Preparation and In-Vitro Evaluation of Antifungal Nail Lacquer for Preungual Drug Delivery

PREPARATION AND IN-VITRO EVALUATION OF ANTIFUNGAL NAIL LACQUER FOR PREUNGUAL DRUG DELIVERY

MASTER OF PHARMACY DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE.

Mr. PRASAD ZILU NAIK GAOKAR

M.PHARM – I

Under The Guidance of

Dr. A. R. SHABARAYA M.Pharm, Ph.D.

DEPARTMENT OF PHARMACEUTICS.

SRINIVAS COLLEGE OF PHARMACY, VALACHIL MANGALORE – 574143.

2010-2012 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BANGALORE, KARNATAKA

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. NAME OF THE CANDIDATE MR. NAIK GAOKAR PRASAD ZILU. AND ADDRESS: 1st M.PHARM, SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE-574143.

2. NAME OF THE INSTITUTION: SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE-574143.

3. COURSE OF STUDY AND MASTER OF PHARMACY SUBJECT: (PHARMACEUTICS)

4. DATE OF ADMISSION: 31ST MAY 2010

5. TITLE OF THE PROJECT:

“PREPARATION AND IN-VITRO EVALUATION OF ANTIFUNGAL NAIL LACQUER FOR PREUNGUAL DRUG DELIVERY” 6. Brief resume of intended work: 6.1 – Need of the study: The nail plate may appear abnormal as a result of, a congenital defect, disease of skin with involvement of the nail bed, systematic disease, reduction of blood supply, local trauma, tumours of the nail fold or nail bed, infection of the nail fold, infection of the nail plate. Diseases of nail include:1  Leuconychia  Onychomycosis  Tinea unguis  Onychatrophia  Onychogryposis  Onychorrhexis Drug delivery to the nail (ungual drug delivery) constitutes a major challenge, with the lack of understanding of both the barrier properties of the nail and formulations to achieve enhanced ungual delivery restricting the efficiency of topical treatments for nail disorders.2 Current topical treatments have limited therapeutic effectiveness possibly because they cannot sufficiently penetrate in the nail plate to transport a therapeutically sufficient quantity of antifungal drug to the target sites to eradicate the protection. The purpose of this study is to explore the difficulties in penetration of drug across nail plate and enhancement of bioavailability of antifungal drug. A nail lacquer or a nail varnish is applied to the toenails or fingernails for appearance, but also as nail protection. The present preparation is effective for the treatment or prevention of fungal infections of nail. The nail lacquer consists of fungicidally effective amount of active ingredient in a clear, stable, film forming lacquer vehicle, film forming polymer, penetration enhancer and volatile solvents.3 Various nail infections can be treated with the use of topical antifungals for local actions. Commonly used antifungals include antibiotics, azoles, allyamines and other topically acting drugs. Some antifungals have good penetrating power hence can be used for local action.4

6.2 – Review of literature:  Patel RP, Naik SA, Patel NA, Suthar AM.2 (2009) reviewed the anatomy of a human nail, diseases related to nail plate, the formulations designed for nail application and some techniques used to enhance the topical bioavailability of the drugs across the nail, latest trends in drug delivery across the nail.  Sabreen J, Divyakumar B, Kiran B5 have formulated and evaluated the Terbinafine Hydrochloride nail lacquer as preungual drug delivery system for the treatment of onychomycosis. Formulations were prepared with and without polymer Eudargit RL 100, within the concentration range of 1% to 5% (w/v) in the polymeric system.  Shireesh KR, Chandra SB, Vishnu P, Prasad MVV6 have formulated and evaluated Ketoconazole nail lacquers as ungula drug delivery system for treatment of onychomycosis. Study indicated that thioglycolic acid is more

enhance agent compare to urea H2O2 of ketoconazole.  Elezovic A, Hadzovic S, Hadzidedic S, Kostic S7 have formulated and characterised nail lacquer containing 0.9 (w/v) fluconazole, eudragit RS 100 and acetone. The formulation contains di-butyl phthalate, polyethylene glycol 400 or propylene glycol as plasticizers.  Xiaoying H, Thomas CKC, Sherry B, Christine L, Howard I, Ronald CW8 have determined the enhancing effect of 2-n-nonyl-1,3-dioxolane on penetration of econazole into the deeper layers of human nail where fungal infection resides.

