Ahirwar Varsha, Dr. Khushwant S. Yadav, Dr. Shailendra
Bindaiya
Rajeev Gandhi College of Pharmacy, Bhopal (M.P)
Rajiv Gandhi Proudyogiki Vishwavidyalaya, Bhopal
(M.P.)
*Corresponding Author E-mail: varsha.ahirwar2010@gmail.com
ABSTRACT:
Our
studies on the performance of formulation development and evaluation of fast
dissolving films of Oloptadine HCL its anti-allergic drug. Prepare mouth
dissolving film of Oloptadine HCl by solvent casting method. To characterize
the prepared mouth dissolving film of Oloptadine HCL in terms of— Thickness,
percent elongation, tack test, swelling index, in-vitro disintegration time and
dissolution test. Oloptadine OLO), 11-[{z}-3-(Dimethlamino)
propylidene]-6-11-dihydrobenz [b, e] oxepin-2-acetic acid hydrochloride, is
widely used as an antihistaminic. Oloptadine HCL is a relatively selective
histamine H1-receptor antagonist that inhibits the release of histamine from
mast cells. Oloptadine does not affect alpha-adrenergic dopamine, muscarinic
type 1 and 2 or serotonin receptor. They are hydrophobic in nature and
non-polar, sparingly soluble in water and freely soluble methanol, ethanol.
Olopatadine HCl is a mouth dissolving film. We is trying to sort out the
problem of allergic. They are rapidly onset of action, when placed upon the
tongue that it is disperse rapidly swallowing within 3-5 seconds without need
of water or chewing.
KEYWORDS: Fast dissolving film, solvent casting method, freely
soluble, onset of action.
1.
INTRODUCTION:
Fast dissolving oral films are the most advanced form
of oral solid dosage form due to more flexibility and comfort. It improve the
efficacy of active pharmaceutical ingredients’ (Al’ls) by dissolving within
minute in oral cavity after the contact with saliva without chewing or 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
is 4-l000 time greater than that of skin.
Recent development in the technology has presented
viable dosages alternatives from oral routes for pediatrics. Geriatric,
bedridden, nauseous or non, compliant patient. Fast dissolving drug delivery
systems were first developed in the late 1970s as an alternative to tablet,
capsule and syrup for pediatric and geriatric patient 'who experience
difficulties swallowing traditional oral solid dosage forms.
In US market OTC films of pain management and motion
sickness are commercialized. More importantly, prescription OTFs have now been
approved in US, EU and Japan which are the three major regions. These approved
Rx films, have potential dominate over dosage forms of the same drugs, it seems
that the value of the oral thin films market will grow significantly.
2. RELATED WORK:
In this work authored described about, give an idea
on to prepare films. Salicylic acid and theophylline were
incorporated into cast chitosan Films as model acidic and basic drugs.1
the penetration rate of Lidocaine (LC) through excised oral mucosa from hamster
cheek pouch and the in vitro release rate of LC from film dosage forms with hydroxypropylcellulose
(HPC) as a film base2 developed a fast-dissolving film made of low
dextrose Equivalent maltodextrins (MDX) containing nicotine
hydrogen tartrate salt3 prepared fast dissolving film of pioxicam
using maltodextrin with low dextrose equivalent as film forming using casting
and solvent evaporation method. Fast dissolving films of piroxicam showed high
loading capacity of dose with dissolution rate.4 The fast dissolving
films of rofecoxib by solvent casting method by use of HPMC as polymer. They
concluded that mouth dissolving films containg rofecoxib 4%w/v of PVA film
exhibited revive tensile strength, folding endurance and percentage elongation.5
3. METHOD AND MATERIALS:
Materials-
1.
Olopatadine HCL
2.
Hydroxy propyl methyl cellulose (HPMC-15)
3.
Maltodextrin (DE-20)
4.
Propylene glycol
5.
Glycerine
6.
Menthol
7.
Di sodium hydrogen phosphate
8.
Potasium dihydrogen phosphate
9.
Sodium chloride
10. Ethanol
11. Methanol
Method-
One
of the following processes may be used to manufacture the oral films-
1-Solvent
casting method:
Fast
dissolving buccal films are preferably formulated using the solvent casting
method, where by the water soluble ingredient are dissolved to form a clear
viscous solution and the drug along with other excipients is dissolved in
suitable solvent then both the solutions are mixed and stirred and finally
casted into the Petri plate and dried.
