7.3Does study requires any investigation or interventions to be conducted on patients or other human or animal? If so, please describe briefly.
7.4 Has ethical clearance been obtained from your institution in case of 7.3
ENCLOSURE - IV
ENCLOSURE - V
ENCLOSURE - VI
ENCLOSURE - VI
LIST OF REFERENCES
ENCLOSURE – VII
Brief resume of the intended work:
ENCLOSURE – I
6.1 – Need for the study:
Controlled drug delivery systems are the dosage forms which are developed to achieve better patient compliance, modified drug release, delivery of drug at the site of action, more efficient administration of drugs by various routes and for better therapeutic effect1.
Niosomes are drug targeting formulation to permit the establishment and maintenance of any concentration at target site for longer intervals of time. Niosomes are promising vehicle for drug delivery and being non-ionic; it is less toxic and improves the therapeutic index of drug by restricting its action to target cells. Niosomes may act as a depot, releasing the drug in a controlled manner. The therapeutic performance of the drug molecules can also be improved by delayed clearance from the circulation, protecting the drug from biological environment and restricting effects to target cells. It enhances the bioavailability by crossing the anatomical barrier of gastrointestinal tract via transcytosis of M cells of Peyer's patches in the intestinal lymphatic tissues.2
Flutamide is a non-steroidal anti androgenic drug used for the treatment of prostate cancer. This drug has quit extensive first pass metabolism, shorter elimination half life and poor bioavailability, which reduces testosteron only when administration on a continuous basis. High dose of Flutamide produces hepatotoxicity.
Flutamide is effective in prostate cancer treatment only when its desired concentration in blood is maintained in longer duration. Flutamide liposome’s using egg phosphotidylcholine and cholesterol retained in plasma where as free drug disappeared from blood circulation after 24hrs. But main disadvantage was long term stability problem in case of liposomes. Niosomes may deliver the flutamide for longer duration in blood and will expect a better stability when compared to other particulate dosage form.3
Hence in the present work an attempt is made to provide niosomes containing flutamide with suitable surfactant by appropriate methods having the following advantages.
Targeting drug to tumor cells
Prolonged therapeutic effect
Decrease frequency of drug administration
ENCLOSURE – II
6.2 REVIEW OF LITERATURE
Abraham Lingan et al., prepared the topical gel containing Clobetasol propionate niosomes to prolong the duration of action and prevent its side effect by three methods such as thin film hydration method, ether injection and hand shaking methods. They have reported that the niosomal delivery of Clobetasol propionate in Carbopol gel base acts as a suitable topical drug delivery system to prolong the duration of action.1
Punitha Sundaresa et al., prepared Aceclofenac niosomes by different techniques namely ether injection method, Ethanol injection method, Sonication method, Thin film hydration and reverse phase evaporation techniques using 1:1:1 ratio of drug, cholesterol and surfactant (span 60). Among the 5 techniques thin film hydration and reverse phase evaporation formulation were reported to sustain the drug release rate for more than 24 hrs.4
Lokeshwar Babu et al., has reviewed the method of preparation and characterization of niosomes. They have reported that poor stabity associated with liposomes on long term storage can be overcome by the formulation of niosomes.5
Pavala et al., prepared the Rifampicin and Gatifloxacin niosomes by lipid hydration technique using rotary flash evaporator. The prepared Rifampicin and Gatifloxacin niosomes were reported as vsesicle size in the range of 100-300nm, the entrapment efficiency are 73% and 70% respectively. The in-vitro release study shows that 98.98% and 97.74% release of Rifampicin and Gatifloxacin niosome respectively.6
Srinivas et al., developed and characterized Aceclofenac niosomes by modified ether injection method using non-ionic surfactant (span 60, 20) and cholesterol in different ratios. They have reported that the prepared formulation shows improved boiavilability.7
Vijay S Jatav et al., prepared the niosomes containing Rifampicin by hand shaking method using surfactant (span 20, 85) and cholesterol. They reported that the cumulative percent Rifampicin released is maximum for span 20 based niosomes and minimum for span 85 based niosomes.8
Mohamed Firthose et al., investigate the feasibility of niosome as a transdermal drug delivery system for Miconazole. The niosomes are prepared by thin film hydration technique by using the cholesterol and span in different ratios. The formulation was evaluated for percentage of drug entrapment and for their cumulative drug release. They reported that the formulation with 1:1 CHOL:SA ratio shows that 92.10% drug release in 24 hrs.9
