FORMULATION AND EVALUATION OF A MEDICATED NAIL LACQUER FOR THE TREATMENT OF ONYCHOMYCOSIS Dissertation work submitted to The Tamilnadu Dr.M.G.R. Medical University ,Chennai In partial Fulfillment for the award of degree of MASTER OF PHARMACY IN PHARMACEUTICS Submitted by ASWANI V M Reg NO.261310753 Under the guidance of Dr. R.MANAVALAN, M.pharm, PhD Professor & Head Department of Pharmaceutics R.V.S College of pharmaceutical Sciences Sulur,Coimbatore (October 2015) DEPARTMENT OF PHARMACEUTICS R.V.S COLLEGE OF PHARMACEUTICAL SCIENCES SULUR, COIMBATORE-641 402, TAMIL NADU. Certificates Evaluation Certificate Dissertation title : FORMULATION AND EVALUATION OF A MEDICATED NAIL LACQUER FOR THE TREATMENT OF ONYCHOMYCOSIS Name of the Candidate : ASWANI V M Course of study : Master of Pharmacy in Pharmaceutics, Institution Name : R V S College of Pharmaceutical Sciences, Sulur, Coimbatore- 641 402 INTERNAL EXAMINER EXTERNAL EXAMINER PLACE: Coimbatoore DATE: Certificate This is to certify that the dissertation work entitled “FORMULATION AND EVALUATION OF A MEDICATED NAIL LACQUER FOR THE TREATMENT OF ONYCHOMYCOSIS “ is a bonafide work done by Aswani V M, RVS college of Pharmaceutical Sciences, Sulur, Coimbatore, for the partial fulfillment of the University rules and regulations for the award of Master of Pharmacy in Pharmaceutics under my guidance and supervision during the academic year 2015-16. Dr.R. MANAVALAN, M.pharm, PhD Professor and Head Department of Pharmaceutics R.V.S College of pharmaceutical Sciences Sulur, Coimbatore-641 402 Dr.R.VENKATANARAYANAN,M.Pharm,PhD Principal R.V.S College of Pharmaceutical Sciences Sulur, Coimbatore-641 402 Certificate This is to certify that the dissertation work entitled “FORMULATION AND EVALUATION OF A MEDICATED NAIL LACQUER FOR THE TREATMENT OF ONYCHOMYCOSIS“ is a bonafide work done by Aswani V M under my direct guidance for the partial fulfillment of the award of degree of Master of Pharmacy in Pharmaceutics, RVS college of Pharmaceutical Sciences, Sulur, Coimbatore, affiliated to The Tamil nadu Dr.M.G.R Medical University ,Chennai. Dr. R. MANAVALAN, M.pharm, PhD Professor and Head Department of Pharmaceutics R.V.S College of Pharmaceutical Sciences Sulur, Coimbatore-641 402 Place: Coimbatoore Date: Certificate This is to certify that the dissertation work entitled “FORMULATION AND EVALUATION OF A MEDICATED NAIL LACQUER FOR THE TREATMENT OF ONYCHOMYCOSIS“ is a bonafide work done by Aswani V M under the guidance of under the guidance of Dr. R. MANAVALAN, M -Pharm,Ph.D in the department of pharmaceutics,in the partial fulfillment of the awsard of degree of Master of Pharmacy in Pharmaceutics,R V S College of Pharmaceutical Sciences,Sulur,Coimbatoore,affiliated to the Tamilnadu Dr.M.G.R Medical University,chennai. Dr.R.VENKATANARAYANAN,M.Pharm,PhD Principal R.V.S College of Pharmaceutical Sciences Sulur,Coimbatore. ACKNOWLEDGEMENT In the name of God, The Most Gracious ,The Most Merciful… At the very outset,I thank my Lord for His Blessing and support in completing this project work. In the first place, I would like to record my sincere and heartfelt gratitude to my Institution Guide Dr.R.Manavalan, M-Pharm, Ph.D ,Professor and head,RVS college of Pharmaceutical Sciences,Sulur,Coimbatore for her supervision,advice and inspiring guidance throughout my dissertation work. Above all, she provided me unflinching encouragement and support. Let me sincerely thank Dr. R. Venkatanarayanan , Professor and Principal, RVS college of Pharmaceutical Sciences, Sulur, Coimbatore for his inspirations and being a great facilitator. Let me express my sincere gratitude to Mr. Barish for his meticulous guidance and encouragement provided to me for the completion of my dissertation work. Let me express my sincere thanks to all the staffs in Hikma herbs Pvt.Ltd. and special thanks to my industrial guide Mr. Vipin K V. Let me express my sincere thanks to my classmates and to all my well-wishers without whose inspiration and suggestions, my work would have been incomplete. Above all,I dedicate myself for the constant love and encouragement given to me by my beloved parents who deserve the credit of success in whatever work I did. ASWANI V M Abstract ABSTRACT Onychomycosis (also known as dermatophytic onychomycosis or Tinea unguium is a fungal infection of the nail. The causative pathogens of onychomycosis include dermatophytes, Candida, and nondermatophytic molds. In the present work, a medicated antifungal nail lacquer of Miconazole nitrate has been developed. The objective of the study was to deliver a sustained release of Miconazole nitrate over extended period of time up to 48 hours, and hence reduce the frequency of administration. This was expected to improve clinical efficacy and also improve the