Chapter on Films and strips

1. Films and Strips:
Formulation, Manufacturing
& Evaluation
1
By:Rajesh L. Dumpala
(B.Pharm, M. Pharm.) PhD. ( Pursuing)
Research Scientist,
Alembic Research Centre. Vadodara
E.Mail:-rdumpala64@gmail.com

2. CONTENTS
 Introduction
 Advantages and Disadvantages
 Types of films
 Formulation aspects of films
 Manufacturing method
 Evaluation
 Conclusion
 References
2

3. INTRODUCTION
 Pharmaceutical film is the thin, flexible solid
unit dosage form meant to use for either local or
systemic action.
 Either orodissolving or transdermal.
 Fast dissolving or slow dissolving.
 Among these two types, oral dissolving films are
widely used in market.
3

4. CONT..
 Technology Catalysts forecasts the market for drug
products in oral thin film formulations to be valued
at $500 million in 2007 and could reach $2 billion
by 2010.
 Synonym: Quick-dissolving delivery systems;
quick-disintegrating, orally disintegrating, mouth
dissolve dosage forms; or melt-in-mouth dosage
forms, Rapidfilm, fast dissolving film, oral
disintegrating film (ODF), Oral thin film (OTF),
and Rapid dissolving film (RDF).
4

5. ADVANTAGES
ORAL SOLUBLE THIN FILM:
 General advantages:
1. Larger surface area.
2. Oral dissolving tablets (ODT) are fragile and
brittle which require special package while films
are flexible so ease of transportation and during
consumer handling and storage .
3. Precision in the administered dose.
5

6.  Patient related advantages:
1. Convenient and easy to administer as it disintegrates and
dissolves in mouth with in fraction of seconds.
2. Improved compliance for patients suffering from
Dysphagia.
3. Pleasant mouth feel and non grittiness.
4. Ease of administration for paediatric, geriatric, travelling
and institutionalized patients (especially for mentally
challenged and psychiatric patients)
6

7.  Clinical advantages:
1. Quick dissolution and rapid absorption provides
rapid onset of action.
2. Bioavailability of drugs that are absorbed from
mouth, pharynx and esophagus is increased.
3. Pregastric absorption of drugs avoids hepatic
metabolism.
4. Combines benefits of liquid formulations with
that of solid dosage form.
7

8.  Technical advantages:
1. Good stability, easy manufacturing, small
packaging size and easy handling by patients.
2. Adaptable and amenable to existing processing
and packaging machinery.
3. Excipients required are relatively safe, economic
and easily available.
4. Compatible with taste masking techniques.
8

9.  Economic and business related advantages:
1. Unique product differentiation in market.
2. Provides value added product line extension.
3. Extended patent protection.
9

10. TRANSDERMAL FILM
 The first pass effect can be avoided, there can be
reduction in the dose which can lead to reduction
in side effects associated with the molecule
hence dose can be reduced.
 Ease in termination of treatment.
10

11.  Oral films
1. Low flux results in low drug bioavailability and the
constant salivary secretion makes it quite difficult for
dosage forms to be retained.
2. Accidental swallowing of dosage forms and salivary
scavenging.
3. Drugs which are very bitter or otherwise have
unacceptable taste have to be first taste masked.
4. Drug should be stable in water.
11
DISADVANTAGES

12.  Transdermal film
1. Highly organized stratum corneum is rate
limiting.
2. Tolerance development is a big challenge to this
technique.
 General disadvantages:
1. Difficult to prove bioequivalence for few drugs.
2. Only a small dose of drugs from 1mg to 20 mg.
3. Specific physicochemical properties of drugs are
required. 12

13.  A number of molecules can be incorporated into
this delivery system.
 They may include cough/cold remedies
(antitussives, expectorants), sore throat, penis
erectile dysfunction drugs, antihistaminics,
antiasthmatics, gastrointestinal disorders, nausea,
pain and CNS (e.g. anti-parkinsons disease).
Other applications comprise caffeine strips,
snoring aid, multivitamins, sleeping aid etc.
13

