Download annexure ii - Rajiv Gandhi University of Health Sciences

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1
NAME OF THE
MR. SHASHANK JAYSING MOHITE
CANDIDATE AND
DEPARTMENT OF PHARMACEUTICS,
ADDRESS
K.L.E SOCIETY’S COLLEGE OF PHARMACY,
J.N.M.C CAMPUS, NEHRU NAGAR,
BELGAUM-10
2
NAME OF THE INSTITUTE
K.L.E SOCIETY’S COLLEGE OF PHARMACY,
BELGAUM-10
3
4
COURSE OF STUDY AND
MASTER OF PHARMACY IN
SUBJECT
PHARMACEUTICS
DATE OF ADMISSION
JUNE 2007
TO THE COURSE
5
TITLE OF THE TOPIC
“FORMULATION AND EVALUATION OF METOCLOPRAMIDE
RAPIDLY DISINTEGRATING TABLET”
1
6
BRIEF RESUME OF THE INTENDED WORK
6.1 NEED FOR THE STUDY :
Oral route of drug administration have wide acceptance up to 50-60% of total
dosage forms. Solid dosage forms are popular because of ease of administration,
accurate dosage, self medication, pain avoidance and most importantly the patient
compliance. The most popular dosage forms are being tablet and capsules, one
important drawback of these dosage forms for some patients however is the difficulty
in swallowing.1
Drinking water plays an important role in the swallowing of oral dosage
forms. Often times people experience inconvenience in swallowing conventional
dosage forms such as tablet when water is not available in the case of motion
sickness (kinetosis) and sudden episodes of coughing during the common cold,
allergic conditions and bronchitis.2 For these reasons, tablet which can rapidly
dissolve or disintegrate in the oral cavity have attracted a great deal of attention.
Rapidly dissolving or disintegrating tablet are not only indicated for people who have
swallowing difficulties, but also are ideal for active people.3
Recently Pharmaceutical industry has become increasingly aware of the need
that elderly be considered as a separate and unique medicare population. Though
geriatric patients constitute a minor proportion of the population, its growth rate is
high and hence will have significant impact on development of drug delivery
systems. Thus mouth dissolving tablet are gaining more demand and popularity from
last few years.4
Mouth dissolving tablets are those when put on tongue, disintegrates
instantaneously, releasing the drug, which dissolves or disperses in the saliva. The
faster the drug into solution the quicker the absorption and onset at clinical effect.
2
Some drugs are absorbed from the mouth, pharynx and oesophagus as the saliva
passes down into the stomach. In such cases, bioavailability of drug is significantly
greater than those observed from conventional tablet dosage form.5
Metoclopramide is chemically related to procainamide. It is a gastric hurrying
agent, it is now a widely used antiemetic. It has more permanent effect on upper
G.I.T, increases gastric peristalsis while relaxing the pylorus and the first part of
deuodenum. Metoclopramide is an effective antiemetic; acting on the CTZ, blocks
apomorphine induced vomiting.
Metoclopramide acts through both dopaminergic and serotonergic receptors.
Metoclopramide is rapidly absorbed orally, enters brain, crosses placenta and is
secreted in milk. It is partly conjugated in liver and excreted in urine within 24 hours.
Half life of Metoclopramide is 3-6 hours. Orally it acts in 30 min -1 hour, but within
10 min after I.M. and 2 min after I.V. injection and lasts upto 4-6 hours. It hastens
the absorption of many drugs, e.g. Aspirin, Diazepam etc. by facilitating gastric
emptying.6
The principle of the present investigation is to develope and characterize
rapidly disintegrating tablets, which disintegrates in the oral cavity in a matter of
second without the need of water. This helps in easy swallowing thereby improved
clinical effects through pregastric absorption, leading to an increase in bioavailability
of the drug and quick onset of pharmacological action can take place.
6.2 REVIEW OF LITERATURE :
From the review of the literature it can be noted that a great deal of work has
been done by scientists in developing rapidly disintegrated tablets.
