Download design and evaluation of fast dissolving oral films of

“DESIGN AND EVALUATION OF FAST DISSOLVING ORAL
FILMS OF GRANISETRON HYDROCHLORIDE”
MASTER OF PHARMACY DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES KARNATAKA,
BANGALORE.
BY
RAWDA KHALIFA ALI
M.PHARM – I
Under The Guidance of
Dr. A. R. SHABARAYA M. Pharm., Ph.D.
DEPARTMENT OF PHARMACEUTICS.
SRINIVAS COLLEGE OF PHARMACY, VALACHIL, MANGALORE – 574143
2010-2012
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1.
Name of the Candidate and
Address:
MS. RAWDA KHALIFA ALI
1st YEAR M.PHARM, DEPT. OF
PHARMACEUTICS,
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, MANGALORE-574143.
2.
Name of the Institution:
SRINIVAS COLLEGE OF PHARMACY,
VALACHIL, FARANGIPETE POST,
MANGALORE-574143.
3.
Course of Study and Subject:
MASTER OF PHARMACY
(PHARMACEUTICS)
4.
Date of Admission:
29th October 2010
5.
Title of the Project:
DESIGN AND EVALUATION OF FAST DISSOLVING ORAL FILM OF
GRANISETRON HYDROCHLORIDE.
6.
Brief Resume of the intended work:
6.1 Need of the study:
Among the various routes of administration, the oral route is the most acceptable for
the patients. Many pharmaceutical companies have directed their research activity in
reformulating existing drugs into new dosage forms. One such relatively new dosage
form is the fast dissolving oral film. The oral mucosa being a highly vascularized,
drugs can be absorbed directly and can enter the systemic circulation without
undergoing first‐pass hepatic metabolism.1
Fast dissolving oral films, a new drug delivery system, was developed based on the
technology of the transdermal patch.
Rapidly dissolving or quick dissolving dosage forms have acquired great importance
in the pharmaceutical industry due to their unique properties and advantages like
availability of larger surface area that leads to rapid disintegrating and dissolution in
the oral cavity ,so there is no need of water, accurate dosing, rapid onset of action,
ease of transportability, ease of handling, pleasant taste and improved patient
compliance especially for paediatric and geariatric.2
Oral film may be preferred over the mouth dissolving tablets in terms of flexibility
and comfort. In addition, they can also circumvent the sticky feeling in the oral
cavity associated with oral gels.3
Granisetron HCl is a 5HT3 antagoinst. It is a novel antiemetic drug, given for
prevention of chemotherapy-induced nausea and for pre-and post-surgical nausea
and vomiting.4
The drug is well absorbed from GIT, but its bioavailability is low due to extensive
first pass metabolism. It is selected as a drug candidate, as it is not available in such
dosage form. And in general, emesis is preceded with nausea and in such condition it
is difficult to administer drug with a glass of water; hence it is beneficial to
administer such drugs as fast dissolving films with good mouth feel.5
In the present study attempt will be made to formulate a “patient friendly” dosage
form of fast dissolving oral film of Granisetron hydrochloride - a possible
application to anti emesis during Cancer Chemotherapy.
6.2 - Review of literature:

Basani G, et.al over viewed on fast dissolving films. They concluded that,
many of the pharmaceutical companies are switching their product franchise
from ODTs to ODFTs. The ODFT is a good tool for product life cycle
management for increasing the patent life of existing molecules or products.
Compared to some of the complicated and expensive process (like
lyophilization) used to manufacture ODTs, the ODFT is relatively easy to
fabricate; thus reducing the overall cost of the therapy.6

Arun A, et.al an innovative fast dissolving oral film drug delivery system and
dosage form. They have concluded that fast dissolving oral films have several
advantages over the conventional dosage forms. So they are of great
importance during the emergency cases such as allergic reactions and
asthmatic attacks whenever immediate onset of action is desired.7

Sumitha C H, et.al has designed a taste masking of Ondansetron
hydrochloride by polymer carrier system and formulation of rapiddisintegrating films. Rapid dissolving film containing taste masked
Ondansetron hydrochloride showed acceptable properties. The drug release
profile indicated that it could be used for the oral delivery of Ondansetron
hydrochloride in chronic and acute post operative or chemotherapy or
radiotherapy induced emesis. Good correlation between in vitro disintegration
behaviour and in the oral cavity was recognized, patient friendly dosage form
has been accomplished.8

