FORMULATION AND EVALUATION OF ORAL CONTROLLED IN-SITU
GEL FOR ANTI DEPRESSANT DRUG BY USING FACTORIAL DESIGN
SYNOPSIS FOR
M.PHARM DISSERTATION
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
N.SRILATHA
I M.PHARM
UNDER THE GUIDENCE OF
DR.B.PRAKASH RAO
PROFESSOR, HEAD OF THE DEPARTMENT
DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF PHARMACY
BENGALURU-560064
(2010-2011)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA, BANGALORE.
ANNEXURE II
PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION
N.SRILATHA
1
Name of the Candidate and Address
Karnataka College of Pharmacy
# 33/2, Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064.
PERMANENT ADDRESS
D/O: N.V.B.RAO,
H.NO:15-75,
Hanuman nagar. Near Water Tank,
ELURU, W.G.District,
Andhra Pradesh
KARNATAKA COLLEGE OF PHARMACY
2
Name of the Institution
# 33/2, Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064.
3
Course of the Study and Subject
4
Date of Admission
5
TITLE OF THE PROJECT:-
MASTER IN PHARMACY
(PHARMACEUTICAL TECHNOLOGY)
18th OCTOBER- 2010
FORMULATION AND EVALUATION OF ORAL CONTROLLED RELEASE INSITU GEL
FOR ANTI DEPRESSANT DRUG BY USING FACTORIAL DESIGN
1
6
BRIEF RESUME OF INTENDED WORK:-
6.1
NEED FOR THE STUDY:Oral administration of drugs has the most common and preferred route for delivery of the most of
the drugs. In recent years oral controlled delivery (OCD) systems have gained increased importance and
interest since it is necessary to improve the systemic absorption of the drugs and patient compliance. In
addition, OCD systems maintain uniform drug levels, reduce dose, side effects and increase the safety.
The oral in-situ gel forming polymeric drug delivery systems are designed with an objective to
retain in stomach for an extended time period and also for achieving systemic drug effects over than
other pharmaceutical dosage forms.
In-situ gel forming polymeric drug delivery systems have shown some advantages such as easy
of administration, reduced frequency of administration, improved patient compliance and comfort and
In-situ gels are prepared to overcome the rapidly increasing cost and to reduce the time required in the
development works over than the other pharmaceutical dosage forms.
In situ gels formations occurs due to one or more combination of different stimuli like pH change,
temperature modulation and solvent exchange.
Insitu gel forming drug deliveries are a revolution in oral drug delivery system. The hydrogels are liquid
at room temperature but undergo gelatin when in contact with body fluids or change in pH. This gelatin
involves formation of double helical junction zones followed by aggregation of double helical segments
two form three dimensional complexes network with cations and hydrogen bonding.
Attention deficit hyperactivity disorder (ADHD) is a problem with inattentiveness, over-activity,
impulsivity or combinations of these problems are diagnosed as ADHD.
ADHD is most commonly diagnosed behavioural disorder of childhood. It affects about 3-5% of
school aged children. It is diagnosed much more often in boys than children.
Imagining studies suggest that the brains of children with ADHD are different from those of other
children. These children handle neurotransmitters (including dopamine, serotonin and adrenaline)
differently from their peers.
Disorders like depression, lack of sleep, learning disabilities, tic disorders, and behavior problems
may be appeared with ADHD. They may also have another psychiatric problem, such as depression or
bipolar disorder.
2
6.2
REVIEW OF LITERATURE:

It was explained the properties and importance of various polymers used in certain drug delivery
systems based on their drug releasing properties (Ankita 2002)

It was formulated in-situ gelling system for periodontal anaesthesia containing chitoson
(0.25%w/v) and hydroxyl propyl methyl cellulose (0.25%w/v) polymer system. It has good
gelling properties at pH7.5 and provides prolonged action (Gupta 2008)

It was formulated and evaluated the oral in-situ gel containing clotrimazole for oral candidiasis
based on the pH triggered and ion activated systems. Triggered system consisting of
carbopol934P(0.2-1.4%w/v) and ion activated system using gellan gum(0.1-o.75%w/v) and
hydroxyl propyl methyl cellulose E50LV for prolonged release of drug and carried out
evaluation studies for gelling capacity, pH, viscosity, clarity, gel strength and in -vitro studies,
microbial studies (Harish 2009)