The rapidly disintegrating calcium carbonate tablets using 3 different forms of
calcium carbonate were prepared and evaluated for disintegration, dissolution
3
properties, surface topography of the granules and tablets, moisture uptake studies,
etc. This study clearly demonstrated RD calcium carbonate tablets can be formulated
without expensive effervescence technology.7
A novel drug delivery was designed and proposed formulation of melt in
mouth or mouth dissolves tablets. Paracetamol was selected as a model drug and the
technology was named as D-Zolv technology. Two steps were involved, one is
masking of the taste and second is formulation of masked paracetamol granules into
tablets. Palatable granules of paracetamol were obtained by solvent evaporation
technique. Tablets were evaluated for various parameters including in-vitro and invivo disintegration time.8
Sumatriptan succinate mouth dissolving tablets were prepared by using
disintegrants such as sodium starch glycolate, carboxy methyl cellulose sodium and
treated agar by direct compression method. The prepared tablets were evaluated for
various parameters. The tablet disintegrate in-vitro and in-vivo within 10 to 16
second and 12 to 18 second, respectively. The formulations containing combination
of sodium starch glycolate and carboxy methyl cellulose found to give the best
result.9
The use of factorial design in formulation of orodispersible tablet of
Rofecoxib were carried out. Preliminary screening was carried out for sodium starch
glycolate, crospovidone and croscormellose sodium. Crospovidone showed effective
against 32 full factorial design was employed for preparation. Percentage of
crospovidone (X1) and mannitol (X2) were selected as independent variables, wetting
and disintegration time were selected as dependent variables. Full and refined models
were derived. It was concluded that lower disintegration time and wetting time could
be obtained when X1 is kept at high time and X2 is kept at lower level.10
Formulation and evaluation of mouth dissolving tablets of salbutamol
sulphate were designed by factorial design technique. Sodium starch glycolate,
4
croscarmellose and treated agar used as super disintegrants. Direct compression
technique was used formulation containing sodium starch glycolate along with other
superdisintegranty, showed rapid in-vitro and in-vivo dispersion time.11
6.3 OBJECTIVES OF THE STUDY :
The main purpose of the rapidly disintegrating tablets is to enhance absorption
and improve bioavailability of the drug.
The objectives of the present study are :
1. To develop metoclopramide rapidly disintegrating tablet using mass extrusion
technique using different polymers.
2. Evaluation of rapidly disintegrating tablet for various parameters like :
Pre –compression parameters
i. Drug-excipient compatibility study-IR spectroscopy
ii. Micromeritic properties-Angle of repose, consolidation index, bulk density etc
Post-compression parameters
1. Shape and colour
2. Uniformity of thickness
3. Hardness test
4. Friability test
5. Drug content uniformity
6. Weight variation test
7. Wetting time
8. Water absorption ratio
9. In vitro dispersion time
10. In vitro disintegration time
11. In vitro dissolution studies
12. Stability studies
5
7.
MATERIAL AND METHODS :
Materials :
1. Drug : Metoclopramide
2. Polymers : Eudragit E-100, sodium starch glycolate
3. Excipient : Agar, Avicel Ph 102, L-HPC, Mannitol, Lactose, Aspartame or
others
4. Analytical reagents – HCl, Disodium hydrogen orthophosphate or other.
Method :
Rapidly disintegrating tablets will be prepared by mass extrusion technique.5
7.1 SOURCE OF DATA :
The data is obtained from the rapidly disintegrating tablets based on the
laboratory experiments.
7.2 METHOD OF COLLECTION OF DATA (INCLUDING SAMPLE
PROCEDURE IF ANY) :
1. Compatibility study : Compatibility of drug with various polymers will be
investigated by using IR spectroscopy.
2. Preparation of standard calibration curve.
3. Evaluation of rapidly disintegrating tablets.
1. Shape and colour
2. Uniformity of thickness
3. Hardness test (Hardness tester)
4. Friability test (Friability apparatus) 12
6
5. Drug content uniformity
6. Weight variation test
7. Wetting time
8. Water absorption ratio 11
9. In vitro dispersion time
10. In vitro disintegration time 12
11. In vitro dissolution studies
12. Stability studies
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.