6.3 – Objectives of the study: 1) To formulate nail lacquer with different penetration enhancers. 2) To evaluate prepared nail lacquer with different physical tests. 3) To carry out in vitro permeation studies. 4) To check drug excipient compatibility.

Materials and Method: 7. Materials: 1. Drug: Antifungal agent. 2. Permeation enhancers: Urea H2O2 & Thioglycolic Acid. 3. Excipients: Propylene Glycol, Glycerine, Ethanol & Polyethylene Glycol 400 Methods: Nail lacquer is prepared in four different formulations. In all four formulations drug quantity is kept constant. The above mentioned permeation enhancers are used and the formulations are compared. All formulations are dissolved thoroughly.

7.1 – Source of data: Review of literature 1) Journals:  International Journal of Current Pharmaceutical Research.  Asian Journal of Pharmaceutics.  International Journal of Applied Pharmaceutics.  Journal of Pharmaceutical Sciences.

 Scientia Pharmaceutica.

2) Internet browsing.

3) Laboratory based studies.

7.2 – Method of Collection of Data: 1. Formulation of nail lacquer. 2. Evaluation of nail lacquer:  Non-volatile content  Drying time  Smoothness of flow  Gloss  In vitro studies  Across artificial membrane  Transungual permeation studies

7.3 – Does the study require any investigations or interventions to be Conducted on patients or other humans or animals? If so, please describe briefly. Not Applicable.

7.4 – Has ethical clearance been obtained from your institution in case of 7.3? Not Applicable.

8. List of references: 1) Pravin DC, Shilpa PC, Pramod KK, Bothiraja C. Drug delivery through nail 2006 cited 2010 Nov 29. 2pm. Available from:URL:http://www.pharmainfo.net/reviews/drug-delivery- through-nail-review. 2) Patel RP, Naik SA, Patel NA, Suthar AM. Drug delivery across human nail. Int J Curr Pharm Res 2009;01:01-7. 3) Zoe DD. Nail cosmetics. Cited 2010 Nov 29. 2pm. Available from:URL:http://emedicine.medscape.com/article/1067468-overview. 4) Tripathi KD. Essentials of medical pharmacology. New Delhi:Jaypee;2008. 5) Sabreen J, Divyakumar B, Kiran B. Preungual drug delivery systems of terbinafine hydrochloride nail lacquer. Asian J Pharm 2008;02:53-6. 6) Shireesh KR, Chandra SB, Vishnu P, Prasad MVV. Ungual drug delivery system of ketoconazole nail lacquer. Int J Appl Pharm 2010;02:17-9. 7) Elezovic A, Hadzovic S, Hadzidedic S, Kostic S. Characterization of antifungal nail lacquer formulations containing fluconazole. Sci Pharm 2010;78:624. 8) Xiaoying H, Thomas CKC, Sherry B, Christine L, Howard I, Ronald CW. Enhanced econazole penetration into human nail by 2-n-nonyl-1,3-dioxolane. J Pharm Sci 2002;92:142-8.

9. Signature of candidate

(Prasad Zilu Naik Gaokar) 10. Remarks of the guide The work, which is assigned to Mr. Prasad Zilu Naik Gaokar is under my guidance.

11. 11.1 Name and Designation Dr. A. R. Shabaraya. M.Pharm, Ph.D. of the Guide Principal & Director, Dept. of Pharmaceutics, Srinivas College Of Pharmacy, Mangalore. 11.2 Signature

11.3 Name and Designation ------of Co-Guide 11.4 Signature ------

11.5 Head of Department Dr. A. R. Shabaraya. M.Pharm. Ph.D. Principal & Director, Dept. of Pharmaceutics, Srinivas College Of Pharmacy, Mangalore. 11.6 Signature

(Dr. A. R. Shabaraya.)

12.1 Remarks of the Recommended and forwarded for favourable 12. Principal considerations.

12.2 Signature

(Dr. A. R. Shabaraya.)