14. Fast Dissolving Oral Films: An Innovative
Drug Delivery System and Dosage Form
 Abstract : Fast-dissolving drug-delivery systems were
first developed in the late 1970s as an alternative to
tablets, capsules, and syrups for pediatric and geriatric
patients who experience difficulties swallowing
traditional oral solid dosage forms.
14

15.  A variety of orally disintegrating tablet (ODT) formats were
commercialized.
 Most ODT products were formulated to dissolve in less
than one minute when exposed to saliva to form a
solution that could then be more easily swallowed.
 Dissolvable oral thin films (OTFs) evolved over the past
few years from the confection and oral care markets in
the form of breath strips and became a novel and widely
accepted form by consumers for delivering vitamins and
personal care products.
15

16.  Special features of mouth dissolving films
 Thin elegant film
 Available in various size and shapes
 Unobstructive
 Excellent mucoadhesion
 Fast disintegration
 Rapid release
 Advantages
 Convenient dosing
 No water needed
 No risk of chocking
 Taste masking
 Enhanced stability
 Improved patient compliance 16

17.  The mouth dissolving films has also a clear advantage
over the Oral dissolving tablets (ODTs):
 ODTs are sometimes difficult to carry, store and handle
(fragility and friability).
 Many ODTs are prepared by using the expensive
lyophillisation process.
 A large number of drugs can be formulated as mouth
dissolving films.
17

18.  Innovative products may increase the therapeutic
possibilities in the following indications.
 Pediatrics (antitussives, expectorants,
antiasthamatics)
 Geriatrics (antiepileptic, expectorants)
 Gastrointestinal diseases
 Nausea (e.g. due to cytostatic therapy)
 Pain (e.g. migraine)
 CNS (e.g. antiparkinsonism therapy)
18

19.  Composition of the system
 Mouth dissolving film is a thin film with an area of 5-
20 cm2 containing an active ingredient.
 The immediate dissolution, in water or saliva respectively, is
reached through a special matrix from water-soluble polymers.
 Drugs can be incorporated up to a single dose of 15mg.
 A typical composition contains the following
 Drug 1-25%
 Water soluble polymer 40-50%
 Plasticizers 0-20%
 Fillers, colours, flavours etc. 0-40%
19

20. 1) Drugs
 Several class of drugs can be formulated as mouth dissolving films
including antiulcer (e.g. omeprazole),anti asthamatics (salbutamol
sulphate), antitussives, expectorants, antihistaminics, NSAID’S
(e.g.paracetamol, meloxicam, valdecoxib).
2) Water soluble polymers
 Water-soluble polymers are used as film formers.
 The use of film forming polymers in dissolvable films has attracted
considerable attention in medical and nutraceutical application.
 The water-soluble polymers achieve rapid disintegration, good
mouth feel and mechanical properties to the films.
 The disintegration rate of the polymers is decreased by increasing the
molecular weight of polymer film bases.
20

21.  Some of the water soluble polymers used as film former are
HPMCE-3 and K-3, Methyl cellulose A-3, A-6 and A-
15,Pullulan,carboxmethylcelluloseceko30,Polyvinylpyrollidone
PVP K-90, Pectin, Gelatin,Sodium Alginate,
Hdroxypropylcellulose, Polyvinylalcohol, Maltodextrins and
EUDRAGITRD108,9,10,11,12 Polymerized rosin is a novel
filmforming polymer.
3) Plasticizers
 Formulation considerations (plasticizer, etc.) have been reported
as important factors affecting mechanical properties of films.
 The mechanical properties such as tensile strength and
elongation to the films have also been improved by the addition
of plasticizers.
 The commonly used plasticizers areglycerol, butylpthallate, and
polyethylene glycolsetc10. 21

