FORMULATION AND EVALUATION OF - RGUHS：制定和評價- rguhs

1、.DESIGN, OPTIMIZATION AND EVALUATION OF ORAL IN-SITU GEL FOR ANTI INFECTIVE DRUGSYNOPSIS FORM.PHARM DISSERTATIONSUBMITTED TORAJIV GANDHI UNIVERSITY OF HEALTH SCIENCESKARNATAKABYM.PRATHYUSHAI M.PHARMUNDER THE GUIDENCE OF DR.B.PRAKASH RAOPROFESSOR, HEAD OF THE DEPARTMENTDEPARTMENT OF PHARMACEUTICAL TE

2、CHNOLOGYKARNATAKA COLLEGE OF PHARMACY BENGALURU-560064(2011-2012) RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCESKARNATAKA, BANGALORE.ANNEXURE IIPROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION1Name of the Candidate and AddressM.PRATHYUSHAKarnataka College of Pharmacy# 33/2, Thirumenahalli Hegde Nag

3、ar Main Road Bengaluru-560064.PERMANENT ADDRESSD/O M.PRABHAKAR REDDY H.NO:7-319,Behind Agro ForumRama Chandra Gudem Miryalaguda-508207             Nalgonda(Dist) Andhra pradesh.2Name of the InstitutionKARNATAKA COLLEGE OF PHARMACY# 33/2, Thirume

4、nahalli Hegde Nagar Main Road Bengaluru-560064.3Course of the Study and Subject MASTER OF PHARMACY (PHARMACEUTICAL TECHNOLOGY)4Date of Admission 13th JUNE- 20115TITLE OF THE PROJECT:-DESIGN, OPTIMIZATION AND EVALUATION OF ORAL INSITU GEL FOR ANTI INFECTIVE DRUG 66.16.2BRIEF RESUME OF INTENDED WORK:-

5、NEED FOR THE STUDY:- Oral administration of drugs has the most common and preferred route for delivery of the most of the drugs. In recent years oral controlled delivery (CR) systems have gained increased importance and interest since it is necessary to improve the systemic absorption of the drugs a

6、nd patient compliance. In addition, CR systems maintain uniform drug levels, reduce dose, side effects and increase the safety. The oral in-situ gel forming polymeric drug delivery systems are designed with an objective to retain in stomach for an extended time period and also for achieving systemic

7、 drug effects over than other pharmaceutical dosage forms. In-situ gel forming polymeric drug delivery systems have shown some advantages such as easy of administration, reduced frequency of administration, improved patient compliance and comfortand In-situ gels are prepared to overcome the rapidly

8、increasing cost and to reduce the time required in the development works over than the other pharmaceutical dosage forms. The current research work of formulating oral in-situ gel by using anti-infective drug having shorter half life. Gastrointestinal absorption occurs mainly in the upper intestine

9、with reaching peak plasma concentrations (Cmax). An Antibiotic is an Anti infective which treats the bacterial infections. Antibiotics are defined as the substances produced by microorganisms, which suppress the growth of microorganisms or kill other microorganisms at very low concentrations. Antibi

10、otics are very commonly used substances to eradicate bacterial infections by bacteriostatic oreven bactericidal effect. There are several classifications for antibiotics, based on bacterial spectrum (broad versus narrow)or type of activity (bactericidal vs. bacteriostatic), the most useful is based

11、on chemical structure. Antibiotics within a structural class will generally have similar patterns of effectiveness, toxicity, and allergic potential. Antibiotics are used for the treatment of infection (Respiratory, GI, UTI and meningitis) due to E. coli, P.mirabilis, enterococci, Shigella, S. typho

12、sa and other Salmonella, nonpenicillinase-producing N. gononhoeae, H. influenzae, staphylococci, streptococci.REVIEW OF LITERATURE:· In-situ forming polymeric drug delivery system to reduce the frequency of administration, improved patient compliance and comfort, fomulations developed based on

