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Investigation of different polymers, plasticizers and superdisintegrating

agents alone and in combination for use in the formulation of fast dissolving
oral films

Article in International Journal of PharmTech Research · October 2013

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 International Journal of PharmTech Research
CODEN (USA): IJPRIF ISSN : 0974-4304
Vol.5, No.4, pp 1465-1472, Oct-Dec 2013

Investigation Of Different Polymers, Plasticizers And

Superdisintegrating Agents Alone And In Combination For
Use In The Formulation Of Fast Dissolving Oral Films

Upendra C Galgatte*, Sunil S Khanchandani,

Yuvraj G Jadhav, Praveen D Chaudhari

Department of Pharmaceutics, P.E.S’s Modern College of Pharmacy, Sector 21,

Yamunanagar, Nigdi, Pune-411044, Maharashtra, India.

*Corres. Author: ucgpharm@rediffmail.com

Mobile No.: +91-9890755938, Tel.: +91-20-27661315, Fax: + 91-20-27661314

Abstract: Natural gums may not essentially form a film with acceptable properties like disintegration time etc.
This is due to high molecular weight and high viscosity of natural gums. Therefore their use is limited in oral
fast dissolving film. To make them useful, it was one of the attempts to combine them with semi-synthetic or
synthetic polymers and to check resultant properties of film for their acceptability. Films were prepared from
aqueous dispersions of polymers. Some natural, semi-synthetic and synthetic polymers were used. Polymers and
their combinations which have proven acceptability were tried to observe the effect of superdisintegrating
agents. Sodium starch glycolate and croscaremellose sodium were used as superdisintegrating agents. Among
them which have shown disintegration satisfactory, were further selected to observe the effect of plasticizer that
is propylene glycol (PG) and polyethylene glycol 400 (PEG 400) on film forming ability, disintegration, weight
variation, thickness and folding endurance etc. Pullulan alone, and HPMC E15 + pectin have shown best film
acceptability. Combination of pullulan, guar gum, xanthan gum and carrageenan has shown excellent of film
formation. Addition of pectin in HPMC E5 has shown increase disintegration time than HPMC E5 alone
indicating that natural polymer pectin increases disintegration time. Films prepared by using PEG 400 were
sticky in nature. Good acceptability was observed in films prepared by using PG. However, both of these
plasticizers have not shown considerable effect on disintegration time of film. Formulation prepared using
propylene glycol as the plasticizer had good appearance, high folding endurance and acceptable disintegration
time.
Keywords: Fast dissolving oral film, Plasticizer, Film-forming polymers and Superdisintegrating agents.

Introduction
Oral administration is the most popular route due to ease of ingestion, pain avoidance, versatility (to
accommodate various types of drug candidates), and most importantly, patient compliance1. But the most
evident drawback of oral dosage forms like tablets and capsules is difficulty in swallowing, leading to patient’s
incompliance particularly in case of pediatric and geriatric, bedridden, nauseous patients2. So, fast-dissolving
drug-delivery systems came into existence in the late 1970’s as an alternative to tablets, capsules and syrups for
Upendra C Galgatte et al /Int.J.PharmTech Res.2013,5(4) 1466

pediatric and geriatric patients who experience difficulties in swallowing traditional oral solid-dosage forms.
These systems consist of the solid dosage forms that disintegrate and dissolve quickly in the oral cavity without
the administration of water3. Fast dissolving films, a new drug delivery system for the oral delivery of the drugs,
was developed based on the technology of the transdermal patch. The delivery system consists of a very thin
oral strip, which is simply placed on the patient’s tongue or any oral mucosal tissue, instantly wet by saliva the
film rapidly hydrates and adheres onto the site of application. It then rapidly disintegrates and dissolves to
release the medication for oromucosal absorption or with formula modifications, will maintain the quick-
dissolving aspects allow for gastrointestinal absorption to be achieved when swallowed4. They impart unique
product differentiation, thus enabling use as line extensions for existing commercial products. This novel drug
delivery system can also be beneficial for meeting the current needs of the industry are improved
solubility/stability, biological half life and bioavailability enhancement of drugs5. Oral film includes various
ingredients for its formulation which includes polymers, active pharmaceutical ingredient, plasticizers,
superdisintegrating agents, sweeteners, flavors, colors, saliva stimulating agents, preservatives, surfactants etc
but the most essential ingredients of oral films are polymers, plasticizers and superdisintegrating agents2. A
variety of polymers are available for preparation of fast dissolving oral films. The use of film forming polymers
in oral films has attracted considerable attention in medical and nutraceutical applications. The selection of
polymer, is one of the most important and critical parameter for successful development of the film
formulation6. The polymers can be used alone or in combination to obtain the desired film properties. The film
obtained should be tough enough so that there won't be any damage while handling or during transportation.
The robustness of the strip depends on the type and amount of polymer in the formulation7. As the strip forming
polymer (which forms the platform for the oral film) is the most essential and major component of the film, at
least 45%w/w of polymer should generally be present based on the total weight of dry film but typically 60 to
65%w/w of polymer is preferred to obtain desired properties8. Plasticizer is a vital ingredient of the fast
dissolving films. Plasticizer helps to improve the flexibility of the strip and reduces the brittleness of the films.
It significantly improves the film forming properties by reducing the glass transition temperature of the
polymer. Typically the plasticizers are used in the concentration of 0–20 percent; w/w of dry polymer weight5.
The disintegration of the strip in the oral cavity depends on the type of superdisintegrating agent and the amount
of disintegrating agent in the formulation. A variety of superdisintegrating agents are available for preparation
of fast dissolving films. Superdisintegrants are used at a low level in the solid dosage form, typically 1–10% by
weight relative to the total weight of the dosage unit9.

