Download formulation and evaluation of oral fast dissolving films of salbutamol

FORMULATION AND EVALUATION OF
ORAL FAST DISSOLVING FILMS OF
SALBUTAMOL SULPHATE
SUBMITTED BY
SYED SHAHABUDDIN SAQQUAF
DEPARTMENT OF PHARMACEUTICS
DISSERTATION PROTOCOL
SUBMITTED TO THE
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE - 560041
KARNATAKA
UNDER THE GUIDANCE OF
VASEEHA BANU T. S.
ASST.PROFESSOR
DEPARTMENT OF PHARMACEUTICS
M.M.U. COLLEGE OF PHARMACY
RAMANAGARAM - 562159
KARNATAKA
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,
KARNATAKA, BANGALORE.
Annexure-I
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1
NAME OF THE CANDIDATE AND
ADDRESS (IN BLOCK LETTERS)
2. NAME OF THE INSTITUTION
3
COURSE OF STUDY AND SUBJECT
4. DATE OF ADMISSION OF COURSE
5. TITLE OF TOPIC
SYED SHAHABUDDIN SAQQUAF
S/O SYED SHAH MOHAMMED SAQQUAF
#10-2-7A,Saqquaf Rouzha, Masjid Mohalla,
Ramanagaram - 562159
M.M.U COLLEGE OF PHARMACY
K.K. DODDI, RAMADEVERA BETTA
ROAD, RAMANAGARAM – 562159
M. PHARM 1st Year
Dept. of Pharmaceutics.
12/12/2011
FORMULATION AND EVALUATION OF
ORAL FAST DISSOLVING FILMS OF
SALBUTAMOL SULPHATE.
6. BRIEF RESUME OF THE
INTENDED WORK
6.1 Need for the study
ENCLOSURE-I
6.2 Review of the literature
ENCLOSURE-II
6.3 Objectives of the study
ENCLOSURE-III
7. MATERIALS AND METHODS
7.1 Source of data
ENCLOSURE-IV
7.2 Method of collection of data
ENCLOSURE-V
7.3 Does study require any
Investigations or interventions to be
conducted on patients or Other
human or animal? If so, Please
describe briefly.
ENCLOSURE-VI
ENCLOSURE-VII
7.4 Has ethical clearance been
obtained from your institution in
case of 7.3
8. LIST OF REFERENCES
ENCLOSURE-VIII
9
SIGNATURE OF CANDIDATE
10. REMARKS OF GUIDE
Recommended for approval
11. NAME AND DESIGNATION OF
11.1 Guide
VASEEHA BANU. T.S
ASST. PROFESSOR,
DEPT. OF PHARMACEUTICS,
M.M.U. COLLEGE OF PHARMACY,
K.K. DODDI, RAMADEVERA BETTA
ROAD, RAMANAGARAM - 562159
KARNATAKA.
11.2 Signature
11.3 Co guide (if any)
11.4 Signature
11.5 Head of department
Not applicable
Not applicable
Mr. VAZIR ASHFAQ AHAMED
HEAD OF THE DEPARTMENT,
DEPARTMENT OF PHARMACEUTICS,
M.M.U COLLEGE OF PHARMACY,
K.K DODDI, RAMADEVERA BETTA
ROAD, RAMANAGARAM - 562159
KARNATAKA.
11.6 Signature
12
12.1 Remarks of the
Chairman and principal
12.2 Signature
SUBMITTED FOR APPROVAL
6.
BRIEF RESUME OF THE INTENDED WORK
ENCLOSURE-I
6.1
Need for the study.
Among the delivery routes, oral route is the most preferred route for the
delivery of the drug till date due to easy of ingestion, pain avoidance and
versatility1, 2. But oral drug delivery system still need some advancements to be
made because of their some drawbacks related to particular class of patients which
includes geriatric, pediatric and dysphasic patients as they have difficulty in
swallowing or chewing and due to fear of choking solid dosage form3. The lower
bioavailability, long onset time and dysphagia, patients turned the manufacture to
the parental and liquid orals. But the liquid orals have the problem of accurate
dosing mainly and parental are painful drug delivery, so most patients
incompliance.4
To overcome the problems associated with solid, liquid and parenteral dosage
form a novel oral dosage form is formulated know as fast dissolving oral films
(FDOFs). FDOFs are the most advanced form of oral solid dosage form due to
more flexibility and comfort. It improve the efficacy of active pharmaceutical
ingredients (APIs) by dissolving with in minute in oral cavity after the contact
with saliva without chewing and no need of water for administration. It gives
quick absorption and instant bioavailability of drugs due to high blood flow and
permeability of oral mucosa.5
Salbutamol Sulphate, (RS)-l-{4-hydroxy-3-hydroxymethyl phenyl)-2-(tertbutylamino)
ethanolSulphate,
Salbutamol
Sulphate
is
a
selective
β 2-
adrenoreceptor agonist, at therapeutic doses, it acts on the β2- adrenoreceptors of
bronchial muscle with little effect on β1- adrenoreceptor of cardiac muscle. With
its fast onset of action, it is particularly suitable for management and prevention of
attack in mild asthma and for the treatment of acute exacerbations in moderate and
severe asthma. It is readily absorbed from the Gastro intestinal track, the plasma
half-life is 1.6hrs. It is subjected to first pass metabolism in the liver. The
prescribed dose of the drug is low (100-400mcg), from the above points it is clear
that Salbutamol Sulphate is a suitable drug to prepare as oral fast dissolving films.
