Download formulation and invitro evaluation of sustained release matrix

FORMULATION AND IN-VITRO EVALUATION OF SUSTAINED
RELEASE MATRIX TABLET OF SELECTED
ANTI-PSYCHIATRIC DRUGS
Synopsis for M.Pharm dissertation
Submitted to
Rajiv Gandhi University of Health Sciences, Bangalore,
Karnataka
BY
Mallikarjun V Simpi
Dept. of Pharmaceutics
BLDEA’s College of Pharmacy,
BLDE University campus, Bijapur-586 103
1
4th
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
‘T’ BLOCK, JAYANAGAR, BANGALORE-560041, KARNATAKA,
ANNEXURE-II
PROFORMA FOR REGISTRATION OF TOPIC FOR M.PHARM DISSERTATION
1
Name of the candidate and address
MALLIKARJUN V SIMPI
S/O V N Simpi, “Bhagyajyoti
Nivas”,Gumaste Colony, Ashram
road,Bijapur-586 103
[email protected]
2
Name of the institution
BLDEA’s College of Pharmacy, BLDEA
University campus, Bijapur-586 103
3
Course of study and subject
4
Date of the admission
5
Title of the topic:
MASTER OF PHARMACY IN
PHARMACEUTICS
28-07-2011
FORMULATION AND IN VITRO EVALUATION OF SUSTAINED
RELEASE MATRIX TABLET OF SELECTED ANTI-PSYCHIATRIC
DRUGS
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6. Brief resume of the intended work:
Need for the study:
 The design of oral modified release dosage form is intended to optimize a
therapeutic regimen by providing controlled delivery of drug over entire dosing
interval. Drug products designed to reduce the frequency of dosing by modifying
the rate of drug absorption for many years.1 The need of any drug delivery system
is to provide a therapeutic amount of drug to the proper site in the body to
achieve results promptly, and then to maintain, the desired drug concentration.
Since there is increasing cost and complication involved in the development and
marketing of new drug entities, this has forced most of the pharmaceutical
industries to focus their attention on the development of sustained/controlled/
prolonged system. This sustained release dosage forms are becoming popular as
these have a number of advantages over conventional dosage form such as dosing
frequencies, less fluctuation in circulating blood levels, increased patient
compliance and more uniform effect. The main aim of a sustained or controlled
release dosage form is to produce an improved therapy by producing a uniform
plasma concentration of drug at steady state and by reducing the ratio of
maximum and minimum plasma levels after each dose. This could be achieved if
the release of the drug form the dosage form is slow first order or slow zero order
absorption of drug occurs from the gastro intestinal tract.
Ziprasidone is a novel anti psychotic with high affinity for dopamine D2 and D3
receptors where it acts as potent agonist. It is not yet official in any
pharmacopeia. Its oral absorption rate is dissolution limited. Ziprasidone is
reported to have a short biological mean half life of 2-5 hrs requiring it to be
administered in 20mg twice daily.5Hence we have selected ziprasidone for the
development of once daily sustained release matrix tablet. The pharmacokinetic
and dosage schedule supports once daily sustained release formulation for
enhanced efficiency and patient compliance.
Regular research is going on in field of use of natural bio compatible polymeric
material in designing of dosage form for oral controlled release administration.2-4
In the present investigation it is planned to utilise the natural polymers such as
resin extracted from olibanum gum as a matrix forming material.
3
6.2 Review of the literature:
1. Dey S et al., have developed the sustained release oral matrix tablet by of rifampicin.
They have studied the effects of different polymers to prolong the release of drug for
extended period of time. In order to formulate the Based on preformulation studies
different batches of rifampicin were prepared using selected excipients using various
polymers viz, Guar gum, Tragacanth Gum, PEG-6000 and Carbopol in different
proportions and combinations by direct compression technique. The results of in
vitro release profile indicated that formulation (F2) was the most promising
formulation as the extent of drug release from this formulation was high as compared
to other formulations. Results of in vitro welling study indicate that the formulation
F2 was having considerable swelling index. It is concluded that formulation of
sustained release tablet of Rifampicin containing Guar gum (1.5%), batch F2 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 tablet6.
