Download design and evaluation of controlled release tablets of

“FORMULATION AND IN-VITRO CHARACTERIZATION OF MATRIX TABLETS CONTAINING
METOCLOPRAMIDE USING NATURAL POLYMERS’’
M. Pharm. Dissertation Protocol Submitted to
Rajiv Gandhi University of Health Sciences, Bangalore,
Karnataka.
By
Mr. SUMAN ARRAM B.Pharm.
Under the Guidance of
Mr. AMARJIT GIRI
Assistant Professor
DEPARTMENT OF PHARMACEUTICS
EAST WEST COLLEGE OF PHARMACY
BANGALORE - 560 091.
2010 – 2012.
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ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1
Name of candidate and address
(In Block Letters)
SUMAN ARRAM,
D.NO: 3-426, MAIN ROAD, PARKAL,
WARANGAL (DIST),
ANDHRPRADESH – 506164.
2
Name of the Institute
EAST WEST COLLEGE OF PHARMACY,
BANGALORE-560091.
3
Course of study and subject:
M.PHARM (PHARMACEUTICS)
4
Date of admission of course:
26-10-2010
5
Title of the topic:
“FORMULATION AND IN-VITRO CHARACTERIZATION OF MATRIX
TABLETS CONTAINING METOCLOPRAMIDE USING NATURAL
POLYMERS”
6
Brief Resume of this intended work:
6.1 Need for the study
6.2 Review of Literature
6.3 Objectives of study
Enclosure-I
Enclosure-II
Enclosure-III
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Materials and Methods:
7.1 Source of data
Enclosure-IV
7.2 Method of collection of data (Including sampling procedure, if any)
Enclosure-V
7.3 Does the study require any investigation or interventions to be conducted on
patients of humans or animals? If so, please describe briefly.
---------NO---------7.4 Has ethical clearance been obtained from your institution in case of 7.3?
-------NOT APPLICABLE-------
8
List of References
9
Signature of the candidate
Enclosure-VI
(SUMAN ARRAM)
2
10
Remarks of the Guide
The proposed research work is recommended for
registration and approval
11
Name and designation of
(in block letters)
11.1 Guide
Mr .AMARJITH GIRI,
Dept. Of PHARMACEUTICS,
EAST WEST COLLEGE OF PHARMACY,
BANGALORE-560 091.
11.2 Signature
11.3 Co-Guide (if any)
11.4 Signature
11.5 Head of Department
DR. JAGADEESH G. HIREMATH,
PROFESSOR & HOD,
EAST WEST COLLEGE OF PHARMACY,
BANGALORE-560 091.
11.6 Signature
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12.1 Remarks of the
Chairman/Principal
12.2 Signature
PROF. K. A. SRIDHAR,
PRINCIPAL,
EAST WEST COLLEGE OF PHARMACY,
BANGALORE-560 091.
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ENCLOSURE-I
6) Brief resume of the intended work:
6.1) Need for the study:
The administration of drug products, through the solid dosage forms via oral route is the most significant and
popular method for systemic effects owing to ease of swallowing, self medication, dose precision and most
economic.1 Oral controlled release (CR) systems continue to be the most popular ones among all the drug delivery
systems.2
Metoclopramide (MCP) is an antiemetic and gastroprokinetic agent. It is primarily used to treat nausea and
vomiting, and to facilitate gastric emptying in patients with gastro paresis. It is a primary treatment for migraine
headaches. It acts as an antagonist by binding to dopamine D2 receptors and 5-HT3 receptor where as agonistic
action on 5-HT4 receptor.3 It is a freely water soluble drug and rapidly absorbed from the gastrointestinal
tract(GIT).It has a relatively short variable biological half life(5h) and is usually administrated in pre-oral dose of
10-15mg as immediate release tablets. Relatively small dose, short half life, undesirable side effects and rapid
absorption from GIT make MCP a good candidate in a sustained release dosage form. MCP was formulated in
matrix tablets by using the natural polymers like guar gum, sterculia gum, karaya gum, xanthum gum or in
combination for the preparation of sustained release matrix tablets containing matoclopramide or any suitable
polymers and excipients will be used. A super disintegrant is employed to produce disintegrating tablets as a
desired property for matrix tablets to avoid failure of release. The post compressional and the release rates of the
tablet will be studied.4
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ENCLOSURE-II
6.2) Review of literature:
Extensive literature review was made for understanding the study and there has been number of reports concerning
sustained release matrix tablets of various drugs like diclofenac sodium, diltiazem, stavudine, tramadol
hydrochloride, etc. Literature review made by referring to various National and International Journals, Databases
such as International Pharmaceutical Abstracts, SciFinder and various other web resources along with general
books for Pharmaceutical Scientists.
Vireden et al., have developed the release of theophylline and carbamazepine from matrix tablets composed of
microcrystalline cellulose, lactose and hydroxypropyl methylcellulose (HPMC) and investigated the effect of