The aim of the proposed work is to formulate oral fast dissolving films of
Salbutamol Sulphate as it is not available in such dosage form to provide better
therapeutic profile, than that of other routes.
ENCLOSURE II
6.2
Review of literature
1. Gavaskar B, Kumars SV, Sharan G, Rao YM. Prepared oral dissolving film
technology (ODFTS) that can administrated in the buccal cavity for a shorter
period of time (i.e., in seconds) and gives better therapeutic action. The
methodologies used in the development of ODFTS for pediatric and geriatric
patient’s population, who are difficult in swallowing larger dosage forms, this
technology has been used for local action, rapid release products. ODFT
offers an alternate platform for molecules that undergoes first pass
metabolism.6
2.
Prasanthi N.L, Sowmya C, Krishna M, Gupta E. In this study sublingual fast
dissolving films for an antiasthamatic drug, were prepared by solvent
evaporation technique using different water soluble polymer. The Tween 80
is used as a solubilizing agent and an Aspartame is used as a sweetener. The
prepared films were evaluated for thickness, uniformity in drug content,
folding endurance, and disintegration time, swelling index, moisture loss, invitro drug release studies and drug-polymer compatibility studies. The results
obtained showed that the prepared films were clear, transparent and smooth
surface. Film containing hydroxyl propyl methylcellulose (2%w/w), Tween
80 (0.5%w/w) and Aspartame (0.5% w/w) showed optimum performance
against all other prepared formulations.7
3. Mishra R and Avani A. In this study rapidly dissolving films of cetirizine
hydrochloride were formulated by solvent casting method using pullulan as
films forming polymer the prepared films were evaluated for the effect of
type of casting surface and plasticizer as film separation and taste masking
properties. The result revealed that the prepared films exhibited satisfactory
thickness, tensile strength, percentage elongation and elastic modulas. In vitro
dissolution studies and In vitro disintegration studies were found to be
satisfactory.8
4. Manish Kumar, Garima G, Pushpendra Kumar, Kulkarni G.T. In this study
buccal patch for systemic administration of famotidine in the oral cavity has
been developed using hydroxy propyl methyl cellulose, sodium carboxy
methylcellulose (SCMC) and polyvinyl alcohol by solvent casting method.
The patches were evaluated for their physical characteristics like weight
variation, thickness, drug content uniformity, surface pH, folding endurance,
tensile strength, mucoadhesion strength, In vitro release studies were
conducted for famotidine patches in phosphate buffer (pH, 6.6) solution.
