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FORMULATION AND EVALUATION OF SUSTAINED
RELEASE MATRIX TABLETS OF ONDANSETRON HCL
M. Pharm. Dissertation Protocol
Submitted to the
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore.
By
Mr. MAYUDIN I. SUMARA B. Pharm.
Under the Guidance of
Mr. R.G. PATIL
Lecturer
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
B L D E A’S COLLEGE OF PHARMACY
BIJAPUR-586103
2012-2013
Rajiv Gandhi University of Health Sciences, Karnataka
Bangalore.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1)
Name of candidate and address
(In Block Letters)
MAYUDIN I. SUMARA
71,AJAWA PARK B/H JAMOURA
PRIMARY SCHOOL,
PALANPUR, GUJARAT-385001.
2)
Name of the Institute
B.L.D.E.A’S COLLEGE OF
PHARMACY, BIJAPUR.
3) Course of study and subject: M.PHARM. PHARMACEUTICAL
TECHNOLOGY.
4) Date of admission of course: 07-01-2012
5) Title of the topic: -
“FORMULATION AND EVALUATION OF SUSTAINED RELEASE
MATRIX TABLETS OF ONDANSETRON HCL”.
6) Brief Resume of this intended work :-
6.1 Need for the study Enclosure-I
6.2 Review of Literature Enclosure-II
2
6.3 Objectives of study Enclosure-III
7) Materials and Methods :-
7.1 Source of data Enclosure-IV
7.2 Method of collection of data (Including sampling procedure, if any)
Enclosure-IV
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 Enclosure-V
9)
Signature of the candidate
10)
Remarks of the Guide
The proposed work can be carried out in the
laboratory. Protocol is as per university guidelines.
11) Name and designation of
(in block letters)
11.1 Guide
11.2 Signature
Mr. R.G. PATIL
Lecturer,
Dept. of Pharmaceutical Technology
B.L.D.E.A’S COLLEGE OF PHARMACY,
BIJAPUR-586103.
3
11.3 Co-Guide (if any)
11.4 Signature
------------
------------
11.5 Head of Department
11.6 Signature
Dr. R V KULKARNI
Professor & HOD
Dept. of Pharmaceutical Technology
B.L.D.E.A’S COLLEGE OF PHARMACY,
BIJAPUR-586103
12)
12.1 Remarks of the
Chairman and Principal
12.2 Signature
This study Can be carried out in our laboratory
4
Enclosure-I
6) Brief resume of the intended work.
6.1) Need for the study: -
The advantages of administering a single dose of a drug that is released over an extended
period of time, instead of numerous doses, have been obvious to the Pharmaceutical
industry for some time. The desire to maintain a near-constant or uniform blood level of a
drug often translates into better patient compliance, as well as enhanced clinical efficacy
of the drug for its intended use. Introduction of matrix tablet as sustained release (SR) has
given a new breakthrough for novel drug delivery system (NDDS) in the field of
Pharmaceutical technology. It excludes complex production procedures such as coating
and pelletization during manufacturing and drug release rate from the dosage form is
controlled mainly by the type and proportion of polymer used in the preparations.
Hydrophilic polymer matrix is widely used for formulating an SR dosage form2-5.
