A review on mouth dissolving films.
ABSTRACT The ultimate goal of any drug delivery system is the successful delivery of the drug to the body; however, patient compliance must not be overlooked. Fast dissolving drug delivery systems, such as, Mouth Dissolving Films (MDF), offer a convenient way of dosing medications, not only to special population groups with swallowing difficulties such as children and the elderly, but also to the general population. MDF are the novel dosage forms that disintegrate and dissolve within the oral cavity. Intra-oral absorption permits rapid onset of action and helps by-pass first-pass effects, thereby reducing the unit dose required to produce desired therapeutic effect. The present review provides an overview of various polymers that can be employed in the manufacture of MDF and highlights the effect of polymers and plasticizers on various physico-mechanical properties of MDF. It further gives a brief account of formulation of MDF and problems faced during its manufacture.
- [show abstract] [hide abstract]
ABSTRACT: Dysphagia, or difficulty in swallowing tablets, may greatly affect compliance. This report presents the results of our survey, which was undertaken to determine the proportion of a general practitioner's patient population who had difficulty in swallowing tablets, and to identify the reasons for the difficulty. 6,158 questionnaires were received from patients who consulted a general practitioner. More than 1/4 (26%) of the total patient population (or 1,576) said they had problems in swallowing tablets. A prominent complaint was the size of the tablet, followed by the surface, form and taste of the tablet. Twice as many women as men experienced swallowing problems. Elderly patients (> 70 years) had less difficulty than younger patients when taking tablets. To achieve good compliance and optimal pharmacotherapy, it is important for medical practitioners and pharmaceutical personnel to be aware of the general problems connected to swallowing tablets, to enable them to select the correctly formulated drug for their patients. New and novel oral drug formulations, such as tablets that dissolve in seconds on the tongue without water, may alleviate the problem of swallowing tablets. They offer substantial advantages over ordinary tablets, are more convenient to administer, and enhance the potential for improved compliance in patients who experience difficulty in taking tablets.Tidsskrift for Den norske legeforening 04/1995; 115(8):947-9.
- [show abstract] [hide abstract]
ABSTRACT: Within the oral mucosal cavity, the buccal region offers an attractive route of administration for systemic drug delivery. The mucosa has a rich blood supply and it is relatively permeable. It is the objective of this article to review buccal drug delivery by discussing the structure and environment of the oral mucosa and the experimental methods used in assessing buccal drug permeation/absorption. Buccal dosage forms will also be reviewed with an emphasis on bioadhesive polymeric based delivery systemsJournal of Pharmacy and Pharmaceutical Sciences 1(1):15-30. · 2.20 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Currently there is a high level of interest in the use of the oral cavity as a portal for drug entry to the systemic circulation. As a site for drug delivery the oral cavity offers advantages over the conventional gastrointestinal route and the parenteral and other alternative routes of drug administration. It provides direct entry into the systemic circulation thereby avoiding the hepatic first pass effect, ease of administration and the ability to terminate delivery when required. In addition the membranes that line the oral cavity are readily accessible and exhibit robustness and fast cellular recovery following local stress or damage. The oral cavity appears therefore to be a potential site for the delivery of drugs to the systemic circulation. However, this site is associated with limitations that restrict its use as a route for the systemic delivery of drugs. The low permeability of the membranes that line the oral cavity results in a low flux of drug; there appears to be the need to develop strategies which enhance drug penetration to improve bioavailability. The environment of the oral cavity and the continual secretion and swallowing of saliva are unique problems which need to be considered pre-formulation to ensure successful delivery of a drug via this route. This review highlights the advantages of systemically delivering drugs via the oral mucosa and discusses the membrane, drug, dosage form and environmental issues which limit its use as a site for systemic drug delivery.Advanced Drug Delivery Reviews. 01/1994;
Current Drug Delivery, 2009, 6, 469-476 469
1567-2018/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd.
A Review on Mouth Dissolving Films
Meenu Dahiya, Sumit Saha and Aliasgar F. Shahiwala*
National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, C/o. B.V. Patel Pharmaceutical
Education and Research Development Centre, S.G. Highway, Thaltej, Ahmedabad-380054, India
Abstract: The ultimate goal of any drug delivery system is the successful delivery of the drug to the body; however, pa-
tient compliance must not be overlooked. Fast dissolving drug delivery systems, such as, Mouth Dissolving Films (MDF),
offer a convenient way of dosing medications, not only to special population groups with swallowing difficulties such as
children and the elderly, but also to the general population. MDF are the novel dosage forms that disintegrate and dissolve
within the oral cavity. Intra-oral absorption permits rapid onset of action and helps by-pass first-pass effects, thereby re-
ducing the unit dose required to produce desired therapeutic effect. The present review provides an overview of various
polymers that can be employed in the manufacture of MDF and highlights the effect of polymers and plasticizers on vari-
ous physico-mechanical properties of MDF. It further gives a brief account of formulation of MDF and problems faced
during its manufacture.
Keywords: Mouth dissolving films, intraoral, film forming polymers, glass transition temperature, tensile strength, blooming.
means of drug administration. Most of the drugs are being
taken in the form of tablets and capsules by almost all pa-
tients, including adult, paediatric and geriatric patients.
