DEVELOPMENT AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF METOPROLOL SUCCINATE
M.PHARM DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
BY
RUDANI SUMITKUMAR ARVINDBHAI
Under the guidance of
Prof. D. NAGENDRAKUMAR
M. Pharm (Ph.D)
DEPARTMENT OF PHARMACEUTICS
S.V.E.TRUST’S COLLEGE OF PHARMACY
HUMNABAD - 585330
(2010-2011)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE
ANNEXURE – II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR M.PHARM DISSERTATION
1. / Name of the candidate and Permanent address: / RUDANI SUMITKUMAR ARVINDBHAIS/o: ARVINDBHAI BHIKHABHAI RUDANI
247, SWAMINARAYAN SOC., OPP. RENUKA BHAVAN, BOMBAY MARKET-PUNA ROAD, VARACHHA,
SURAT, GUJARAT-395006.
2. / Name of the institute: / S.V.E.T’S COLLEGE OF PHARMACY
HUMNABAD, DIST–BIDAR.
3. / Course of the study & subject: /
Master of Pharmacy
(Pharmaceutics)4. / Date of admission to the course: / 20 June 2010
5. / Title of the topic: / DEVELOPMENT AND EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF METOPROLOL SUCCINATE.
6. / Brief resume of the intended work
A
6.1 / Need for the study:
The rationale for development of a extended release formulation of a drug is to enhance its therapeutic benefits, minimizing its side effects while improving the management of the diseased condition.[1]
Sustained drug delivery systems significantly improve therapeutic efficacy of drugs. Drug-release-retarding polymers are the key performers in such systems. Regarding this, researchers investigated various natural, semi-synthetic and synthetic polymeric materials.[2]
Matrix system is most commonly used method for modulating the drug release in oral controlled drug delivery to obtain a desirable drug release profile, cost effectiveness and broad regulatory acceptance.[3,4]
Metoprolol succinate is a selective β-1 adrenergic receptor blocker used in the treatment of cardiovascular diseases, especially hypertension. It is readily and completely absorbed from the gastrointestinal tract but is subjected to considerable first-pass metabolism having half life 3 to 7 hours and bioavailability about 12%. It is freely soluble in water.[5,6] These physicochemical properties of metoprolol succinate make it suitable candidate for sustained release matrix tablets.
So, In the present study, aim is for preparation and evaluation of sustained release matrix tablets of metoprolol succinate, in order to overcome first-pass effect, dose related side effects, dosing frequency, problems in disease control and many other difficulties.
6.2 / Review of Literature:
6.3
/ Literature review shows that no work has been published on sustained release matrix tablets of metoprolol succinate. Some of the published reports of similar work for various medicinal agent are:
· Pandey et al.[7] have formulated sustained release tablets of diltiazem hydrochloride by wet granulation method by using hydroxy propyl methyl cellulose K4M, ethylcellulose and eudragit S100 which resulted in the drug:polymer ratio 1:0.6 at 7.5 kg/cm2 hardness showed better drug release profile.
· Haung et al.[8] have optimized formulations of extended release tablets of propranolol containing hydroxy propyl methyl cellulose, microcrystalline cellulose and lactose by using response surface methodology.
· Hayashi et al.[9] have prepared sustained release matrix tablets of a theophylline and compared drug release mechanism of each preparation by using release kinetics theories.
· Hu et al.[10] have prepared sustained release pellets of metformin hydrochloride by centrifugal granulation method by using methacrylic acid copolymers (eudragit L30D-55, NE30D), hydroxy propyl methyl cellulose and microcrystalline cellulose which were subjected to surface modification by talc before coating and resulted that it controls drug release and avoids drug dumping.
· Harish et al.[11] have formulated sustained release matrix tablets of terbutaline sulphate by wet granulation method using isopropyl alcohol with stearyl alcohol as granulating agent, hydroxy propyl methyl cellulose (K4M, K10M) and eudragit RLPO as hydrophilic and hydrophobic matrix materials respectively.
· Kumar et al.[12] have evaluated natural gum bhara as noble sustain release matrix forming materials in tablet formulation prepared by wet granulation method using tramadol hydrochloride as the model drug and resulted in the bhara gum possess substantial matrix forming properties that could be used for sustained drug delivery.
· Purnima et al.[13] have prepared extended release tablets of nimesulide by wet granulation technique by using methocel (A4M, E4M, K100LV, K4M), eudragit (RS, RL), ethocel (7 cps) and microcrystalline cellulose.
· Mandal et al.[14] have optimized in vitro release profile of metformin hydrochloride 500 mg sustained release matrix tablets using artificial neural network (ANN) based on multilayer perceptrons (MLP) model by using hydroxy propyl methyl cellulose K15M, microcrystalline cellulose Avicel PH 101 and polyvinyl pyrrolidone K30.
· Abdelbary et al.[15] have developed an extended release matrix tablets of nicorandil by direct compression method by using chitosan, hyaluronic acid, pectin, sodium alginate in a hydrophilic interpolymer complexes and glyceryl monostearate (imwitor 900K) used as a hydrophobic waxy retardant polymer.