2. Jain S et al., have developed sustained release tablets of furosemid 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 hrs7.
3. Kar R K et al., have developed sustained release matrix tablets of zidovudine in
order to improve efficacy and better patient compliance. The tablets were prepared
by direct compression method using various proportions of hydrophilic polymers.
From the results obtained the authors concluded that stable formulation could be
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developed by incorporating both hydrophilic and hydrophobic polymer in a definite
proportion, so that sustained released profile is maintained for an extended periods of
time.8
4. Nair A et al., have developed controlled release matrix uncoated tablets of enalapril
maleate using HPMC alone. Controlled release uncoated tablets were prepared by
direct compression technique. Two grades of HPMC (K100 and K4M) in different
proportions were used to prepare the tablets, and were evaluated for physical
properties, drug content, in vitro drug release and drug release kinetics as well. All
the formulations demonstrated good physical integrity and the drug content were in
the official limits. The formulation with HPMC K100 (25 mg/tablet) and K4M (15
mg/tablet) have been found to release the required amount of drug (2.97 mg/h)
throughout the study period (14 h). The calculated regression coefficients showed
higher r2 value with Higuchi model and zero order kinetics. Given the excellent
release profile, the study concluded that HPMC in different grades with low
concentration alone can control the enalapril maleate release over a period of time
(14 h).9
5. Patel R et al., have prepared propranolol Hydrochloride controlled release matrix
tablets and investigated the effect of the polymer blends and the polymer
concentration on drug release. Propranolol Hydrochloride controlled release matrix
tablets were prepared by direct compression technique. HPMC K15M and Carbopol
934P were used for formulating the matrix tablets. A 32 full factorial design were
applied to carry out systematic studies. The blending ratio of HPMC K15M and
Carbopol 934P (X1) and their concentrations (X2) were selected as independent
variables. The times required for 50% (t50) and 80% (t80) drug release were selected
as dependent variables. The results clearly indicate that the values of t50, t80, f2 and
MDT are strongly dependent on the independent variables. The results of in-vitro
drug release profile indicated that batch F7 showed the highest value among all the
batches. Conclusions were observed that the blending ratio of HPMC K15MCarbopol 934P and polymer concentration have distinct effect on in-vitro drug
release profile. Release rate of Propranolol hydrochloride decreased proportionally
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with increased in concentration of Carbopol 934P and total polymer concentration.10
6. S. P. Hiremath et al., have developed oral controlled release formulations of
rifampicin and studied effect of formulation variables and process parameters on in
vitro release. In their investigation they attempted to further study the effect of
HPMC viscosity, ratio, and rifampicin particle size on the release of rifampicin from
CR matrix tablets. The results indicated that the release rate of the drug and the
mechanism of release were mainly controlled by the polymer viscosity/molecular
weight and polymer ratio. The authors concluded that the drug release could be
extended from 12 hr to beyond 24 hr by varying polymer ratio and viscosity
character of the polymer.11
7.