Renuka M, et.al has formulated and characterized Rapidly Dissolving Films
of Cetirizine hydrochloride using Pullulan as a Film Forming Agent. It was
concluded that pullullan could be used as film forming polymer for
formulation of rapidly dissolving films containing Cetrizine hydrochloride.
Effective film separation could be achieved using Teflon as a casting surface.9

Nagendra D K, et.al has designed a fast dissolving tablet of Granisetron
hydrochloride using super disintegrant blends for improved efficacy by direct
compression method with a view to enhance patient compliance.10

Choudhary D R, et.al has formulated and evaluated a quick dissolving film of
Levocetirizine dihydrochloride with the aim to have rapid onset of action and
increased bioavailbility in allergic condition. Various cellulose derivatives
like HPMC, CMC, and HPC. Films with 3% HPMC and 10% w/v propylene
glycol showed better results as compared to HPC and CMC. Films showed
good mechanical properties like, tensile strength, folding endurance and %
elongation in comparison to other films prepared by using HPC and CMC.
These results suggest that HPMC is an excellent film former which gives
rapid drug release (80% in 120 sec) amongst different cellulose derivatives
used.11

Yoshifumi M, et.al has prepared a fast dissolving film for oral dosage from
natural polysaccharides. In this study the thickness and surface shape were
affected by the concentration of the material used for film formation. The
films were able to disintegrate quickly in physiological saline.12

Tadao T, et.al has prepared a fast dissolving oral thin film containing
Dexamthasone. This preparation showed excellent uniformity and stability
when stored at 4o degree and 75 in humidity for up to 24 weeks. The film was
disintegrated within 15 seconds after immersion in to distilled water
dissolution study showed that 90% of Dexamethasone was dissolved in 5
minutes.13

Renuka S, et.al has developed a taste masked oral film of Valdecoxib, using
Eudragit EPO and HPMC.The bitter taste of the drug was masked by using
aspartame and menthol accompanied by the synergistic effect of Eudragit and
glycerol. The films containing the higher proportion of glycerol showed
higher water uptake and faster drug release at all the sampling time in the test.
The study revealed that taste masked Valdecoxib films can be developed by
the selection of appropriate film former and by the use of auxiliary
excipients.14

Kulkarni P K, et.al have formulated and evaluated mouth dissolving film
containing Rofecoxib. The film of HPMC and PVA were prepared with an
objective to dissolve the film. It exhibited acceptable film endurance. Time
required for the film to dissolve and release the drug was found to be 30
second and 1 minute respectively. It is concluded that mouth dissolving film
can be a potential novel drug dosage form for poorly water soluble drug.15

Kunte S, et.al has developed a fast dissolving Oral Strips for the delivery of
Verapamil. Thus the patient-friendly dosage form of bitter drugs such as
Verapamil can be successfully formulated using this technology and it
can be especially useful for geriatric, bedridden, and non cooperative patient
due to its ease of administration.16

Chandak, et.al has prepared and optimized a fast dissolving oral Film of
Selegiline hydrochloride which can be useful in Parkinsonism treatment. The
experimental results indicated that polymer concentration; plasticizer
concentration had complex effects on % drug release. It was found that the
optimum values of the responses for fast release film could be obtained at
optimum levels of Poly Vinyl Pyrolidine and low level of propylene glycol.
The results showed that drug dissolve quickly and have good onset of
action.17

Mashru RC, et.al has developed and evaluated a fast dissolving film of
Sulbutamol sulphate. The prepared film was clear, transparent with smooth
surface and has an acceptable mechanical characteristics and satisfactory
% drug release. Tmax for fast dissolving film was lower than that of
conventional tablets. A fast dissolving film of salbutamol sulphate could be
helpful for fast onset asthmatic attack management.18