· Keny et al.[16] have formulated once daily minocycline hydrochloride extended release matrix tablets by wet granulation method by using hydroxy propyl methyl cellulose (K4M, K15M) and ethyl cellulose (20 cps).
· Garbacz et al.[17] have compared dissolution profiles obtained from nifedipine extended release formulations by using the paddle apparatus and the reciprocating cylinder as pharmacopoeial test devices as well as two newly developed test apparatuses: the rotating beaker and the dissolution stress test apparatuses.
· Khan et al.[18] have formulated and evaluated sustained release matrix tablets of propranolol hydrochloride by wet granulation method by using sodium carboxymethyl guar as rate sustaining polymer and resulted in all the selected formulations were found to be physically and chemically stable at different storage conditions at the end of the eight week.
· Tajiri et al.[19] have developed two types of extended release tablets of cevimeline: simple matrix tablets and press coated tablets by fluidized hot-melt granulation method by using hydroxy propyl cellulose.
· Moghal et al.[20] have optimized formulation of sustained release matrix tablet of ambroxol hydrochloride using central composite design by direct compression technique using methocel K15M as matrix former.
· Subramaniam et al.[21] have formulated sustained release matrix tablets of aceclofenac by wet granulation method by using hydrophilic polymer like hydroxy propyl methyl cellulose K100 which resulted in suitability of hydrophilic polymers in the preparation of matrix based sustained release formulation of aceclofenac.
· Chatterjee et al.[22] have developed micronized sustained release matrix tablet of carvedilol by direct compression method by using hydroxy propyl β cyclodextrin as a bioavailability enhancing agent and polyethylene oxide (PEO 301) as release retarding polymer.
· Viriden et al.[23] have studied the release of a model drug substance, methylparaben from matrix tablets composed of hydroxy propyl methyl cellulose batches of the USP 2208 grade that had different chemical compositions by using USP-II paddle dissolution apparatus.
Objectives of the study:
In the present work, studies will be carried out on the development and evaluation of sustained release matrix tablets of metoprolol succinate with respect to,
· Improve patient convenience and compliance by reducing frequency of drug administration.
· To maximize drug utilization and improve therapy.
· To increase the bioavailability of drug and make shortest treatment for patient.
· To reduce fluctuation in steady-state level of drug for better control of disease condition.
· To achieve the greater therapeutic efficacy.
· To reduce intensity of local or systemic side effects.
7. / MATERIALS AND METHODS
Sources of Data:
1. Internet
2. RGUHS (Helinet)
3. S.V.E.TRUST’S College Digital Library, Humnabad
4. Gulbarga University Library, Gulbarga
5. International Pharmaceutical Abstracts.
7.1 / Materials:
7.2 / Drug: Metoprolol succinate.
Polymers: Carboxy methyl cellulose, Polyethylene glycol, Hydroxy propyl methyl cellulose,
Sodium alginate, Carboxy vinyl polymer, Ethyl cellulose, etc.
Equipments:
1. UV- visible spectrophotometer (1800-Shimadzu)
2. pH-meter
3. Electronic balance (Shimadzu)
4. USP tablet dissolution test apparatus (Campbell, TDR-06N)
5. Monsanto hardness tester
6. Roche friabilator
7. Single pan electronic balance
Preparation of metoprolol succinate sustained release matrix tablets:
In the present study, sustained release matrix tablets of metoprolol succinate will be prepared by any one of these methods like solvent evaporation method, compression method and fusion method which may used to disperse drug and additives into retardant material.
Solvent evaporation method:- In which a solution or dispersion of drug and additives is incorporated in to molten wax phase. The solvent is removed by evaporation.
Compression method:- This involves compression of granules, which may be prepared by wet granulation or dry granulation method or by direct compression of a blend of drug, release retardant material and other additives.
Fusion method:- In which drug and additives are blended into molten wax matrix at temperature slightly above the melting point. A more uniform dispersion can be obtained by this method.
A matrix tablets are considered to be the commercially feasible sustained action dosage form that involve the least processing variables, utilize the conventional facilities and accommodate large doses of the drug.
Evaluation parameters:
1. Hardness
2. Uniformity of weight
3. Uniformity of drug content
4. Friability
5. In vitro drug release studies
6. Drug-polymer interactions
7. Stability studies
7.3 / Does the study require any investigation or intervention to be conducted on patients or other human or animals? If so please describe briefly.
Not under the plan of the work.
7.4 / Has ethical clearance have been obtained from your institution in cases of 7.3?
Not applicable.
8. / List of References:
1. Jain KK, editors. Methods in molecular biologyTM 437, Drug Delivery Systems. Humana Press; 2008. p. 217.
2. Morkhade DM, Fulzele SV, Satturwar PM, Joshi SB. Gum copal and gum damar: Novel matrix forming materials for sustained drug delivery. Indian J Pharm Sci 2010;68:53-8.