Because of increased complication and expense involved in marketing of new drug
entities, has focused greater attention on development of sustained release or controlled
release drug delivery systems. Matrix system is widely used for the purpose of sustained
release.1
Matrix tablets composed of drug and polymer as release retarding material offer the
simplest approach in developing a sustained-release drug delivery system. Recent trend in
development of sustained-release drug delivery systems was the use of gums of plant
origin to fulfil the aim of retarding the drug release. Natural gums are biodegradable,
non-toxic and have capability to swell on contact with aqueous media. The natural
polymers used do hold advantages over the synthetic polymers generally because they are
non toxic, less expensive and freely available. Most common examples of natural gums
are Guar gum, Xanthan gum, Pectin and GumTragacanth. Guar gum is a polysaccharide
derivative having glycosidic linkage which is intended to be used as a matrix former for
controlled release of drugs like Diltiazem. Pectin , a natural hydrophilic polymer is rich in
galacturonic acid is used as a gelling agent and thickening agent.2
5
Ondansetron HCl is a selective serotonin 5-HT3 receptor blocking agent. It is a potent
antiemetic drug used in the treatment of chemotherapy or radiotherapy induced emesis
and also used in the early onset of alcoholism. Although, it is well absorbed in the
gastrointestinal tract. ODN undergoes first pass-metabolism resulting in low
bioavailability. The physicochemical and pharmacological properties of ODN like half-
life (3-5 h), low dose (8 mg), and low molecular weight (365.86 Da) make it as a suitable
candidate for buccal delivery. It has been classified as BCS Class III drug owing to its
low permeability and high solubility. Therefore, it was excogitated to use permeation
enhancer in delivering ODN through buccal mucosa.10
The main drawback of conventional dose of Ondansetron hydrochloride is its oral
bioavailability, which is about 60% with peak plasma concentrations 1.5 hr after an oral
dose. The elimination half-life is 3-3.5 hr.11
6
Enclosure-II6.2) Review of literature: -
1) Sharma A. et al., have developed and evaluate Salbutamol sulphate sustained
release tablets using different polymers as release retarding agent. Preformulation
study was done initially and results directed for the further course of formulation.
Based on Preformulation studies different batches of Salbutamol sulphate were
prepared using Xanthan gum, Carbopol and ethyl cellulose chosen for their
different hydrophilic properties to calculate the sustained release properties.
Analysis of Salbutamol is done by UV visible spectrophometer using wavelength
276nm. Results of in-vitro swelling study indicate that the formulation F6 was
having considerable swelling index. From the discussion it is concluded that the
tablets of batch F4 had considerable swelling behaviors and in vitro drug release.
Batch F6 can be taken as an ideal or optimized formulation of sustained release
tablets for 12 hour release as it fulfills all the requirements for sustained release
tablet.3
2) Archita M. et al., have prepared and characterized twice-daily sustained-release
matrix tablets of Timolol maleate (TM) using different concentrations of
hydrophilic Hydroxypropylmethylcellulose (HPMC K100M CR) alone and its
combination with hydrophobic ethyl cellulose (EC). Formulations prepared by the
wet granulation technique and were evaluated for the release of TM over a period
of 12 hrs using United States Pharmacopoeia (USP) type-II dissolution apparatus.
The in-vitro drug release study revealed that formulation F3 (40% wt/wt HPMC
K100M) could extend the drug release up to 8 hours. The most successful
formulation of the study, F5 (HPMC to EC, 1:1), extended the drug release up to
12 hours, exhibited satisfactory drug release in the initial hours, and the total
release pattern was close to the theoretical release profile. The drug release from
optimized formulation (F5) followed first-order kinetics via Non-Fickian
(anomalous) diffusion. FTIR studies revealed that there was no interaction
7
between the drug and excipients. In conclusion, the results indicated that the
prepared sustained-release tablets of TM could perform therapeutically better than
conventional tablets with improved efficacy and better patient compliance.4
3) Jain S. et al., have formulated Sustained release tablets of Furosemide were
fabricated using pectin, guar gum and xanthan gum. The tablets were evaluated
for physical characteristic like hardness, weight variation, friability, and drug
content. In-vitro release of drug was performed in PBS pH 7.2 for fifteen hours.
All the physical characters of the fabricated tablet were within acceptable limits.
The tablet with guar gum exhibited greater swelling index than those with pectin
and xanthan gum. A better controlled drug release (80.74%) was obtained with
the matrix tablet (G4) made-up of the guar gum than with the pectin and xanthan
gum. It is cleared through the dissolution profile of Furosemide from matrix
tablets prepared using different natural polymers were retarded approx 15 hrs.5
4) Raju D.B et al., have formulated oral controlled release matrix tablets of Losartan
potassium. Tablets were prepared by direct compression and evaluated for
hardness, friability, thickness, drug content and in vitro dissolution parameters.