2-Hotmelt
Extrusion:
Usually,
when designing RDFs, polymers with low molecular weight or viscosity, such as
HPMC E5, HPMC E15 and Malt dextrin are preferred. A combination of various
grades of polymer may also be used to achieve desired physical properties.
3-Semisolid
Casting method:
Solution
of water soluble film forming polymer is prepared resulting solution is added
to a solution of acid insoluble polymer (e.g. cellulose acetate phthalate,
cellulose acetate butyrate) appropriate amount of plasticizers is added so that
gels mass obtained finally the gel mass is casted into the films or ribbons
using heat controlled drums. The thickness of the films should be about
0.015-0.05inches.
4-Rolling
method:
In
this method the films is prepared by preparation of a pre-mix, addition of an
active and subsequent formation of a film
Evaluation:
The
fast dissolving films of Olopatadine HCL were evaluated for the following
properties-
1.
Morphology of film
2.
Foulding endurance of film
3.
Surface of pH of film
4.
Petridis method
5.
Percent elongation
6.
Tensile strength
7.
Weight uniformity of film
8.
Thickness of film
9.
Drug content uniformity
4.
EXPERIMENTS AND RESULTS:
Method
Development:
1.
Determination of solubility.
2.
Selection of solvent system.
3.
Study of spectra of drug and selection of
suitable method.
4.
Wavelength selection for linearity study.
5.
Linearity range and calibration graph.
Solubility:
Solubility
of drug was observed by dissolving in different solvents.
Table
1- Solubility of Oloptadine HCl
S. No
|
Solvent |
Solubility of Drug Oloptadine HCl |
|
1 |
Water |
Sparingly Soluble |
|
2 |
Methanol |
Soluble |
|
3 |
Ethanol |
Soluble |
|
4 |
Acetone |
Soluble |
|
5 |
Acetonitrile |
Soluble |
Selection
of Solvent System:
The
solution of Oloptadine HCl were prepared in various solvent systems and scanned
over the UV range (200-400) in spectrum mode at slow scan speed, distilled
water and Methanol was selected as the best solvent system. The Methanol is
selected because-
1. Drug is soluble in it.
2. Drug is stable in it.
Study
of Spectra and Selection of Suitable Method:
From
stock solution concentration of 10µg/ml for Oloptadine HCL was prepared. Drug
was scanned over the range of 200-400nm, while studying the spectra it was
observed that Oloptadine HCL shows maximum absorbance at 290.5nm, drug can be
estimated by simple direct measurement of absorbance at its l max.
Selection
of Wavelength for Linearity:
The
wavelength was selected, to study the linearity of Oloptadine HCL in the
maximum absorbance maxima (λmax). i.e. λ max of Oloptadine
HCl: 290.5nm
Linearity
and Calibration Graph:
[A]
Linearity Range:
Different
dilutions of Oloptadine HCl between 0-100 µg/ml were scanned at their λmax
in UV range and found that Oloptadine HCl follow linearity between 2-10µg/ml.
[B]
Calibration Graph:
Accurately
weighed 50mg Oloptadine HCl was transferred into 50ml volumetric flask and
dissolved in Methanol, then volume was made up to 50ml with Distilled Water to
get a concentration of 1000µg/ml (Stock-A). 2.5ml of stock-A of Oloptadine HCl
was taken in 25ml volumetric and diluted up to 25ml to get concentration of
100µg/ml (Stock-B). Finally from stock solution-B different of 2, 4, 6, 8 and
10µg/ml were prepared for analysis. Absorbance’s were observed at 290.5nm.
(Table5.3). Linearity was observed by the linear regression equation (Figure.
5.2) and correlation coefficient was found to be 0.999.