Patches exhibited drug release in the range of 72.58 to 91.91% in 20 min.9
5. Choudhury A, Sujoy Das, Dhangar S, Sumit K, Kanango A. In this study
sustained release films of ciprofloxacin hydrochloride were formulated for
the treatment of periodontal diseases. Films were formulated using different
concentration of hydroxyl propyl methyl cellulose and polyvinyl alcohol. The
prepared films were subjected to different evaluation like determination of
weight, thickness, surface pH, folding endurance, swelling index,
mucoadhesion time, mucoadhesion strength, drug content, in vitro drug
release study, ex-vivo release study and release kinetic behavior. From the
results of evaluation it was concluded that all the prepared films having desire
flexibility and mucoadhesive properties, along with that they shows good invitro and ex-vivo drug release performance. Drug release from the films
follows desire sustained release phenomenon as needed in buccoadhesive
drug delivery.10
6. Vijay kumar G, Ajay kumar P, Satish kumar P, Karunasri, Sri konda,
Raghavender K and Priya P . In this study Montelukast sodium fast
dissolving films were prepared by solvent casting method using HPMC as
film base with different concentrations of super disintegrates like
microcrystalline cellulose (MCC) and crospovidone using PEG400 as
plasticizer. The Compatibility of the drug in the formulation was confirmed
by IR and DSC studies. Scanning electron Microscopy revealed the
morphology of the films. In vitro dissolution studies and mechanism of drug
release was identified. The data demonstrated that 4% crospovidone and 10%
MCC with 4% HPMC as a film base was suitable for developing fast
dissolving films of Montelukast sodium.11
7. Dhagla RC, Vishnu A, Usmangani KC, Harsha V Patel, Aliasgar J
Kundawala. To developed fast dissolving films of levocetirizine for the
treatment of acute allergic rhinitis and chronic urticaria to produce faster on
set of action. Fast dissolving films were prepared by solvent casting method
using different grades of methocel K3, E3, E5, and E15 as film former and
PG, PEG 400 and tween 80 as plasticizer. Bitterness of levocetirizine was
masked by forming inclusion complex with HPBCD. The complex was
evaluated by XRD, DSC and FT-IR. Optimized films were evaluated form
mechanical properties, The research work done here suggested the exciting
possibility of levocetirizine as fast dissolving film.12
8.
Takashi Isobe, Kyoko K, Nishid. Fast dissolving films (FDFs) were prepared
from natural polysaccharides, such as pullulan, without heating, controlling
the pH, or adding other materials. The release profiles of model drugs from
the films were investigated. In the absence of a drug, the casting method and
subsequent evaporation of the solvent resulted in the polysaccharide forming
a circular film. The presence of drugs (both their type and concentration)
affected film formation. The thickness of the film was controllable by
adjusting the concentration of the polysaccharide, and regular unevenness
was observed on the surface of 2% pullulan film. All films prepared with
polysaccharides readily swelled in dissolution medium, released the
incorporated compound, and subsequently disintegrated. Therefore, FDFs
prepared from polysaccharides could be promising candidates as oral dosage
forms containing drugs, and would be expected to show drug dissolution in
the oral cavity.13
9. Koland M, Sandeep VP and Charyulu NR. In this study formulation and
evaluation of fast dissolving films of ondansetron hydrochloride for
sublingual administration. The films were prepared from polymers such as
polyvinylalcohol, polyvinyl pyrrolidone, Carbopol 934P in different ratios by
solvent casting method. Propylene glycol or PEG 400 as plasticizers and
mannitol or sodium saccharin as sweeteners were also included. The films
showed Satisfactory results were obtained when subjected to physicochemical tests such as uniformity of weight, thickness, surface pH, folding
endurance, uniformity of drug content, swelling index, bioadhesive strength,
and tensile strength. Films were also subjected to in vitro drug release studies
by using USP dissolution apparatus. The stability studies conducted for a
period of 8 weeks showed no appreciable change in drug content, surface pH,
and in vitro drug release.14
10. Kunte S, Tandale P. In this study the fast dissolving strips were prepared by
solvent casting technique with the help of HPMC E6 and maltodextrin. The
strips were evaluated for drug content uniformity, film thickness, folding
endurance, in vitro disintegration time, in vitro dissolution studies, surface pH
study, and palatability study of verapamil. The result rerealed that varapamil
fast dissolving strips can be made by solvent casting technique with enhanced
dissolution rate, taste masking, and hence better patient compliance and
effectivetherapy.15
ENCLOSURE-III
6.3
Objectives of the study
1. The main objective of the present study is to formulate and evaluate oral fast
dissolving films (OFDFs) of Salbutamol Sulphate.
2. To select suitable polymer for formulation of Salbutamol Sulphate oral fast
dissolving films.
3. To evaluate physicochemical properties for the prepared formulation.
4. To carry out in vitro release study of oral fast dissolving films.
7
ENCLOSURE-IV
MATERIAL AND METHODS:Material:Drug:
Salbutamol Sulphate.
Polymer:
HPMC (E-3, E-5, K-15), Methyl cellulose, Carboy methyl cellulose,
Pullulan etc.
Plasticizer: Polyethylene glycol 400, etc.
Method of Preparation:Salbutamol Sulphate oral fast dissolving films will be prepared by any one of
the following methods.


Solvent casting
Semisolid casting


Hot melt extrusion
Solid dispersion extrusion Rolling
7.1Sources of Data:1) Review of literature from :
a. Journals : such as
- Indian journal of pharmaceutical sciences.
-International journal of comprehensive pharmacy.
- International journal of pharmaceutical research.
-European journal of pharmaceutical sciences.