However, around 26 – 50% of patients find it difficult to
swallow tablets and hard gelatin capsules . These patients
mainly include, elderly (who have difficulties taking conven-
tional oral dosage forms because of hand tremors and
dysphagia), paediatric patients (who are often fearful of tak-
ing solid oral dosage forms, owing to their underdeveloped
muscular and nervous systems)  and others which include
the mentally ill, developmentally disabled, patients who are
uncooperative, on reduced liquid-intake plans or nauseated,
and travellers who may not have access to water [3, 4]. In
addition, the relatively poor absorption, presence of abundant
digestive enzymes in the GI lumen and epithelium, post-
absorption efflux (i.e., by P-glycoprotein, etc.), and first-pass
metabolism by the hepatic enzymes and subsequent elimina-
tion, limit the ability of many drugs to reach therapeutic lev-
els by oral route . Moreover, a tablet (most common dos-
age form for this route) has to disintegrate in the gastrointes-
tinal tract followed by dissolution of the drug. These proc-
esses extend the time until efficacy to some extent, which is
undesirable in conditions, such as pain .
Oral route is most preferred and patient-convenient
linings of the nasal, rectal, vaginal, ocular, and oral cavity)
offer distinct advantages over oral administration for sys-
temic drug delivery. These advantages include possible by-
pass of first pass effect, avoidance of pre-systemic elimina-
tion within the GI tract, and, low enzyme activity. The nasal
Transmucosal routes of drug delivery (i.e., the mucosal
*Address correspondence to this author at the National Institute of Pharma-
ceutical Education and Research (NIPER)-Ahmedabad, C/o. B.V. Patel
Pharmaceutical Education and Research Development Centre, S.G. High-
way, Thaltej, Ahmedabad-380054, India; Tel: +91-79-27439375, 27416409;
Fax: +91-79-27450449; E-mail: email@example.com
administration of drugs, including numerous compound, pep-
tide and protein drugs, for systemic medication has been
widely investigated in recent years. However, the potential
irritation and the irreversible damage to the ciliary action of
the nasal cavity from chronic application of nasal dosage
forms, as well as the large intra- and inter-subject variability
in mucus secretion in the nasal mucosa, significantly affects
drug absorption from this site. Even though the rectal, vagi-
nal, and ocular mucosa offer certain advantages, the poor
patient acceptability associated with these sites renders them
reserved for local applications rather than systemic drug ad-
offers advantages over the conventional gastrointestinal
route and the parenteral and other mucosal routes of drug
administration. It provides direct entry into the systemic cir-
culation thereby avoiding the hepatic first pass effect, ease of
administration and the ability to terminate delivery when
required . Intraoral drug delivery has become an important
route of drug administration. Various intraoral dosage forms
have been developed, which includes adhesive tablets, gels,
ointments, patches, fast-dissolving drug delivery systems
(FDDDS). A fast-dissolving drug delivery system (FDDDS)
is the most convenient mode of administering drugs to over-
come problems related to swallowing difficulties. These de-
livery systems dissolve or disintegrate in the mouth rapidly,
without requiring any water to aid in swallowing . Disso-
lution within oral cavity also permits intra-oral absorption,
thus bypassing first-pass effects. FDDDS offer advantages
such as disintegration without water, rapid onset of action,
ease of transportability, ease of handling, pleasant taste, and
improved patient compliance. Fast dissolving drug delivery
was pioneered by scientists at Wyeth Laboratories in the UK
during the late 1970s, which resulted in patenting of the
"Zydis" drug delivery system . Most fast dissolving drug
delivery systems are in a tablet form . WOWTAB, Zydis,
Orasolv and Shearform are some of fast dissolving technolo-
As a site for drug delivery, oral cavity (intraoral route)
470 Current Drug Delivery, 2009, Vol. 6, No. 5 Dahiya et al.
gies that are in the form of tablets. However, Mouth Dissolv-
ing Tablets (MDT) are associated with certain limitations,
1. Despite the short disintegration/dissolution times of
MDT, the fear of taking solid tablets and the risk of
choking persists .
2. For their production , many MDT requires the expensive
3. MDT are sometimes difficult to carry, store and handle
(fragility and friability) .
4. MDT requires specialized and expensive packaging and
The above mentioned limitations of MDT have paved the
way for development of Mouth Dissolving Films (MDF) as
fast drug delivery systems. MDF are gaining interest as an
alternative to MDT to definitely eliminate patients’ fear of
MOUTH DISSOLVING FILMS (MDF)
ploys a water-dissolving polymer (generally a hydrocolloid,
which may be a bioadhesive polymer), which allows the
dosage form to quickly hydrate, adhere, and dissolve to re-
lease the drug when placed on the tongue or in the oral cav-
ity [12,13]. They are also known as fast-dispersing, mouth
dissolving, orally disintegrating, fast-melting, Quick-
dissolving films . MDF can provide a convenient and
effective vehicle for delivering active ingredients such as
pharmaceutical compounds and breath freshening agents, to
the mucosa of humans and animals . It allows the drug to
be delivered to the blood stream either intragastrically, buc-
cally or sublingually . As soon as MDF are taken, rapid
absorption of drug, through the sublingual route is possible,
which finally leads to quick onset of drug action.
A film or strip can be defined as a dosage form that em-
ents for formulating MDF is very important as MDF have to
disintegrate and/or dissolve quickly into the oral cavity. Be-
sides water-dissolving polymer, the formulation may include
other components depending on its intended use , viz.
pharmaceutical agents, antimicrobial agents, nutraceutical
ingredients, plasticizers, surfactants, colorants, sweetening
agents, saliva stimulating agents, flavors, flavor enhancers
and other excipients. A typical composition contains the fol-
The proper selection of incorporated excipients/ ingredi-
1 - 25 %
40 - 50 %
Plasticizers 0 - 20 %
Fillers, colour, flavour etc.