Cilurzo, et.al evaluated the feasibility of a fast dissolving film made of a
Maltodextrin plasticized by glycerine by solvent free hot-melt extrusion
technology. Loading capacity and the in vivo performances of the film were
assayed by using Paracetamol as model drug because its bioavailability can be
determined.19

Christopher Yu, et.al developed Oral Quick- Dissolving Strips for Rotavirus
Vaccine the novel drug-delivery system is needed because rotavirus is a
common cause of severe diarrhoea and vomiting in children, leading to about
600,000 deaths annually. In addition, newborns sometimes spit out the liquid,
a problem that is less likely to occur with a strip that sticks to and dissolves
on the tongue in less than a minute.20

Nagendra D K, et.al designed a fast dissolving Granisetron hydrochloride
tablets using novel co-processed super disintegrants .It can be concluded from
this study that co-processed super disintegrants of crospovidone and
crosscarmellose sodium are superior to physical mixture of crospovidone and
crosscarmellose sodium used in Granisetron hydrochloride fast dissolving
tablets.21

Venkatalakshmi R, et.al has formulated and evaluated Granisteron
hydrochloride mouth dissolving tablets In vitro dispersion, wetting time and
in vivo dispersion parameters signified that cros povidone in ratio 10 mg per
tablet act as good disintegrants prepared by direct compression method.22
6.3 - Objectives of the study:
Specific objectives of the present study are as follows:
1) To design a fast dissolving oral film of Granisetron HCl.
2) To perform the characterization of the drug.
3) To perform In vitro evaluation studies.
4) To study Drug and excipient interaction.
5) To compare with the marketed dosage forms.
7.
Materials and Methods:
Materials:
1. Drug
: Granisetron hydrochloride.
2. Polymers
: HPMC,E-3,and K-3, Pullulan, CMC, PVP K-90, pectin,
Eudragit etc
3. Plasticizers
: Glycerol, di-butylpthallate, Polyethylene glycol etc.
4. Solvent
: Water or Organic solvent.
5. Flavours
: Intense mint , sour fruit flavour, sweet confectionary flavour
etc
Methods:
Solvent Casting Technique.
Water soluble Polymers are dissolved in water and the drug along with other
excipients is dissolved in suitable solvent using a high shear processor. Flavours are
added. Both mixtures are mixed to form homogenous viscous solution. Suitable
plasticizer was added under constant stirring.
The resultant solution was left over night at room temperature to ensure a clear,
bubble-free solution. The solution was poured out into a glass Petri dish. The coated
film is sent to aeration drying oven. The film is removed. Films of specific size are
cut, packed in aluminium foil and stored in desiccators for evaluation.
7.1 Source of data:
Review of literature from
a) Journals such as
 International Journal of ChemTech Research.
 International Journal of Pharma Professional’s Research.
 Journal of Chemical and Pharmaceutical Research.
 Indian Journal of Pharmaceutical Sciences.
 International Journal of Pharmacy and Technology.
 European Journal of Pharmaceutics and Bio pharmaceutics.
 International Journal of Pharmaceutical Sciences Review and
Research.
 International Journal of Pharmacy and Pharmaceutical Sciences
b) Internet Browsing.
c) Laboratory based studies.
7.2 – Method of Collection of Data:
1. Study of research article
2. Laboratory investigation: Evaluation of fast dissolving oral films which
includes
 Appearance 1
 Weight Variations 2
 Thickness4
 Percentage elongation6
 Tensile strength 4
 Folding endurance 2
 Surface PH1
 Drug content6
 Disintegration/dissolving time2
a. Drug and excipients interaction:
 By FT-IR Spectroscopy
b. In vitro drug release study:
 USP II dissolution by basket method.
