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FORMULATION AND EVALUATION OF ORAL
SUSTAINED RELEASE SUSPENSIONS OF TORSEMIDE
MICROENCAPSULATION USING ION EXCHANGE
RESINATES
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA
BANGALORE.
BY
G.Rudrasekhar Reddy
B.pharm
UNDER THE GUIDANCE OF
Mr.B.R.Kirupakr M.Pharm,
DEPARTMENT OF PHARMACEUTICS,
SRI K.V. COLLEGE OF PHARMACY,
CHICKBALLAPUR,
KARNATAKA-562101,
2011-2012
RAJIV GANDHI UNIVERSITY OF HEALTH AND SCIENCES, KARNATAKA
BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
1
NAME OF THE CANDIDATE &
ADDRESS
G.RUDRASEKHARREDDY,
SRI K.V COLLEGE OF PHARMACY,
M.G.ROAD,
CHICKABALLAPUR(DIST),
KARNATAKA-562101.
PERMANENT ADDRESS
S/O G.NAGIREDDY,
BYRAPURAM (VILLAGE AND POST),
KOTHACHERUVU (MANDAL),
PENUKONDA(TALUK),
ANANTAPUR(DIST),
ANDHRA PRADESH.
PIN : 515110
2
NAME OF THE INSTITUTE
SRI K.V.COLLEGE OF PHARMACY,
M.G.ROAD,
CHICKBALLAPUR (DIST),
KARNATAKA-562101
3
COURSE OF THE STUDY
MASTER OF PHARMACY
(PHARMACEUTICS)
4
DATE OF ADMISSION
5
TITLE OF THE TOPIC
21-10-2011
FORMULATION AND EVALUATION OF
ORAL SUSTAINED RELEASE
SUSPENSIONS OF TORSEMIDE
MICROENCAPSULATION USING ION
EXCHANGE RESINATES
6.
6.
BRIEF RESUME OF INTENDED WORK
6.1 NEED FOR STUDY:
The goal of any drug release system is to provide a therapeutic amount of drug to the proper
site in the body, to achieve and maintain the desired drug concentration at the site of action1.
This objective points towards to most important aspects of drug delivery, namely spatial
placement and temporarily delivery of the drug. The sustained release system induces any period
of time. If the system is successfully maintaining a constant drug level in blood or targeted
tissue, it is considered as controlled release system. An oral sustained release suspension could
be the best suitable dosage form for the geriatric patients, because of the easiness of swallowing
and flexibility in the administration of the dosage. Many therapeutic benefits could be gained by
incorporating functions of sustained drug release into suspension dosage forms. They include
improvement of rate and extent of drug absorption, the higher patient compliance, reduce the
side effects and taste masking for bitter drugs 2,3 .
Reduction of side effects and improvement of bioavailability can be achieved by fabricating
a drug with sustained or controlled released and incorporating it into a suspension. A larger part
of attention has been devoted to the development of oral liquid dosage forms containing
sustained release drugs. Hence, it is desirable to develop a well-formulated sustained release
suspension.
Torsemide is a pyridine-sulfonylurea type loop diuretic mainly used in the management of
edema associated with congestive heart failure. It is also used at low doses for the management
of hypertension. It is marketed under the brand name Demadex, for the treatment of edema
associated with congestive heart failure, renal disease or hepatic disease, also for the treatment
of hypertension alone or in combination with other antihypertensive agents.
Torsemide inhibits the Na+/K+/2Cl--carrier system (via interference of the chloride binding
site) in the lumen of the thick ascending portion of the loop of Henle, resulting in a decrease in
reabsorption of sodium and chloride. This results in an increase in the rate of delivery of tubular
fluid and electrolytes to the distal sites of hydrogen and potassium ion secretion, while plasma
volume contraction increases aldosterone production. The increased delivery and high
aldosterone levels promote sodium reabsorption at the distal tubules and by increasing the
delivery of sodium to the distal renal tubule, torsemide indirectly increases potassium excretion
via the sodium-potassium exchange mechanism. Torsemide's effects in other segments of the
nephron have not been demonstrated. Thus torsemide increases the urinary excretion of sodium,
chloride and water, but it does not significantly alter glomerular filtration rate, renal plasma flow
or acid-base balance. Torsemide's effects as a antihypertensive are due to its diuretic actions. By
reducing extracellular and plasma fluid volume, blood pressure is reduced temporarily, and
cardiac output also decreases4,5.
Torsemide is soluble in water,methanol6, Physico chemical properties of torsemide like
hydrophilicity, moderatly hygroscopic, low molecular weight etc., make it as a ideal candidate
for administration by oral sustained release suspension.
The different methods for sustaining the release of drugs are described by ariens. One of the
methods to sustain the drug release is the use of ion exchange resins. In the present work,
torsemide was absorbed on cationic exchange resin, amberlite [ IR-120] and later a coating of
ethyl cellulose was given. Then these resonates was formulated into a suspension form, which
can release the drug in a slow controlled manner, the dissolution rate and bio-availability from
suspensions are reported to the adversely affected by the suspending agents which are used to
increase the viscosity of the media to maintain uniform dispersion during storage7,8 .
