FILM AND STRIP FOR

DRUG DELIVERY

Presented by: Harshad Parmar

 Introduction

The film drug delivery uses a dissolving film or oral

drug strip to administer drugs via absorption in the
mouth (buccally or sublingually) and/or via the small
intestines (enterically).
The film drug delivery has emerged as an advanced
alternative to the traditional tablets, capsules and liquids
often associated with prescription and OTC medications.
Similar in size, shape and thickness to a postage stamp,
film and strips are typically designed for oral
administration, with the user placing the strip on or
under the tongue or along the inside of the cheek.
A film is prepared using hydrophilic polymers that rapidly
dissolves on the tongue or buccal cavity, delivering the
drug to the systemic circulation via dissolution when
contact with liquid is made.
As the strip dissolves, the drug can enter the
bloodstream enterically, buccally  or sublingually.
Evaluating the systemic transmucosal drug delivery,
the buccal mucosa is the preferred region as compared to
the sublingual mucosa.
History

Undergraduate biomedical engineering students

at Johns Hopkins University , have created a new drug
delivery system based on the thin film technology
used by a breath freshener.
Laced with a vaccine against rotavirus, the strips
could be used to provide the vaccine to infants in
impoverished areas.
The first commercial non-drug product to use thin
films was the Listerine PocketPaks,breath freshening
strips.
Since then, thin film products for other breath
fresheners, as well as a number of cold, cough, flu and
anti-snoring medications, have entered the
marketplace.
 There are currently several projects in development
that will deliver prescription drugs utilizing the thin
film dosage form.
 Advantages

The sublingual and buccal delivery of a drug via film has

the potential to improve the onset of action, lower the
dosing, and enhance the efficacy and safety profile of the
medicament
All tablet dosage forms, softgels and liquid formulations
primarily enter the blood stream via the gastrointestinal
tract, which subjects the drug to degradation from stomach
acid, bile, digestive enzymes and other first pass effects. As
a result, such formulations often require higher doses and
generally have a delayed onset of action.
Thin film is more stable, durable and quicker dissolving
than other conventional dosage forms
The film enables improved dosing accuracy relative to liquid
formulations since every strip is manufactured to contain a
precise amount of the drug.
The film not only ensures more accurate administration of
drugs but also can improve compliance. These properties are
especially beneficial for pediatric, geriatric and
neurodegenerative disease patients where proper and complete
dosing can be difficult.
The film’s ability to dissolve rapidly without the need for water
provides an alternative to patients with swallowing disorders
and to patients suffering from nausea, such as those patients
receiving chemotherapy.
The film drug delivery has the potential to allow the
development of sensitive drug targets that may otherwise not
be possible in tablet or liquid formulations.
 Oral drug strip development
Formulation of oral drug strips involves the application of both
aesthetic and performance characteristics such as
strip-forming polymers, 
plasticizers,
active pharmaceutical ingredient,
 sweetening agents, 
Saliva stimulating agent,
flavoring agents, coloring agents,
 stabilizing and thickening agents.
 From the regulatory perspectives, all excipients  used in the
formulation of oral drug strips should be approved for use in
oral pharmaceutical dosage forms.
 Strip forming polymers
The polymer employed should be non-toxic, non-irritant and devoid
of leachable impurities. It should have good wetting and
spreadability property.
The polymer should exhibit sufficient peel, shear and tensile
strengths. The polymer should be readily available and should not
be very expensive.
Film obtained should be tough enough so that there won't be any
damage while handling or during transportation.
Combination of microcrystaline cellulose and maltodextrin has been
used to formulate
Oral Strips of piroxicam made by hot melt extrusion technique.
Plasticizer

Plasticizer is a vital ingredient of the Oral Strip formulation. It

helps to improve the flexibility of the strip and reduces the
brittleness of the strip.
Plasticizer significantly improves the strip properties by
reducing the glass transition temperature of the polymer. 
Glycerol, Propylene glycol, low molecular weight
polyethylene glycols, phthalate  derivatives
like dimethyl, diethyl and dibutyl phthalate   Citrate derivatives
such as tributyl, triethyl, acetyl citrate, triacetin and castor oil
are some of the commonly used plasticizer excipients.
Active pharmaceutical ingredient

Since the size of the dosage form has limitation, high dose
molecules are difficult to be incorporated in Organic
Solvent.
Generally 5%w/w to 30%w/w of active pharmaceutical
ingredients can be incorporated in the Organic Solvent.
Sweeting, flavoring and coloring
agents

An important aspect of thin film drug technology is

its taste and color.
The sweet taste in formulation is more important in
case of pediatric population.
Natural sweeteners as well as artificial sweeteners
are used to improve the flavor of the mouth
dissolving formulations for the flavors changes from
individual to individual. Pigments such as titanium
dioxide is incorporated for coloring.
Stabilizing and thickening agents
The stabilizing and thickening agents are employed to improve
the viscosity and consistency of dispersion or solution of the
strip preparation solution or suspension before casting.
 Drug content uniformity is a requirement for all dosage forms,
particularly those containing low dose highly potent drugs.
To uniquely meet this requirement, thin film formulations
contain uniform dispersions of drug throughout the whole
manufacturing process.
 Since this criteria is essential for the quality of the thin film
and final pharmaceutical dosage form, the use of Laser
Scanning Confocal Microscopy (LSCM) was recommended to
follow the manufacturing process.
 TYPES OF FILMS

Matrix type( Bi-directional): The buccal film designed in a

matrix configuration contains drug, adhesive, and additives
mixed together.
Bi-directional (Figure 1) films release drug in both the
mucosa and the mouth

Film designed for Bidirectional drug release

 2. Reserviour type(Unidirectional): The buccal film
designed in a reservoir system contains a cavity for the
drug and additives separate from the adhesive. An
impermeable backing is applied to control the
direction of drug delivery; to reduce film deformation
and disintegration while in the mouth; and to prevent
drug loss.