patient compliance. The nail lacquer formulation were prepared by simple mixing and analyzed for non -volatile content, gloss, smoothness to flow, drug diffusion studies, drug content estimation, anti -microbial studies. Among all formulation, nail lacquer prepared with 2% Miconazole nitrate, 6% nitrocellulose, 1% ethyl cellulose, 15 % salicylic acid, 10% propylene glycol and 10% 2-H- β-CD exhibited good non- volatile content, drug release, drug content estimation and zone of inhibition. The drug release could be extended up to 48 hour and a complete release of 98.12% was observed. FTIR studies reveled that drug and excipients are compatible. Accelerated stability study of selected optimized formulation, F11 was done as per ICH guidelines for 1 month at 40±20C, which revealed that no significant change with respect to the initial characteristics was observed. Formulation and usage of these systems are considered to be safe, without any complication. So we can conclude that the antifungal nail lacquer may be one of the novel dosage forms that can revolutionize the pharmaceutical and health care sector. LIST OF ABBREVIATIONS mm Millimeter µ Micron % Percentage e.g. Example OM Onychomycosis PAS Periodic acid Schiff MIC Minimal inhibitory concentration FDA Food and drug administration h or hr. Hour pH Hydrogen ion concentration Da Dalton SH Sulfhydryl group SC Subcutaneous V/cm Volt per centimeter HP- β- CD Hydroxyl propyl- β-cyclodextrin λmax Wave length of maximum absorption FTIR Fourier Transform Infrared CAS No Chemical abstracts service ⁰C Degree centigrade g/mol Gram per mol ICH International Conference on Harmonisation mg Milligram mPa S Millipascal second PO Per os (by mouth) ml Milliliter CP Centipoise USP United states pharmacopoeia ⁰F Degree farenheat mmHg Millimeters of mercury PG Propylene glycol AR grade Analytical reagent grade BP British Pharmacopoeia JP Journal of Perinatology USPNF United states pharmacopoeia and National Formulary OTC Over the Counter uv Ultraviolet M Molar concentration PBS Phosphate buffer solution RH Relative humidity MALDI- Matrix-assisted laser desorption/ionization time-of- TOFMS flight mass spectrometry IP Indian Pharmacopoeia IR Infrared Sec Seconds TABLE OF CONTENTS S.NO. CONTENTS PAGE NO. 1 Introduction 1 2 Aim and Objectives of 25 study 3 Review of Literature 27 4 Drug and Polymer 33 Profile 5 Materials And Methods 42 6 Results And 54 Discussion 7 Summary 79 8 Conclusion 80 9 Bibliography 82 LIST OF TABLES TABLE TITLE PAGE NO. NO. 1 Treatment and mycological 12 cure rates 2 Properties of miconazole 33 nitrate 3 Properties of Nitrocellulose 35 4 Properties of Ethylcellulose 37 5 Properties of 2- 39 Hydroxypropyl -β- Cyclodextrin 6 Properties of Salicylic Acid 40 7 Properties of Propylene Glycol 41 8 List of materials used 42 9 List of equipments used 43 10 Drug- polymer compatibility 46 study 11 Optimization of nitrocellulose 47 film former 12 Formulation of Nail Lacquer 50 13 Standard curve data for 55 Miconazole nitrate in phosphate buffer of pH 7.4 14 Solubility studies of 56 miconazole nitrate 15 FTIR Compatibility study 61 interpretation 16 Optimization of nitrocellulose 64 film former 17 Water (W) resistance of nail 64 lacquers 18 Nonvolatile content of nail 65 lacquers. 19 Drying time of nail lacquers 66 20 Viscosity of nail lacquers 67 21 Adhesive strength of nail 67 lacquers 22 Percentage drug content 68 23 Comparative study and 70 optimization of salicylic acid concentration 24 Comparative study and 71 optimization of 2-HP- β-CD concentration 25 Comparative study and 72 optimization of Ethyl cellulose concentration 26 Comparison of drug diffusion 74 across artificial membrane and hoof’s membrane 27 Zone of inhibition of miconazole 76 nitrate Nail lacquers 28 Stability studies data of F11 76 29 Invitro Diffusion profile of F11 77 upon stability studies LIST OF FIGURES FIGURE TITLE PAGE NO. NO. 1 Structure of human nail 2 2 Nail anatomy 5 3 Classification of 9 onychomycosis 4 Structure of miconazole 33 nitrate 5 Structure of Nitrocellulose 35 6 Structure of Ethyl cellulose 38 7 Structure of β-cyclodextrin (7 38 glucose units) 8 Structure of salicylic acid 40 9 Structure of propylene glycol 41 10 Tensile strength apparatus 49 11 Schematic representation of 50 preparation of nail lacquer 12 UV spectrum of Miconazole 54 nitrate in phosphate buffer solution of pH 7.4 13 Calibration curve of 55 Miconazole nitrate in phosphate buffer solution pH 7.4 14 IR spectra of Miconazole 57 nitrate 15 IR spectra of Nitrocellulose 57 16 IR spectra of Ethyl cellulose 58 17 IR spectra of beta hydroxyl 58 propyl cellulose 18 IR spectra of Miconazole 59 nitrate and Nitrocellulose 19 IR spectra of Miconazole 59 nitrate and beta hydroxyl propyl cellulose 20 IR spectra of Miconazole 60