different substituent heterogeneities of HPMC on the drug release from matrix tablets which was composed of
either 35% or 45% HPMC. Explained the release of the poorly soluble carbamazepine that was considerably
affected by the HPMC heterogeneity, and the time difference at 80% drug release was more than 12 h between the
formulations of different HPMC batches. They explained the comparable results of the release of the sparingly
soluble theophylline from the two formulations even though the polymer erosion and the swelling of the tablets
were considerably different. Thus, they concluded that the drug release were highly affected by the substituent
heterogeneity, especially in the case of carbamazepine, which was released mainly by erosion.5 (2011)
Jeong et al., have used polyethylene oxide (PEO)–polyethylene glycol (PEG) blends for sustained release matrix
tablets, and evaluated the effects of PEG or PEO on the matrix tablets. In order to evaluate gelling behaviour and
drug release profiles of PEG, various contents of the polymers were investigated through a robust experimental
design method. The optimal settings of PEO and PEG were 94.26 and 140.04 mg, respectively (PEG rate of
148.57%). Moreover, as the amount of PEG increased, the release rate was also increased. In their formulation
containing more than 150% of PEG, then most of the drug loaded in the tablet was released in about 12 h. When
the amount of PEG was less than 100%, the drug release rate was sustained significantly. Based on the RD
optimization model for drug release, the optimal settings were PEG and PEO of 124.3 and 110 mg, respectively
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(PEG rate of 88.50%). Therefore, they suggested PEG rate of about 90–150% for matrix tablet formulations, and
the exact ratio could be formulated according to the resulting table.6 (2010)
Larsson et al., have reported four different HPMC batches and characterized properties related to critical
functionality for their use in hydrophilic matrix tablets. In their study, the HPMC batches were chemically
characterized and correlated to the behaviour of pure HPMC tablets. They kept the parameters such as the
molecular weight, viscosity; intrinsic viscosity and radius of gyration were in a rather limited range, which
resulted in a weak correlation to polymer release and degree of swelling. The hydrophilic/hydrophobic character
of the HPMC samples was elucidated by the degree of substitution and by the clouding behaviour, where an
increased hydrophilicity increased the tablet swelling. They interpreted this phenomenon in a refined model for
water transport into HPMC tablets. A five times slower polymer release and a considerably larger degree of
swelling were found for one batch of HPMC tablets compared to the others. They had concluded that the existence
of aggregates in aqueous solution seems to perturb the functionality of HPMC tablets and that seemed important to
understand and characterize these aggregates to fully predict the polymer release and swelling of HPMC tablets.7
(2009)
Rahman et al., have studied the formulations of metoclopramide hydrochloride (MCP) by incorporating the
different polymers. MCP was incorporated in 12 formulae containing different polymers and/or different polymer
ratios. These polymers were hydroxypropylmethylcellulose (HPMC), carboxymethylcellulose (CMC) and ethyl
cellulose (EC).They added sodium starch glycolate (SSG) to some of their formulae in different amounts in order
to soften or disintegrate the tablets. Both direct compression and granulation techniques were used to prepare
tablets. The physical properties were found to be satisfactory for all their formulae. The dissolution profiles of
their tablets were constructed using the change-over method. The drug release involved a combination of both
diffusion and polymer-chain relaxation mechanism were reported.4 (2009)
Shiyani et al., had prepared the bi-layer tablet of metoclopramide hydrochloride (MTH) and ibuprofen (IB) for the
effective treatment of migrane. MTH and IB were formulated as immediate and sustained release layer
respectively. They have reported that metoclopramide increases the absorption of acidic non – steroidal antiinflammatory drug (NASID) by increasing gastric motility.So sequential release of MTH (as immediate release)
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and IB (as sustained release) were suitable for the treatment of migraine. Metoclopramide hydrochloride was
degraded when prolonged contact with acidic non-steroidal anti-inflammatory drug (NASID). Finally,they have
concluded that bi-layer tablet were suitable for preventing direct contact of these two drugs and thus to maximize
the efficacy of combination of two drugs for migraine.8 (2008)
He et al., had investigated and developed sustained release matrix tablets with a mixture of the polysaccharides,
