Download “FORMULATION AND EVALUATION OF FLOATING TABLETS

“Study of Formulation of Dexamethasone Sodium Phosphate Injection to Stabilize The
Product to Avoid Particulate In The Formulation On Aging”
DISSERTATION PROTOCOL
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA.
BY
MAHENDRA SINGH RATHORE
M.PHARM, PART-I
DEPARTMENT OF PHARMACEUTICS
(2008-2010)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
BANGALORE, KARNATAKA.
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
NAME OF THE CANDIDATE
AND ADDRESS (IN BLOCK
LETTERS)
MAHENDRA SINGH RATHORE
NARGUND COLLEGE OF PHARMACY,
DATTATREYANAGAR, II MAIN,
100 FT RING ROAD, BSK III STAGE,
BANGLORE-85
KARNATAKA.
2.
NAME OF THE INSTITUTION
NARGUND COLLEGE OF PHARMACY,
DATTATREYANAGAR, II MAIN,
100 FT RING ROAD, BSK III STAGE,
BANGLORE-85
KARNATAKA.
3.
COURSE OF STUDY AND
SUBJECT
MASTER OF PHARMACY IN
PHARMACEUTICS
4.
DATE OF ADMISSION OF
COURSE
5TH MAY 2008
5.
TITLE OF TOPIC
“Study of Formulation of Dexamethasone
Sodium Phosphate Injection to Stabilize The
Product to Avoid Particulate In The
Formulation On Aging”
6.
BRIEF RESUME OF THE INTENDED WORK:
6.1 NEED FOR THE STUDY:
Dexamethasone Sodium Phosphate Injection, IP is a synthetic adrenocortical steroid
anti-inflammatory drug. Dexamethasone Sodium Phosphate Injection, IP 4 mg/mL is a
sterile solution for intravenous, intramuscular, intra-articular, intralesional and soft tissue
administration[1].
Dexamethasone Sodium Phosphate Injection, IP has a rapid onset but short duration of
action when compared with less soluble preparations. Because of this, it is suitable for
the treatment of acute disorders responsive to adrenocortical steroid therapy, such as
Primary or secondary or Acute adrenocortical insufficiency.It is also used in the event of
serious trauma or illness, in patients with known adrenal insufficiency or when
adrenocortical reserve is doubtful,Shock unresponsive to conventional therapy etc.,[2,3]
Currently Dexamethasone Sodium Phosphate is also available for oral administration.
However its bioavailability followed by oral administration is poor. Hence
Dexamethasone Sodium Phosphate injections are currently considered as important. But
formation of particulates in Dexamethasone Sodium Phosphate injections IP during and
after storage for 6 months has been reported. The present study is aimed to study the
formation of particulates in Dexamethasone Sodium Phosphate injections IP during and
after storage for 6 months. Many samples of Dexamethasone Sodium Phosphate
injections that failed to meet strength requirements; This is a problem with the shelf-life
stability of dexamethasone sodium phosphate injections. This problem may be because,
it is highly hygroscopicity or its polymorphic form or may be due to its interactions with
glass containers or degradation by oxidation [3,4,5,6].
6.2 REVIEW OF LITERATURE :
The stability of sterile dexamethasone acetate suspensions and dexamethasone sodium
phosphate injections that had been stored in hospital pharmacies across the United
States was studied. Through a voluntary FDA drug stability program, all hospital
pharmacies in the United States were asked in October 1981 to complete a response
card indicating information about the sterile dexamethasone acetate suspensions and
dexamethasone sodium phosphate injections they had in stock. All samples that
failed to meet strength requirements showed evidence of degradation by oxidation.
Sterile dexamethasone acetate suspensions appear to be stable when stored under
actual marketplace conditions, but there is a problem with the shelf-life stability of
dexamethasone sodium phosphate injections made by some manufacturers[1,2,3]
2. The stability of 10 mg/mL dexamethasone sodium phosphate injection was
evaluated using a validated, stability-indicating liquid chromatographic method
during 91 days storage in glass and 55 days storage in plastic syringes with rubber
plungers. Analysis of samples for leachates on day 101 failed to demonstrate any
contamination. However, re-analysis of the syringes following 18 months storage
indicated contamination by a number of compounds. The results indicate that
sorption of dexamethasone phosphate to the syringe barrel or plunger did not occur
to a clinically important degree. However after 101 days there was no measurable
contamination of the dexamethasone phosphate solution, although after 18 months
considerable contamination was observed [1,3].
3. High – performance liquid chromatography studies were performed to determine
whether dexamethasone sodium phosphate is degraded either in vials or in an
infusion pump at 37 (degrees) C a period of weeks [2,3,4].
4. Dexamethasone Sodium Phosphate Injection, USP has a rapid onset but short
duration of action when compared with less soluble preparations. Because of this, it
is suitable for the treatment of acute disorders responsive to adrenocortical steroid
therapy. This is also used in Hypercalcemia associated with cancer, Rheumatic
disorders,
Congenital
adrenal
hyperplasia,
Nonsuppurative
thyroiditis
Hypercalcemia associated with cancer, Rheumatic disorders etc [5,6,7].
