A STUDY ON THE EFFICACY AND CORNEAL PENETRATION OF BESIFLOXACIN IN ROUTINE CATARACT SURGERY CASES Thesis submitted to THE TAMILNADU Dr.M.G.R. MEDICAL UNIVERSITY Chennai - 600 032. In partial fulfillment of the requirements For the award of the degree of MASTER OF PHARMACY in PHARMACY PRACTICE Submitted by Reg. No.: 261640151 DEPARTMENT OF PHARMACY PRACTICE PERIYAR COLLEGE OF PHARMACEUTICAL SCIENCES TIRUCHIRAPPALLI – 620 021. An ISO 9001:2015 Certified Institution SEPTEMBER – 2018 Dr. A. M. ISMAIL, M.Pharm., Ph.D., Professor Emeritus Periyar College of Pharmaceutical Sciences Tiruchirappalli – 620 021. CERTIFICATE This is to certify that the thesis entitled “A STUDY ON THE EFFICACY AND CORNEAL PENETRATION OF BESIFLOXACIN IN ROUTINE CATARACT SURGERY CASES” submitted by B. NIVETHA, B. Pharm., during September 2018 for the award of the degree of “MASTER OF PHARMACY in PHARMACY PRACTICE” under the Tamilnadu Dr.M.G.R. Medical University, Chennai is a bonafide record of research work done in the Department of Pharmacy Practice, Periyar College of Pharmaceutical Sciences and at Vasan Eye Care Hospital, Tiruchirappalli under my guidance and direct supervision during the academic year 2017-18. Place: Tiruchirappalli – 21. Date: 10th Sep 2018 (Dr. A. M. ISMAIL) Dr. R. SENTHAMARAI, M.Pharm., Ph.D., Principal Periyar College of Pharmaceutical sciences Tiruchirappalli – 620 021. CERTIFICATE This is to certify that the thesis entitled “A STUDY ON THE EFFICACY AND CORNEAL PENETRATION OF BESIFLOXACIN IN ROUTINE CATARACT SURGERY CASES” submitted by B. NIVETHA, B. Pharm., during September 2018 for the award of the degree of “MASTER OF PHARMACY in PHARMACY PRACTICE” under the Tamilnadu Dr.M.G.R. Medical University, Chennai is a bonafide record of research work done in the Department of Pharmacy Practice, Periyar College of Pharmaceutical Sciences and Vasan Eye Care Hospital, Tiruchirappalli under the guidance and supervision of Prof. Dr. A. M. Ismail, M.Pharm., Ph.D., Professor Emeritus, Department of Pharmacy Practice, Periyar College of Pharmaceutical sciences during the academic year 2017-18. Place: Tiruchirappalli – 21. Date: 10th Sep 2018 (Dr. R. SENTHAMARAI) ACKNOWLEDGEMENT Through words are seldom sufficient enough to express gratitude and feelings, it somehow gives me an opportunity to acknowledge those who helped me during the tenure of my study. The work of dissertation preparation was a daunting task and fascinating experience. Every man-made action starts with a thought, an idea, a vision, a mental image- from there it materializes into a form. But all the scattered ideas and concepts at the outset of this full-fledged project could be completed because of the watchful and in depth guidance of my esteemed guide Dr. A. M. Ismail, M.Pharm., Ph.D., Professor Emeritus, Periyar College of Pharmaceutical Sciences, Tiruchirappalli. His continuous guidance and support have always propelled me to perform better. I convey my sincere thanks and gratitude to our most respectful professor Dr. R. Senthamarai, M.Pharm., Ph.D., Principal, Periyar College of Pharmaceutical Sciences, Tiruchirappalli for arrangement of all necessary provision to carry out this project. Moreover for her parental affection and ever-willing to solve difficulties and providing all the facilities and support for my work, I consider myself lucky to study under her in this College. I put forward my respectful gratitude to our most respected Dr. K.Veeramani, M.A.,B.L., Chairperson, Periyar College of Pharmaceutical Sciences, Tiruchirappalli for providing all infrastructural facilities to carry out this work during my course of study. I submit my amiable thanks to Mr. GnanaSebestian, Correspondent, Periyar College of Pharmaceutical Sciences, Tiruchirappalli, for his constant support and encouragement to carry out my studies and this research work. I proclaim my deepest recognition to Dr. ShibuVarkey, MS., DO., FRCS., Regional Medical Director, Vasan Eye Care Hospital, Tiruchirappali for his constant cooperation and guidance. I evince my warm thanks and gratitude to Dr. G.Krishnamoorthy, B.Sc., M. Pharm., Ph.D., Vice Principal, Periyar College of Pharmaceutical Sciences, Tiruchirappalli for providing empowerment of knowledge. I express my sincere thanks to Mr. K. Sakthivel, M. Pharm., Head i/c, Department of Pharmacy Practice, Periyar College of Pharmaceutical Sciences, Tiruchirappalli for his constant support. I extend my warm thanks to Prof. G. Uma Devi, M.Sc., M.Phil., Head of Department of Medical Laboratory Technology, Periyar College of Pharmaceutical Sciences, Tiruchirappalli for her constant support and help in completing this project successfully. I extend my genuine thanks to all the staff members of Periyar College of Pharmaceutical Sciences, Tiruchirappalli. 7th September 2018 B. Nivetha TABLE OF CONTENTS S. No. CHAPTER PAGE No. I INTRODUCTION 1 II LITERATURE REVIEW 35 III DRUG PROFILE 58 IV NEED FOR THE PRESENT STUDY 65 V AIM & OBJECTIVE 72 VI PLAN OF THE WORK 73 VII METHODOLOGY 74 VIII RESULT & DISCUSSION 86 IX CONCLUSION 103 X BIBLIOGRAPHY 105 XI APPENDICES 111 LIST OF TABLES Table .No. DETAILS Page .No 1. Composition of Nutrient agar 78 2. Composition of MacConkey agar 82 3. Colony Morphology on MacConkey Agar 83 Categorization of patients according to Age – Regimen–A 4. 