Preparation
of Standard Solution for Calibration Graph:
From
the stock solutions B aliquots diluted up to 25 ml with Distilled water to
obtain the concentrations
Table
2-: Preparation of Standard Solution for Calibration Graph
|
Volume taken in Ml from Stock B |
Conc. (µg/ml) |
|
0.5 |
2 |
|
1.0 |
4 |
|
1.5 |
6 |
|
2.0 |
8 |
|
2.5 |
10 |
Table
3-: Linearity for at 290.5nm
|
Conc. (µg/ml) |
Absorbance at 290.5nm |
||||||
|
Rep 1 |
Rep 2 |
Rep 3 |
Rep 4 |
Rep 5 |
Mean |
S. D |
|
|
2 |
0.0732 |
0.0739 |
0.0722 |
0.0738 |
0.0742 |
0.0731 |
0.001647 |
|
4 |
0.1492 |
0.1482 |
0.1473 |
0.1460 |
0.1455 |
0.14724 |
0.001527 |
|
6 |
0.2212 |
0.2112 |
0.2310 |
0.2210 |
0.2312 |
0.22312 |
0.008331 |
|
8 |
0.3012 |
0.3011 |
0.3022 |
0.3018 |
0.3014 |
0.30154 |
0.000456 |
|
10 |
0.3655 |
0.3659 |
0.3650 |
0.3645 |
0.3657 |
0.36532 |
0.000567 |
|
R2 |
0.9990 |
0.9997 |
0.9994 |
0.9998 |
0.9995 |
|
|
|
Slope |
0.073 |
0.074 |
0.076 |
0.070 |
0.073 |
||
|
Intercept |
0.001 |
0.001 |
0.001 |
0.001 |
0.001 |
||
Fig.1-Calibration
Curve of Olopatadine HCl
Standardization
of the Method:
In
order to confirm the validity of the method, laboratory samples containing
Olopatadine HCl were prepared, in the range of 2µg – 10µg/ml. The amount of
drug present in the standard solution was calculated by using the selected
linearity equation and the results are tabulated.
Table
4: Data for laboratory samples Analysis
|
S.No |
Conc. of drug (µg/ml) |
Replicate |
Abs at 290.5nm |
Concentration Found |
% Mean |
|
1 |
2 |
i |
0.0732 |
1.99 |
98.1 |
|
ii |
0.0739 |
1.98 |
|||
|
iii |
0.0722 |
1.92 |
|||
|
2 |
6 |
i |
0.2212 |
5.97 |
99.72 |
|
ii |
0.2112 |
5.97 |
|||
|
iii |
0.2310 |
6.01 |
|||
|
3 |
10 |
i |
0.3655 |
9.89 |
98.83 |
|
ii |
0.3659 |
9.97 |
|||
|
iii |
0.3650 |
9.79 |
|||
|
|
Mean |
98.88 |
|||
|
S.D. |
0.8113 |
||||
Analysis
of Formulation:
Formulation
that was used for analysis (OLPD film) contains 2mg Olopatadine HCL per film.
For analysis, accurately weighed there average weight was determined and
dissolved in methanol equivalent to 2mg of Olopatadine HCL film was accurately
weighed and transferred to a volumetric flask and made up to the mark with the
solvent. This solution was sonicated for 20 min and filtered through whatman
filter paper (41 numbers) to get a solution of 1000μg/ml. Further diluted
samples in the range of 2µg – 10µg/ml were prepared.
The
amount of drug present in the sample solution was calculated by using the
selected linearity equation and the results are in the Table
Table
5: Data for Film Analysis
|
S. No |
Conc. of drug (µg/ml) |
Replicate |
Abs at 290.5 nm |
Concentration Found |
% Mean |
|
1 |
2 |
i |
0.0738 |
1.96 |
98.61 |
|
ii |
0.0737 |
1.97 |
|||
|
iii |
0.0732 |
1.99 |
|||
|
2 |
6 |
i |
0.2214 |
5.79 |
99.72 |
|
ii |
0.2120 |
5.88 |
|||
|
iii |
0.2332 |
6.1 |
|||
|
3 |
10 |
i |
0.3660 |
9.94 |
98.33 |
|
ii |
0.3624 |
9.87 |
|||
|
iii |
0.3698 |
9.99 |
|||
|
|
Mean |
98.88 |
|||
|
S.D. |
0.7689 |
||||
Method
Validation:
Linearity:
The
linearity of a method is a measure of how well a calibration plot of response
versus concentration approximates a straight line. Linearity range for any drug
refers to that concentration range in which it follow the Beer Lamberts law
that states, “The absorbance of a solution is directly proportional to the
concentration of the absorbing species when the length of the light path is
fixed and directly proportional light path when the concentration is fixed”.