Materials And Methods

Materials

All the chemicals used were of analytical grade and were used without further purification. Distilled water was
used as a solvent throughout the study.

Method

Preparation Of Oral Fast Dissolving Films

Oral fast-dissolving film was prepared by the solvent-casting method. Water soluble film polymers (35% w/w)
were dissolved in sufficient volume of distilled water and then superdisintegrating agents (4% w/w), citric acid
(6% w/w) (Saliva stimulating agent) were added slowly so as to form uniform viscous solution by using
magnetic stirrer at speed of 300 rpm for 3 hr. After that plasticizers (20% w/w) and saccharin sodium
(sweetener) (5% w/w) Peppermint oil (flavour), Tartrazine (colour) added in polymeric solution to form a clear
viscous solution. The excipients were added in such a quantity that they form smooth, transparent and flexible
film. Then both the solutions were mixed by using magnetic stirrer at speed of 300 rpm for 1hour,degassed
under vacuum, resulting solution was cast as a film into the petri-dishes (area of 63.585 cm2) and kept at room
temp. for a period of 24 hours. After that film was dried in drying oven, collected and cut into 2cm×2cm size.
Upendra C Galgatte et al /Int.J.PharmTech Res.2013,5(4) 1467

Evaluation Of Fast Dissolving Films

Appearance Of Films
Films were evaluated visually for appearance such as smooth surface, transparency, colour etc.
Film Forming Capacity
It is ability of film formers to form film with desired properties. Relative film forming ability was determined on
the basis of rating given to each film. Rating was given out of +++++ such as poor (+), average (++), good
(+++), best (++++) and excellent (+++++) 10.
Thickness Of The Film
The thickness of films was measured with the help of micrometer screw gauge at different strategic locations
like four corners and centre of the each film. Mean SD is calculated. The standard range for film thickness
should not be less than 5 %. This is essential to assure uniformity in the thickness of the film.
Weight Variation Of The Film
Weight variation was studied by individually weighing 6 randomly selected film strips. Average weight of films
calculated. The weight of each film should not deviate significantly from average weight11.
Folding Endurance
It is measured manually for the prepared oral film. A film was repeatedly folded at 1800 at the same place till it
breaks. This test was performed on three films of each formulation and mean ±SD was calculated.
in vitro Disintegration Time
In vitro disintegration time was determined visually in a beaker of 25 ml phosphate buffer pH 6.8 with swirling
every 10 seconds. The disintegration is the time when film breaks or disintegrates. All studies were performed
in triplicate.

Results And Discussion

Polymers: The different batches of oral films of natural and semi-synthetic polymers were prepared and
evaluated for their different parameters, which are shown in table 1 and effect of polymers on film forming
capacity shown in fig. 1. Some of natural polymers which were used alone or combination showed good film
forming capacity and have smooth and transparent appearance such as pullulan, pullulan + guar gum +xanthan
gum + carageenan, and pectin. However, semi-synthetic polymers which were alone or combination showed
good film forming capacity and have smooth and transparent appearance such as HPMC E5, HPMC E15,
HPMC E50, HPMC E5 +xanthan gum, HPMC E15 + guar gum, and HPMC E15 +xanthan gum. The
combination of natural as well as semi-synthetic polymers also provide best oral film such as HPMC
E15+pectin, which showed good film forming capacity and have smooth and transparent appearance.
Depending on the appearance and film forming capacity of different polymers used alone or combination, the
selected polymers which showed good appearance and film forming capacity were further prepared with
superdisintegrating agents and evaluated for disintegration time.

