Formulation and Evaluation of Hydrogel Based Modified Release Matrix Tablet of Metoprolol

FORMULATION AND EVALUATION OF HYDROGEL BASED MODIFIED RELEASE MATRIX TABLET OF METOPROLOL SUCCINATE

M. Pharm. Dissertation Protocol

Submitted to the

Rajiv Gandhi University of Health Sciences, Karnataka.

Bangalore.

By

MANSUR MOHMADSHAHID ISMAIL

B. Pharm.

Under the guidance of

M. A. SALEEM

m.pharm., (Ph.d.)

Asst. Professor

Dept. of Pharmaceutics,

Luqman College Of Pharmacy, Gulbarga

DEPARTMENT OF PHARMACEUTICS

LUQMAN COLLEGE OF PHARMACY, GULBARGA

2011-12

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA

BANGALORE

ANNEXURE - II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the Candidate (In block letters) Permanent Address / MANSUR MOHMADSHSHID I.
B-12 DAMAN GANGA CANAL COLONY BALITHA (VAPI) 396 191
GUJARAT
2 / Name of the Institution / LUQMAN COLLEGE OF PHARMACY,
GULBARGA-585 102.
3 / Course of Study and Subject / M.PHARM (PHARMACEUTICS)
4 / Date of Admission to Course / 15th OCT 2011
5. / Title of the Topic / FORMULATION AND EVALUATION OF HYDROGEL BASED MODIFIED RELEASE MATRIX TABLET OF METOPROLOL SUCCINATE
6. Brief Resume Of The Intended Work
6.1 Need for the study:
High patient compliance and flexibility in designing dosage forms attracted the oral drug delivery systems to be the most convenient mode of drug administration when compared to other dosage forms. Of these, matrix systems have gained widespread importance in controlled drug delivery due to cost-effective manufacturing technology. Hydrophilic matrix tablets are among the most popular delivery systems for oral controlled release dosage forms. These hydrophilic matrices are widely accepted because of their biopharmaceutical and pharmacokinetics advantages over conventional dosage forms. This is largely because they offer precise modulation of drug release as a result of hydration of the constituent polymer(s), flexibility to obtain desired drug release profiles, cost effectiveness, patient compliance, providing a constant, prolonged, and uniform therapeutic effect.1 Matrices containing swellable polymers are also referred to as hydrogel systems.2 Regular research is going on in field of use of natural occurring biocompatible polymeric material in designing of dosage form for oral controlled release administration.3 Varieties of natural polymers are being used effectively in pharmaceutical products. These include proteins (gelatin), polysaccharides (chitosan, agar, acacia, agarose) and gummy exudates (guar gum, gum karaya). Agar is being used as sustained release agent in tablets, gel beads, microspheres and topical formulations, as swelling agent, viscosity increasing agent in aqueous systems and as suspending agent in pharmaceutical suspension.4 Natural polymers like cellulose, xanthan gum, locust bean gum, gaur gum and chemically modified gums have been studied in hydrophilic matrix tablets for controlled drug delivery. These natural polymers are usually cost effective, nontoxic and easily available.5 Natural materials like ispaghula husk, guar gum and alginates are relatively inexpensive, nontoxic, and easily available. Ispaghula husk (dried seed coat of Plantago ovate (Plantaginaceae)) and guar gum have been used as matrixing agents by researchers for the development of modified release dosage forms.6 Plantago ovate seed husk is found to have high swellability and it has been used in the formulation of nimesulide dispersible tablets. Ocimum basilicum (basil) seed powder contain mucilage and this powder can be used as swelling agent and disintegrating agent in pharmaceutical tablet formulation.7 Sago palm (Metroxylan sagu) is a rich source of starch sago palm contains high amount of starch. Starch from different sources is a well known tablet binder.8
Metoprolol succinate is a selective adrenergic receptor blocking agent used in the management of hypertension, angina pectoris, cardiac arrhythmias, myocardial infarction, heart failure, hyperthyroidism and in the prophylactic treatment of migraine. The half-life of drug is approximately 4-6 hr.9 Metoprolol succinate is freely soluble in water, methanol, sparingly soluble in ethanol, slightly soluble in dichloromethane and 2-propanol, practically insoluble in ethyl acetate, acetone, diethyl ether and heptane. The recommended dose of Metoprolol succinate is 25 to 100 mg once daily.
The present work will be planned to formulate and evaluate modified release matrix tablet of Metoprolol succinate using natural hydrogel forming polysaccharides for the management of CVS disorders effective and safe.
6.2 Review of literature:
Extensive literature survey was carried out on the proposed research work by referring various scientific research journals, internet, facilities and data retrieval system.