3. Malviya R, Srivastava P, Bansal M, Sharma P. Formulation and optimization of sustained release matrix tablets of diclofenac sodium using pectin as release modifier. Int J Drug Dev & Res 2010;2:330-5.
4. Reddy KR, Mutalik S, Reddy S. Once-daily sustained-release matrix tablets of nicorandil: Formulation and in vitro evaluation. AAPS Pharm Sci Tech 2003;4:article no. 61
5. Sweetman SC, editors. Martindale, The complete drug reference, 36th ed. London: The pharmaceutical press; 2009. p. 1338
6. Wikipedia, The free encyclopedia. [updated on 2010 Nov 22; cited on 2010 Nov 28]. Available from: http://en.wikipedia.org/wiki/Metoprolol.
7. Pandey VP, Manavalan R, Sundar RT, Ganesh KS. Formulation and release characteristics of sustained release diltiazem hydrochloride tablet. Indian J Pharm Sci 2003;65:44-8.
8. Huang YB, Tsai YH, Yang WC, Chang JS, Wu PC, Takayama K. Once-daily propranolol extended-release tablet dosage form: Formulation design and in vitro/in vivo investigation. Eur J Pharm Biopharm 2004;58:607-14.
9. Hayashi et al. Formulation study and drug release mechanism of a new theophylline sustained release preparation. Int J Pharm 2005;304:91-101.
10. Hu LD, Liu Y, Tang X, Zhang Q. Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets. Eur J Pharm Biopharm 2006;64:185-92.
11. Harish NM, Kiran AB, Rathnanand M, Shirwaikar A, Shenoy KRP. Sustained-release matrix tablets of terbutaline sulphate: Fomulation and in vitro evaluation. Indian drugs 2007;44: 233-5.
12. Kumar NV, Balakrishna K, Rout PK. Sustained release matrix tablet of bhara gum based tramadol hydrochloride. Indian drugs 2007;44:906-8.
13. Purnima DA, Namita SR. Formulation and evaluation of extended release nimesulide tablets. Indian drugs 2008;45:105-8.
14. Mandal et al. Optimization of metformin hydrochloride 500 mg sustained release matrix tablets using artificial neural network (ANN) based on multilayer perceptrons (MLP) model. Chem Pharm Bull 2008;56:150-5.
15. Abdelbary GA, Tadros MI. Design and in vitro/in vivo evaluation of novel nicorandil extended release matrix tablets based on hydrophilic interpolymer complexes and a hydrophobic waxy polymer. Eur J Pharm Biopharm 2008;69:1019-28.
16. Keny RV, Mankame SA, Loureno CF. Formulation and evaluation of once daily minocycline hydrochloride extended release matrix tablets. Indian J Pharm Sci 2009;71:295-302.
17. Garbacz et al. Comparison of dissolution profiles obtained from nifedipine extended release once a day products using different dissolution test apparatuses. Eur J Pharm Sci 2009;38:147-55.
18. Khan AB, Nanjundaswamy NG. Formulation and evaluation of sustained release matrix tablets of propranolol hydrochloride using sodium carboxymethyl guar as rate sustaining polymer. Arch Pharm Sci Res 2009;1:203-6.
19. Tajiri S, Kanamaru T, Makoto K, Konno T, Nakagami H. Dosage form design and in vitro/in vivo evaluation of cevimeline extended release tablet formulations. Int J Pharm 2010;383:99-105.
20. Moghal MR, Islam MS, Roni MA, Ahmed I, Islam MR, Mohmmad HR. Development and optimization of sustained release matrix tablet of ambroxol hydrochloride using central composite design. Indian J Pharm Educ Res 2010;44:28-35.
21. Subramanium K, Rangasamy M, Kugalur G, Parthiban KN, Natesan SK. Formulation and evaluation of sustained release tablets of aceclofenac using hydrophilic matrix system. Int J Pharmtech Res 2010;2:1775-80.
22. Chatterjee B, Pal TK. Development and in vitro evaluation of micronized sustained release matrix tablet of carvedilol. Int J Pharm Sci Res 2010;1:96-102.
23. Viriden A, Larsson A, Schagerlof H, Wittgren B. Model drug release from matrix tablets composed of methocel with different substituent heterogeneity. Int J Pharm 2010;401:60-7.
9. / Signature of the Candidate / RUDANI SUMITKUMAR ARVINDBHAI
10. / Remarks of the Guide:
The sustained release formulations of metoprolol succinate improves patient compliance by reducing dosing frequency, reduce fluctuation in drug level with greater therapeutic efficacy.
11. / Name & Designation (in BLOCK LETTERS)
11.1 Guide / Prof. D. NAGENDRAKUMAR
Department of pharmaceutics,
S.V.E.T’S College of Pharmacy,
Kallur road, Humnabad,
Dist.-Bidar, Karnataka.
11.2 Signature of Guide / O
INI 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
The facilities are available for the work undertaken.
12.2 Signature of the principal / Prof. D. NAGENDRKUMAR
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