It was developed and evaluated pluronic and chitosan based in-situ gel system for periodontal
application by explaining the behaviour of in-situ gel at pH 6 and temperature 25oc it is in liquid
form, then converted into gel at body pH and temperature ( pH 7.4, 37oc ) based on the polymeric
system like as chitosan ( pH stimulant) combination with pluronic F-127 (temperature stimulant)
and also explained to check the efficacy of the developed in-situ gel by using prilocaine
hydrochloride as the model drug (Himanshu 2009)

It was explained the formulation and examination thermo-responsive and bio adhesive in-situ
gelling drug delivery system containing fluconazole, which can be used in oral thrush. Bio
adhesive polymer was used as a thermo responsive material, because poloxmer188 and
carbopol934 has thermal gellation properties at certain temperature (jaya raj kk 2010)

It was formulated and developed in-situ forming polymeric drug delivery systems by using
various types of polymers including gellan gum, alginic acid, xyloglucon, pectin, chitosan, poly
caprolactone, poly(DL-lactic acid),poly(DL-lactide-glycoside) etc; and also explained selection
of solvents(water, dimethylsulphoxide, N-methyl pyrrolidone,2-pyrrolidone etc;) depends on the
solubility of polymers (Madan M 2009)

It was designed and evaluated oral in-situ gelling system for sustained release drug delivery of
3
famotidine, in-vitro release study revealed that drug released from the in-situ gel followed nonfickian diffusion. In vivo study for the sodium alginate was carried out by pylorus legation
method in rats, which showed gel formation in gastric juice and reduction in ulcer index.
Stability study was also carried out for three months, which showed no major changes from their
initial state (Moin KM 2010)

It was designed and has done research on in-situ forming polymeric drug delivery system to
reduce the frequency of administration, improved patient compliance and comfort, formulations
developed based on the factors are temperature modulation, pH range, presence of ions and
ultraviolet irradiation (Nirmal HB 2009)

It was formulated, optimized and evaluated of sodium alginate based in-situ gel of clarithromycin
and metronidazole benzoate. Sodium alginate used as a polymer and CaCO3 was used as a crosslinking agent, this formulations exhibits good viscosity properties and sustained drug release and
explained accelerated stability studies (Patel RP 2010)

