122 Indian Journal of Pharmaceutical Sciences March - April 2012
*Address for correspondence
Formulation Development and Evaluation of Fast
Dissolving Film of Telmisartan
VAISHALI Y. LONDHE* AND KASHMIRA B. UMALKAR
Department of Pharmaceutics, School of Pharmacy and Technology Management, NMIMS, Vileparle, Mumbai‑400 056, India
Londhe and Umalkar: Fast Dissolving Film of Telmisartan
Hypertension is a major cause of concern not just in the elderly but also in the youngsters. An effort was made to
formulate a fast dissolving film containing telmisartan which is used in the treatment of hypertension with a view
to improve the onset of action, therapeutic efficacy, patient compliance and convenience. The major challenge in
formulation of oral films of telmisatran is that it shows very less solubility in the pH range of 3–9. Various film
forming agents and polyhydric alcohols were evaluated for optimizing composition of fast dissolving films. Fast
dissolving films using hydroxypropyl methylcellulose, polyvinyl alcohol, glycerol, sorbitol, menthol and an alkalizer
were formulated using solvent casting method. Optimized formulations were evaluated for their weight, thickness,
folding endurance, appearance, tensile strength, disintegration time and dissolution profile.
Key words: Fast dissolving film, hydroxypropyl methylcellulose, polyvinyl alcohol, solvent casting, telmisartan
Rapidly dissolving or quick dissolving dosage
forms have acquired great importance in the
pharmaceutical industry due to their unique properties
and advantages[1,2]. They undergo disintegration
in the salivary fluids of the oral cavity within a
minute, where they release the active pharmaceutical
ingredient. The major amount of the active
pharmaceutical ingredient is swallowed orally
with the saliva where subsequent absorption takes
place in the gastrointestinal tract[3,4]. The rapidly
dissolving dosage forms are referred by various
names by researchers like quick disintegrating, orally
disintegrating, mouth dissolve or melt in mouth
dosage forms[1,3,4]. These dosage forms possess
certain specific advantages like no need of water for
disintegration, accurate dosing, rapid onset of action,
ease of transportability, ease of handling, pleasant
taste and improved patient compliance.
Telmisartan (TLM) is an antihypertensive agent which
is a nonpeptide angiotensin receptor ΙΙ antagonist,
that cause inhibition of the action of angiotensin
II on vascular smooth muscle in the symptomatic
treatment of hypertension[5,6]. The major drawback of
this drug is its low aqueous solubility. It is insoluble
in water and hence the drug may be slowly or
incompletely dissolved in the gastro intestinal tract.
The bioavailability of TLM is poor about 45%, which
is due to extensive first pass hepatic metabolism.
The available formulation of TLM in market is
an immediate release tablet. Conventional TLM
tablets are not suitable where quick onset of action
is required. To provide the patients with the most
convenient mode of administration, there is a
need to develop rapidly dissolving dosage form,
particularly one that disintegrates and dissolves/
disperses in saliva and can be administered without
need of water. Fast dissolving films are useful in
patients such as paediatric, geriatric, bedridden, or
developmentally disable who may face difficulty
in swallowing conventional tablets. So the patients
would be benefited from acute treatment by using
proposed drug delivery system. Thus, a fast dissolving
film is a unique solid oral dosage form and has
Initial investigations were focused on the development
of placebo fast dissolving films with good peelability,
appearance and a quick disintegration time. After
choosing the components for the placebo film,
TLM loaded films were formulated. Although, fast
dissolving film is an attractive dosage form for the
delivery of TLM, its poor water solubility is a real
challenge in the development of fast dissolving films.
March - April 2012 Indian Journal of Pharmaceutical Sciences 123
Finally fast dissolving films using hydroxypropyl
methylcellulose (HPMC) and polyvinyl alcohol (PVA)
were formulated and evaluated.