Sahu D et al., have developed sustained release matrix tablets of quetiapine
fumarate using different polymers viz. hydroxy propyl methyl cellulose (HPMC) and
PVP K30. Varying ratios of drug and polymers were selected for the study. The
results of pre and post compression parameters were found to be within the
acceptable official limits. They finally concluded that the formulations prepared with
HPMC & PVP K30 polymer show 100% drug release in 12hrs and formulations
could retard the drug release up to desired time period. The tablets containing
polymer blend of HPMC K 15M and PVP K30 retard the drug release because both
are swellable polymer. From the release study it is observed that as concentration of
HPMC increases the drug release of drug was found to be decreased. This is possibly
due to slower erosion of HPMC and may be due to the increased viscosity of PVP
K30 which might have helped to keep the hydrated gel intact thus releasing the drug
for 12 hrs.12
8. Moin A et al., developed sustained release matrix tablets of diltiazem hydrochloride
(DTZ) using karaya gum (K) alone or in combination with locust bean gum (LB) and
HPMC (H). Matrix tablets of DTZ were prepared at different ratios of drug: gum
(1:1, 1:2, and 1:4) and of the gum blends K, K/LB, K/H and K/LB/H) by direct
compression. Tablets with only K or K/H had the highest mean dissolution time
(MDT), the least dissolution efficiency (DE, 12 %), and released drug by swelling,
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diffusion and erosion mechanisms. Karaya gum or combinations with locust bean
gum sufficiently controlled drug release, while combinations of KH and KLBH
exhibited high and low drug release efficiency, respectively. They finally concluded
that karaya gum alone or in suitable combination with locust bean gum and HPMC is
suitable for formulating sustained-release matrix tablets of diltiazem.13
9. Singh I et al., have studied the drug release retardant property of katira gum in a
matrix tablet containing tremadol as a model drug. Katira gum, an insoluble gum
derived from cochlopermum religiosum was used as a matrix forming material. The
results indicated rapid swelling over the first one hour. All the batches of matrix
tablets were formulated under similar condition to avoid variation in processing
variables. The prepared tablets were evaluated for various physical tests. From the
results obtained the authors concluded that katira gum could effectively used as a
drug release retardant in matrix tablet formulation.14
10. Sung-Hyun P et al., have carried out the preparation of an extended-release matrix
tablet of theophylline using chitosan/carbopol interpolymer complex. They found
that chitosan/carbopol IPC showed a similar release pattern to that of HPMC used as
a sustained- and extended-release matrix former, and showed pH-independent release
profile during the first 2 h of the dissolution study. The main release mechanisms of
theophylline from the IPC tablet were diffusional release at pH 6.8 and relaxation of
the polymer at pH 1.2. They finally concluded that the pH dependency of carbopol
can be reduced by the formation of a complex with chitosan, and can be used as a pH
independent extended-release tablet matrix.15
7
6.3 Main objectives of the study:
The objectives of the present study are as follows:
1. To design and evaluate the sustained release matrix tablets of Antipsychotic
drugs.
2. To characterize the physicochemical properties of the selected formulations.
3. To carry out the in vitro drug release profile of the selected formulations.
4. To carry out the stability studies of the selected formulations.
7 Materials and methods:
7.1 Source of data:
 The data will be obtained from the literature survey and internet source.

The data will be obtained from the experimental work, which includes formulation
of sustained release matrix tablets by using different polymers, evaluation of drug
content and stability studies.
7.2 Method of collection of data (including sampling procedures if any):

The data will be collected from prepared formulations subjected to different
evaluation techniques, estimation of drug content, in-vitro drug release and stability
studies.
7.3 Does the study require any investigation or interventions to be conducted on
patients or other humans or animals?
- NO –
7.4 Has ethical clearance been obtained from your institution in case of
7.3?
- Not applicable –
8
8 LIST OF REFERENCES:
1. Ansel HC, Loyyd VA., 1999 “Pharmaceutical dosage forms and drug delivery
system”. Lippincott’s Williams and Wilking, Hong Kong. 8:275-80.
2. Bonferoni MC, Rosi ST. 1993.“On the employment of λ-carrageenan in a matrix
system.
I. Sensitivity to dissolution medium and comparison
with Na
carboxymethylcellulose and xanthan gum.” J.control Rel. 26:119.
3. Sujja AJ, Munday DL, Khan KA. 1999 “Development and evaluation of a multipleunit oral sustained release dosage form for S (+)-ibuprofen: preparation and release
kinetics”. Int. J.Pharm.193:73-84.
4. Khullar P, Khar RK, Agarwal SP. 1999 “Guar gum as a hydrophilic matrix for
preparation of theophylline controlled release dosage form”. Indian. J. Pharm. Sci.