In the present study an attempt is made to evaluate different suspending agents for their
stability for the formulation of sustained release suspension containing torsemide microcapsules.
6.2 REVIEW OF THE LITERATURE:
1. Mahore J G et al., Ion exchange resins are cross-linked water insoluble polymercarrying, ionizable functional groups. IER have received considerable attention from
pharmaceutical scientists because of their versatile properties as drug delivery vehicles.
Research over the last few years has revealed that IER are equally suitable for drug
delivery technologies, including controlled release, transdermal, nasal, topical and taste
masking.Drug resin complexation converts drug to amorphous form leading to improved
drug dissolution9.
2. Manish R et al., Eudragit RS100 coated ion exchange resinate of Ambroxol Hcl were
prepared using Indion-244 by Solvent evaporation method. Among the various
formulation of microcapsule (drug resinate Eudragit ratio) prepared. An ideal
formulation (drug resinate 1:1) and 10% eudragit coating was selected for the
formulation of sustained release suspension. This suspension was evaluated for physical
stability, redispersibility and in vitro drug release pattern10.
3. Sompur C K et al., Has review an article on approach for development of oral sustained
release suspension which review rapidly changing conventional dosage form of
pharmaceutical drug delivery are being replaced by new drug delivery system.One search
drug delivery sustained on controlled release drug delivery system i.e on oral
pharmaceutical suspensions has been one of the most fevarable dosage form are pediatric
and geriatric patents 11.
4. Suthar A M et al., Non‐compliance which is mostly associated with bitter taste can lead
to worsening of diseased condition The purpose of this research was to prepare palatable
liquid formulation by masking the intensely bitter taste of metronidazole (MNZ). Taste
masking was done by complexing of MNZ with different rasins Kyron T‐114, Kyron
T‐134 and Indion 234 in different ratios. Prepared suspensions were tested for drug
content, in vitro drug release, taste masking, stability study, and molecular properties.
Kyron T‐134 at pH 8 showed potential to prepare palatable formulation with MNZ. Thus
to overcome taste problem of traditional paediatric dosage form, IER is dominating
method to prepare palatable liquid formulation of MNZ12.
5. Malay Kumar Samanta et al., Microspheres of Ferrous Sulphate were prepared by
congealable disperse-phase encapsulation technique with Agar, Agar and Hydroxy
propyl methyl cellulose mixture, and Ethylcellulose. Suspension of Agar and Hydroxy
propyl methyl cellulose mixture showed a better sustained release than Agar and
Ethylcellulose13.
6. Katare O K, Jain S K, Vyas S P et al., Polymers and copolymers of acrylic series were
synthesised and drug embedded matrices were prepared by common solvent solution
evaporation technique. Suspension adjuvants were blended with the fine particles of drug
embedded matrix and the formulated suspension of alpha-methyl dopa was investigated
for in vitro release and stability. Results indicated possibility of preparing a sustained
release dry suspension of alpha-methyl dopa14.
7. Bhalekar et al., In the present study resinates of verapamil HCl were formulated using
Indion resins. Drug loading process was optimized with respect to drug:resin ratio, pH of
loading solution, and particle size of resin. Resinates were characterized using
XRPDHence resinates were incorporated in pellets using extrusion spheronization to
achieve desired release pattern. Optimum drug loading was seen at pH of 3.5 in drug
resin ratio of 1:1 and was seen to increase with temperature. XRPD studies revealed
verapamil to be present in amorphous form in resinates 15.
8.
Kadam A U et al., An oral controlled release suspension of chlorpheniramine maleate
was prepared using ion-exchange resin technology. A strong cation exchange resin
Indion 244 was utilized for the sorption of the drug and the drug resinates was evaluated
for various physical and chemical parameters. The drug-resinate complex was
microencapsulated with a polymer Eudragit RS 100 to further retard the release
characteristics. Stability study indicated that elevated temperature did not alter the
sustained release nature of the dosage form indicating that polymer membrane
surrounding the core material remained intact throughout the storage period16.
6.3 OBJECTIVES OF THE STUDY:
1) Compatability studies between torsemide and polymers used.
2) Development of the calibration curve of torsemide.
3) Formulation of torsemide resonates.
a) Preparation of drug resinates.
b) Determination of ion exchange capacity.
4) Formulation of microencapsules of
torsemide
resinates using solvent evaporation
technique.
5) Evaluation of the microencapsule of torsemide resonates.
a) Determination of percentage yield.
b) Determination of the drug content.
c) Determination of particle size in microcapsule.
d) In vitro drug release from the microcapsules
6) Preparation of suspensions.
7) Physical stability of suspensions.
8) In-vitro release studies from suspensions
9) Stability studies as per ICH guidelines.