Superdisintegrating Agents: The batches of oral films of natural and semi-synthetic polymers with
superdisintegrating agents were prepared and evaluated for appearance and disintegration time, which are shown
in table 2 and effect of superdisintegrating agents on disintegration time shown in fig. 2. Oral films were
suitably prepared using different superdisintegrating agents such as sodium starch glycolate (SSG) and
croscaremellose sodium (CCS). Film gives better result prepared with HPMC E15 +pectin+ SSG, which showed
smooth, transparent appearance and disintegration time of 45 sec; and HPMC E15 +pectin+ CCS showed
smooth, transparent appearance and disintegration time of 50 sec. The selected polymers (alone or combination)
used with superdisintegrating agents which showed good appearance, film forming capacity and accepted
disintegration time were further prepared with different plasticizers and evaluated for folding endurance and
disintegration time.
Upendra C Galgatte et al /Int.J.PharmTech Res.2013,5(4) 1468

Table 1: Evaluation of films of explored polymers

Sr. Polymers Used *Film forming Appearance

no. capacity
1) HPMC E5(500mg) +++ Transparent,smooth,good
appearance
2) HPMC E15(500mg) +++ Transparent,slightly rough
3) HPMC E50(500mg) +++ Transparent,rough appearance
4) Carboxy methyl cellulose(500mg) ++ NotTransparent,rough,turbid
5) Pullulan(500mg) ++++ Very Transparent,smooth
6) Pullulan(250mg) + Guar gum +++++ Smooth,transparent
(100mg)+xanthan gum(100mg) +
carageenan(50mg)
7) PVA(500mg) +++ Transparent
8) Sodium alginate(500mg) - Does not form film
9) PVP K30(500mg) + Semitransparent
10) Chitosan(500mg) ++ Transparent
11) Guar gum(500mg) + Not Transparent, rough, turbid
12) Carageenan(500mg) ------ Does not form film
13) HPMC E5(400mg)+ Carageenan(100mg) ++ Semi Transparent,rough, turbid
14) HPMC E5(400mg) + Guar gum(100mg) +++ Transparent,smooth
15) Xanthan Gum(500mg) ++ Sticky, transparent
16) HPMC E5(400mg) +Xanthan +++ Smooth,transparent
Gum(100mg)
17) HPMC E15(400mg) + Guar gum(100mg) +++ Transparent,smooth
18) HPMC E15(400mg) +Xanthan +++ Smooth,transparent
Gum(100mg)
19) Pectin(500mg) ++ Smooth, transparent
20) HPMC E15(300mg)+Pectin(200mg) ++++ Smooth, transparent
*Rating was given out of +++++

Figure 1: Effect of polymers on film forming capacity

Upendra C Galgatte et al /Int.J.PharmTech Res.2013,5(4) 1469

Table 2: Evaluation of films using superdisintegrating agents

Sr. Polymer+ superdisintegrating agent Appearance Disintegration time (in

no. phosphate buffer pH
6.8 )
1) Xanthan Gum(500mg) + SSG(30mg) Sticky, Transparent 6 minute
2) Xanthan Gum(500mg) + CCS(30mg) Sticky, Transparent 4 minute
3) HPMC E15(500mg) + SSG(30mg) Smooth, transparent 35 sec
4) HPMC E15(500mg) + CCS(30mg) Smooth, transparent 25 sec
5) HPMC E15(300mg) +Pectin(200mg)+ Smooth, transparent 45 sec
SSG(30mg)
6) HPMC E15(300mg)+Pectin(200mg) + Smooth, transparent 50 sec
CCS(30mg)
7) HPMC E15(400mg) + guar gum(100mg) + Smooth, transparent, 5 minute
SSG(30mg) turbid
8) HPMC E15(400mg) +guar gum(100mg) + Smooth, 4 minute
CCS(30mg) transparent,turbid
9) HPMC E50(500mg)+ SSG(30mg) Smooth, transparent 2 minute
8) HPMC E50(500mg)+ CCS(30mg) Smooth, transparent 1 minute 40 sec
9) HPMC E5(500mg) + CCS(30mg) Smooth, transparent 1 minute 6 sec
10) HPMC E5(500mg) + SSG(30mg) Smooth, transparent 35 sec
11) HPMC E5(300mg) + Pectin(200mg)+ Smooth, transparent 55 sec
CCS(30mg)
12) HPMC E5(300mg) + Pectin(200mg)+ Smooth, transparent 50 sec
SSG(30mg)
15) Pectin(500mg) + CCS(30mg) Smooth, transparent 1 minute 15 sec
16) Pectin(500mg) + SSG(30mg) Smooth, transparent 1 minute 19 sec
*SSG-sodium starch glycolate, CCS- croscarmellose sodium

