Rajiv Gandhi University of Health Sciences s76

“FORMULATION AND EVALUATION OF NIOSOMAL GEL CONTAINING KETOCONAZOLE FOR TOPICAL APPLICATION”M.PHARM DISSERTATION PROTOCOL SUBMITTED TO THERAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA.BY KANANI KINJAL MANSUKHLALUnder the guidance ofProf .D.NAGENDRAKUMAR M. Pharm,( Ph. D)DEPARTMENT OF PHARMACEUTICSS.V.E.T’S COLLEGE OF PHARMACYHUMNABAD-5853302009-20101 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA.ANNEXURE-II PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATIONName of the Candidate (In block KANANI KINJAL MANSUKHLAL 1. letters):MANSUKHLAL P. KANANI ‘ Permanent Address: Shaligram’, Near Innovative School, Shakti Nagar-2, University Road, Rajkot- 360005 Gujarat.S.V.E.T’S COLLEGE OF PHARMACY, 2. Name of the Institution: Kallur Road, Humnabad- 585330 Dist- Bidar, Karnatka.3. Course of Study and Subject: MASTER OF PHARMACY ( Pharmaceutics )4. Date of Admission to the Course: 11.08.2009FORMULATION AND EVALUATION OF 5. Title of the Topic: NIOSOMAL GEL CONTAINING KETOCONAZOLE FOR TOPICAL APPLICATIONBrief Resume of the Intended Work: 6.6.1 Need for the study Niosomes are a novel drug delivery system which aims to deliver the drug at a rate directed by the needs of the body during the period of treatment and channel the active entity to the site of action.[1] The niosomes are very small, microscopic in size, unilamellar or multilamellar vesicles formed from synthetic non-ionic surfactants, in which the drug is incorporated.[2] These vesicles were first reported in the cosmetic industry. [3] The entrapment of drug in vesicles is viewed to help in an improved availability of drug at the site will reduce the dose.[4] This system offer many advantages over oral dosage forms including by passing hepatic metabolism, avoiding gastric degradation and minimizing systemic side effects. Niosomes are2 preferred over other vesicular systems because they are biodegradable, biocompatible, non-toxic and acting as depot in deeper layers of skin.[5] They behave in vivo like liposomes prolonging the circulation of entrapped drug and altering its organ distribution.[6] As carriers for enhanced delivery to specific cells niosomes may improve therapeutic index by restricting drug effects to target cells.[7] Niosomes appears to be a well preferred delivery system because the former exhibit high chemical stability.[8] The present research, is an attempt towards development of topical application of ketoconazole niosomes. It is an imidazole antifungal agent having broad spectrum activity. It impairs the biosynthesis of ergosterol, which is a vital component of fungal cell membranes as well as certain enzymes. Ketoconazole is usually effective for topical infections such as athlete’s foot, ringworm, candidiasis and jock itch. Common side effects associated with ketoconazole therapy include mild burning at the application site, severe allergic reactions (rash, itching, swelling of the mouth, face, lips or tongue), blisters, irritation, pain, redness or severe burning.[9,10] Ketoconazole is readily but incompletely absorbed after oral dosing and it is varies among individuals. It is metabolized extensively and the inactive products appear in the feces. Concentration of active drug in urine is very low. Encapsulation of ketoconazole in niosomes increases the half life providing prolonged drug delivery and minimizes the commonly occurring side effects as well as drug accumulation will be high after incorporation of drug.[11,12]6.2 Review of LiteratureLiterature review shows that no work has been published on the proposed topic and some of the related work is quoted below. Pillai et al.[13] have prepared niosomes to achieve sustained effect from niosomal encapsulated Indomethacin on platelet function such as inhibition of aggregation and ATP release. Niosomes were prepared from Tween-60 by the lipid hydration method.  Manconi et al.[14] have prepared Tretinoin loaded niosomes from polyoxyethylene lauryl ether, sorbitan esters and a commercial mixture of octyl/decyl polyglucosides.The influence of vesicle composition and preparation method on the vesicle structure, size distribution, entrapment efficiency and in vitro release of incorporated tretinoin was studied.  Hao et al.[15] have prepared niosomes which possess high encapsulation capacity for soluble drugs, starting from span 60 and cholesterol. An evaporation-sonication improved method, was proposed. The corresponding Colchicine niosomes show a good stability and high encapsulation capacity.  