7
MATERIAL AND METHODS:
7.1.MATERIALS:
Drug: Torsemide.
Polymer: Ethyl cellulose, Cyclohexane, Light liquid paraffin, carboxy methyl cellulose.
All other materials used were analytical grade.
7.2. METHODS:
Preparation of the microencapsulation by solvent evaporation technique.
Preparations of the suspension using microencapsulation and different suspending agents.
7.3. SOURCE OF DATA:

The literature survey will be done by referring the abstracts & articles of all the National
and International journals of pharmaceutical sciences.

The day to day development in this area will be updated by literature survey through epublishing and current periodicals in library of Sri K.V. College of Pharmacy,
Chickballapur.
7.4. Does the study require any investigations to be conducted on humans or animals?
No
7.5. Has ethical clearance been obtained from your institution in case of above?
Not applicable
7.6. Duration of the study:
The study will be conducted over a period of 9 months.
7.7. Place of study:
Department of Pharmaceutics, Sri K.V.College of Pharmacy, Chickballapur.
8
REFERENCES
1. Gennaro A D. Remington’s Pharmaceutical Sciences,18thed. Pennsylvania:Mack
Publishing Co;1990:p.1676-7.
2. Samanta M K, Udayakumar T, Suresh B. Preparation of suspensions microspere
Indian J Pharm Sci, 57(5);1995:189-93.
3. Swarbrick J, Boylan J C. Encyclopedia of Pharmaceutical Technology, Vol-8, New
York; Marcel Dekker; 1993-P.204-9.
4. URL: http://www.drugbank.ca/drugs/DB00214
5. URL: http://en.wikipedia.org/wiki/Torsemide
6. URL: www.chemicalbook.com/ChemicalProductProperty_EN_CB1397929.htm
7. Ariens E J. Drug design, New York;Academic press;1973:(4):p.47.
8. Howard S A, Mauger J W, Hsieh J W, Amin K, Preparation of suspensions microspere
J Pharm. Sci; 1979:p.1475.
9. Mahore J G, Wadher K J, Umekar M J, Bhoyar P K. ion exchange resins:
pharmaceutical application and recent advancement. Int J Pharm Sci Rev Res
2010;1:8-13.
10. Manish R, Bhise Y Raju, Thenge R, Krodhi G, Mahajan. Formulation and evaluation
of
Sustained release suspension of Ambroxol Hcl Using Ion Exchange Resin. Int J
Pharm Tech Res. Oct-Dec 2009:1(4),1322-5.
11. Sompur C K, Doijad R C, Patil S M, Maske A P. An approch for development of oral
sustained releasesuspension. Int J Pharm Bio Sci 2011;2:320-9.
12. Suthar A M, Patel M M . Formulation and evaluation of taste masked suspension of
metronidazole. Int J App Pharm 2011;3:16-9.
13. Malay Kumar Samanta,
sustained
Udaykumar T, Suresh B. Preparation and evaluation of
release preparations of ferrous sulphate. Ind J Pharm sci 1995;5:189-93.
14. Katare O P, Jain S K, Vyas S P. Sustained release dry suspension for reconstitution of
alpha-methyl dopa. Ind J Pharm Sci 1988;50:1:19-22.
15. Bhalekar M R , Avari J, Umalkar R A . Preparation and in vitro evaluation of
sustained release drug delivery system for verapamil HCL.
Ind J Pharm Sci
2007;69:418-22.
16. Kadam A U, Sakarkar D M, Kawtikwar P S. Development and evaluation of oral
controlled release chlorpheniramine-ion exchange resinate suspension. Ind J Pharm Sci
2008;70(4):531–4.
9
SIGNATURE OF THE CANDIDATE
10
REMARKS OF THE GUIDE
11
11.1 NAME AND DESIGNATION OF
GUIDE
G.RUDRASEKHARREDDY
The proposed research work is original and
designed on rational basis. It would be a good
contribution.
Mr.B.R.KIRUPAKR
M.Pharm,
ASSOC PROFESSOR ,
Department of Pharmaceutics,
Sri K.V. College of Pharmacy,
CHICKBALLAPUR-562101.
GUIDE SHIP REFERENCE NO. OF ACA\CDC\PGT-Mph\SKVCPC\46\2010-11
RGUHS
11.2
SIGNATURE
11.3
CO-GUIDE
NOT APPLICABLE
11.4
SIGNATURE
NOT APPLICABLE
11.5 HEAD OF THE DEPARTMENT
Mr.N.SURESH
M.Pharm, (PhD.)
PROFESSOR AND HEAD
Department of Pharmaceutics,
Sri K.V. College of Pharmacy,
CHICKBALLAPUR-562101,
11.6 SIGNATURE
12
[N.SURESH]
12.1 REMARKS AND SIGNATURE OF
PRINCIPAL
Dr. D. SHESHADRI SHEKAR
M.Pharm., PhD