As polymers and plasticizers form the main body of
MDF, therefore, their properties greatly affect the character-
istics of MDF.
0 - 40 %
OTC products addressing therapeutic categories such as
cough/cold, sore throat, and antacid/gas relief as well as a
number of nutritional supplement applications. However, it
is finding increased use as a delivery system for prescription
To date, the commercial launch of MDF is primarily in
drugs as well. Oral mucosal delivery via MDF could become
a preferential delivery method for therapies in which rapid
absorption is desired, including those used to manage pain,
allergies, sleep difficulties, and central nervous system dis-
orders. Some of the commercially available MDF are listed
in Table 1.
for the selection of various excipients/ ingredients for the
development of MDF.
The review will subsequently deal with the brief outlines
SELECTION OF DRUG CANDIDATE FOR MDF
portant to take into consideration, the properties of the drug
candidate, like taste, irritancy, allergenicity and adverse
properties such as discolouration or erosion of the teeth .
Drug should have sufficient water-solubility and intraoral
absorption. In case of poorly soluble drugs, the solubility of
drug should be enhanced by the use of water-soluble salts or
complex. Even if the drug has little or no intra-oral absorp-
tion, rapid onset of action due to rapid dissolution within oral
cavity and hence rapid absorption through GIT can be a driv-
ing force in the selection of MDF as dosage forms.
The amount of medicament that can be used in the MDF
depends on the dose needed to provide an effective amount
of the medicament. However, intraoral absorption directly
into systemic circulation permits dose reduction. In order to
maintain its fast-dissolving characteristics, the thickness of
the film should be carefully controlled. This limits its load-
ing capacity for API to some extent . The amount of
drug that can be loaded onto a film delivery system is guided
by visual inspection results for blooming when loading vari-
ous levels of API onto film. Some of the API with their dose,
to be used per one strip of MDF are mentioned in Table 2
[19, 20, 21, 22]. The maximum loading of API depends on
the compatibility of the film forming polymers with APIs
and parameters such as pH of the system. Generally the
amount at which the drug does’nt bloom to the surface is
incorporated. Studies have shown that upto 10.1% benzo-
caine can be delivered in edible film systems consisting of
polymers, plasticizers, benzocaine or caffeine, sweeteners,
flavors, colorants, and processing aids without blooming. In
another system, which was a buccal film delivery system
containing polymers, benzocaine, and colorants upto 17.2%
benzocaine could be delivered without blooming .
Before selecting MDF as drug delivery systems, it is im-
SELECTION OF POLYMER
pend on the characteristics of film-forming polymer, which
forms 20 to 75% (w/w) of total dry wt. of the MDF [19, 23].
The selection of polymer, therefore, is one of the most im-
portant and critical parameter for the successful development
of the formulation. The polymers used should have good
hydrophilicity, rapid disintegration, good mouth feel, and
suitable mechanical properties. Along with its good solubil-
ity, the polymer should have sufficient mechanical, physico-
chemical and permeability properties. In order to remain
intact against the internal and external stresses developed
during storage and especially when exposed to environ-
mental conditions, a film should have high mechanical
strength with sufficient elongation and elasticity properties.
The physical and mechanical properties of the MDF de-
A Review on Mouth Dissolving Films Current Drug Delivery, 2009, Vol. 6, No. 5 471
Table 1. Commercial Oral Thin Film Dosage Form Products
Distributor API Strength(mg)
Diphenhydramine Hcl 2.5
Dextromethorphan 2.5 – 5.5 – 15
Folic Acid 1 – 5
Loratidine 10 – 20
Hughes medical corp.
Donepezil 5-10 Labtec
Dextromethorphan HBr 7.5, 15
Diphenhydramine HCl 12.5, 25
Phenylephrine HCl 2.5
Phenylephrine HCl/ Diphenhydramine HCl 5/12.5, 10/25
Phenylephrine HCl/ Dextromethorphan HBr 2.5/5, 10/20
Diphenhydramine HCl 12.5, 25 Pfizer
Phenylephrine HCl 10
Innozen Menthol 2.5
Table 2. Examples of Suitable Drug Candidate for MDFs
Drug Dose (mg) Indication
Dextrometrophan 10-20 Cough
Loratadine 10 Seasonal allergies
Sildenafil citrate 25-100 Erectile dysfunction
Cetrizine 5-10 Allergic Reaction
Nicotine 2 Smoking cessation
Diphenhydramine Hydrochloride 25
Dextromethorphan Hydrochloride 10-20 Cough
Azatadine Maleate 1 Allergic reactions
Chlorpheniramine Maleate 4 Allergic reactions
Brompheniramine Maleate 4 Allergic Reaction
Acrivastine 8 Symptoms of allergy
Famotidine 10 Ulcers
Ketoprofen 12.5 Menstrual pain
472 Current Drug Delivery, 2009, Vol. 6, No. 5 Dahiya et al.
These properties of films developed from the polymers are
dominated by polymer chemistry, solvent effects, and addi-
tives such as plasticizer, sugars, and humectants. The poly-
mers used in the films are cellulose derivatives (hydroxypro-
pylmethyl cellulose, hydroxyethyl cellulose, hydroxypropyl
cellulose, carboxymethyl cellulose), synthetic polymers
(polyvinyl alcohol, polyethylene glycol, polyacrylic acid,
methylmethacrylate copolymer, polyvinyl pyrrolidone, car-
boxyvinyl polymer), natural gums (xanthan gum, tragacanth
gum, guar gum, acacia gum, arabic gum), starch derivatives
(amylose, high amylose starch, hydroxypropylated high
amylose starch), polysaccharides (dextrin, pectin, chitin,
chitosan, levan, sodium alginate) and peptides (elsinan, col-
lagen, gelatin, zein, gluten, soy protein isolate, whey protein
isolate, casein) and others .