MATERIALS AND METHODS
Telmisartan was a gift sample from IPCA
Laboratories, Mumbai. Polyvinyl alcohol, Fisher
Scientific, India, hydroxypropyl methylcellulose,
Colorcon Asia Pvt. Ltd., Mumbai, India, d-sorbitol and
potassium hydroxide, S. D. Fine-chem Ltd., Mumbai,
India, glycerin, Qualigens Fine Chemicals, Mumbai,
India, and menthol, Loba Chemie Pvt. Ltd., India
were purchased for carrying out various experiments.
All other chemicals used were of analytical grade.
Screening of the components for formulation of
placebo fast dissolving films:
HPMC is known for its good film forming properties
and has excellent acceptability. Hence, various
grades of HPMC namely Methocel E3, Methocel E5
and Methocel E15 Premium LV were evaluated as
film formers. For the fabrication of films, glycerin
was used as a humectant. PVA is also reported as
film former with moisture barrier ability. Therefore
PVA along with glycerol was also used for placebo
films. Apart from these film formers, polyvinyl
pyrrolidone 30, polyvinyl pyrrolidone 90, kollicoat IR,
copovidone alone or in combination with each other
along with plasticizers like lutrol E400 were tried.
The composition of various placebo films is given in
Table 1. The films were prepared by solvent‑casting
method. The polymer was soaked in water for 30 min
or heated in water bath to 80º to get a clear solution.
Then a plasticizer was added to it and mixed so as
to get homogeneous solution. This solution was then
casted onto a glass petridish (9.6 mm in diameter)
and was dried in hot air oven at 45° for 24 h. The
films were evaluated for imperfections, peelability
without rupturing, surface roughness, appearance
and in vitro disintegration time as shown in Table 2.
Optimization was further performed for the polymer
and plasticizer compositions which showed good film
properties. These are shown in Table 3.
Preparation of drug loaded fast dissolving film:
TLM containing fast dissolving films were fabricated
as per the method described for the fabrication of
blank fast dissolving films. The composition of TLM
containing films is shown in Table 4. The detailed
procedure for final optimized formulation is as follows.
HPMC was weighed and soaked for 30 min while
PVA was heated to 80º to obtain a clear solution.
Glycerol and sorbitol were added to each of these
solutions and mixed well. Specified amount of
menthol and sucralose which were previously
dissolved in very small amount of ethanol and water,
respectively were added to above polymer solutions.
TLM was dissolved in potassium hydroxide solution,
added to the above formulation and stirred to get a
uniform distribution. The films were casted on perti
dishes and allowed to dry at 45º for 24 h. They were
further peeled and cut into 3×3 cm2 area. Films K3
and K4 were further evaluated.
The thickness of the film was evaluated using
calibrated vernier caliper (Mitutoyo, Japan). The
sample equivalent to dose of the drug was taken.
Anvil of the thickness gage was lifted and the film
was inserted after making sure that pointer was set to
zero. The film was held on the anvil and the reading
on the dial was noted down. The thickness was
measured at three different positions. The average of
six readings was taken as mean thickness.
TABLE 1: COMPOSITION OF PLACEBO TRIALS#
All values are expressed in %w/v. HPMC is hydroxypropyl methylcellulose, PVA is polyvinyl alcohol
124 Indian Journal of Pharmaceutical Sciences March - April 2012
Weight variation and content uniformity test:
For weight variation, the films of size 3×3 cm2 which
includes dose of drug were cut and weighed on
analytical balance (Shimadzu Corporation Japan AUX
220). For content uniformity test, the films of size
3×3 cm2 were cut from different positions of casted
film. Each film of 9 cm2 was placed in volumetric
flask containing 60 ml of 0.1 N hydrochloric acid and
was sonicated for 15 min using ultrasonicator. The
volume was made upto 100 ml and the absorbance of
solution was measured by UV spectrophotometer at
296 nm after appropriate dilutions.
Folding endurance test:
The folding endurance is expressed as the number of
folds required to break the specimen or to develop
visible cracks. This gives the indication of brittleness
of the film. It was measured manually for the
prepared film for the area 3×3 cm2. Film of specified
area was subjected to this test by folding the film
repeatedly at the same plane for several times till
visible cracks developed.