Figure 2: Effect of superdisintegrating agents on disintegration time

Upendra C Galgatte et al /Int.J.PharmTech Res.2013,5(4) 1470

Plasticizers: The different batches of oral films with different plasticizers were prepared which are shown in
fig. 3 and evaluated for various parameters, which are shown in table 3 and Effect of plasticizers on
disintegration time and folding endurance are sown in fig. 4 and 5 respectively. Oral films were suitably
prepared using different plasticizers such as propylene glycol (PG) and polyethylene glycol (PEG 400).
Formulation prepared using PG as the plasticizer had good appearance. Film prepared using PEG 400 as the
plasticizer did not possess good appearance and/or were somewhat sticky to touch. This may have been due to
the formation of a moist layer on the surface of film, which could potentially affect its appearance and handling.
Therefore, PG was found to be better plasticizer than PEG 400 for the preparation of films. Polyethylene glycol
400 (PEG 400) and propylene glycol (PG) were selected as the plasticizers to be used separately. In addition,
concentration of PEG 400 and PG less than 10% was not enough to plasticize the films because the formed
films were brittle and fragmented easily. On the other hand, concentration of PEG and PG higher than 30%
posed problems in drying the films. Moreover, the formed films were sticky, difficult to handle and remove
from the petri dish. From the data shown in Table 3, it can be seen that films prepared using PG resulted in
higher folding endurance than those prepared using PEG 400. Formulation containing PEG 400 or PG as the
plasticizer at the same respective polymer concentration exhibited almost similar disintegration times indicating
that the concentration as well as the type of plasticizer used not much affect on the disintegration of the film.

Figure 3: Images of different batches of fast dissolving oral films-

a) HPMC E15+pectin+glycerol, b) HPMC E15+pectin+propylene glycol, c) HPMC E15+pectin+sorbitol,

d) HPMC E15+pectin+PEG 400, e) HPMC E15+PG and f) HPMC E15+pectin+propylene glycol (2 cm x 2 cm)
Upendra C Galgatte et al /Int.J.PharmTech Res.2013,5(4) 1471

Table 3: Evaluation of films using plasticizers

Disintegration
Weight Folding
Sr. Polymer + superdisintegrating Thickness time (phosphate
of film endurance
no. agent + plasticizer (mm) buffer pH 6.8)
(mg) (no.)
(sec)
HPMC E15(500mg) +CCS(30mg)
1) 85 0.13 50 80 sec
+ PG(0.5ml)
HPMC E5(500mg) +CCS(30mg)
2) 78 0.11 80 85 sec
+ PG(0.5ml)
HPMCE15(300mg)
3) +Pectin(200mg)+CCS(15mg) 108 0.14 285 95 sec
+SSG(15mg)+ Sorbitol(0.5ml)
HPMCE15(300mg)
4) +Pectin(200mg)+CCS(15mg) 100 0.11 275 40 sec
+SSG(15mg)+ Glycerol(0.5ml)
HPMCE15(300mg)
5) +Pectin(200mg)+CCS(15mg) 81 0.08 135 60 sec
+SSG(15mg)+ PEG 400(0.5ml)
HPMCE15(300mg)
6) +Pectin(200mg)+CCS(15mg) 74 0.07 185 66 sec
+SSG(15mg)+PG(0.5ml)
*PG- Propylene glycol, PEG- Polyethylene glycol

Figure 4: Effect of plasticizers on disintegration time

Figure 5: Effect of plasticizers on folding endurance

 Upendra C Galgatte et al /Int.J.PharmTech Res.2013,5(4) 1472

Conclusion
According to literature a film should be flexible and tough without being brittle. From the screening of
components used in formulation of fast dissolving oral films, the film prepared by using combination of
polymers such as HPMC E15, pectin, plasticizer such as propylene glycol and superdisintegrants such as SSG
and CCS improve hydrophilicity, mouth feel, disintegration time, flexibility of the strip and reduces the
brittleness of fast dissolving films.

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