Guinedi et al.[17] have prepared niosomally entrapped Acetazolamide to improve the low corneal penetration and bioavailability. Niosomes formed from span 40 or span 60 and cholesterol in different ratios and were prepared using reverse-phase evaporation and thin film hydration method.  Jain et al.[18] have prepared niosomes containing Rifampicin using various nonionic surfactants of sorbitan ester class and cholesterol in 50:50 percent mol fraction ratio. The drug-entrapped vesicles were characterized for their shape, size, drug entrapment efficiency and in vitro release rate. Suwakul et al.[19] have formulated Propylthiouracil, a lyophobic drug with an antiproliferative activity, into niosomes using various classes of nonionic surfactants. Vesicle formation by the sonication method was evaluated and characterization of 3 niosomes was performed by different methods. Lakshmi et al.[20] have prepared niosomal Methotrexate in chitosan gel in the treatment of localized psoriasis and to test the same for irritation and sensitization on healthy human volunteers. In this niosomes were prepared by lipid layer hydration method. Mukherjee et al.[21] have developed and compared Acyclovir containing nano-vesicular liposomes and niosomes. Niosomes could be a better choice for intravenous delivery of Acyclovir because of high drug loading, sustained release and better stability was observed. Manosroi et al.[22] have developed a novel elastic bilayer vesicle entrapped with the non- steroidal anti-inflammatory drug, Diclofenac Diethyammonium for topical use. Transdermal absorption through excised rat skin was performed by vertical franz diffusion cell. Balakrishnan et al.[23] have prepared niosomes containing Minoxidil from polyoxyethylene alkyl ether or sorbitan monoesters with cholesterol using thin film-hydration method. The prepared systems were characterized for entrapment efficiency, particle size, zeta potential and stability. Gupta et al.[24] have prepared Meloxicam entrapped niosomes by thin film hydration technique using nonionic surfactants (Span-80, Span-60, Tween-80 and Tween-60), cholesterol and drug in different ratios. The prepared niosomes were characterized for size, shape, entrapment efficiency, in vitro drug release and in vivo performance. Manosroi et al.[25] have loaded Gallidermin in anionic niosomes composed of Tween 61/CHL/DP (1:1:0.05 molar ratio) gave the highest entrapment efficiency, this formulation is having topical antibacterial activity.6.3 Objectives of the StudyIn the proposed research work Ketoconazole niosomes will be prepared with the following objectives.  To reduce side effects of the drug.  To prepare controlled delivery of drug at a particular site.  To increase bioavailability of the drug.  To increase skin penetration of the drug.  To increase amount of drug retention into the skin.7. Materials and Methods:Source of Data  Internet  RGUHS(Helinet)  S.V.E.T’s college library, Humnabad  International Pharmaceutical Abstract4 7.1 Materials Drug: KetoconazoleExcipients: 1. Sorbitan Monoesters 2. Diethyl Ehter 3. Cholesterol 4. Carbopol 5. Dicetyl Phosphate 6. Glycerin Equipments: 1. UV/Visible double-beam spectrophotometer-1800 (Shimadzu) 2. IR spectrophotometer 3. Rotary Flash Evaporator 4. Optical microscope 5. Stability Chamber 6. Hot air oven 7. Ultra sonicator 8. Digital pH meter 9. Electronic Balance (Shimadzu) 10.Thermostatic hot plate with magnetic stirrer 11.Digital over head stirrer7.2 MethodNiosomes incorporated in Ketoconazole will be prepared by thin film hydration technique, the prepared Ketoconazole niosomes are incorporated in carbopol gel.Evaluation of Ketoconazole Niosomes includes: 1. Size and Shape 2. In vitro drug release and Entrapment Efficiency 3. In vitro antifungal activity by cup-plate method 4. Drug leakage on storage and stability 7.3 Does the study require any investigation or intervention to be Conducted on patients or other humans or animals? If so please describe briefly.------Not applicable ------7.4 Has ethical clearance have been obtained from your institution in case of 7.3?------Not applicable ------58. List of References: 1. Biju SS, Talegaonkar S, Mishra PR, Khar RK. Vesicular systems: An overview. Indian J Pharm Sci. 2006;68(2):141-53.2. [updated 2010 April 11; cited 2010 May 2]. Available from: http:// pharmaxchange.info/articles/niosomes/niosomes/html.3. Uchegbu IF, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm. 1998;172:33-70.4. Agarwal R, Katare OP, Vyas SP. Preparation and in vitro evaluation of liposomal /niosomal delivery system for antipsoriatic drug dithranol. Int J Pharm. 