86 Categorization of patients according to Age – Regimen – B 5. 87 Gender wise categorization of patients in Regimen – A 6. 89 Gender wise categorization of patients in Regimen – B 7. 90 Categorization of patients according to Associated diseases 8. each Regimen 91 Categorization of patients in both the study teams according to 9. Microbes isolated each Regimen 93 Categorization of patients according to Diagnosis in Regimen – A 10. 95 Categorization of patients according to Diagnosis in Regimen – B 11. 96 Mean Penetration of Besifloxacin in different types of Cataract 12. Regimen – A 97 Mean Penetration of Besifloxacin in different types of Cataract 13. Regimen – B 98 Overall Percentage of drug penetration in Aqueous humour both in 14. Regimen – A and Regimen –B 98 TABLE OF FIGURES Fig. No. Particulars Page No. 1. Anatomy of the Eye 2 2. Difference between Normal & Cataract Vision 2 3. Lens – Normal & Cataract 3 4. Cataract Surgery 13 5. Phaco Tip 16 6. Fluid Dynamics in Phaco Machines 16 7. Foot Switch Positions 18 8. Capsulorrhexis (CCC) 22 9. Stop & Chop Technique 27 10. Subconjunctival injection of a Steroidal drug 57 11. Various routes of Ophtalmic administration 75 12. Structures of the Eye (Labelled) 76 13. Showing the lower part of the right eye after a Central and 77 Horizontal section 14. S. aureus in nutrient agar media 80 15. S. epidermidis in nutrient agar media 80 16. Colonies of common gram negative bacteriae 81 17. Colony Morphology on MacConkey Agar 84 18. Age wise Categorization of patients - Regimen A 86 19. Age wise Categorization of patients - Regimen B 87 20. Regimen A&B Comparison of age wise distribution 88 21. Gender wise Categorization of patients - Regimen A 89 22. Gender wise Categorization of patients - Regimen B 90 23. Comparison between Gender classes in Regimen A & B 90 24. Associated diseases Categorization in Regimen A & B 92 25. Microbial Isolates in Regimen A & B 93 26. Diagnosis-wise Categorization of Regimen A 95 27. Diagnosis-wise Categorization of Regimen B 96 28. Comparison of Diagnosis-wise types in Regimen A & B 97 29. Conjunctival base-line bacterial load on two Agar Plates- 99 Regimen A 30. Conjunctival base-line bacterial load on MacConkey agar - 100 Regimen B 31. Conjunctival pre-operative bacterial load on two agar plates – 101 Regimen B ABBREVIATIONS USED ABBREVIATION EXPANSION AC Anterior Chamber ADR Adverse Drug Reaction AIIMS All India Institute of Medical Sciences BAK Benzalkonium chloride CCC Continuous curved capsulorrhexis CDC Crater Divide and Conquer CI Confidence interval Cm Chloramphenicol CME Cystoid macular edema CSC Cataract surgical coverage CSR Cataract surgical rate ESCRS European Society of Cataract and Refractory Surgeons FDA Food and Drug Administration ICB Iris and Ciliary Body IEC Institutional Ethics Committee IOL Intraocular Lens IOP Intraocular Pressure LA Local Anaesthetic LD50 Lethal Dose 50 MAC MacConkey Agar MIC Minimum Inhibitory Concentration MRSA Methicillin-resistant Staphylococcus aureus MRSE Methicillin-resistant Staphylococcus epidermidis NOAEL No Observed Adverse Effect Level PAGE Polyacrylamide gel electrophoresis PSA Polar surface area R/L Right / Left RAAB method Rapid Assessment of Avoidable Blindness method RPEC Rajendra Prasad Eye Centre SDS Sodium Dodecyl Sulphate SRR Sight Restoration Rate (per year) TASS Toxic anterior shock syndrome TDC Trench, Divide and Conquer Vd Apparent volume of distribution WHO World Health Organization Introduction I. INTRODUCTION CATARACT Cataract is an eye disease in which the clear lens of the eye becomes cloudy or opaque, causing a decrease in vision. Although the word cataract to describe this condition has been part of the English language since only the 15th century, the eye disease has been recognized and surgically treated since ancient times. According to WHO: “Cataract is clouding of the lens of the eye which impedes the passage of light. Although most cases of cataract are related to the ageing process, occasionally children can be born with the condition, or a cataract may develop after eye injuries, inflammation, and some other eye diseases.”The lens is a portion of the eye that is normally clear. It focuses rays of light entering the eye onto the retina, the light-sensitive tissue at the back of the eye. In order to get a clear image onto the retina, the portions of the eye in front of the retina, including the lens, must be clear and transparent. The light striking the retina initiates a chemical reaction within the retina. The chemical reaction, in turn, initiates an electrical response which is carried to the brain through optic nerve. The brain then interprets what the eye sees. In a normal eye, light passes through the transparent lens to the retina. The lens must be clear for the retina to receive a sharp image.