Rajesh Mujoriya et al., investigeted the method of preparation of niosomes such as ether injection, sonication, hand shaking and thin film hydration method. They have reported vesicles prepared from hand shaking method shows greater vesicle diameter compared to those prepared by ether injection method.10
Naresh Ahuja et al., prepared the Lansoprazole niosome by reverse phase evaporation method using homogenizers. The formed niosomes are characterized for its size range, entrapment efficiency and in vitro release of drug. The result can be concluded that lansoprazole niosomes are prepared by reverse phase evaporation method lead to the production of spherical stable uniform vesicle with excellent entrapment efficiency.11
Rangasamy M et al., prepared Acyclovir entrapped niosomes by hand shaking and ether injection process with different ratios of cholesterol and span. They have reported that the in-vitro release of drug was significantly extended a period of 1day and 16hr for release and shows prolonged activity with simultaneously reduces the side effect. 12
Anupriya kapoor et al., prepared Acyclovir niosomes by reverse phase evaporation method using different sorbitan ester (span 20, 40, 60 and 80) and cholesterol in different molar ratio. They have reported in vitro release drug significantly retarded indicating more sustained release pattern can be obtained by incorporating the drug in niosomes formed with span 60.13
Navdeep Ranghuwanshi et al., developed and characterize the niosomal encapsulated Levofloxacin and in vitro behaviour of the prepared system and ocular irritancy test in albino rabbit eye .They concluded that the encapsulated Levofloxacin released at a constant and controlled rate and found reduced side effects associated with frequent administration of drug.14
Sathyavathi et al., developed Brimonidine tartarate in situ niosomal gel for glaucoma treatement, prepared by thin film hydration method using different ratio of cholesterol and surfactant (span 60). They have reported that antiglaucoma activity of the prepared gel formulation shows significant and sustain the effect in reducing intra ocular pressure than marketed niosomal drops and also improve the ocular bioavailability with minimal loss of drug.15
Shaniwala A et al., prepared Nimesulide niosomes by lipid film hydration technique using tween and span for topical application.They have concluded that the prepared Nimesulide niosomes enhanced the anti-inflammatory activity compared to plain drug gel and marketed formulation.16
Chawda Himmat Singh et al., prepared niosome-encapsulated drug delivery for anti-inflammatory drugs like Nimesulide by lipid film hydration method and ether injection technique using Non-ionic surfactants (span 20, 40, and 60) and cholesterol in different ratios. They have reported that the niosomes prepared by lipid film method shows higher entrapment efficiency compared niosomes prepared by ether injection method.17
Singla Kapil et al., prepared the Lornoxicam niosomal gel by thin film hydration method using surfactant (span 60, 40, and 80) and cholesterol in different ratios. They reported that physicochemical characterization and in vitro permeation studies of the prepared vesicles were promising to formulate transdermal drug delivery system.18
Madhvi M et al., reported Metformin niosome drug delivery system and evaluate its in vitro performance. The formulations were prepared with different types of surfactant (span20, 80, tween 20, 80). The study is based on the formulation of Metformin niosomes which provide most promising oral bioavailability of Metformin.19
Prabhu P et al., prepared and evaluated the Brimonidine tartarate niosome by thin film hydration method using different ratio of cholesterol and surfactant (span 60). They have reported that the formulation shows significant and sustain the effect in reducing intra ocular pressure than marketed niosomal drops.20
ENCLOSURE – III
6.3 OBJECTIVE OF STUDY
The broad objective of the study includes:
Pre-formulation studies which include evaluation of various physicochemical characteristics of drug substance and compatibility between drug and excipients.
Formulation of niosomes containing anticancer drug Flutamide using non-ionic surfactant in different ratios.
Evaluation of prepared microspheres for the following parameters
7.1 Source of Data: From Science Direct & other internet facilities.
Presentations like pharmaceutical poster presentation.
International and Indian journals.
Textbooks and reference books.
JOURNALS: Journals & articles :
Asian Journal of Pharmacy & Life Science.
International Journal of Parma Tech and Research.
International Journal of Parma and Bio Sciences.
Journal of Applied Pharmaceutical Science
International Journal of Pharmacy and Pharmaceutical Sciences.
International Journal of Advances in Pharmaceutical Research.
Journal of Pharmacy Research.
International Journal of Life Science & Pharma Research.
Journal of Chemical and Pharmaceutical Research.
International Journal of Pharmacy.