PHYSICO-MECHANICAL PROPERTIES OF FILMS
Tensile Strength, Elastic Modulus, Elongation at Break
and elasticity of the film, reflected by the parameters, strain,
tensile strength (TS), elastic modulus (EM) and elongation at
break (E/B). Strain is the geometrical measure of deforma-
tion representing the relative displacement between particles
in a material body, when stress induced by either external
force or temperature change. A high strain value indicates
that the film is strong and elastic. Tensile strength is the
stress at which a material breaks or permanently deforms.
Tensile strength is an intensive property and, consequently,
does not depend on the size of the test specimen. However, it
is dependent on the preparation of the specimen and the tem-
perature of the test environment and material. An elastic
modulus also referred as young’s modulus, is the mathemati-
cal description of a material's tendency to be deformed elas-
tically when a force is applied to it. 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 tensile testing gives an indication of the film strength
EM and E/B; a hard and brittle polymer is defined by a mod-
erate TS, high EM and low E/B; a soft and tough polymer is
characterized by a moderate TS, low EM and high E/B;
A soft and weak polymer is characterized by a low TS,
whereas a hard and tough polymer is characterized by a high
TS, EM and E/B . Hence, it is suggested that a film
should have a moderately high TS, E/B and Strain but a low
Glass Transition Temperature (Tg)
at which brittle polymer becomes soft or plastic. Cohesive
strength and inter-chain attraction, and, thus glass transition
temperature (Tg) of the polymer are related to the presence,
concentration, location and relative polarities of functional
groups along the polymer chain, rigidity of the polymer
backbone, bulkiness of side groups and also molecular
weight of the polymer. Polymer with low Tg form films that
are flexible, with a low elastic modulus and exceptionally
high percent elongation . Films formed with polymer
having very high values of Tg are stiff, with a high elastic
modulus and a very low percent elongation. Above parame-
ters dictate the selection of polymers to obtain desired MDF.
Therefore it is important to consider all the above parameters
of the polymer. Tg values of some of the important polymers
have been enlisted in Table 3.
The Glass transition temperature, Tg, is the temperature
EFFECT OF POLYMERS
pullulan, a glucan consisting of maltotriose units, produced
from starch by the fungus Aureobasidium pullulans .
This review further deals with brief introduction to various
polymers that are being used widely.
The first material employed to produce edible films was
good film forming properties and has excellent acceptability.
Lower grades of HPMC like Methocel E3, Methocel E5 and
Methocel E15 are particularly used for MDFs because of
their low viscosity. The Tg of HPMC grades were deter-
mined to be 160, 170, and 175 oC, respectively . For the
HPMC E series, the maximum puncture strength of the E
series increased when the molecular weight of the polymer
increased: E3 < E5 < E15 < E50. Mishra and Amin (2009)
formulated and developed taste-masked fast dissolving film
of cetirizine using HPMC with various viscosity grades (i.e.,
E3, E5 and E15) as the film-forming polymer, and solvent
Hydroxypropyl Methylcellulose (HPMC) is known for its
Table 3. Properties of Some Important Film Forming Polymers
Polymer Molecular wt, g/mol. Glass transition temp., K Tensile strength, MPa
Hydroxypropyl cellulose 336 298 13.8
Cellulose 106 503 200-800
Poly(vinyl alcohol) 25,000 -100,000 358 36 (extruded)
Poly(ethylene oxide) 44 232 -
Poly(vinyl acetate) 86.09 301-304 29.0-49.0
Poly(vinyl chloride) 62.5 353 (at 90 deg C) 56.6(Unplasticized)
Corn starch 1.45 ? 107 496 46.1
A Review on Mouth Dissolving Films Current Drug Delivery, 2009, Vol. 6, No. 5 473
casting as a method of manufacture . They found that the
in vitro disintegration time and in vitro dissolution profiles
of the MDF were highly affected with the various grades of
HPMC and concluded that HPMC E3 LV was the most suit-
able grade for the manufacture of MDFs. In another study, it
is found that Methocel E3 (with 5% glycerol) has in-vivo
disintegration time of 6 seconds and in-vivo dissolution time
of 37 seconds . Dinge and Nagarsenker (2008) formu-
lated fast dissolving films containing HPMC (Methocel E3,
E5, E15), xanthan gum, and xylitol for intraoral delivery of
Triclosan. The solubility of TC was improved by incorpora-
tion of solubilizers such as HPBCD and poloxamer 407.
