adriana M, et al [5]., Studied on Rapid High-Performance Liquid Chromatographic assay of Dorzolamide in rabbit aqueous humor.
5.  Nevin Erk, et al [6]., Studied on Voltametric and HPLC determination of Dorzolamide Hydrochloride in eye drops.
6.  Constanzer ML, et al [7]., Studied on Low level determination of Dorzolamide and its de-ethylated metabolite in human plasma by Liquid Chromatography with atmospheric pressure chemical ionization Tandem Mass Spectrometry.
6.4. OBJECTIVES OF THE STUDY:
In view of the need for a suitable method for routine analysis of Dorzolamide HCl in pure form and formulations, attempts are being made to develop simple, precise and accurate analytical methods for estimation of Dorzolamide HCl and extend it for their determination in formulation.
In the proposed work attempts shall be made to:
·  To establish sensitive and accurate methods for the quantitative estimation of Dorzolamide HCl in pure and dosage form.
·  To validate the newly developed methods in accordance with the analytical parameters mentioned in the ICH guidelines. [8, 9]
·  To apply the newly developed, validated analytical methods for quantitative estimation of Dorzolamide HCl in bulk and pharmaceutical dosage form.
ENCLOSURE-II
MATERIALS AND METHODS:
In the present investigation of the new analytical methods for quantitative estimation of Dorzolamide HCl is in need and HPLC with different detectors (UV detector, electrochemical detector, diode array detector) and different solvent system and other chromatographic instruments.
The entire instruments like SPECTROPHOTOMETER, HPLC, HPTLC, GC, IR; etc are available. Analytical method and validation development on Dorzolamide HCl shall be carried out at Lake Chemicals Pvt.Ltd, Bangalore. Analytical Laboratory adequately equipped with necessary analytical set up to carry out desired work. The pure sample of Dorzolamide HCl for the research work will be furnished from Lake Chemicals Pvt.Ltd, Bangalore.
7.1. Source Of Data:
1.  Library: Bharathi College of Pharmacy.
2.  E-library: Bharathi College of Pharmacy.
3.  Library, RGUHS, Bangalore.
4.  Library IISc, Bangalore.
5.  Internet.
7.2. Method Of Collection Of Data:
DATA COLLLECTED FROM:
JOURNALS:
1.  Analytical Chemicals Acta.
2.  Indian Journal of Pharmaceutical Science.
3.  Indian Drugs.
4.  Journal of Chromatography B.
5.  Journal of Pharmaceutical and Biomedical Analysis.
6.  Asian Journal of Chemistry.
RELATED LINKS:
www.sciencedirect.com
www.pubmed.com
www.google.com
www.wikipedia.com
www.medline.com
www.dogpile.com
www.chemworld.com
www.rxlist.com
7.3. DOES THE STUDY REQUIRE ANY INVESTIGATION OR INTERVENTIONS TO BE CONDUCTED ON PATIENTS OR OTHER HUMANS OR ANIMALS?
NOT APPLICABLE
7.4. HAS ETHICAL CLEARENCE BEEN OBTAINED FROM YOUR INSTITUTION IN CASE OF 7.3?
NOT APPLICABLE
ENCLOSURE- III
REFERENCES:
1.  www.wikipedia.com.
2.  Nevin Erk. Simultaneous determination of Dorzolamide HCl and Timolol Maleate in eye drops by two different spectroscopic methods. J Pharm Biomed Anal 2002; 28(2):391-397.
3.  Lories IB. Application of TLC-densitometry, first-derivative UV-Spectrophotometry and Ratio Derivative Spectrophotometry for the determination of Dorzolamide Hydrochloride and Timolol Maleate. J Pharm Biomed Anal 2002; 27(5):737-746.
4.  Nevin Erk. Rapid and sensitive HPLC method for the simultaneous determination of Dorzolamide Hydrochloride and Timolol Maleate in eye drops with diode-array and UV detection. Pharmazie 2003; 58(7):491-493.
5.  Adriana M, Claudio B. Rapid High-Performance Liquid Chromatographic assay of Dorzolamide in rabbit aqueous humor. Biomed Chromat 2002; 16(4):274-276.
6.  Nevin Erk. Voltametric and HPLC determination of Dorzolamide Hydrochloride in eye
drops. Pharmazie 2003; 15(12):870-873.
7.  Constanzer ML, Chavez CM, Matuszewski BK. Low level determination of Dorzolamide and its de-ethylated metabolite in human plasma by Liquid Chromatography with atmospheric pressure chemical ionization Tandem Mass Spectrometry. J Pharm Biomed Anal 1997; 15(7):1001-1008.
8.  ICH, Q2A Text on validation of analytical procedures, Oct, 1994.
9.  ICH, Q3B Validation of analytical procedures: methodology, Nov, 1996.