DESIGN,FORMULATIONAND EVALUATIONOF SUSTAINED RELEASED DOSAGE FORMS OF NABUMETONE DRUG
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
J ARIF BASHA
I M.PHARM
UNDER THE GUIDANCE OF
R.K.MOHAMED MUTAHAR
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
OXBRIDGE COLLEGE OF PHARMACY
BANGALORE-560091
2012-2013
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1. / Name of theCandidate and Address: / J ARIF BASHAOxbridge College of Pharmacy
#8&9, Mahadeshwara Nagar Extn,
Vishwaneedam Post,Herohalli cross,
Magadi Main Road,
Bangalore-560091.
PERMANENT ADDRESS
S/O Jined basha,
D.No:3/47-D,
Mandalapalli(V),
Gudibanda(M),
Anantapur(Dist)-515271
Andhra Pradesh.
2. / Name of the Institute: / Oxbridge College of Pharmacy
#8&9, Mahadeshwara Nagar Extn,
Vishwaneedam Post,Herohalli cross,
Magadi Main Road,
Bangalore-560091.
3. / Course of the Study & Subject: / Master of Pharmacy in
Pharmaceutics
4. / Date of admission to the course: / 10thNOV2012
5. / Tittle ofTopic :
DESIGN, FORMULATION AND EVALUATION OF SUSTAINED RELEASED DOSAGE FORMS OF NABUMETONE DRUG
6 / BRIEF RESUME OF INTENDED WORK:
6.1
6.2
6.3
7.0
7.1
7.2
7.4
7.5
7.6
7.7
7.8
8 / NEED OF STUDY:
The word new or novel in the relation to drug delivery system is a search for something out of necessity. An appropriately designed sustained drug delivery system can be major advance towards solving the problem associated with the existing drug delivery systems1.
The oral route is the most common route used for administration of drugs. In long-term therapy for the treatment of chronic disease conditions, conventional formulations are required to be administered in multiple doses and therefore have several disadvantages2.
Drugs can be administered through different routes; however, of all the routes of administration, oral route is most convenient for administering drugs for systemic effect because of ease of administration by manufacturing and dosage adjustments. Oral route of drug administration has wide acceptable and of the drugs administered orally in solid dosage forms represents the preferred class of products.
Sustained releasedrug delivery system that achieves slow release of drugs over an extended period of time not particularly at a pre-determined rate3.
Sustained release (SR) drug delivery systems are developed to modulate the release ofdrug, in order to achieve specific clinical objectives that cannot be attained with conventional dosage forms. Possible therapeutic benefits of a properly designed SR dosage form include low cost, simple processing, improved efficacy, reduced adverse events and flexibility in terms of the range of release profiles attainable4.
Sustained release dosage forms to complement the pharmaceutical activity of the medicament inorder to achieve better selectivity and longer duration of action5. Sustained release products are helpful to reduce the dose frequency and side effects of drugs and improve patient convenience6.
The main objective of the present study is aimed to develop, formulate and evaluate sustained release dosage form of anti inflamatorytablets by using suitable polymers.
REVIEW OF LITERATURE:
The developed metformin HCL sustained release tablets containing 13% HPMC K100 with binder PVP K30. Their study was undertaken with an aim to formulate, develop and evaluation of metformin sustained release tablets using different polymers as release retarding agent. It was concluded that formulation of sustained release tablet of metformin containing 13 % HPMC K100 with binder PVP K30 was taken as an ideal or optimized formulation of sustained release tablets for 10 hr release as it fulfilled all the requirements for sustained release tablet was reported7.
The sustained release bilayer tablets of metformin HCL and pioglitazone HCL by wet granulation method using different viscosity grade of HPMC (HPMC K4M AND HPMC K100M) as polymers and immediate release layer was prepared by direct compression method using superdisintegrants such as sodium starch glycolate and crosscarmellose sodium. The tablets had been evaluated for physicochemical properties. All the values had been found to be within limit. In-vitro release studies was carried out by using USP type‐2 paddle apparatus. Their result showed that combinations of polymers namely HPMC K100M and HPMC K4M in sustained layer can control the release of drug. Their study concluded that bilayer tablets of pioglitazone HCl and metformin HCl as an alternative to the conventional dosage form8.