61:342-45.
5. http://www.drugbank.com
6. Samiran Dey, Ajay SL, Pandiselvi A, Nidhi R, Das RC, Bharat Kumar B, P.
Malairajan, KalaVeni JK, R. Murugand, Ahmed S. 2011 “Formulation and
evaluation of sustained release oral matrix tablet by using rifampicin as a model
drug”. www.ajpst.com. Vol 1|Issue 1|18-32.
7. Jain S, SK Yadav and UK Patil.2008 “Preparation and Evaluation of Sustained
Release Matrix Tablet of Furosemide using Natural Polymers”. Research J. Pharm.
and Tech. 1(4).
8. Kar RK, Mohapatara S, Barik BB., 2009 “Design and characterization of controlled
release matrix tablets of zidovudine”. Asian J. Pharm. Clin. Res. 2:54-61.
9. Nair AB, H.Vyas, Ashok Kumar., 2010 “Controlled release matrix uncoated tablets
of enalapril maleate using HPMC alone” J of Bas and Cli Pharm. Vol-1, Issue-:7075.
10. Patel R, Patel H, Patel G.,2010 “Optimization Of Propranolol Hydrochloride
Controlled Release Matrix Tablet Using Factorial Design”.Webmed.Central.pharm
sci. 1(10):wmc00914.
9
11. Hiremath SP, Ranendra N S.2008 “Oral Controlled Release Formulations of
Rifampicin.Part II: Effect of Formulation Variables and Process Parameters on In
Vitro Release”. Drug. Deli; 15:159-68.
12. Deepak S, Rana A. C. 2010 “Formulation development of Quetiapine Fumarate SR
matrix tablets”. Der Pharmacia Sinica, 1 (1): 48-57.
13. Moin A, HG Shivakumar. 2010 “Formulation of sustained-release diltiazem matrix
tablets using hydrophilic gum blends”. Trop. J.Pharm. Res. 9 (3): 283-91.
14. Inderbir S, Pradeep Kumar, Sanjeev Kumar, and Rana V.2010 “Formulation and
development of tremadol drug using katira gum as a release modifier”. The Pham.
Soc. Of. Japan.Yakugaku Zasshi 130(9), 1225-31.
15. Park S H, Myung K C, Hoo-K C. 2008 “Preparation of an extended-release matrix
tablet using chitosan/Carbopol interpolymer complex” Int.J. Pharmaceu. 347:39-44.
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9.
Signature of the candidate:
10
.
Remarks of the guide:
11 Name And Designation of:
.
11.1 Guide
(MALLIKARJUN SIMPI)
Recommended.
MR.J.S.PATIL
Assistant Professor,
Department of Pharmaceutics,
BLDEA’s College of Pharmacy,
BLDEA’s University campus,
Bijapur-586 103
11.2 Signature
11.3 Co-Guide
NOT APPLICABLE
11.4 Signature
11.5 Head of the department
11.6 Signature
12
.
12.1 Remarks of the Principal:
12.2 Signature
11
13
Remarks of the Guide:
The present work is aimed to formulate the sustained release matrix tablets of
the selected anti psychiatric drugs such as ziprasidone. The ziprasidone is a
novel anti psychotic drug with high affinity for dopamine D2 and D3 receptors
where it acts as potent agonist. It is not yet official in any pharmacopeia.
Ziprasidone is reported to have a short biological mean half life of 2-5 hrs
requiring it to be administered in 20mg twice daily,
but the frequent
administration may leads to dose accumulation and toxicity. Hence, to conquer
this limitation, development of sustained release system for such drugs is
necessary. Hence we have selected ziprasidone as model drug for the
development of once daily sustained release matrix tablet. The pharmacokinetic
and dosage schedule of the ziprasidone supports once daily sustained release
formulation for enhanced efficiency and patient compliance. The proposed study
can be carried out in the laboratory.
.
Mr. J.S.PATIL
(Research Guide)
12
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