From the in vitro and in vivo evaluation, it was concluded
that films could be considered as an innovative dosage form
to improve delivery of TC .
and in vitro bioadhesive strength of SCMC films (sodium
carboxymethyl cellulose/polyethylene glycol 400/carbopol
934P) and HPMC films (hydroxypropylmethyl cellu-
lose/polyethylene glycol 400/carbopol 934P) as drug vehicle
for buccal delivery. HPMC films were found to be tougher,
more elastic, more bioadhesive in vivo and swelled in a more
tolerable manner in the oral cavity compared to SCMC films
Peh and Wong (1999) have investigated the mechanical
Poly (Ethylene Oxide)
weight water-soluble polymer. Poly (ethylene oxide) (PEO)
is a thermoplastic semicrystalline polymer with a melting
point ranging from 60 oC to 75 oC and a glass transition tem-
perature of – 67 oC. PEO films, because of their negative
glass transition temperature (–67 oC)  and chemical
structure of PEO, were found to be flexible with a low elastic
modulus and exceptionally high percent elongation. PEO
films exhibit higher bioadhesivity because of the extremely
flexible PEO structure, which can result in stronger inter-
penetration of the polymer and mucin chains . It is com-
mercially available under tradename of POLYOX™. Polyox
polymer that may be used in the oral film is Polyox N-80.
Polyox N-80 has an approximate molecular weight of
200,000 and a viscosity of about 65 to 115 mPa/s (5% aque-
ous solution at 25 oC) . They exhibit many properties
that are typical of other classes of water-soluble polymers –
lubricity, binding, water retention, thickening, and film for-
mation. In a study, various grades of Polyox were analysed
for mechanical properties. It was found that the increase in
molecular weight causes an increase in mechanical strength.
It was also found that due to the nature of poly(ethylene ox-
ide) chemistry with lower Tg and more flexibility, the punc-
ture strength of PEO is much lower than that of cellulose
based MC and HPMC polymers . Polyox N-80 has in-
vivo disintegration time of 4 seconds and in-vivo dissolution
time of 23 seconds which is comparable with the commer-
cially available Listerine films.
Poly (ethylene oxide) is a nonionic, high molecular
soluble thermoplastic polymer. It is partially substituted poly
(hydroxypropyl) ether of cellulose. It is an amorphous poly-
mer that softens between 100 oC and 150 oC based on its
Hydroxypropyl cellulose (HPC) is a non-ionic water-
molecular weight. HPC is commercially available in a num-
ber of different grades, which have different solution viscosi-
ties. The molecular weight of the HPC ranges from about
50,000 to about 1,250,000 . It is known that films
formed with polymers having very high glass transition temp
values are stiff , therefore, cellulose (Tg = 500) is not
suitable as film forming polymer. Its synthetic derivatives,
such as HPC, HPMC having comparatively lower Tg values
are therefore preferred. Because of relatively high glass tran-
sition temperatures (compared to other film forming poly-
mers) of HPC , the formed films were shown to exhibit
brittle fracture and were found to be stiff, with a high elastic
modulus and a very low percent elongation (less than 5%)
. Typically slow dissolving, the films have good carrying
capacity and reasonable clarity.
consisting of ?–1, 6-linked maltotriose residues. It is a fungal
exopolysaccharide produced from starch by Aureobasidium
pullulans . Films formed with pullulan are highly water-
soluble, colorless, tasteless, odourless, transparent, flexible,
possess low permeability to oil and oxygen, and heat-
sealable. These properties make them an ideal material for
edible films . Pullulan-based films are easy to manufac-
ture, however, the use of this material is limited by its low
availability and high costs. To overcome this limitation Tong
et al. (2008) blended them with other compatible polymers
that are abundant and lower in cost, such as sodium alginate
and CMC. Kawahara et al. studied the dependence of prepa-
ration temperature on the Mechanical properties of a Pullu-
lan Film. It was found that the films obtained at higher tem-
perature were more brittle, less flexible than films formed at
lower temperature. Pullulan has been shown to have in-vivo
disintegration time of 6 seconds and in-vivo dissolution time
of 48 seconds.
Pullulan is a water soluble, neutral linear polysaccharide
Modified Carboxymethyl Cellulose
cally modified to reduce molecular weight. This type of ma-
terial is ideal for applications requiring a fast dissolving
base. Also capable of carrying a range of active components,
CMC has a neutral flavour and produces films with excellent
clarity and good dimensional stability .
CMC is a cellulose derivative which has been enzymati-
apples. Pectins are good film formers with good capacity to
carry drugs and are particularly suitable for low pH applica-
tions. Solubility of the films depends on molecular weight of
the polymer, but generally it dissolves slowly in the oral cav-
ity . It has been found that pectin (X-939-04) films have
an in-vivo disintegration time of 15 seconds and in-vivo dis-
solution time of 141 seconds . The high intrinsic viscos-
ity of pectin prevents formation of thin films with high load-
ing levels of actives. Pectin films are also known to impart
uncomfortable mouth feel during dissolution of the film in
the mouth. In a study, it was found that degradation of pectin
(modified pectin) reduces its intrinsic viscosity from 4.9 dl/g
to 2.5 dl/g making it more suitable for use in MDF .
Pectin is a carbohydrate obtained from citrus fruits and
474 Current Drug Delivery, 2009, Vol. 6, No. 5 Dahiya et al.
teins of high molecular weight. Gelatin is nearly tasteless,
odorless, colorless or slightly yellow, transparent, brittle
flakes, or powder. Gelatin swells and absorbs 5-10 times its
weight of water to form a gel in aqueous solutions between
30-35°C . Derived from the natural protein collagen,
gelatin is widely used in food and pharmaceutical industry.