For establishing the linearity range samples of five concentration of
Olopatadine HCL in the range of 2µg – 10µg/ml in three replicas was prepared
as: From Stock-B further diluted samples (5 replicates) in the range of 2µg –
10µg/ml were prepared. The results obtained were interpreted for any variation
and data was statistically validated.
Table
6: Response Ration Data for Linearity
|
S. No. |
Concentration (mg/ml) |
Absorbance |
Response Ratio |
|
1 |
2 |
0.0732 |
0.0366 |
|
2 |
4 |
0.1492 |
0.0373 |
|
3 |
6 |
0.2212 |
0.0368 |
|
4 |
8 |
0.3012 |
0.0376 |
|
5 |
10 |
0.3655 |
0.0365 |
|
Mean |
0.0369 |
||
|
S.D. |
0.00047 |
||
Fig.2:
Response ratio curve of Olopatadine HCl
Accuracy
(Recovery Studies):
To
test accuracy, recovery studies were performed. To a preanalyzed sample
solution, a definite concentration of standard drug was added and then its
recovery was studied. Different concentration of pure drug was added to
preanalysed tablet sample, and then the solution was analyzed in the same
manner as the laboratory sample. It was repeated for three times to emphasize
validation. Results of recovery study were reported.
Table
7: Recovery Study Data for Accuracy
of Olopatadine HCl
|
S. No. |
Conc. of Drug in film(µg/ml) |
Replicates |
Conc. added to the film samples (µg/ml) |
Amount Recovered |
% Found |
|
1 |
4 |
i |
2 |
1.93 |
98.21 |
|
ii |
2 |
1.89 |
|||
|
iii |
2 |
1.98 |
|||
|
2 |
4 |
i |
4 |
4.01 |
99.55 |
|
ii |
4 |
3.98 |
|||
|
iii |
4 |
3.88 |
|||
|
3 |
4 |
i |
6 |
6.02 |
98.29 |
|
ii |
6 |
5.89 |
|||
|
iii |
6 |
5.76 |
|||
|
|
Mean |
98.68 |
|||
|
S.D. |
0.6789 |
||||
|
|
%CV |
|
|||
Table
8: Repeatability Data for Precision of Olopatadine HCl
|
S. No |
Conc. of drug(µg/ml) |
Replicate |
Abs at 290.5nm |
Concentration Found |
% Mean |
|
1 |
2 |
i |
0.0732 |
1.94 |
98.0 |
|
ii |
0.0739 |
1.99 |
|||
|
iii |
0.0722 |
1.95 |
|||
|
2 |
4 |
i |
0.1492 |
3.91 |
94.0 |
|
ii |
0.1482 |
3.84 |
|||
|
iii |
0.1483 |
3.84 |
|||
|
3 |
6 |
i |
0.2212 |
5.98 |
99.94 |
|
ii |
0.2112 |
5.98 |
|||
|
iii |
0.2310 |
6.03 |
|||
|
4 |
8 |
i |
0.3012 |
7.96 |
99.54 |
|
ii |
0.3011 |
7.95 |
|||
|
iii |
0.3022 |
7.98 |
|||
|
5 |
10 |
i |
0.3655 |
9.69 |
96.83 |
|
ii |
0.3659 |
9.71 |
|||
|
iii |
0.3650 |
9.65 |
|||
|
|
Mean |
95.66 |
|||
|
S.D. |
2.3 |
||||
Table
9: Intermediate Precision: Day to Day
|
S. No |
Conc. of drug (µg/ml) |
Replicate |
Abs at 290.5nm |
Concentration Found |
% Mean |
|
1 |
2 |
i |
0.0788 |
1.84 |
94.16 |
|
ii |
0.0764 |
1.92 |
|||
|
iii |
0.0757 |
1.89 |
|||
|
2 |
4 |
i |
0.1458 |
3.65 |
94.83 |
|
ii |
0.1469 |
3.89 |
|||
|
iii |
0.1478 |
3.49 |
|||
|
3 |
6 |
i |
0.2235 |
5.78 |
98.11 |
|
ii |
0.2169 |
5.89 |
|||
|
iii |
0.2378 |
5.99 |
|||
|
4 |
8 |
i |
0.3049 |
7.97 |
98.88 |
|
ii |
0.3071 |
7.89 |
|||
|
iii |
0.3068 |
7.89 |
|||
|
5 |
10 |
i |
0.3639 |
9.48 |
97.55 |
|
ii |
0.3658 |
9.69 |
|||
|
iii |
0.3672 |
9.12 |
|||
|
|
Mean |
98.35 |
|||
|
S.D. |
1.08 |
||||
Table
10: Intermediate Precision: Analyst to Analyst
|
S. No |
Conc. of drug(µg/ml) |
Replicate |
Abs at 290.5nm |
Concentration Found |
% Mean |
|
1 |
2 |
i |
0.0722 |
1.44 |
80.33 |
|
ii |
0.0798 |
1.89 |
|||
|
iii |
0.0712 |
1.49 |
|||
|
s2 |
4 |
i |
0.1482 |
3.55 |
98.36 |
|
ii |
0.1428 |
3.92 |
|||
|
iii |
0.1483 |
3.91 |
|||
|
3 |
6 |
i |
0.2222 |
5.78 |