ENCLOSURE - V Method of collection of data:
Laboratory based studies including:
Study for drug surfactant interaction using FTIR
Formulation of niosomes using hand shaking method or any suitable method.
Evaluation of above preparation for
Size and shape analysis
Drug entrapment efficiency
In vitro drug release study
ENCLOSURE VI - Does the study require any investigations or interventions to be conducted on patients or other humans or animals? If so, Please describe briefly.
7.4 - Has ethical clearance been obtained from your Institution in case of 7.3
LIST OF REFERENCE Abrahamlingan M, Abdulhasansathali A, Vijaykumar M R, Gokila A. Formulation and evaluation of topical drug delivery system containing Clobetasol propionate niosomes. Sci Revs Chem Commun,2011;1(1):7-17.
Nirmala V Patel, Darshan Modi, Dr Bharodia P T. Formulation and evaluation of niosome. IJ UPLS,2012; 2(3):160-167.
Umarethia M L, Ghosh P K, Majithiya R J, Murthy RSR. Pharmacokinetics and hepatotoxicity of Glutamine niosomes after 1V administration. Online J Pharmaco Users comcen com au,2005;3:1-15.
Punitha Sundaresan, Sravanthi, Tananki Gowtham. Evaluation of Aceclofenac niosomes prepared by various techniques. Int J Pharm Sci Rev Res,2012;16(1):75-78.
Lokeswara Babu V, Sam Mathew T, Jayaveera K.N, Prasanth V V. Niosomes-Vesicular drug delivery system. Int J Pharm,2013;3(1):180-185.
Pavala Rani N, Suriyaprakash T N K, Senthamarai R. Formulation and evaluation of Rifampicin and Gatifloxacin niosomes on logarithamic-phase cultures of mycobacterium tuberculosis. Int J Pharma Bio Sci,2010;1(4):379-386.
Srinivas S, Anandkumar Y, Hemanth A, Anitha M. Preparation and evaluation of niosome containing Aceclofenac. Dig J Nanomater Bios,2010;5(1):249-254.
Vijay S Jatav, Santosh K Singh, Ashish K Sharma, Rambir Singh. Formulation and in vitro evaluation of Rifampicin loaded niosomes. J Chem Pharm Res,2011;3(2):199-203.
Mohamed Firthose P U, Mohamed Halith S, Wahab S U, Sirajudeen M et al., Formulation and evaluation of Miconazole niosomes. Int J Pharm Tech Res,2011;3(2):1020-1022.
Naresh Ahuja, Vipin Saini, Vijay Kumar Bishnoi, Atul Garg et al., Formulation and evaluation of Lansoprazole niosomes. Rasayan J Chem,2008;1(3):561-563.
Rangasamy M, Balasubramanium A, Sandeep G, Sanaullan S. Formulation and in vitro evaluation of noisome encapsulated Acyclovir. J Pharm Res,2008;1(2):163-168.
Anupriya kapoor, Gahoi R, Kumar D. In-vitro drug release profile of Acyclovir from niosomes formed with different sorbitan esters. AJPLS,2011;1(1):64-69.
Navdeep Raghuwanshi, Swati Dikshit, Amit Sharma, Niraj Upamanyu et al., Formulation and evaluation of noisome encapsulated Levofloxacin for ophthalmic controlled delivery. IJAPR,2012;3:901-906.
Sathyavathi V, Abdul Hasansathali, Ilavarasan R, Sangeetha. Formulation and evaluation of niosomal in situ gel ocular delivery system of Brimonidine tartarate. Int J Life Sci Pharma Res,2012;2(1):82-94.
Shahiwala A, Misra A. Studies in topical application of niosomally entrapped Nimusulides. J Pharm Pharmaceut Sci,2002;5(3):220-225.
Chawda Himmat Singh, Jain C P, Bairwa Narendra Kumar. Formulation, characterization, stability and in vitro evaluation of Nimesulide niosomes. Pharmacophore,2011;2(3):168-185.
Singla Kapil, Rao Rekha, Saini Vipin. Preparation and evaluation of Lornoxicam niosomal gel. IRJP,2012;2(4):378-383.
Madhavi M, Maher C P, Pochaiah B, Rao A M et al., Formulation and evaluation of Metformin based niosome. IJPRR,2013;2(1):1-7.
Prabhu P, Marina Koland, Vijaynarayan K, Harish N M et al., Preparation and evaluation of niosomes of Brimonidine tartrate as ocular drug delivery system. JPRHC,2:293-301.