- International journal of pharmaceutical sciences and Nanotechnology.
b. Internet browsing.
2) Library: M.M.U College of Pharmacy.
3) Laboratory based studies.
ENCLOSURE-V
7.2. Method of Collection of Data
Data on drugs, their property of oral fast dissolving film of Salbutamol Sulphate.
Studies are to be collected through literature survey by reviewing several research
articles and physiochemical databases. Extensive pre-formulation trials would
provide in the selection of excipients and other ingredients’. Such as below.
1.
Pre-formulation study







2.
Drug excipient compatibility studies.
Identification of drug.
PH determination.
Melting point determination.
Solubility.
Preparation of standard cure of Salbutamol Sulphate using UVVisible spectroscopy.
The films will be evaluated for...



Uniformity of film thickness.
Tensile Strength.
Percentage elongation of the films.







Folding endurance.
Percentage moisture absorption.
Percentage moisture loss.
Drug content uniformity.
Disintegration time.
Surface PH study.
In-Vitro release profile of formulated films.
ENCLOSURE-VI
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-
ENCLOSURE-VII
7.4. Has ethical clearance been obtained from your institution in case of 7.3?
-NOT APPLICABLE8
ENCLOSURE-VIII
LIST OF REFERENCES
1. Bhyan B, Jangra S, Kaur M, Singh H. orally fast dissolving films:
innovations in formulation and technology. Int J pharmaSci, Rev & Res.
2011; 9(2): 50-57.
2. Dixit RP, Puthli SP. oral strips technology: overreview and future potential
journal of control release. 2009; 139: 94-107.
3. Patel R, Prajapati S, Raval A. fast dissolves films (FDFs) as a newer
venture in fast dissolving dosage forms. Int J Drug Dev. & Res 2010; 2(2):
232-236.
4. M.D nehal Siddiqui, Garima G. and Promod Kumar S. A noval approach in
oral fast dissolving Drug delivary system and their Patent. Advance in
Biological Research. 2011; 5(6): 291-303.
5. Ventolin remains a breath of fresh air for asthma suffers, after 40 years”.
The Pharmaceutical Journal. 279 (7473); 404-405.
6. Gavaskaar B, Vijay kumar S, Sharan G, Madhusudan Y, Rao. Overview on
fast Dissolving Films. Int. J. pharmacy and pharma. Sci.2012; 3(2): 47-52.
7. Prasanthi N.L, Sowmya C, Krishna, Eswar Gupta M, Manikiran S.S and
Rama Rao. Design and development of fast dissolving films for an
Antiasthmatic drug. Der pharmacia letter. 2011; 3(1): 382-395.
8. Mishra R and Avani A. Formulation and Characterization of Rapidly
Dissolving Films of Cetirizine hydrochloride using Pullulan as a Film
Forming Agent. Indian J of pharma & research. 2010; 342-348.
9. Manish K, Garima G, Pushpendra K, G.T Kulkarni. Design and in vitro
Evaluation of Muco adhesive Buccal film containting Fomotidine. Int J of
pharma Sci. 2010; 2(3): 105-108.
10. Koland M, Sandeep VP and Charyulu NR. Development and
Characterization Buccoadhesiv Film of Ciprofloxacin Hydrochloride. Int J
pharma tech, 2010; 2(2): 1050-1057.
11. Vijaykumar G, Ajaykumar P, Satishkumar P, Sri konda K, Raghavender K
and Priya P. Developement and evaluation of fast-dissolving film of
Montelukast sodium. Journal of medical pharma & bio- Sci. 2011;1(1): 0612.
12. Dhagla R C, Vishnu Patel A, Usmangani K C, Harsha Patel V, Aliasgar
Kundawala J. Formulation and Evaluation of Fast Dissolving Film of
Levocetirizine Dihydrochloride Using Different Grades of Methocel.
Journal of pharma.2011;4(9): 2919-2924.
13. Takashi Isobe, Kyoko K, Nishid. Preparation of Fast Dissolving Films for
Oral Dosage from Natural Polysaccharides. Ind j Pharm Sci. 2010; 3(8):
4291-4299.
14. Koland M, Sandeep VP and Charyulu .Fast Dissolving Sublingual Films of
Ondansetron Hydrochloride: Effect of Additives on in vitro Drug Release
and Mucosal Permeation, Int J pharma, sep 2010; 2(3): 216-222.
15. Kunte S, Tandale P. Fast dissolving strips: A novel approach for the
delivery of verapamil. Dept of pharma Sci, 2010; 2(4): 325-328.