Developement and evaluation of sustained release tablets of aceclofenac using hydrophilic matrix system and studied its release rate studies. Their objective of the study was to develop “once daily” sustained release tablets of aceclofenac (200mg) by wet granulation using hydrophilic polymer like hydroxy propyl methyl cellulose K ‐100. The drug excipient mixtures had been subjected to preformulation studies. The tablets had been subjected to physicochemical studies, in- vitro drug release, kinetic studies and stability studies. Their FTIR studies showed there was no interaction between drug and polymer. The physicochemical properties of tablets were found within the limits. Results of their study indicated the suitability of hydrophilic polymers in the preparation of matrix based sustained release formulation of Aceclofenac9.
An oral sustained release metformin tablet was prepared by direct compression method, using hydrophilic eudragit RSPO and RLPO alone or in combination with hydrophobic ethyl cellulose polymer as rate controlling factor. All the batches were evaluated for thickness, weight variation, hardness and drug content uniformity and in-vitro drug release. Mean dissolution time was used to characterize drug release rate from a dosage form and it indicated the drug release retarding efficiency of polymer. When eudragit RSPO and RLPO were used alone as the only retarding polymer, a sustained drug release pattern were not observed while, inclusion of ethylcellulose in the matrix almost doubled (12 h) the time required for releasing the drug. Kinetic modeling of in-vitro dissolution profiles revealed that drug release mechanism was diffusion controlled to anomalous type10.
studied a model system using interferon-α (IFN-α) as the test protein by developing a novel delivery system for proteins based on polyglycerol esters of fatty acids (PGEFs) In an in-vitro release study using an enzyme-linked immunosorbent assay (ELISA) as a detection method, the matrices prepared from a monoglyceride (used for comparison) and from diglycerol esters exhibited a biphasic release pattern with a large initial burst followed by slow release. In an in vivo release study, initial bursts of IFN-α release were, also, dramatically reduced when the matrices were prepared from the tetraglycerol esters of palmitate and stearate, and the mean residence time (MRT) of IFN-α was prolonged, whereas the matrices prepared from monoglyceride and from diglycerol esters showed large initial bursts of IFN-α release. It was concluded that the bioavailability of IFN-α after implantation of the matrix formulation prepared using all types of PGEFs, except for tetraglycerol triesters, was almost equivalent to that after injection of IFN-α solution; consequently, IFN-α in these matrices appears to remain stable during the release period.
OBJECTIVE OF THE STUDY:
To carry out preformulation studies of sustained released matrix tablets.
Formulation by suitable methods.
Evaluation parameters of tablets.
Characterisation of optimized formulation.
To prepare sustained released tablets wet granulation/dry granulation/direct compression methodfluid bed granulation method/ hot melt extrusion/spray drying or any other suitable method
To carry out stability studies according to ICH guidelines for the optimized formulation.
MATERIALS & METHODS :
SOURCE OF DATA:
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 Pharmaceutics
Web sites :
•World Wide Web.
•J-Gate@Helinet
•Science Direct
MATERIALS :
Drug:-Nabumetone(NSAID) will be procured/obtained from suitable pharma manufacturer.
Polymers:-
Different grades of hydroxyl propyl methyl cellulose(HPMC) like
HPMC K4M, HPMC K100M, HPMC E50LV etc.
Carbopol, Eudragit, guar gum,PVP,CMC, synthetic.These polymers will be used in different proportions along with other tablet excipients.
METHODS :
The active agent and excipients will be formulated into tablet by wet granulation &direct compression technique. Different polymers will be screened to achieve desired physicochemical properties.