Carbopol 934P and HPMC K 100M (hydroxyl propyl methyl cellulose) were used
as the polymers. In vitro release studies were conducted in phosphate buffer pH
6.8 for 24 hours. All the formulations showed controlled release of Losartan
potassium over a period of 24 hours. The release profile of Losartan potassium
from all the formulations (except F2, F3, F8 which showed first order release) are
close to zero order and follow diffusion dependent release. Irrespective of the
polymer type and its concentration, the prepared hydrophilic matrix tablets
showed non-fickian (anomalous) release, coupled diffusion and polymer matrix
relaxation as the values of release exponent (n) are in between 0.584 and 0.8692.
Finally it was clear that HPMC K100M and Carbopol 934P are good candidates
for preparing controlled release matrix tablets of losartan potassium.6
8
5) Salger S. V et al., have developed sustained release matrix tablets of anti
hypertensive drug propranolol hydrochloride. Hydroxypropyl methyl cellulose
K100M used as a rate retarding polymer where as lactose and dibasic calcium
phosphate are used as diluent. The effects of the proportion of the polymer and
the influence of co-excipients like lactose and dibasic calcium phosphate on the
release rate of drug was investigated. The results of the present study point out
that the rate of propranolol hydrochloride release from HPMC K100M matrices
are mainly controlled by the drug – HPMC ratio. When the influence of excipients
on the release of drug was examined, the excipients lactose enhanced the release
rate of propranolol hydrochloride7
6) Sankar V.R et al., have worked to investigate the possibility of sustaining the
Losartan potassium release from matrix tablet, prepared by hydrophilic and
hydrophobic polymer. The Preformulation studies were carried out the interaction
between the drug and polymers. The granules were punched into tablet, which
was evaluated for the parameters like thickness, weight variation, hardness,
friability, and drug content. All six formulations were showed acceptable Indian
pharmacopeia specifications with required hardness, weight variation, friability
and drug content. The hardness was slightly higher with tablet containing
hydrophobic polymer (Ethyl cellulose). The in-vitro drug release was studies with
USP XXII dissolution apparatus in both simulated gastric fluid and intestine fluid
for a period of 12hrs. The results of dissolution studies were indicated that
formulation (Losartan potassium with SCMC with Ethyl cellulose) produced
sustained effect with 74.19% of drug release over a period of 12hr. in comparison
to other formulation. The mechanism of drug release was diffusion coupled with
erosion. It can be concluded that the polymer plays a major role in the design of
sustained release matrix tablet. The study reveals that the release of drug is low
when the matrix tablet contained hydrophilic and hydrophobic polymers as a
combination than the other matrices and also shows anomalous(non-fickian)
diffusion kinetics. Hence, it is clearly manifest the necessity of combining
9
different classes of polymer is to get an acceptable pharmacokinetic profile in the
fluctuating in vivo environment.8
7) Umarunnisha M.A et al., have prepared Controlled release matrix tablets of
famotidine were prepared using a hydrophilic polymer Hydroxypropyl
methylcellulose K100M (HPMC K100M) with three concentrations (Drug: polymers
1:0.5, 1:0.75 and 1:1) by wet granulation method. The granules were evaluated for
angle of repose, bulk density, tapped density, bulkiness, compressibility index and
Hausners ratio. The tablets were subjected to weight variation, hardness, friability
and drug content test. Invitro release studies revealed that famotidine formulation
with high proportion of HPMC K100M (1:1) was able to sustain the drug release for
10 hours (84.1% ±1.85). all the formulations followed the mechanism of both
diffusion and erosion. All the formulations were stored at 450±20C, 75 ± 5%RH and
subjected to stability studies up to 45 days. It showed that all the formulations are
physically and chemically stable.9
10
Enclosure-III
6.3) Objectives of the study: -
The present study is planned with the following objectives: -
1) To prepare controlled release matrix tablets of Ondansetron Hcl using
different polymers.
2) Drug-polymer interactions by using DSC and FT-IR instruments.
3) To characterize the formulations for various physico-chemical parameters such as
weight variation, hardness, friability, disintegration time and drug content.
4) To evaluate the tablets for in vitro dissolution studies.
5) To carry out stability studies for selected formulations as per ICH guidelines.