Ø  Pavithra TK et al1., formulated and evaluated hydrogel based oral controlled drug delivery system for antihypertensive drug by using hydroxypropyl methyl cellulose 15cps and ethyl cellulose as a polymer and successfully developed an oral controlled release dosage form of losartan potassium by wet granulation method.
Ø  Aggarwal G et al2., investigated controlled release of a poorly water soluble drug prednisolone from heterodisperse hydrogel system by using xanthan gum, lactose, hydroxypropyl methyl cellulose as polymers and conclude that to increase the therapeutic efficacy of prednisolone, heterodisperse hydrogel system was prepared.
Ø  Jain S et al3., prepared and evaluated sustained release matrix tablet of furosemide using Natural Polymers like guar gum, pectin, xanthan gum by direct compression technique.
Ø  Saxena A et al4., investigated effect of gelatin-agar composition on the release of salbutamol tablets by wet granulation and biopolymer blend technique and reported that agar-gelatin matrix tablet had better control on release of salbutamol.
Ø  Deshmukh VN et al9., reported sustained release metoprolol succinate tablet using hydrophilic gums like karaya gum and xanthan gum as release modifiers by wet granulation method and concluded that karaya gum & xanthan gum can be used as an effective matrix former to retard the release of metoprolol succinate for extended period of time.
Ø  Sandeep G et al10., formulated and optimized metoprolol succinate extended release matrix tablet using hydrophilic polymers like hydroxypropyl methyl cellulose, hydroxypropyl cellulose, ethyl cellulose, carbopol 934 by direct compression method and concluded that the formulation provide effective drug release for 20 hr. and it shows nearly zero-zero order drug release governed by diffusion through swollen matrix and erosion of the matrix, showing the anomalous diffusion or non-fickian transports.
Ø  Reddy TR et al11., investigated independent release behavior of glipizide matrix tablet containing chitosan and xanthan gum as polymer by two different methods direct compression and hot melt extruded technique and conclude that in acidic media, the sustained release property of the hot melt extruded tablet containing chitosan and xanthan gum was not affected in acidic media and retard drug release in pH 6.8 and 7.4 phosphate buffer.
Ø  Shankar SJ et al12., formulated and evaluated controlled release matrix tablet of an antimicrobial drug containing chitosan and guar gum as polymer by direct compression and concluded that an addition of cationic chitosan as matrix component could prolong the drug release greater than that containing single polymer.
Ø  Ramana Murthy KV et al13., prepared and evaluate matrix tablet of tramadol hydrochloride using ispaghula husk powder by wet granulation technique and concluded that the increase in concentration of husk increase the percentage drug release and formulation with 15% ispaghula husk to that of drug has extended drug release up to 12 hr.
Ø  Satyam G et al14., reported binding property of sago starch in paracetamol tablet by wet granulation and concluded that that the starch obtained from sago palm possesses significant binding properties. So it can be used as tablet binder in pharmaceutical formulations.
Ø  Matsuo M et al15., developed delayed-release tablets using hydroxyethylcellulose as a gel-forming matrix by direct compression method and concluded that delayed-release tablet using hydroxyethylcellulose will be useful for control of time-related symptoms which need time-controlled or site-specific delivery in the gastrointestinal tract.
Ø  Prakash P et al16., developed and evaluated sustained release matrix tablet of venlafaxine hydrochloride using ethylcellulose and hydroxyethyl cellulose eudragit RS100 as release retardants by wet granulation technique and concluded that the sustained release from ethylcellulose and hydroxyethylcellulose as due to interaction between ethylcellulose and hydroxyethylcellulose which result in favorable increase in the water uptake capacity and gel viscosity leading to better control over the release of venlafaxine.
6.2  Objectives of the Study
Matrix tablet of Metoprolol succinate will be prepared using hydrogel forming polysaccharides with the following objectives.
1.  To prepare the drug loaded matrix tablets by wet granulation / direct compression method.
2.  To evaluate the granules and tablets for different parameters(flow properties, weight variation, thickness, hardness, friability, content uniformity)
3.  To evaluate the tablet for swelling behavior and in-vitro release.
4.  To characterize swellable tablets by IR and SEM.
5.  To study the effect of concentration of polymer, drug-polymer ratio on in-vitro swelling and drug release.
7  MATERIAL AND METHODS
7.1 Materials
Drugs : Metoprolol succinate.
Polymers : Natural hydrogel forming polymers like Chitosan, Agar, Ispaghula etc.
Excipients: Diluents, binder, lubricant, glidents.