2001;228:43-52.5. Kaur K, Jain S, Sapra B, Tiwary AK. Niosomal gel for site-specific sustained delivery of anti- arthritic drug: In vitro-in vivo evaluation. Curr Drug Deliv. 2007;4:276-82.6. Shyamala B, Lakshmi PK. Comparative evaluation of niosomes formulations prepared by different techniques. Acta Pharm. 2009;51:27-32.7. Udupa N. Niosomes as drug carriers. In: Jain NK, editor. Controlled and Novel Drug Delivery. 1st ed. New Delhi: CBS Publishers and Distributors; 1997.p.292-303.8. Biswal S, Murthy PN, Sahu J, Sahoo P, Amir F. Vesicles of non-ionic surfactants (niosomes) and drug delivery potential. Int J Pharm Sci Nanotechol. 2008;1(1):1-8.9. [updated 2010 may 6; cited 2010 may 10]. Available from: http://www.drugs.com/ cdi/ ketoconazole-gel.html.10.[updated 2010 May 5; cited 2010 May 10]. Available from: http://en.wikipedia.org/wiki /ketoconazole.11.Bennett J. Antimicrobial agents: Antifungal agents. In: Hardman JG, Limbird LE, editors. Goodman and Gilman’s the Pharmacological basis of therapeutics.10th ed. USA: Mc Graw Hill Publications; 2001.p.1301.12.Patel RP, Patel H, Baria AH. Formulation and evaluation of liposomes of ketoconazole. Int J Drug Del Technol. 2009;1(1):16-23.13.Pillai GK, Maher S. Enhanced inhibition of platelet aggregation in-vitro by noisome- encapsulated indomethacin. Int J Pharm. 1999;193:123-27.14.Manconi M, Sinico C, Valenti D, Loy G, Fadda AM. Niosomes as carriers for tretinoin. I. Preparation and properties. Int J Pharm. 2002;234:237-48.15.Hao Y, Zhao F, Li N, Yang Y, Li K .Studies on a high encapsulation of colchicine by a noisome system. Int J Pharm. 2002;244:73-80.16.Ning M, Guo Y, Pan H, Chen X, Gu Z. Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole. Drug Dev Ind Pharm. 2005;31: 375-83.6 17.Guinedi AS, Mortada ND, Mansour S, Hathout RM. Preparation and evaluation of reverse- phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide. Int J Pharm. 2005;306:71-82.18.Jain CP, Vyas SP, Dixit VK. Niosomal system for delivery of rifampicin to lymphatics. Indian J Pharm Sci. 2006;68(5):575-78.19.Suwakul W, Ongpipattanakul B, Vardhanabhuti N. Preparation and characterization of propylthiouracil niosomes. J Liposome Res. 2006;16:391-401.20.Lakshmi PK, Devi GS, Bhaskaran S, Sacchidanand S. Niosomal methotrexate gel in the treatment of localized psoriasis: Phase I and II studies. Indian J darmatol Venereol Leprol. 2007;73(3):157-61.21.Mukherjee B, Patra B, Layek B, Mukherjee A. Sustained release of acyclovir from nano- liposomes and nano-niosomes: An in vitro study. Int J Nanomedicine. 2007;2(2):213-25.22.Manosroi A, Jantrawut P, Manosroi J. Anti-inflammatory activity of gel containing novel elastic niosomes entrapped with diclofenac diethylammonium. Int J Pharm. 2008;360:156-63.23.Balakrishnan P, Srinivasan S, Lee WS, Lee WM, Kim JO, Oh DH, et al. Formulation and in vitro assessment of minoxidil niosomes for enhanced skin delivery. Int J Pharm. 2009;377:1-8.24. Gupta KS, Nappinnai M, Gupta VR. Formulation and evaluation of topical meloxicam niosomal gel. Int J Biopharm. 2010;1:7-13.25. Manosroi A, Khanrin P, Lohcharoenk.al W, Werner R, Gotz F, Manosroi W, et al. Transdermal absorption enhancement through rat skin of gallidermin loaded in niosomes. Int J Pharm. 2010;392:304-10.7Signature of the Candidate: 9. KANANI KINJAL MANSUKHLAL10. Remarks of the Guide: The proposed research topic is a novel one. Niosomal gel of Ketoconazole can improve efficacy, increase the residence time and overcome the common side effects.11. Name & Designation (in BLOCK LETTERS):11.1 Guide: Prof. D.NAGENDRAKUMAR Assistant Professor Department of Pharmaceutic, S.V.E.T’S College of Pharmacy, Kallur road, Humnabad, Dist- Bidar. Karnataka. 11.2 Signature of Guide:(Mrs. ROHINI R. M.)11.3 Co-Guide:11.4 Signature of Co-Guide:11.5 Head of the Department: Prof. D.NAGENDRAKUMAR Professor and HOD, Department of pharmaceutics, S.V.E.T’S College of Pharmacy, Kallur road, Humnabad, Dist-Bidar, KARNATAKA.11.6 Signature of HOD:12. 12.1 Remark of the Principal:12.2 Signature of the Principal: Prof. D. NAGENDRAKUMAR S.V.E.T’S College of Pharmacy, Kallur road, Humnabad, Dist.-Bidar, KARNATAKA.8 9

Rajiv Gandhi University of Health Sciences s76

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