Gelatin films dissolves rapidly, are excellent carriers for fla-
vours and produces a smooth mouth feel . It has been
found that gelatin films have an in-vivo disintegration time of
8 seconds and in-vivo dissolution time of 40 seconds .
However, the property of gelatin to form a highly viscous gel
(upon hydration with saliva in the mouth) makes it less ac-
ceptable for use in MDF in comparison to other polymers.
Gelatin is a heterogeneous mixture of water-soluble pro-
lymerized Rosin (PR) was examined for its drug delivery
applications . Neat PR films were found to be slightly
brittle and posed the problem of breaking during handling.
Incorporation of Hydrophobic plasticizers improved the me-
chanical properties of films. Cilurzo et al. studied maltodex-
trins (MDX) with a low dextrose equivalent as film forming
material and their application in the design of oral fast-
dissolving films. It was found that Maltodextrins having low
dextrose equivalent, plasticized with 16–20% w/w glycerine
were found to be suitable for producing fast-dissolving films
Choa et al. (2007) prepared edible films from membrane
processed soy protein concentrate (MSC) at various film
forming solution pHs, and their mechanical, barrier, and
physical properties were compared with soy protein isolate
(SPI) films. They also observed that as the film solution pH
increased from 7 to 10, the resulted MSC films were more
transparent, yellowish, and had lower oxygen permeabilities.
However, tensile strength (TS), modulus of elasticity (ME)
and water vapor permeabilities of MSC films were not af-
fected by film solution pHs .
A low molecular weight film forming biopolymer, Po-
EFFECT OF PLASTICIZERS
change hard and brittle films to more pliable and tougher
form. Plasticizer is usually low molecular weight organic
solvent, having Tg values of -50oC to -150oC. Most of the
polymers used in film coating are either amorphous or have
very little crystallinity. Most commonly employed plasticiz-
ers are glycerol, propylene glycol, sorbitol, and/or polyethyl-
ene glycol. The plasticizer may be present in any desired
amount, particularly from 0 to about 50 percent, more typi-
cally from 5 to about 20 by weight of the active containing
formulated film . Plasticizer molecules interpose them-
selves between the individual polymer strands; thus, break
down polymer-polymer interactions to a large extent. This
action is facilitated as the polymer plasticizer interaction is
considered to be stronger than the polymer-polymer interac-
tion thus providing greater opportunity to polymer strands to
move past each other. The interaction of the plasticizer with
the polymer generally decreases the elastic modulus, lowers
the softening temperature, and decreases the Tg . As a
Plasticizers are the essential additives that are able to
result of decrease in the Tg, the films formed are more flexi-
ble . Plasticizers also tend to decrease the tensile strength
of polymeric films.
cal properties of methyl cellulose(MC) films were deter-
mined. It was observed that among (polyethylene glycols
[PEG] 400, 1,450, 8,000 and 20,000, glycerol [G] and pro-
pylene glycol [PG]),with the exception of PG, all plasticizers
decreased the tensile strength of MC films, with PEG 400
causing the largest decrease. With the exception of PG and
PEG 400, all plasticizers increased percent elongation values
of MC films, with PEG 1,450 having the greatest effect.
Glycerol and PEG were found to be the most effective plas-
ticizers for MC . Chetty et al. (2002) investigated the
physical and mechanical characteristics of HPC films plasti-
cized with glycerin, propylene glycol or sorbitol. The HPC
films displayed increasing puncture strengths with higher
concentrations of polymer. Film strengths were function of
both the nature and concentration of the plasticizers. Higher
concentrations (3 % w/w) of glycerin reduced puncture
forces (from 342.9 g to 80.3 g for the 5 % HPC film) while
lower concentration (1 %) was shown to have a negligible
effect on the puncture force of HPC films. The increased
plasticizer content of the films caused higher water retention
by the polymer, which resulted in more flexible films. An
increase of plasticizer from 1 to 3 % in the 5 % HPC film
caused a 68 % increase in water retention. Further incre-
ments of plasticizer concentration showed little reduction of
puncture forces. The authors concluded that the plasticiza-
tion of hydrophilic films facilitates manipulation of the me-
chanical properties of films thereby allowing optimization of
drug delivery rates .
In a study, the effects of various plasticizers on mechani-
film permeability to moisture and oxygen, make the film
more labile to hydrolytic and oxidative degradation .
However, Plasticizers have disadvantage of increasing
FORMULATION ASPECTS OF MOUTH DISSOL-
sion extrusion, Rolling, Semi-solid casting, and Solvent cast-
ing are used to manufacture the films. The current preferred
manufacturing process for producing films is solvent casting.
Solvent casting involves preparation of solution containing
drug and film-forming excipients with volatile solvents fol-
lowed by casting of a thin coat of solvent blend onto a mov-
ing, inert substrate. Drying of the coated film is done by
passing through hot air flow such as drying oven to evapo-
rate the solvent before die-cutting the dried film into strips.
Mashru et al. (2005) prepared Salbutamol films using Sol-
vent-casting method . Triclosan films were also prepared
by the same method. MDFs can also be produced using hot-
melt extrusion (HME) technique. This technique involves
melting of drug–excipients mixture followed by extruding it
through a die under molten conditions. The thin film is then
cooled to room temperature and die-cut into small strips.
Extruders are not common in the pharmaceutical industry
due to the high cost of the extruders . Prodduturi et al.
