Download studies on formulation and evaluation of floating tablet

RAJIV GANDHI UNIVERSITYOF HEALTH
SCIENCES, KARNATAKA, BANGALORE.
M. PHARM. SYNOPSIS
YEAR OF ADMISSION JUNE- 2012
TITLE OF THE SYNOPSIS
“STUDIES ON FORMULATION AND EVALUATION OF FLOATING
TABLET CONTAINING NIZATIDINE ’’
BY
Mr. Rushikesh B. Katkar
M.Pharm, Part-I
Department of Pharmaceutics
UNDER THE GUIDANCE OF
Prof. SIDHARTH M. PATIL M.Pharm.
DEPARTMENT OF PHARMACEUTICS.
KLES’s COLLEGE OF PHARMACY,
Akkol Road, NIPANI,
KARNATAKA.
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
NAME OF THE
CANDIDATE
AND ADDRESS
Mr. Rushikesh B. Katkar
S/o –Bajirao Katkar, A/P : Balinge
Tal : Karveer, Dist : Kolhapur
Pin code – 416010
MAHARASHTRA
2.
NAME OF THE
INSTITUTION
KLES’s COLLEGE OF PHARMACY
Akkol road, NIPANI
DIST:- BELGAUM
KARNATAKA.
3.
COURSE OF STUDY AND
SUBJECT
Master Of Pharmacy In Pharmaceutics
4.
DATE OF ADMISSION
JUNE - 2012
5.TITLE OF THE TOPIC
“STUDIES ON FORMULATION AND EVALUATION OF
FLOATING TABLET CONTAINING NIZATIDINE’’
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6.0
BRIEF REVIEW OF THE INTENDED WORK -:
6.1 - Need for the study
A peptic ulcer is a break in the inner lining of the esophagus, stomach, or
duodenum. A peptic ulcer of the stomach is called a gastric ulcer. Peptic ulcer leads to
decrease the pH and mainly acetylcholine and histamine is responsible for development
of peptic ulcer(Because of sensation of food). Peptic ulcers can be broadly classified into
gastric ulcers and duodenal ulcers. Normally the stomach wall is protected by the
mucosa against irritation of gastric acid. When the mucosa is damaged or when the
stomach produces so much gastric acid that the protective lining is eroded with
subsequent inflammation or necrosis, a local ulcer will develop. Peptic ulcer is usually
caused by pepsin and acid a digestive stomach enzyme. The commonest symptom of
peptic ulcers is intermittent abdominal pains, especially in the middle of the night or
when you are hungry.
Causes of peptic ulcers are:
1. Congenital hyperacidity.
2. Mental strain and emotional stress that make the nervous system stimulate the
excessive production of gastric acid.
3. Undesirable eating habits, irregular meals or overeating.
4. Smoking and excessive alcohol are direct causes of increased morbidity.
5. Drugs such as aspirin and painkillers for rheumatism irritate and damage gastric
mucosa.1
Drugs for peptic ulcers are mainly classified into three categories:
1. Antacids: They neutralize gastric acid, thereby relieving or eliminating the irritation
and erosion to the stomach wall and the ulcer sites. Common examples include
magnesium trisilicate and aluminum hydroxide. They are available in the form of Chewable
pills and liquids.
2. Anticholinergics: They suppress the secretion of gastric acid, reduce
Gastro intestinal movement and relieve stomach cramps. Common examples
Include propantheline bromide and scopolamine methyl bromide.
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3. H2 receptor antagonists: They are commonly known as specific drugs. They directly
suppress the secretion of gastric acid. common example is cimetidine , ranitidine.2
Nizatidine is used for the treatment of acid-reflux disorders, peptic ulcer disease, active
benign gastric ulcer and active duodenal ulcer.