99.14 |
|
ii |
0.2132 |
5.56 |
|||
|
iii |
0.2320 |
5.89 |
|||
|
4 |
8 |
i |
0.3027 |
7.69 |
98.96 |
|
ii |
0.3034 |
7.77 |
|||
|
iii |
0.3052 |
7.79 |
|||
|
5 |
10 |
i |
0.3657 |
9.98 |
99.61 |
|
ii |
0.3642 |
9.87 |
|||
|
iii |
0.3648 |
9.97 |
|||
|
|
Mean |
|
|||
|
S.D. |
1.31 |
||||
Precision:
Repeatability:
As
per section 5.1.3.5 standard dilutions were prepared and three replicates of
each dilution were analyzed in same day for repeatability of precision.
Statistical analysis was carried out.
Intermediate
Precision:
Standard
dilutions were prepared in three replicates and were analyzed in different days
by different analysis. Statistical analysis was carried out.
5.
CONCLUSION:
In
the present work, fast dissolving film of olopatadine HCl were prepared by
solvent casting method using HPMC E-15, Maltodextrin as a polymer. The
olopatadine HCl is insoluble in water and its bioavailability is limited and
hence this method is useful for improving its bioavailability of the drug. The
disintegration time of film was reduced by use of maltodextrin with HPMC E-15
as a combination from the finding obtained it can be concluded that-
The
prepared film containing olopatadine HCl was clear and colorless.
1 Formulated film gives
satisfactorily results for various physicochemical evaluation of film like
physical appearance, surface texture, weight uniformity, thickness, folding
endurance surface PH invitro disintegration time drug release, the value of
standard deviation for average weight and drug content of the prepared films
indicate weight and drug content uniformity within the batches prepared.
2 Short term stability
studies of promising formulation indicated that there is no significant change
in drug content and invitro disintegration time.
3 From the present study
it may be concluded that fast dissolving films of olopatadine HCl can be
prepared by solvent casting method using HPMC and Maltodextrin.
6. REFERENCES:
1.
Puttipipatkhachorn S etal (2001) conducted
studies on four different grades of chitosan to prepare films.
Salicylic acid and theophylline were incorporated into cast chitosan Films as
model acidic and basic drugs.
2.
Hirokazu O etal (2001) examined the
penetration rate of Lidocaine (LC) through excised oral mucosa from hamster
cheek pouch and the in vitro release rate of LC from film dosage forms with
hydroxypropylcellulose (HPC) as a film base.
3.
Francesco C etal (20l0), developed a
fast-dissolving film made of low dextrose Equivalent maltodextrins
(MDX) containing nicotine hydrogen tartrate salt.
4.
Cillurzo F et al. (2008) prepared fast
dissolving film of pioxicam using maltodextrin with low dextrose equivalent as
film forming using casting and solvent evaporation method. Fast dissolving
films of piroxicam showed high loading capacity of dose with dissolution rate.
5.
Kulkarni et al (2009) take the fast
dissolving films of rofecoxib by solvent casting method by use of HPMC as
polymer. They concluded that mouth dissolving films containg rofecoxib 4%w/v of
PVA film exhibited revive tensile strength, folding endurance and percentage
elongation.
Received on 24.11.2020
Modified on 28.12.2020
Accepted on 30.01.2021
©Asian Pharma Press All Right Reserved
Asian J. Res. Pharm. Sci. 2021; 11(2):103-108.
DOI: 10.52711/2231-5659.2021-11-2-2