EVALUATION STUDIES :
- Precompression studies
Tapped density
Carr’s index
Angle of repose
Hausner ratio
- Post compression studies
Thickness
Hardness
Friability
Weight variation
Content uniformity
Drug content
Dissolution studies
Method of Collection of Data (including sampling procedure, if any) :
The data will be collected from prepared formulations subjected to different evaluation techniques, scale-up techniques and stability studies obtained from ICH guidelines.
Does the study require any investigations or interventions to be conducted
on patients or other human or animals ? If so please describe briefly
NOT APPLICABLE
Has the Ethical Clearance been obtained from your Institution in case of 7.5 ?
NOT APPLICABLE
LIST OF REFERENCES :
- Najmuddin M, Vishalpatel, Aejazahmed, Shelar S, Khan T. Int J Pharm Pharmaceu Sci 2010; 2(2): 83-87.
- Joint United Nations Programme on HIV/AIDS (UNAIDS) and World Health Organization (WHO). AIDS Epidemic Update2005. Geneva, Switzerland: UNAIDS. Available at: doc/EPIupdate2005_pdf_en/epi-update 2005_en.pdf. Accessed. December 10, 2006.
- Chien YW. In Novel Drug Delivery Systems,2nd edition,Chien Y W, Ed, New York, Dekker, 1992:1.
- Wadher KJ, Kakde RB, Umekar MJ.Formulation and evaluation of sustainedrelease matrix tablets of metformin hydrochloride using pH dependent and pH independent methacrylate polymers. Br J Pharm Res 2011;1(2):29-45.
- Pandey VP, Manavalan R, Rajan TS and Ganesh KS. Indian J Pharm Sci 2003 ; 65 : 44.
- Udupa N. Eastern Pharmacist 1987 ; 30 : 129.
- Senthilkumar K, Ehizilmuthu R. Formulation, development and evaluation of metformin hydrochloride. Int J Pharm Bio Sci 2011;2:77-82.
- Rajendran NN, Natarajan R, Subashini R, Patel H. Formulation and evaluation of sustained release bilayer tablets of metformin Hcl and pioglitazone Hcl. Int J Curr Pharm Res 2011;3:118-22.
- Shaikh AC, Nazim S, Siraj S,Khan T, Patel MS, Shaikh A et al., Formulation and evaluation of sustained release tablets of aceclofenac using hydrophilic matrix system. Int J Pharm Pharm Sci 2011;3:145-48.
- Wadher KJ, Kakde RB, Umekar MJ. Development of a sustained release tablet of metformin hydrochloride containing hydrophilic eudragit and ethyl cellulose polymer. Int J Comp Pharm 2011;2:01-06.
- Jayaswa, SB, Gode KD and Khanna SK. Sustained release tablet formulation of propranolol hydrochloride with Eudragit. Aust. J. Pharm. Sci. (1980) 9: 22-26.
9 / Signature of the Candidate / (J ARIF BASHA)
10 / Remarks of the Guide
The topic selected for dissertation is satisfactory. Adequate equipment & chemicals are available to carry out the project work.
11 / Name & Designation (in BLOCK LETTERS)
11.1 / Guide / R.K.MOHAMED MUTAHAR
PROFESSOR
DEPARTMENT OF PHARMACEUTICS
OXBRIDGE COLLEGE OF PHARMACY
BANGALORE-560091.
11.2 / Signature of Guide / (R.K.MOHAMED MUTAHAR)
11.3 / Co-Guide / NOT APPLICABLE
11.4 / Signature of Co-Guide / NOT APPLICABLE
11.5 / Head of the Department / MANJUNATH.U.MACHALE
PROFESSOR AND HEAD OF THE DEPARTMENT OF PHARMACEUTICS
11.6 / Signature of HOD / (MANJUNATH .U.MACHALE)
12 / Remark of the Principal
All the required facilities will be provided to carry out dissertation work under the supervision of the guide.
12.1 / Principal / R.K.MOHAMED MUTAHAR
PRINCIPAL
OXBRIDGE COLLEGE OF PHARMACY
BANGALORE-560091
12.2 / Signature of the Principal / (R.K.MOHAMED MUTAHAR)
1