Buccal film designed for Uni directional drug release

METHOD OF PREPARATION
1 Solvent casting
In this, all film excipients including the drug co-
dispersed in an organic solvent and coated onto a
sheet of release liner.
After solvent evaporation, a thin layer of the
protective backing material is laminated onto the
sheet of coated release liner to form a laminate
that is die-cut to form patches of the desired size
and geometry.
Direct milling
 In this, fims are manufactured without the use of solvents
(solvent-free). Drug and excipients are mechanically
mixed by direct milling or by kneading, usually without
the presence of any liquids. After the mixing process, the
resultant material is rolled on a release liner until the
desired thickness is achieved. The backing material is
then laminated as previously described.
 While there are only minor or even no differences in film
performance between flms fabricated with the two
processes, the solvent-free process is preferred because
there is no possibility of residual solvents and no
associated solvent-related health issues.
Evaluation

Physical evaluation
It includes- Weight uniformity, Content uniformity,
Thickness- uniformity.
Mass uniformity tested in different randomly selected
patches from each batch and patch thickness
measured at 5 different randomly selected spots using
a screw gauge.
Swelling index:

Buccal films were weighed individually (W1) and placed

separately in 2% agar gel plates with the core facing the
gel surface and incubated at 37-C ±1-C. At regular 1-
hour time intervals until 6 hours, the tablet was
removed from the Petri dish, and excess surface water
was removed carefully with filter paper. The swollen was
then reweighed (W2) and the swelling index (SI) was
calculated using the formula given in equation.
Swelling Index = (W2-W1) X 100
W1
In vitro drug release
The United States Pharmacopeia (USP) XXIII rotating
paddle method used to study the drug release film or
strip. The dissolution medium consisted of phosphate
buffer pH 6.8.
The release was performed at 370C ± 0.50C, with a
rotation speed of 50 rpm. The backing layer of buccal
film attached to the glass disk with instant adhesive
(cyanoacrylate adhesive).
 The disk was allocated to the bottom of the dissolution
vessel. Samples (5 mL) were withdrawn at predetermined
time intervals and replaced with fresh medium.
 The samples filtered through Whatman filter paper and
analyzed after appropriate dilution by UV
spectrophotometry at suitable nm.
 Measurement of Mechanical Properties

Mechanical properties of the films (patches) includes tensile

strength and elongation at break evaluated using a
microprocessor based advanced force gauze equipped with a
motorized test stand equipped with a 25 kg load cell OR The
istronâ tensile tester.
Film or strip with the dimensions 60 x 10 mm and without
any visual defects cut and positioned between two clams
separated by a distance of 3 cm.
 Clamps designed to secure the film without crushing it
during the test, the lower clamp held stationary and the strips
were pulled apart by the upper clamp moving at a rate of 2
mm/sec until the strip broke.
The force and elongation of the film at the point when
the strip break are recorded. The tensile strength and
elongation at break values are calculated using the
formula.

Tensile strength = Force at break (kg)

(kg/mm-2) Initial cross sectional area of sample(mm2)
Folding Endurance

The folding endurance of films was determined by

repeatedly folding 1 film at the same place till it breaks.
Repeat the experiment thrice and note down average
value.
Ageing
Films subjected to accelerated stability testing. Films
packed in glass Petri dishes lined with aluminum foil
and kept in an incubator maintained at 37±0.5 0C and
75±5% RH for 6 months.
Changes in the appearance, residence time, release
behavior and drug content of the stored bioadhesive
films investigated after 1, 2, 3, 4, 5, and 6 months.
 The data presented the mean of three determinations.
Fresh and aged medicated patches, after 6 months
storage, investigated using scanning electron
microscope.
Commercial Oral strip drugs
There are not yet many medications available in a thin
film form on the market. Those that are include:
Benadryl
Gas-X
Melatonin PM
Orajel Kids
Sudafed
Suppress
TheraFlu
Triaminic
An application to the Food and Drug Administration
(United States) for a thin-film formulation of
ondansetron has been accepted for review .
On 9 July 2010 MonoSol Rx(in collaboration
with APR Applied Pharma Research s.a.and Labtec
GmbH) announced that its partner, Strativa
Pharmaceuticals, the proprietary products division
of ParPharmaceutical, received approval from the US
FDA for Zuplenz® (ondansetron) oral soluble film
(OSF) for the prevention of postoperative, highly and
moderately emetogenic cancer chemotherapy-induced,
and radiotherapy-induced nausea and vomiting
References
"Oral Thin Films," in Orally Disintegrating Tablet and
Film Technologies, 5th ed. (Technology Catalysts
International, Falls Church, VA, 2008).
"Drug Delivery Via Dissolving Strips.". Drug Discovery
& Development 10 (7): 10. 2007.ISSN 1524783X.
Dixit, R., & Puthli, S."Oral strip technology: Overview
and future potential.". Journal of Controlled
Release (Mumbai,India) (2): 94–107.
"FDA Office of Regulatory Affairs, Sec. 460.600 Content
Uniformity Testing of Tablets and Capsules". Fda.gov.
Retrieved 2009-09-21.
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