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

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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

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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.

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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