-No7.4
HAS
ETHICAL
CLEARANCE
BEEN
INSTITUTION?
-Not required-
7
OBTAINED
FROM
YOUR
8.
LIST OF REFERENCES :
1. Indurwade NH, Rajyaguru TH, Nakhat PD. Novel Approach - Fast Dissolving
Tablets, Indian Drugs 2002; 39(8) : 405-9.
2. Watanabe Y, Koizumi K, Zama Y, Matsumoto Y, Motsumoto M. New
compressed tablet rapidly disintegrating in saliva in the mouth using crystalline
cellulose and a disintegrant. Biol Pharm Bull 1995; 18(9) : 1308-10.
3. Bi Y, Yonezawa Y, Sunada H. Rapidly disintegrating tablets prepared by the wet
compression method: Mechanism and Opthmization. J Pharm Sci 1999; 88(10) :
1004-10.
4. Yeola BS, Pisal SS, Paradkar AR, Mahadik KR. New drug delivery system for
elderly. Indian Drugs 2000, 37(7): 312-8.
5. Kuchekar BS, Badhan AC, Mahajan HS. Mouth dissolving tablets; A novel drug
delivery systems. Pharma Times June 2003; 35 : 7-9.
6. Tripathi KD. Essentials of Medical Pharmacology, 5th Ed. New Delhi : Jaypee
Brothers Medical Publishers (P) Ltd. ; 2003.
7. Hector Fausett, Charles Gaysu Jr., Dash AK. Evaluation of quick disintegrating
calcium carbonate tablets. AAPS Pharma Sci Tech 2000; 1(3): article 20
(http//www.pharniascitech.com).
8. Kamdar NM, Shah SS, Devarajan PV.. D-Zolv-Mouth Dissolve Tablets. Indian J
Pharm Sci 2000; 62(2): 527-8.
8
9. Mahajan HS, Kuchekar BS, Badhan AC. Mouth dissolving tablets of Sumatriptan
succinate. Indian J Pharm Sci 2004; 66(2) : 238-40.
10. Patel DM, Patel NM, Shah RR, Jagani PD, Balapatel A. Studies in formulation of
Orodispersible tablets of Rofecoxib. Indian J Pharm Sci 2004; 66(5): 621-5.
11. Kuchekar BS, Badhan AC, Mahajan HS. Mouth dissolving tablets of salbutamol
sulphate; A novel drug delivery system. Indian Drugs 2004; 41 (10): 592-8.
12. Lachman L, Libermann HA, Kanig JL. The Theory and Practice of Industrial
Pharmacy, 3rd Ed. Bombay : Varghese Publishing House ; 1991.
9
9
Signature of candidate
10
Remarks of the Guide
The above information and literature has been extensively investigated, verified and was
found to be correct. The present study will be carried out under my supervision and
guidance.
11
Name and designation of
(in block letters)
11.1 Guide
11.2
SHRI. PANCHAXARI. M. DANDAGI M. PHARM
ASSOCIATE PROFESSOR,
DEPARTMENT OF PHARMACEUTICS,
K.L.E.S’S COLLEGE OF PHARMACY
BELGAUM-10
Signature
11.3 Co-guide (if any)
11.4 Signature
11.5 Head of the
Dept.
DR. F. V. MANVI M.PHARM, PH. D
PRINCIPAL
PROFESSOR AND HEAD,
DEPARTMENT OF PHARMACEUTICS,
K.L.E.S’S COLLEGE OF PHARMACY
BELGAUM-10
11.6 Signature
12
12.1 Remarks of Chairman
and Principal
The above-mentioned information is correct and I
recommend the same for approval.
12.2 Signature
DR. F. V. MANVI M.PHARM, PH. D
PRINCIPAL
DEPARTMENT OF PHARMACEUTICS,
K.L.E.S’S COLLEGE OF PHARMACY
BELGAUM-10
10