(2007) used this technique to produce Lidocaine films .
Cilurzo et al. (2008) prepared films using both solvent cast-
ing and hot-melt extrusion. It was reported that the solvent-
Various processes like Hot-melt extrusion, Solid disper-
A Review on Mouth Dissolving Films Current Drug Delivery, 2009, Vol. 6, No. 5 475
casting method is more reliable for the production of fast-
dissolving films compared to the hot-melt extrusion method.
Moreover, MDFs produced from solvent casting method
exhibited the highest patients’ compliance and best perform-
ances in terms of in vitro and in vivo disintegration time .
However, it has been shown that the solvent cast method
suffers from several disadvantages over the HME method.
Gutierrez-Rocca et al. (1999) demonstrated that polymeric
films prepared by a solvent cast method turned brittle during
the storage, as indicated by decrease in the percentage of
elongation due to the evaporation or loss of the residual sol-
vent in the film with time . In addition, HME has several
advantages including it being a solvent-free, continuous, less
time and energy consuming process.
turing like foaming (during the film formation due to the
heating of the material or solvent evaporation), flaking (dur-
ing the slitting) and cracking (in the cutting phase) limit its
market reach. Moreover, the MDF are greatly affected by
environmental conditions such as high humidity .
However, various problems observed during its manufac-
circumvent problems associated with solid dosage forms.
The commercial launch of MDFs was primarily in OTC, but
now their use has been extended to prescription drugs. MDF
are preferred to MDT which requires expensive manufactur-
ing, special packaging due to their fragile nature. Selection
of polymers and plasticizers greatly affects physico-
mechanical properties of MDF. Parameters such as, glass
transition temperature, and molecular weight of polymers
has a significant influence on mechanical properties of MDF.
Thus, with a proper polymer-plasticizer combination, desired
MDF can be formed and can be used as reliable delivery
systems for most of the therapeutic agents.
MDFs are convenient and reliable dosage forms that can
Anderson, O.; Zweidorff, O.K.; Hjelde, T. Problems when swal-
lowing tablets. A questionnaire study from general practice [in
Norwegian]. Tidsskr Nor Laegeforen, 1995, 20, 947-9.
Slowson, M.; Slowson, S. What to do when patients cannot swal-
low their medications. Pharm. Times, 1985, 51, 90-96.
Lindgren, S.; Janzon, L. Dysphagia: Prevalence of swallowing
complaints and clinical findings. Med. Clin. N. Am., 1993, 77, 3-5.
Chang, R.K.; Guo, X.; Burnside, B.A. Fast-dissolving tablets.
Pharm. Tech., 2000, 24(6), 52-58.
Vollmer, U.; Galfetti, P. RapidFilm: Oral Thin Films (OTF) as an
Innovative Drug Delivery System and Dosage Form, Technology
overviews. Drug Delivery Report Spring/Summer, 2006, 18-21.
Shojaei, A.H. Buccal Mucosa As A Route For Systemic Drug
Delivery: A Review. J. Pharm. Pharmaceut. Sci., 1998, 1(1), 15-
Rathbone, M.J.; Drummond, B.K.; Tucker, I.G. The oral cavity as a
site for systemic drug delivery. Adv. Drug Deliv. Rev., 1994, 13, 1-
Liang, A.C.; Chen, L.H. Fast-dissolving Intraoral drug delivery
systems. Expert Opin. Ther. Pat., 2001, 11(6), 981-986.
Virley, P.; Yarwood, R. Zydis - a novel, fast-dissolving dosage
form. Manuf. Chem., 1990, 61, 36-37.
Borsadia, S.B.; Halloran, D.O.; Osborne, J.L. Quickdissolving
films—a novel approach to drug delivery. Drug Deliv. Technol.,
Cilurzo, F.; Cupone, I. E.; Minghetti, P.; Selmin, F.; Montanari, L.
Fast dissolving films made of maltodextrins. Eur. J. Pharm. Bio-
pharm., 2008, 70(3), 895-900.
Ghosh, T.K.; Pfister, W.R. Drug delivery to the oral cavity: Mole-
cules to Market; Marcel Dekker Inc., New York, 2005.
Dinge, A.; Nagarsenker, M. Formulation and Evaluation of Fast
Dissolving Films for Delivery of Triclosan to the Oral Cavity.
AAPS PharmSciTech., 2008, 9(2), 349-56.
Saigal, N.; Baboota, S.; Ahuja, A.; Ali, J. Fast-dissolving Intraoral
drug delivery systems. Expert Opin. Ther. Pat., 2008, 18(7), 769-
Barnhart, S.D.; Full, A.P.; Moritz, C. Rapidly dissolving films for
delivery of pharmaceutical or cosmetic agents. U.S. Patent
60/513,547, December 03, 2004.
Thin film drug delivery, http://en.wikipedia.org/wiki/Thin_film_
Hang, J. Dissolving films. U.S. Patent 20070184093, August 09,
Chen, M.J.; Tirol, G.; Bass, C.; Corniello, C.; Watson, G.; Sanchez,
I. Castable Edible Pharmaceutical Films. Poster presented at An-
nual Meeting and Exposition of the American Association of
Pharmaceutical Scientists November 11–15, 2007; American Asso-
ciation of Pharmaceutical Scientists, San Diego, California.