In vitro disintegration test and pH:
Disintegration test was performed by placing the film of
size 3×3 cm2 in the glass Petri dish containing 20 ml of
water. It was stirred at every 10 s time interval. The time
required for the film to disintegrate was recorded and
results are expressed as mean of 6 determinations. The
pH of the film was measured by dissolving 3×3 cm2 film
in 4 ml of water, using a calibrated pH meter.
Tensile strength and % elongation:
Mechanical properties of the film are important from
packaging point of view. Tensile test was performed
to assess strength and elasticity of optimized film
formulation. The elongation-to-break (also called
ultimate elongation) is the strain on a material when
it breaks and it gives an indication of toughness and
stretch-ability prior to breakage. These parameters
dictate the end-use handling properties and mechanical
performance of the films. This quality control test was
adapted from the textile industry (Star tensile tester).
Casted film was cut into specimens of the size specified
in Table 5. The thickness of the specimens was
determined by standard micrometer screw gauge. Then
5 specimens were applied on tensile tester to determine
the tensile properties. The tensile stress is expressed
in terms of MPa and strain in terms of % elongation.
Tensile strength = (Load at failure×100) / (Strip
thickness × Strip width) and % Elongation = (Increase
in length of strip × 100) /Initial length of strip.
DSC thermograms of TLM and TLM containing films
(only K3) were recorded on a thermal analyzer (DSC,
Q200, VA 24.2). The samples were heated from
30° to 300° at a heating rate of 10°/min in an inert
In vitro dissolution study:
The dissolution medium selected was pH 7.5
phosphate buffer which is a media specified for
TLM tablets as per FDA OGD guidelines (900 ml,
TABLE 2: EVALUATION OF PLACEBO FILM TRIALS
TrialsFilm forming capacityAppearance Disintegration
TABLE 3: OPTIMIZATION OF QUANTITY OF PVA, HPMC
Water (ml)14 14
PVA is polyvinyl alcohol, HPMC is hydroxypropyl methylcellulose
TABLE 4: COMPOSITION OF DRUG LOADED FILM
Water q.s. (ml)16
HPMC is hydroxypropyl methylcellulose, PVA is polyvinyl alcohol, TLM is
March - April 2012 Indian Journal of Pharmaceutical Sciences 125
75 rpm maintained at 37±0.5°). At predetermined
time intervals, 5 ml aliquots of samples were
taken and same volume of buffer was replenished.
Absorbance was measured at 296 nm after appropriate
dilutions. The results are expressed as mean of
3 determinations. Apart from this, multimedia
dissolution study was performed in phosphate buffer
pH 4.5, 6.4 and in 0.1 N hydrochloric acid.
RESULTS AND DISCUSSION
Based on film forming capacity, appearance and
disintegration time HPMC 5 cps and PVA were
selected as film forming agents. Placebo film
containing PVA gave most desired properties at
concentration 2.75% of PVA polymer with 0.375%
of glycerol as a plasticizer. Placebo film containing
HPMC E5 gave most desired properties at
concentration 2.85% with 0.71% of glycerol.
Since TLM is insoluble between the pH of 3–7, hence
an attempt was made to increase the solubility of
TLM by use of alkalizers like sodium hydroxide and
potassium hydroxide as used by the innovator of TLM
tablets namely Micardis®.
In trial K1 drug was just dispersed in polymer
solution, where as for trial K2, combination of
sodium hydroxide and tween 80 was used. As both
these trials did not show satisfactory dissolution
profile, trials K3 and K4 were further taken by use of
potassium hydroxide as an alkalizer to solubilize the
drug. To mask the slight salty/alkaline taste imparted
by potassium hydroxide in trial K3 and K4; the
concentration of sucralose was increased and menthol
was incorporated as coolant. The incorporation
of potassium hydroxide did not adversely affect
appearance, peelablity and flexibility of the film.