13、the factors are temperature modulation, pH range, presence of ions and ultraviolet irradiation1.· In-situ gel formulation by using 33 factorial design to retain in the stomach for extended period of time based on the three independent factors: concentrations of like gellan gum(x1), sodium algin

14、ate(x2) and anti-diabetic drug metformin(x3) and also considered five dependent variables are release exponents (Y1), dissolution efficiency(Y2), drug release at 30min(Y3), drug release at 210min(Y4), drug release at 480min(Y5). Three dimensional surface response plots were drawn to evaluate the int

15、eraction of independent variables on the chosen dependent variables. Three factorial levels coded for low, medium, and high settings (1, 0 and +1, respectively) were considered for three independent variables2.· Oral in-situ gel containing clotrimazole for oral candidiasis based on the PH trigg

16、erd and ion activated systems was formulated and evaluated. Triggerd system consisting of carbopol934P(0.2-1.4%w/v) and ion activated system using gellangum(0.1-o.75%w/v) and hydroxyl propyl methyl cellulose E50LV for prolonged release of drug and carried out evalution studies for gelling capacity,

17、PH , viscosity, clarity, gel strength and in -vitro studies, microbial studies3.· The properties and importance of various polymers used in certain drug delivery systems based on their drug releasing properties were explained4.· In-situ forming polymeric drug delivery systems by using vari

18、ous types of polymers including gellan gum, alginic acid, xyloglucon, pectin, chitosan, poly caprolactone, poly(DL-lactic acid),poly(DL-lactide-glycoside) etc were formulated and developed; and also explained selection of solvents(water, dimethylsulphoxide, N-methyl pyrrolidone,2-pyrrolidone etc;) d

19、epends on the solubility of polymers5.· In-situ gelling system for periodontal anesthesia containing chitoson (0.25%w/v) and hydroxyl propyl methyl cellulose (0.25%w/v) polymer system was formulated. It has good gelling properties at 7.5PH and provides prolonged action6.· Pluronic and chit

20、osan based in-situ gel system for periodontal application was developed and evaluated by explaining the behaviour of in-situ gel at PH6 and temperature 25oc it is in liquid form, then converted into gel at body PH and temperature ( PH7.4, 37oc ) based on the polymeric system like as chitosan ( PH st

21、imulant) combination with pluronic F-127 (temperature stimulant) and also explained to check the efficacy of the developed in-situ gel by using prilocaine hydrochloride as the model drug7.· Thermo-responsive and bio adhesive in-situ gelling drug delivery system containing fluconazole, which can

22、 be used in oral thrush. Bio adhesive polymer was used as a thermo responsive material, because poloxmer188 and carbopol934 has thermal gellation properties at certain temperature8.· Sodium alginate based in-situ gel of clarithromycin and metronidazole benzoate was formulated, optimized and eva

23、luated. Sodium alginate used as a polymer and CaCO3 was used as a cross-linking agent, this formulations exhibits good viscosity properties and sustained drug release and explained accelerated stability studies9.· Oral in-situ gelling system for sustained release drug delivery of famotidine was

24、 designed and evaluated; in-vitro release study revealed that drug released from the in-situ gel followed non-fickian diffusion. In vivo study for the sodium alginate was carried out by pylorus legation method in rats, which showed gel formation in gastric juice and reduction in ulcer index. Stabili

25、ty study was also carried out for three months, which showed no major changes from their initial state10.· Vaginal has been used as a mucosal drug delivery route for a long time. Gels are semi-solid, three-dimensional, polymeric matrices comprising small amounts of solid, dispersed in relativel

26、y large amounts of liquid, possessing more solid-like character. These systems have been used and are receiving a great deal of interest as vaginal drug delivery systems11. · A new intra-gastric floating in situ gelling system for controlled delivery of amoxicillin for the treatment of peptic u