Kulkarni, N.; Kumar, L.D.; Sorg, A. Fast dissolving orally con-
sumable films containing an antitussive and a mucosa coating
agent. U.S. Patent 20030206942, April 04, 2003.
Leung, S.S.; Leone, R.S.; Kumar, L.D. Fast dissolving orally con-
sumable films. U.S. Patent 6596298, July 07, 2003.
Labtec Pharma- Rapidfilm® Technology, http://www.labtec-
Zerbe, H.G.; Guo, J.; Serino, A. Water soluble film for oral admini-
stration with instant wettability. U.S. Patent 6177096, September
Peh, K.K.; Wong, C.F. Polymeric Films As Vehicle For Buccal
Delivery: Swelling, Mechanical, and Bioadhesive Properties. J.
Pharm. Pharm. Sci., 1999, 2(2), 53-61.
Aulton, M.E.; Abdul-Razzak, M.H.; Hogan, J.E. The mechanical
properties of hydroxypropylmethylcellulose films derived from
aqueous systems Part1: The influence of Plasticizers. Drug Dev.
Ind. Pharm., 1981, 7(6), 649-668.
Prodduturi, S.; Urman, K.L.; Otaigbe, J.U.; Repka, M.A. Stabiliza-
tion of Hot-Melt Extrusion Formulations Containing Solid Solu-
tions Using Polymer Blends. AAPS PharmSciTech, 2007, 8(2), E1-
Leathers, T.D. Biotechnological production and applications of
pullulan. Appl. Microbiol. Biotechnol., 2003, 62, 468–473.
Mark, J.E. Polymer Data Handbook; Oxford University Press Inc.,
New York, 1999.
Kararli, T.T.; Hurlbut, J.B.; Needham, T.E. Glass-rubber transitions
of cellulosic polymers by dynamic mechanical analysis. J. Pharm.
Sci., 1990, 79(9), 845-8.
Mishra, R.; Amin, A. Formulation Development of Taste-Masked
Rapidly Dissolving Films of Cetirizine Hydrochloride. Pharm.
Tech., 2009, 33(2), 48-56.
Odian, G.G. Principles of Polymerization; Polyethylene oxide;
John Wiley and Sons, New York, 2004.
Fankhauser, C.E.; Slominski, G.; Meyer, S. Disintegrable Oral
Films. EP 20070757022, November 26, 2007.
Rangineni, S.; Bhagwatwar, H.P.; Devarakonda, S.N.; Agarwal,
S.K. Zafirlukast Composition. U.S. Patent 20070197467, August
Physical and Chemical Properties. Klucel, Hydroxypropylcellulose.
2-6. Wilmington, DE: Hercules Incorporated, Aqualon Division;
American Association of Pharmaceutical Scientists Annual Meet-
ing, Boston, MA, November 4, 1997, American Association of
Pharmaceutical Scientists, Boston, USA, 1997.
Tong Q.; Xiao Q.; Lim L. T. Preparation and properties of pullu-
lan-alginate-carboxymethylcellulose blend films. Food Res. Int.,
2008, 41, 1007-1014.
rticle&id=59&Itemid=22. Biofilm, Principal Film Formers.
Puri, R.; Zielinski, R.G. Dissolvable film. EP 06017352.3, August
Gelatin processing, National Organic Standards Board Technical
Advisory Panel. Review Compiled by Organic Materials Review
Institute for the USDA National Organic Program, 2002, 1-25.
476 Current Drug Delivery, 2009, Vol. 6, No. 5 Dahiya et al.
Fulzele, S.V.; Satturwar, P.M.; Dorle, A.K. Polymerized rosin:
novel film forming polymer for drug delivery. Int. J. Pharm., 2002,
Choa, S. Y.; Park, J. W.; Batt, H. P.; Thomas, R. L. Edible films
made from membrane processed soy protein concentrates. LWT-
Food Sci. Technol., 2007, 40(3), 418–423.
Puri, R.; Zielinski, R.G. Dissolvable film. EP1757279, February
McGinity, J.W.; Felton, L.A. Aqueous polymeric coatings for
pharmaceutical dosage forms; Marcel Dekker Inc., New York,
Cole, G.; Hogan, J.; Aulton, M.E. Pharmaceutical coating technol-
ogy; Informa Health Care, 1995.
Donhowe, G.; Fennema, O. The effects of plasticizers on crystallin-
ity, permeability, and mechanical properties of methylcellulose
films. J. Food Process. Pres., 2007, 17(4), 247-257.
Chetty, D.J.; Deshpande, G.S.; Lech, S.J. Physical and Mechanical
Characterization of Hydrophilic Films for Rapid Intra-Oral Drug
New Product Development,
Han, J.H. Innovations in food packaging, Elsevier academic press:
Amsterdam, 2005, pp. 414-415.
Mashru, R.C.; Sutariya, V.B.; Sankalia, M.G.; Parikh, P.P. Devel-
opment and Evaluation of Fast-Dissolving Film of Salbutamol Sul-
phate. Drug Dev. Ind. Pharm., 2005, 1, 25-34.
Are Orally Dissolving Strips Easy for Manufacturers to Swallow?
Gutierrez-Rocca, J.C.; McGinity, J.W. Influence of aging on the
physical-mechanical properties of acrylic resin films cast from
aqueous dispersions and organic solutions. Drug Dev. Ind. Pharm.,
1999, 19(3), 315–332.
Received: June 16, 2009 Revised: August 12, 2009 Accepted: August 12, 2009