Equipments :
1.  UV/Visible spectrophotometer 1700 (Shimadzu)
2.  Digital pH meter
3.  Digital Over head stirrer
4.  Electronic Balance (Shimadzu Corporation BL-220H Pune)
5.  Thermostatic hot plate with magnetic stirrer (Remi motors. Mumbai)
6.  Hot air oven
7.  Ultra Sonicator (Flexit)
8.  Electro lab Dissolution Apparatus (USP XXIII)
9.  IR spectrophotometer (JASCO/ FT /IR-5300)
10.  Tablet compression machine (Remek)
11.  Hardness tester (Monsanto)
12.  Optical Microscope (Olympia®)
7.2 Method :
1.  UV/Visible spectrophotometric estimation of Metoprolol succinate.
2.  Preparation of extended release matrix tablets of Metoprolol succinate using hydrogel forming polymers by direct compression method/ wet granulation method.
3.  Characterization of prepared matrix tablet by scanning electron microscopy, Fourier transformer infrared spectroscopy.
4.  Evaluation of prepared matrix tablets of Metoprolol succinate for drug content, swelling behavior, in-vitro drug release studies.
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 been obtained from your institution in case of 7.3?
-Not applicable.-
8. List of References :
1.  Pavithra TK, Harshitha .R, Panneer K, Renuka S, Rao PB, Narendra C. “Formulation and evaluation of hydrogel based oral controlled drug delivery system for antihypertensive drug”. J. Pharm. Sci Tech. 2010; 2 (8): 276-283.
2.  Aggarwal g and sharma a. “Controlled release of a poorly water soluble drug prednisolone from heterodisperse hydrogel system”. Int. J. Pharm. Bio Sci. 2010; 1(2): 1-8
3.  Jain S, Yadav SK, Patil UK. “Preparation and evaluation of sustained release matrix tablet of furosemide using natural polymers”. Research J. Pharm. Tech. 2010; 1(4): 374-376.
4.  Saxena A, Tahir A, Kaloti M, Ali J, Bohidar HB. “Effect of agar-gelatin composition on the release of salbutamol tablets”. Int. J. Pharm. Inv. 2011; 1(2): 93-98.
5.  Zafar I, Khan R, Nasir F, Khan JA, Ahmad L, Khan A, Shah Y, Dayo A. “Preparation and in-vitro evaluation of sustained release matrix diclofenac sodium tablets using HPMC KM100 and gums”. Arch Pharm. practice. 2010; 1(2): 9-17.
6.  Lalvani AN, Parikh JR. “Preparation and evaluation of an ispaghula based directly compressible matrixing agent for controlled release”. Acta. Pharm. 2008; 58: 309-316.
7.  Srinivas K, Prakash K, Kiran HR, Prasad PM, Rao MEB. “Study of Ocimum basilicum and plantago ovata as disintegrates in the formulation of dispersible tablets”. Indian J. Pharm. Sci. 2003; 65(2): 180-183.
8.  Murthy KVR, Nyamathulla, Parveen TD, Ashok Z, Archana K, Mohan EG, Meghana K. “Effect of SAGO starch on controlled release matrix tablet of tramadol HCL”. J. of Chem. Pharm. Research. 2010; 2(4): 232-239.
9.  Deshmukh VN, Singh SP, Sakarkar DM. “Formulation and Evaluation of Sustained Release Metoprolol Succinate Tablet using hydrophilic gums as Release modifiers”. Int. J. of Pharm. Tech. Research. 2009; 1(2):159-163.
10.  Sandeep G, Rangasamy M. “Formulation and optimization of metoprolol succinate extended release matrix tablet”. J. Pharm. Research. 2009; 2(4): 619-621.
11.  T. Ramanji reddy, Dhachinamoorthi D, Chandrasekhar KB. “Independent release behavior of glipizide matrix release tablets containing chitosan and xanthan gum”. Int. J. Pharm. Bio. Research. 2010; 1(2): 64-70
12.  Shankar SJ, Bansal GS, Basvraj BV. “Formulation and evaluation of controlled release matrix tablets of an antimicrobial drug”. Int. J. Pharma. Research and development. 2010; 2(10): 8-14.
13.  Murthy KVR, Nyamathulla S, Parveen TD, Subramanyam GSV, Ganpaty S. “Preparation and evaluation of twice daily matrix tablets of tramadol HCL using ispaghula husk powder”. Int. J. Pharm. Tech. 2010; 2(4): 969-976.
14.  Satyam G, Shivani S, Garima G, Vivek P, Sharma PK. “Isolation and evaluation of binding property of SAGO STARCH in paracetamol tablet”. Int. J. Pharm. Research & Development 2010; 2(1): 1-7.
15.  Matsuo M, Arimori C, Nakamura C, Nakano M. “Delayed-release tablets using hydroxyethylcellulose as a gel-forming matrix”. Int. J. Pharm. 1996; 138(2): 225–235
16.  Rao KS, Jadhav S, Patil P, Dattatraya BU. “Development and evaluation of sustained release formulation of venelafaxine HCL”. Int. J. Research in ayurveda and pharmacy 2011; 2(3): 948-960.
9. / Signature of Candidate / MANSUR MOHMADSHSHID ISMAIL
S10. / Remarks of the Guide / The proposed work is new approach towards development of sustained release matrix tablet using natural polysaccharides. Hence recommended for registration.
11. / Name & Designation of (in block letters)
11.1 Guide / M.A. SALEEM
asst. professor,
DEPARTMENT OF PHARMACEUTICS,
LUQMAN COLLEGE OF PHARMACY,
GULBARGA.
11.2 Signature
11.3 Co-guide
11.4 Signature
12. / 12.1 Remarks of the Chairman & Principal / We provide all the necessary facilities required for the proposed research work. Hence recommended for registration.
12.2 Signature