It was developed, evaluated and optimised the in-situ gel formulation by using 33 factorial design
to retain in the stomach for extended period of time based on the three independent factors:
concentrations of like gellan gum(x1), sodium alginate(x2) and anti-diabetic drug metformin(x3)
and also considered five dependent variables are release exponents (Y1), dissolution
efficiency(Y2), drug release at 30min(Y3), drug release at 210min(Y4), drug release at
480min(Y5). Three dimensional surface response plots were drawn to evaluate the interaction of
independent variables on the chosen dependent variables. Three factorial levels coded for low,
medium, and high settings (−1, 0 and +1, respectively) were considered for three independent
variables (Ramesh CN 2009)
4
6.3
OBJECTIVE OF THE STUDY:The objectives of the present research work was to develop controlled release of in situ gel for anti
depressant drug for ADHD disease by using factorial design
6.4
PLAN OF WORK:1) Survey of literature
2) Procurement of chemicals
3) Pre-formulation studies.
4) Optimization.
5) Formulation of oral in-situ gel by suitable method.
6) Evaluation of oral in-situ gel for their physicochemical studies (Viscosity, Clarity, Gel
Strength, Gelling capacity, Gellation pH ,temperature, and In-vitro studies) and
7) Stability studies for selected formulations.
8) Thesis preparation
7
MATERIALS & METHODS:-
7.1
SOURCE OF DATA:•
Review of literature from:
Journals such as:
•
Indian Journal of Pharmaceutical Sciences
•
International Journal of drug delivery
•
International Journal of Pharm Tech research
•
International Journal of Pharma. Research and development
•
Journal of Biomedical Sciences and Research
•
Asian Journal of Pharmaceutics
Web sites :
• World Wide Web.
• J-Gate@Helinet
• Science Direct
• Khup.com
5
7.2
Materials
Anti diabetic drug and polymers will be procured from Pharma grade suitable manufacturer. Other
reagents will be of Analytical grade.
7.3
Methods
1) Preparation of oral in-situ gel by simple mixing method.
2) Evaluation
a) clarity
b) solution-gel transition temperature and gelling time
c) gel- strength
d) viscosity
e) pH
f) in-vitro drug release studies
g) Microbial studies.
3) Stability studies as per ICH guidelines
7.4
Method of collection of data (including sampling procedures if any):
The data will be collected from prepared formulations subjected to different evaluation
techniques, scale-up techniques and stability studies obtained from ICH guidelines.
[[
7.5
Does the study require any investigation or interventions to be
Conducted on patients or other humans or animals?
- Dose Not Required-
7.6
Has ethical clearance been obtained from your institution in case of
7.5?
-NO-
6
8
LIST OF REFERENCES:1. Ankita R, Anil B, Brijesh K. Polymers in drug delivery. Int J Pharm Res Dev 2002 Oct; 2(8):920.
2. Gupta H, Singh RM, Singh GN, Kaushik D, Sharma A. PH-induced in-situ gel for periodontal
anaesthesia. Indian J Pharm Sci 2008 Dec; 70(6):776-8.
3. Harish NM, Prabhu P, Charyulu RN, Gulzar MA, Subrahmanyam EVS. Formulation and
evaluation of in-situ gels containing clotrimazole for oral candidiasis. Indian J Pharm Sci 2009
Jul-Aug; 10(8):421-7.
4. Himanshu G, Arti S, Birendra S. Pluronic and chitosan based in-situ gel system for periodontal
application. Asian J Pharm Sci 2009 Apr-Jun: 94-6.
5. Jaya raj KK, Jayachandran E, Srinivas GM, Giridhar B, Rahul N, Jayakandan M. A Novel
thermo-sensitive sol-gel reversible buccal adhesive property of fluconazole in situ gel for oral
thrush. J Biomed Sci and Res 2010; 2(2):100-9.
6. Madan M, Bajaj A, Lewis S, Udupa N, Baig JA. In-situ forming polymeric drug delivery
systems. Indian J Pharm Sci 2009 May-Jun; 71(2):242-51.
7. Moin KM, Bupendra GP, Vishnu MP, Patel2 JK. Sodium alginate based in-situ gelling system of
famotidine preparation and in-vivo characterizations. e-J SciTech 2010 Sep;5(5):67-82
8. Nirmal HB, Bakliwal SR, Pawar SP. In-situ gel: new trends in controlled and sustained drug
delivery system. Int J PhamTech res 2010 Apr-Jun; 2(2):1398-408.
9. Patel RP, Dadhani B, Ladani R, Baria AH, Patel J. Formulation, evaluation and optimization of
stomach specific in situ gel of clarithromycin and metronidazole benzoate. Int J Drug Deliv
2010; 2:141-53.
10. Ramesh CN, Srinatha A, Jayanta KP. In-situ forming formulation: development, evaluation and
optimization using 33 factorial design. AAPS PharmSciTech 2009 Sep; 10(3):977-84.
7
9
Signature of the Candidate
(N.SRILATHA)
10
Remarks of the Guide:
11
Name And Designation
11.1
Guide
11.2
Signature of the Guide
The topic selected for dissertation is satisfactory. Adequate
equipments and chemicals are available to carry out the
project work
DR.B.PRAKASH RAO
DEPARTMENT OF
PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64
(DR.B.PRAKASH RAO)
11.3
Co- Guide
11.4
Signature of the Co- Guide
11.5
Head of the Department
-NOT APPLICABLE-
-NOT APPLICABLE-
DR.B.PRAKASH RAO
HEAD OF THE DEPARTMENT OF
PHARMACEUTICAL TECHNOLOGY
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64
8
11.6
Signature of the HOD
(Dr. B.PRAKASH RAO)
12
12.1
Remarks of the Principal
12.2
Principal/DIRECTOR
All the required facilities will be provided to carry out
dissertation work under the supervision of the Guide.
DR.K. RAMESH.
DIRECTOR
KARNATAKA COLLEGE OF PHARMACY
#33/2, THIRUMENHALLI
HEGDE NAGAR MAIN ROAD
BENGALURU-64.
12.3
Signature of the
Principal/DIRECTOR
(DR.K.RAMESH)
9