Nizatidine is a competitive, reversible inhibitor of histamine at the H2-receptors,
particularly those in the gastric parietal cells. By inhibiting the action of histamine on stomach
cells, Nizatidine reduces stomach acid production. Nizatidine had no demonstrable anti
androgenic action. Full-dose therapy for the problems treated by Nizatidine lasts no longer
than 8 weeks. It has been demonstrated that treatment with a reduced dose of Nizatidine is
effective as maintenance therapy following healing of active duodenal ulcers.
Nizatidine undergoes less extensive hepatic metabolism. Less than 7% of an oral dose
is metabolized as N2-monodes-methylnizatidine, an H2-receptor antagonist, which is the
principal metabolite excreted in the urine. Other likely metabolites are the N2-oxide (less than
5% of the dose) and the S-oxide (less than 6 % of the dose).
Nizatidine is having a half-life of 1-2 hrs. The bioavailability of Nizatidine is
approximately 85% with little intersubject variations. The serum concentration reaches its peak
(c) within 1-2 hrs after oral administration.3
Oral delivery of drugs is by far the most preferable route of drug delivery due
to the ease of administration, low cost of therapy, patient compliance and flexibility in
formulation etc. Oral sustained drug delivery formulations show some limitations
connected with the gastric emptying time. Variable and too rapid gastrointestinal transit
could result in incomplete drug release from the device into the absorption window
leading to diminished efficacy of the administered dose. It is evident from the recent
research and patent literature that an increased interest in novel dosage forms that are
retained in the stomach for a prolonged residence time.4
The floating drug delivery system is oral dosage form designed to prolong the
residence time of dosage form, with in the gastrointestinal tract . Such dosage form
having density less than that of the gastric fluid floats on the gastric juice for an extended
period of time while slowly releasing the drug. On contact with the gastric fluid, the intra
gastric floating dosage form forms a water impermeable colloid gel barrier around its
surface and maintains bulk density of less than 1, so it remains buoyant in the gastric
fluid in stomach until the entire loading dose has been released.5
Gastric emptying of dosage forms is an extremely variable process. The ability to
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prolong and control the emptying time is a valuable asset for dosage forms which reside in
the stomach for a longer period than conventional dosage forms. Drug absorption from the
gastro intestinal tract (GIT) is a complex procedure and is subject to many variables. Factors
affecting Gastric emptying are 1)Volume of meal 2)composition of meal 3)viscosity of meal
4)Temperature of meal 5)Body posture 6)drug interaction 7)Disease state.
The small intestinal transit time is an important parameter for drugs that are
incompletely absorbed. Gastro retentive systems can remain in the gastric region for several
hours and hence significantly prolong the gastric residence time of drugs. Prolonged gastric
retention improves bioavailability, reduces drug waste and improves solubility for drugs that
are less soluble in a high pH environment. It has applications also for local drug delivery to the
stomach and proximal small intestine.6
Floating drug delivery systems provides better bioavailability for the drugs
that are unstable in the intestinal and colonic environment. The controlled gastric retention
of solid dosage forms may be achieved by the mechanisms of mocoadhesion, flotation,
sedimentation, expansion, modified shape systems.7
Hence, from the study we concluded that, it could play a good role in a therapy for
peptic ulcer, which will lead to increase the gastric residence time in stomach.