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.
- Not applicable
7.4 Has ethical clearance been obtained from your institution in case of 7.3?
-
Not applicable
8.
LIST OF REFERENCES:
1. Basani G, Subash VK, Guru S, Madhusudan R Y. Overview on fast
dissolving films. Int J of Pharmacy and Pharm Sci. 2010;2(3):29-33.
2. Arun A, Amrish C, Vijay S, Kamla P. Fast dissolving oral films:
An innovative drug delivery system and dosage form. Int J of chem Tech
research. 2010; 2(2):576-583.
3. Sumitha CH, Karuna SN, Divya B, Madhavi K, Vimal Kumar Varma M,
Charbe NN .Taste masking of Ondansetron hydrochloride by polymer carrier
system and formulation of rapid-disintegrating films. Int J of Chem research
2009;1(2):24-27.
4. Renuka M, Avani A. Formulation and Characterization of Rapidly Dissolving
Films of Cetirizine hydrochloride using Pullulan as a Film Forming Agent.
Indian J Pharm Educ Res.2011;45(1):72-77.
5. Nagendra k, Raju SA, Shirsand SB, Para MS. Formulation design of novel
fast dissolving tablet of Granisetron hydrochloride using super disintegrant
blends for improved efficacy. Int J of Research n Ayurveda and
pharmacy.2010;1(2):468-474.
6. Choudhary DR, VA Patel, HV Patel, Kundawala AJ. Formulation and
evaluation of quick dissolving film of Levocetirizine dihydrochloride. Int J of
pharmacy and technology.2011;3(1):1740-1744.
7. Yoshifumi M, Takashi I, Kyoko K, Norihisa N, Ryosei K. Preparation of fast
dissolving film for oral dosage from natural polysaccharides.
Materials. 2010;(3):4291-4299.
8. Tadao T, Hirotaka Y, Naoki I, Kazuyuki H, Mayumi Y, Yasutomi k,
Yoshinovi J. Preparation of fast dissolving oral thin film containing
Dexamthasone. Euro J of pharmaceutics and Biopharmaceutics.2009;73(3):
361-365.
9. Renuka S, Pavikh RH, Gohel MC, Soniwala MM. Development of taste
masked film of Valdecoxib for oral use. Indian J of pharm
Sci.2007;69(2):320-323.
10. Kulkarni PK, Dixit M, Gunashekava K, Shahnawaz A, Kulkarni A.
Formulation and evaluation of mouth dissolving film containing Rofecoxib.
Int research J of pharmacy.2011;2(3):273-278.
11. Kunte S, Tandale P. Fast dissolving oral strips for the delivery of Verapamil.
J of pharmacy and Bio allied Sci.2010;2(4):325-328.
12. Mashru RC, Sutariya VB, Sankalia MG, Parikh PP. Development and
Evaluation of Fast Dissolving Film of Salbutamol Sulphate. Ind Pharm
2005;31(1):25–34.
13. Cilurzo F, Cupone IE, Minghetti P. Selmin F, Montanari L. Fast dissolving
films made of Maltodextrins. Eur J Pharm Biopharm. 2008;70(3):895–900.
14. Nagendrakumar D, Raju S.A, Shirsand S.B Para M.S. Design of a fast
dissolving Granisetron Hcl tablets using novel co–processed super
disintegrants. J Biosci Tech.2009;1(1):8-14.
15. Venkatalakshmi R, Sasikala C, Swathi R, Tejaswini G, Srujana.D, Sravan k
Formulation and Evaluation of Granisetron hydrochloride mouth dissolving
tablet. Int. J. Ph. Sci. 2009;1(2):336-341.
16. Kalina, Santacruz E. Formulation and Evaluation of Fast dissolving Films for
delivery of Triclosan to the oral cavity. AAPS Pharm Sci tech. 2008;9(2):349356.
9.
Signature of the candidate
(RAWDA KHALIFA ALI)
10.
Remarks of the Guide
11.
11.1 Name and
Designation of the
Guide
The work, which is assigned to
MS. RAWDA KHALIFA ALI is under my
guidance.
Dr. A. R. SHABARAYA M.Pharm., Ph.D.
Principal and Director,
Srinivas College of Pharmacy
Valachil, Mangalore- 574143
11.2 Signature
11.3 Name and
Designation of the
Co-Guide
-----------
11.4 Signature
-----------
11.5 Head of the
Department
Dr. A. R. SHABARAYA M.Pharm., Ph.D.
Principal and Director,
Srinivas College of Pharmacy,
Valachil, Mangalore- 574143
11.6 Signature
12.
12.1 Remarks of the
Principal
Recommended and forwarded for favourable
consideration.
12.2 Signature
Dr. A. R. SHABARAYA