konjacglucomannan (KGM) and xanthan gum (XG), as the sustained release material. They have selected a simple
enzymatic procedure that mimicked the environment of colon in-vitro assessments. They have determined the
concentration of b-mannanase solution by comparing the hydrolytic ability of the mimicked colon solution with
that of 4% (w/v) rat ceacal content media. In-vitro, investigations were carried out and they characterized the drug
release process. Their model drug cimetidine released from polysaccharides gel layer of matrix tablets over 10 h.
They had shown that the synergistic interaction between konjac glucomannan and xanthan gum in the gel phase
affected the drug diffusion, which had effectively retarded the drug release from their matrix tablets. Further they
have investigeted on the mixed polysaccharides indicated that there was a strong synergistic interaction between
KGM and XG in solution and in the gel phase. Their experimental results predicted that the polysaccharide
mixtures of konjac glucomannan and xanthan gum had a good potential to be applied to sustained release drug
delivery systems.9(2008)
Tadros et al., had prepared and developed an extended release matrix tablets of nicorandil which are freely water
soluble and that were used in the treatment of cardiovascular diseases. They had prepared interpolymer complexes
(IPCs) chitosan(CH)/hyaluronate sodium(HA), pectin(PE) or alginate sodium(AL). They prepared IPCS based on
the electro static interactions between protonated amine groups of CH and carboxylate groups of HA, PE, or AL.
Nicorandil matrix tablets had been prepared by using the optimum IPCs, alone or in combination with Imwitor.
They have performed the different evaluations such as weight variation, thickness, content uniformity, friability,
disintegration and in vitro release studies.10(2008)
Hiremath et al., had prepared and developed controlled release (C.R) matrix tablets of rifampicin and isoniazid
combination, studied the design parameters and evaluated in vitro release characters. They had developed a series
of different formulations release rates and durations, using hydrophilic polymers like hydroxypropyl methylcellose
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(HPMC) and hydroxypropyl cellulose, polymer ratio and processing techniques. They have incorporated the
Eudragit L100 in the matrix tablets to compensate for the pH-dependent release of rifampicin. Rifampicin
followed linear release profile with time from HPMC formulations, incase of hpc formulations, there was an initial
higher release in simulated gastric fluid (SGF) followed by zero order release profiles in simulated intestinal fluid
(SIFsp) for rifampicin. They found that the release of isoniazid was predominantly by diffusion mechanism in case
of HPMC formulations, and with HPC formulations release was due to combination of diffusion and erosion. The
initial release was sufficiently higher for rifampicin from HPC thus ruling out the need to incorporate a separate
loading dose. The initial release was sufficiently higher for isoniazid in all their formulations. Thus they concluded
that with the use of suitable polymer or polymer combinations and with the proper optimization of the processing
techniques it was possible to design the controlled release formulations of rifampicin and isoniazid combination
that could provide the sufficient initial release and release extension up to 24hr for both the drug despite of the
wide variations in their physicochemical properties.11(2008)
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ENCLOSURE-III
6.3) Objective of the study:
The present study is planned with the following objectives:
1. To prepare the metoclopramide containing matrix tablets by using the natural polymers.
2. To perform the precompressional parameters of prepared granules.
3. To perform the postcompressional parameters of prepared tablets.
4. To estimate the drug content of the tablet.
5. To carry out in-vitro drug release studies.
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ENCLOSURE-IV
7) Materials and Methods:
Materials:
Drug
: Metoclopramide.
Polymers: Natural polymers like guar gum, sterculia gum, karaya gum, xanthum gum, or any other suitable
polymer will be selected alone or in combination for the preparation of sustained release matrix tablets
containing metoclopramide or any other suitable polymer and excipients will be used.
Methods:
Development of sustained release matrix tablets containing metoclopramide will be carried out using different
natural polymers with suitable method/s such as wet granulation/dry granulation/direct compression/fluid bed
granulation/hot melt extrusion/spray drying or any other suitable methods by using natural polymers.
7.1) Source of data:
Data is collected from:

Internet

National and International Research and Review publications

Poster presentations

Textbooks and reference books

RGUHS Library
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ENCLOSURE-V
7.2) Method of collection of data:
 Preparation of Metoclopramide sustained matrix tablets using natural polymers.
 Evaluations of precompression and postcompression parameters for developed formulations are as follow.
Pre compression parameters
 Angle of repose
 Bulk density
 Tapped density
 Hausner’s ratio
 Compressibility index
Post compression parameters:

Weight variation

Hardness

Thickness

Friability

Disintegration
 Estimation of drug content in the developed formulation.
 To carry out in-vitro drug release studies for the prepared formulations.
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ENCLOSURE- VI
List of References:
1. Lachman L, Lieberman AH. The theory and practice of industrial pharmacy. Special Indian ed 2009; New
Delhi, CBS Publishers 2009;293-94.
2. Chien. Novel Drug Delivery System, In Swarbrick J ed oral drug delivery systems;Newyork, Marcel
Dekker 1992;139-96.
3. Tripathi KD. Essentials of Medical Pharmacology Jaypee Brother Medical Publications, 8th ed New
Delhi:India 2008;642.
4.
Rahman A, Mahrous GM, Badrey ME. Preparation and comparative evaluation of sustained release
metoclopramide hydrochloride matrix tablets. Sau Pharm J 2009;17:283-88
5. Viriden A, Wittgren B, Larsson A, The consequence of the chemical composition of HPMC in matrix
tablets on the release behavior of model drug substances having different solubility. Eur J Pharm Biopharm
2011; 77:99-10.
6.
Jeong SH, Yoon JH, Lee J, Choi YW, Shin S, Park JS et al., A pharma-robust design method to
investigate the effect of PEG and PEO on matrix tablets. Int J Pharm 2010;393:79-87.
7. Larsson A, Wittgren B, Viriden A. Investigation of critical polymer properties for polymer release and
swelling of HPMC matrix tablets. Eur J Pharm Sci 2009;36:297-09.
8. Shiyani B, Gattani S, Surana S. Formulation and evaluation of bi-layer tablet of metoclopramide
hydrochloride and ibuprofen. AAPS Pharmsci Tech 2008;9:3.
9. He zhimin, Far J, Wang K, Liu M. In- vitro evaluation of konjac glucomanan and xanthumgum mixture as
the sustained release material of matrix tablet. Carbohydr-polym 2008;73:241-47.
10. Tadros MI, Abdelbary GA, 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 Bio Pharm 2008;69:1019-28.
11. Hiremath PS, Saha RN. Oral matrix tablet formulations for concomitant controlled release of anti12
tubercular drugs: design and in-vitro evaluations. Int J Pharm 2008;362:118-25.
.
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