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6.2- Review of Literature-:
 Pannala S et. al. (2011) Have carried out preparation and in-vitro evaluation of
Nizatidine immediate release tablets. Immediate release drug-containing core
tablets of Nizatidine were prepared by wet granulation method by using avicel,
sodium starch glycolate, PVP K-30, HPMC E 5, magnesium stearate. The
obtained tablets were evaluated for weight variation, thickness, hardness, drug
content, disintegration and in-vitro dissolution studies.7
 Thakkar VT, et. al. (2008)
Have carried out fabrication and evaluation of
Levofloxacin hemihydrate floating tablet. Batches were prepared by direct
compression method using gelucire 43/01 and HPMC in different ratios. Invitro release study reveals that the release rate of drug was decreased by
increasing the proportion of Gelucire 43/01, 5 to 40%. The release rate of
Levofloxacin hemihydrates from matrices was mainly controlled by the
hydrophilic and hydrophobic polymer ratio. Optimal batch (F4 containing
gelucire 43/01, HPMC K4 M) was selected by regression analysis which
followed Higuchi kinetics. 8
 Pare A, et. al. (2008) have carried out formulation and evaluation of effervescent
floating tablet of Amlodipine besylate. The tablets were prepared in ten different
formulations (F1 to F10) by employing different grades of polymers (HPMC K
100M, HPMC K15M & Carbopol 934P) and agents such as sodium bicarbonate
and citric acid by direct compression technique. Amlodipine is a potent drug use
for the treatment of angina & hypertension. 9
 Sharad NS, et. al. ( 2010) Have carried out development and evaluation of
floating tablets of Salbutamol sulphate Formulations were prepared by using
HPMC sodium bicarbonate and citric acid. Formulations were evaluated for in6
vitro drug release profile, swelling characteristics. The in-vitro drug release
followed Korsemeyer-Peppas kinetics and the drug release mechanism was
found to be of anomalous type. For the developed formulation, the value of n
was found to be 0.6039 while for the marketed formulation the value was 0.5889
indicating the anomalous transport .10
 Ramesh B, et. al. (2009) has carried out development and evaluation of gastro
retentive Norfloxacin floating tablets. Tablets were prepared by the wet
granulation technique using polymers such as hydroxypropylmethylcellulose
(HPMC K4M, HPMC K100M) and xanthan gum. Optimized formulations F4 &
F9 containing HPMC K4 & HPMC K100M floated with a lag time of less than 1
min and continued to float for 24 hrs. Formulation F16 containing xanthumgum
floated with a lag time of 9 min continued to float for 24 hrs.11
 Bagherwal A. et. al. (2010) Studies on formulation and evaluation of floating
tablets of ciprofloxacin hcl. In the present study, it was aimed to formulate
floating tablet of ciprofloxacin hcl with HPMC and carbomer in different
proportion (4%, 8% and 12%) by direct compression techniques using polymers
lactose, magnesium streate, talc with sodium bicarbonate. All the prepared
formulation were found to complies with the official tests like precompression
parameter like angle of repose and post compression parameters like shape,
tablet dimensions, hardness, friability test, weight variation test, floating test,
content uniformity and in-vitro dissolution study. 12
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6.3
Objectives of the study -:
Following are the objectives of the present study -:
1) The current study is to develop an ideal floating drug delivery system.
2) Formulation of floating tablet by suitable method.
3) Evaluation of floating tablet for their physicochemical studies.
4) To carry out stability studies as per as ICH guidelines.
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7.0 MATERIALS AND METHODS
Materials-:
Drug
: Nizatidine.
Polymers
:HPMC, HPMC E5, MCC ,
sodium bicarbonate, citric acid, chitosan.etc.
Additives
: Magnesium stearate, Talc etc.
Binding agent
: PVP-K 30, etc.
Distntergrant
: Sodium starch glycolate etc.
Method :

Development of Nizatidine floating tablet by Direct compression method
or any
suitable method or any developed method.
7.1 - Source of Data:
a) Journals such as,
1) Indian Drug.
2) Indian Journal of Pharmaceutical Sciences.
3) Indian Journal of Pharmaceutical Education and research.
4) European Journal of Pharmaceutical Sciences.
5) International Journal of Pharmaceuticals.
6) Drug Development & Industrial Pharmacy.
7) Journal of Controlled Release.
b) Review articles
c) World Wide Web.
d) J-gate@Helinet.
e) Science Direct, Pub med.
f) Library: KLES’s College of Pharmacy.
g) E-library: KLES’s College of Pharmacy.
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7.2 - Method of collection of data
1) Preformulation studies for possible drug or other excipient.