6.3 OBJECTIVES OF THE STUDY:
The present study is aimed at the stability study of Dexamethasone sodium phosphate
injection which includes the
1. Study of Dexamethasone sodium phosphate Polymorphism ,
2.
To study its interactions with glass containers upon storage,
3. stability studies due to its hygroscopic characteristics and its degradation due to
oxidation etc.,
Finally study of reasons for formation of particulates in Dexamethasone Sodium
Phosphate injections and to improve the Shelf-life stability of Dexamethasone sodium
phosphate injections.
7.
MATERIALS AND METHODS:
Materials
1. Dexamethasone Sodium Phosphate is a water-soluble inorganic ester of
dexamethasone. It occurs as a white to yellow crystalline powder, is odorless or
has a slight odor of alcohol, is exceedingly hygroscopic, and is freely soluble In
water (25 mg/ml - clear to slightly hazy, colorless solution), Ethanol (96%),
Slightly soluble in Chloroform and Practically insoluble in Ether.
2. Water for injection and other organic solvents etc.
3. Preservative like Parabens and benzyl Alcohol etc.,
7.1. Source of Data
1. Library: Nargund college of pharmacy
2. e-library: Nargund college of pharmacy
3. The data will be collected by Laboratory investigation and Recording the data.
7.2. Method of Collection of Data
1.
Data on drug will be collected through literature survey and from
physiochemical data base such as Solubility in various solvents, pH of the drug
solution and compatibility of the drug with various formulation additives.
2. Polymorphism studies using O-XRD method, Crystallography techniques and
Thermal analysis.
3. Spectrophotometery analysis of the preparations.
4. Formulation compatibility studies using DST techniques.
5. Solubility studies using Co-solvents like Poly Ethylene glycol, Propylene glycol,
Di Isosorbide, etc.
6.
Stability studies as per ICH guidelines.
7.3. Does the study require any investigation or intervention to be conducted on
patients or other humans or animals? If so, please mention briefly.
-NO-
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
- NOT APPLICABLE8.
LIST OF REFERENCES:
1. Kroin,s Jeffrey, Schaefer, B S S Richard, Penn, MD D Richard, “ Chronic
Intrathecal
Administration
of
Dexamethasone
Sodium
Phosphate:
Pharmacokinetics an Neurotoxicity in an Animal Model.” “Neurosurgery
Jan.2000 46(1): 178-183.
2.
Coffman HD, Crabbs WC, Joachims GL,Kolinski RE,and Page DP, “, Stability
of sterile dexamethasone acetate suspensions and daxamethasone sodium
phosphate injection submitted by U.S.hospitals” “ American Journal of hospital
Pharmacy” vol.40: 2165-2169.
3. N Mahesh, J Jusko Williom and Samtani, “Stability of dexamethasone sodium,
phosphate in rat plasma” “ Internationl Journal of Pharmaceutics” 2005 July 27.
4. V Dilova, V Zlatarova, N Spirova, K Filcheva, A Pavlova, P Grigorova, “Study
of insolubility problems of dexamethasone and digoxin : cyclodextrin
complexation. ” Int. J. of Pharmaceutics, vol.25: 216-219.
5.
DW Law, S Law, SE Walker, J Iazzetta,” Dexamethasone phosphate stability
and contamination of solution stored in syringe” “J.Pharma Sci.Technol. 1996
Aug.
6.
G Della Porta, SF Ercoline, L Parente, E Reverchon “ Corticosteriod
Microparticals
produced
by
susperitical
assisted
atomization
process
optimization, product characterization, and in vitro performance.” “J Pharma
Sci.2006 Sep: 95(9): 2062-76.
7. The Indian Pharmacopoeia 1996 VOL.1; 233.
9.
Signature of the candidate
MAHENDRA SINGH RATHORE
10.
Remarks of the Guide
RECOMMENDED FOR DISSERTATION WORK
11.
Name & Designation of
(in block letters)
11.1 Guide
11.2 Signature
12.
Mr. SATEESHA S.B.
LECTURER
M.PHARMACY
NARGUND COLLEGE OF PHARMACY,
DATTATREYANAGAR, II MAIN,
100 FT RING ROAD, BSK III STAGE,
BANGLORE-85
KARNATAKA
Name & Designation of
(in block letters)
12.1
Co- Guide
K.M Prasad, DGM (Works)
Karanataka Antibiotics and Pharmaceuticals Limited,
No, 14, II Phase, Peenya Industrial Area, Bangalor-
12.2 Signature
13.
13.1 Remarks of the
Principal
560058
RECOMMENDED FOR DISSERTATION WORK
13.2 Signature.
PROF. M.S HARISH
Principal
Nargund college of Pharmacy