27、lcer disease caused by Helicobacter pylori (H. pylori) was developed. Gellan based amoxicillin floating in situ gelling systems (AFIG) were prepared by dissolving varying concentrations of gellan gum in deionized water containing sodium citrate, to which varying concentrations of drug and calcium ca

28、rbonate, as gas-forming agent, was added and dissolved by stirring12.· A minocycline-loaded wound dressing with an enhanced healing effect was developed. The cross-linked hydrogel films were prepared with polyvinyl alcohol (PVA) and chitosan using the freeze-thawing method. Their gel properties

29、, in vitro protein adsorption, release, in vivo wound healing effect and histopathology were then evaluated13. 6.377.1 OBJECTIVE OF THE STUDY:-To prepare and develop controlled drug delivery system of oral in-situ gel for anti-infective drug having shorter half-life The objectives of the study is as

30、 follows:1) Pre-formulation studies.2) The current study is to develop an ideal oral in-situ polymeric drug delivery system by using factorial design (Design expert software). 3) Optimization. 4) The oral in-situ gel is design for to retain in the stomach for extended period of time. 5) Formulation

31、of oral in-situ gel by suitable method. 6) Evaluation of oral in-situ gel for their physicochemical studies (Viscosity, Clarity, Gel Strength, Gelling capacity, Gellation PH and temperature, In-vitro studies) and 7) Stability studies for selected formulations.MATERIALS & METHODS:-SOURCE OF DATA:

32、- Review of literature from: Journals such as: Indian Journal of Pharmaceutical Sciences International Journal of drug delivery International Journal of Pharm Tech research International Journal of Pharma. Research and development Journal of Biomedical Sciences and Research Asian Journal of Pharmace

33、utics Web sites : World wide web. J-GateHelinet Science Direct K7.27.3 7.47.57.68Materials Anti infective drug and polymers will be procured from Pharma grade suitable manufacturer. Other reagents will be of Analytical grade.Methods 1) Preparation of oral in-situ gel by simple mixing method. 2) Eval

34、uationa) clarityb) solution-gel transition temperature and gelling timec) gel- strengthd) viscosity e) PH f) in-vitro drug release studiesg) microbial studies. 3) Stability studies as per ICH guidelines Method of collection of data (including sampling procedures if any): The data will be collected f

35、rom prepared formulations subjected to different evaluation techniques, scale-up techniques and stability studies obtained from ICH guidelines. Does the study require any investigation or interventions to be conducted on patients or other humans or animals? - Does Not Require-Has ethical clearance b

36、een obtained from your institution in case of 7.5? -NO-LIST OF REFERENCES:-1. Nirmal HB, Bakliwal SR, Pawar SP. In-situ gel: new trends in controlled and sustained drug delivery system. Int J PhamTech res 2010 Apr-Jun;2(2):1398-408.2. Ramesh CN, Srinatha A, Jayanta KP. In-situ forming formulation: d

37、evelopment, evaluation and optimization using 33 factorial design. AAPS PharmSciTech 2009 Sep:10(3):977-84.3. Harish NM, Prabhu P, Charyulu RN, Gulzar MA, Subrahmanyam EVS. Fomulation and evaluation of in-situ gels containing clotrimazole for oral candidiasis. Indian J Pharm Sci 2009 Jul-Aug;10(8):4

38、21-7.4. Ankita R, Anil B, Brijesh K. Polymers in drug delivery. Int J Pharm Res Dev 2002 Oct;2(8):9-20.5. Madan M, Bajaj A, Lewis S, Udupa N, Baig JA. In-situ forming polymeric drug delivery systems. Indian J Pharm Sci 2009 May-Jun;71(2):242-51.6. Gupta H, Singh RM, Singh GN, Kaushik D, Sharma A. PH-induced in-situ gel for periodantal anesthesia. Indian J Pharm Sci 2008 Dec;70(6):776-8.7. Himanshu G, Arti S, Birendra S. Pluronic and chitosan based in-situ gel system for