2) Prepration of floating tablet of Nizatidine drug by Direct compression or
any suitable method.
3) Evaluation of the various properties of Tablet.
 Weight variation
 Thickness of tablet
 Hardness of tablet
 Friability
 % Friability
 Friability test.
 Drug content uniformity.
 In vitro buoyancy studies.
 Swelling index
 In vitro dissolution studies
4) Carry out stability studies as per ICH guidelines.
7.3 - Does the study require any investigations or interventions to be conducted on
patients or other humans or animals? If so, please describe briefly.
“NO”
(The study do not requires animal to evaluate Antiulcer activity.)
7.4 - Has ethical clearance been obtained from your institution in case of 7.3?
“ NOT APPLICABLE ”
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8.0 : Reference1) Tripathi K. D. ‘‘Essential of medical pharmacology’’,Jaypee; 2008 :627-640.
2) Satoskar R. S. , Bhandarkar S. D. ,Ainapure S. S. , ‘‘Pharmacology and
pharmacotherpeutics’’,S. Chand ;2003:8th :602-609.
3) Barar F.S. K. ‘‘Essential Of pharmacotheraputics’’,S. Chand;2006:537-540.
4) Jain Amit K. , Hatila Umashankar , ‘‘A Review of Floating Drug Delivery
System,’’International journal Of pharmaceutical studies and research 2011;2:1-6.
5) Dixit Nikita , ‘‘Floating drug delivery system,journal of current pharmaceutical
research;2011 ,7(1):6-20.
6) Mayavanshi AA , Gajjar SS , ‘‘Floating drug delivery system to increase gastric
retention Of drugs:A Review,’’Research journal pharmaceutical and technology;
2008.1(4):345-348.
7) Pannala S, Rathnanand M. ‘‘Preparation and in-vitro evaluation of Nizatidine
immediate release tablets’’, Int.J. Pharm.Tech.Res 2011; 3(3):1688-92.
8) Thakkar VT, Shah PA, Soni TG, Parmar MY, Gohel MC, Gandhi TR. ‘‘Fabrication
and evaluation of Levofloxacin hemihydrate floating tablet.’’, Res Pharm Sci 2008;
3(2):65-72.
9) Pare A, Yadav SK, Patil UK. ‘‘Formulation and evaluation of effervescent floating
tablet of Amlodipine besylate’’, Res J Pharm Technol.2008; 1(4):526-30.
10) Sharad NS, Satej SM, Shekhar BW, Maesh RM, Kamla KC. , ‘‘Development and
evaluation of floating tablets of Salbutamol sulphate,’’ Int. J. Pharm. Res. Dev 2010;
2(5):1-7.
11
11) Ramesh B, Rongala ASN, Madhusudan RY, Kishan V. Development and
evaluation of gastroretentive Norfloxacin floating tablets. Acta Pharm., 2009; 59:211–
21.
12) Bagherwal A. , Kumar D. , Patidar K. ,Sharma P., ‘‘Studies On Formulations And
Evaluations
Of
Floating
Tablet
Of
Ciprofloxacin
HCL’’,
Pharmaceutical
Globale;2010:1(5);1-3.
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9.
SIGNATURE OF THE
CANDIDATE
10.
REMARKS OF THE GUIDE
11.
NAME AND DESIGNATION
OF
11.1 Guide
Recommended
Prof. Sidharth M. Patil
M. Pharm.
Professor of Pharmaceutics
11.2 Signature
11.3 Co-Guide ( If any)
11.4 Signature
11.5 Head of the Department
Prof. J. K. Saboji, M.Pharm
Professor & Head
Department of Pharmaceutics
11.6 Signature
12.
12.1 Remarks of the Chairman
Principal
Forwarded to the University for approval
12.2 Signature
Principal
Prof. J.K.SABOJI
KLES’s College of Pharmacy
Akkol Road,
NIPANI-591237.
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