PVA film of formulation K3 was found to be clearer
and more transparent as compared to HPMC film
formulation K4. The pH of the film was found to be
Folding endurance of formulation K3 was found to
be 432±2 and that of formulation K4 was found to
be 53±2. The folding endurance value of formulation
K3 was found to be optimum. The results of average
weight, average thickness and disintegration time
of formulations K3 and K4 are shown in Table 6.
Therefore on the basis of appearance and folding
endurance, we can say that PVA formulation K3 was
superior to HPMC formulation K4. Tensile strength,
% elongation study, surface morphology study and
DSC analysis were further carried out on formulation
K3. The tensile strength was found to be 12.84±2.82
MPa and % elongation was found to be 332.2±3.01
which suggests that the final optimized formulation
K3 has good flexibility and can withstand high strain
before rupture. DSC thermogram of TLM and final
film K3 is shown is fig.1. The thermogram of pure
drug showed endothermic peak at 270° corresponding
to its melting point. DSC thermogram for drug loaded
film also shows peak at around 270° indicating
compatibility of the drug.
The theoretical TLM content in K3 and K4 was
20 mg/9 cm2 film. Considering this content, as 100%,
the TLM content in the formulations K3 and K4 was
evaluated. The TLM content in K3 and K4 was found
to be 99.31±1.63% and 99±1.09%, respectively (n=6).
The results of content uniformity indicated that drug
has been uniformly distributed in the film.
TABLE 5: PARAMETERS FOR TENSILE STRENGTH AND
Specimen width10 mm
Gauge length 50 mm
Travel speed50 mm/min
Instrument CRE (Constant rate of extension) tensile tester
TABLE 6: EVALUATION OF FORMULATION K3 AND K4
Parameter Formulation K3
Weight variation test (mg)
Disintegration time (DT)
The values are expressed as mean±SD
Fig. 1: DSC thermograph of TLM.
(a) pure telmisartan (TLM), (b) drug‑loaded film
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126 Indian Journal of Pharmaceutical Sciences March - April 2012
The dissolution studies of formulations K1 and
K2 showed only around 20 and 60% drug release,
respectively. Almost 100% drug release was obtained
from formulations K3 and K4 in 5 min in pH 7.5
phosphate buffer due to alkalizers. Apart from 7.5
buffer, multimedia dissolution of final optimized film
K3 was done in 0.1 N hydrochloric acid (which is
the official medium given for telmisartan tablets in
IP 2010), as well as in pH 6.4 buffer and pH 4.5
buffer to understand the behavior of the film over a
wide range of pH. Multimedia dissolution profile of
formulation K3 is shown in fig. 2. More than 80%
drug release was obtained on 0.1 N hydrochloric acid
and pH 7.5 phosphate buffer within 5 min, whereas
the same results was obtained after 20 min in pH 4.5
buffer. In pH 6.4 buffer, almost 100% drug release
was obtained within 15 min. From this dissolution
profile it can be noted that as the pH of buffer
was decreased from 7.5 to 6.5 and 4.5, the rate of
dissolution also decreased.
Fast dissolving film of telmisartan was formulated
satisfactorily. It showed a good dissolution profile
along with elegant appearance and other physical
characteristics like tensile strength, % elongation,
folding endurance. Therefore it can be a good
alternative to conventional telmisartan tablets.
Authors thankfully acknowledge, IPCA Laboratories Ltd.
for providing gift sample of Telmisartan, Micro Labs Ltd.
Mumbai for carrying out DSC analysis, Bombay Textile
Research Association, Mumbai for carrying out tensile
strength analysis and scanning electron microscopy.
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Accepted March 21, 2012
Revised March 17, 2012
Received May 24, 2011
Indian J. Pharm. Sci., 2012, 74 (2): 122‑126
Fig. 2: Dissolution of formulations in various media.
Multimedia dissolution study of formulation K3 ‑■‑ pH 7.5 buffer;
‑♦‑ 0.1 N HCl; ‑▲‑ pH 6.8 buffer; ‑×‑ pH 4.5 buffer
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