11
Enclosure-IV
7) Materials and Methods: -
7.1) Source of data: -
Primary data: - This data will be collected by conducting laboratory
experiments and recording the observation.
Secondary data: - This will be collected from various journals and textbooks.
7.2) Method of collection of data: -
The study is planned to collect the data from the laboratory-based experiments,
which include the following:
1) Preformulation studies like solubility, melting point and compatibility of the drug
with polymers using IR and DSC instrument will be carried out by adopting
reported methods.
2) Matrix tablets of Ondansetron will be prepared using different polymers.
3) Evaluation of matrix tablet for weight uniformity, hardness, friability,
disintegration time and drug content by adopting standard methods.
4) In Vitro release studies will be carried out by using dissolution test apparatus USP
XXIV.
5) Stability studies for selected formulation will be carried out using stability
chambers as per ICH guidelines.
6) Finally, the prepared matrix tablets will be subjected to compatibility studies
using FT-IR and DSC instruments.
12
ENCLOSURE-V
8) List of references: -
1. Modi S.A., Gaikwad P.D., Bankar V.H., Pawar S.P. 2011 “sustained release drug
delivery system”. Int. J. Pharm. Res. & Dev., 2, 12: 147-160.
2. Vummaneni V., Nagpal D. 2012 “formulation and evaluation of sustained release
matrix tablets of frusemide using natural hydrophilic polymers” . World J. Pharm.
And Pharmaceut. Sci,, 1, 1: 347-356.
3. Sharma A., Sharma S., Jha K.K. 2009 “The study of salbutamol matrix tablets
using different polymer as release retarding agents” The Pharm. Res., 1, 15-22.
4. Architha M., Kishore R., Madhu babu D., Prabhakar Reddy V. 2011 “Design and
in- vitro evaluation of sustained release matrix tablets of timolol maleate” Ame. J.
Pharm. tech. Res., 1, 4: 340-354.
5. Jain S., Yadav S. K., Patil U.K. 2008 “Preparation and evaluation of sustained
release matrix tablets of furosemide using natural polymers” Res. J. Pharm. And
Tech, 1, 4: 374-376.
6. Raju D.B., John K.S., Verma M.M. 2010 “Formulation and evaluation of losartan
potassium matrix tablets for controlled oral release” J. Chem Pharm. Res. 2, 2:
130-135.
7. Salger V. R., Danki L. S., Hiremath S., Sayeed A. 2010 “Preparation and
evaluation of sustained release matrix tablets of propranolol hydrochloride” Int. J
Pharm. and Bio Sci. 1, 4: 227-241
8. Sankar V.R., Reddy Y.D., Rao A.N., Dhachinamoorthy D., Chandra sekhar K.B.
2010 “Effect of hydrophylic and hydrophobic polymers on losartan potassium
matrix tablets” J. Pharm. Res, 3, 9: 2195-2197.
9. Umarunnisha A.M., Palanichamy S., Rajesh M., Jeganath S. 2010 “Formulation and
evaluation of matrix tablets of famotidine using hydrophilic polymers” Scholars Res.
Lib, 2, 3: 212-220.
10. Kumar M. P., Prasad M. R., M. Pramod., Reddy V. P. 2011 “ effect of permeation
enhancer on ex-vivo permeation of ondansetron hcl buccal tablets” Int. J. Pharm.
Sci. and Res, 2, 11: 2841-2845.
13
11. Nagich U., Chaudhary V., Karki R., Yadav A., Sharma P. 2010 “ formulation of
medicated chewing gum of ondansetron hydrochloride and its pharmacokinetic
evaluations”. Int. J. Pharm. Sci. and Res, 1, 2: 32-40.
14
ENCLOSURE-VI
10) Remarks of the Guide
The present work is aimed to develop and evaluate the sustained release matrix
tablet of Ondansetron HCl. Ondansetron HCl is a widely used as anti emetic drug. The
drug has a shorter biological half-life of about 5-7 hrs and its bioavailability is only 60%.
Sustained released tablet possibly improve oral bioavailability of Ondansetron HCl. The
proposed study can be carried out in the laboratory.
Mr. R. G. Patil.
Lecturer
Research Guide
15
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