22. 4) Surfactants
 Surfactants are used as solublising or wetting or
dispersing agent so that the film is getting dissolved within
seconds and release active agent immediately.
 Some of the commonly used are sodium lauryl sulfate,
benzalkonium chloride, bezthonium chloride, tweens etc.
 One of the most important surfactant is polaxamer 407
that is used as solubilizing, wetting and dispersing agent.
5) Flavour
 Any flavor can be added, such as intense mints, sour
fruit flavors or sweet confectionery flavors.
22

23. 6) Colour
 A full range of colors is available, including FD&Ccolors, EU Colours,
Natural Colours and customPantone-matched colours.
 Some saliva stimulating agents may also be added to enhance the
disintegration and to get rapid release.
 Some of these agents are citric acid, tartaric acid, malicacid, ascorbic
acid and succinic acid.
7)Manufacturing Methods
 One or combination of the following process can be used to
manufacture the mouth dissolving films.
i) Solvent casting
ii) Semisolid casting
iii) Hot melt extrusion
iv) Solid dispersion extrusion
v) Rolling
23

24. 1) Solvent casting method
 In solvent casting method water soluble polymers are in
water and the drug along with other excipients is dissolved
in suitable solvent then both the solutions are mixed and
stirred and finally casted in to the Petri- plate and dried.
2) Semisolid casting
 In semisolid casting method firstly a solution of water
soluble film forming polymer is prepared.
 The resulting solution is added to a solution of acid
insoluble polymer (e.g. cellulose acetate phthalate,
cellulose acetate butyrate), which was prepared in
ammonium or sodium hydroxide. 24

25. 25

26. 3) Hot melt extrusion
 In hot melt extrusion method firstly the drug imixed with
carriers in solid form.
 Then the extruder having heaters melts the mixture.
Finally the melt is shaped in to films by the dies.
 There are certain benefits of hot melt extrusion.
 -Fewer operation units
 -Better content uniformity
 -An anhydrous process
4) Solid dispersion extrusion
 In this method immiscible components are extrude with
drug and then solid dispersions are prepared.
 Finally the solid dispersions are shaped in to films by
means of dies. 26

27. 5) Rolling Method
 In rolling method a solution or suspensiocontaining
drug is rolled on a carrier.
 The solvent is mainly water and mixture of water and
alcohol.
 The film is dried on the rollers and cutted in to desired
shapes and size.
27

28. 28

29. TECHNOLOGIES19
1) SOLULEAVES™ technology is used to produce a
range of oral delivery films that can incorporate active
ingredients, colours and flavours.
 SOLULEAVES™ films can be designed to dissolve rapidly
on contact with saliva, quickly releasing the active
ingredients and flavours.
 This quality makes edible films an excellent delivery
method for a large range of products requiring fast release
in the mouth. 29

30.  For pharmaceutical uses this method of administration is
especially useful for paediatric or elderly patients who
may have difficulty swallowing traditional tablets or
capsules.
 The delivery system can be used for the cough/cold,
gastrointestinal and pain therapeutic areas as well as
delivering nutritional products.
 SOLULEAVES™ films can also be designed to adhere to
mucous membranes and to release the active ingredient
slowly over 15 minutes.
30

31. 2) WAFERTAB™ is a drug delivery system that
 Incorporates pharmaceutical actives into aingestible
filmstrip.
 The system provides rapid dissolution and release of
actives when the strip comes into contact with saliva in the
mouth.
 The WAFERTAB™ filmstrip can be flavoured for
additionally improved taste masking.
31

32.  The active ingredient is precisely dosed and integrated
into the body of a pre-manufactured XGEL™ film, thus
preventing exposure to unnecessary heat and moisture
and potentially enhancing product stability.
 The WAFERTAB™ system lends itself to many
possibilities for innovative product design, enabling
multiple films with different actives to be bonded together.
 WAFERTAB™ can be prepared in a variety of shapes and
sizes and is an ideal method for delivery of medicines,
which require fast release, or for use by patients who have
difficulty swallowing.
32

33. 3) FOAMBURST™ is a special variant of the
SOLULEAVES™ technology where an inert gas is passed
into the film during production.
 This results in a film with a honeycombed structure, which
dissolves rapidly giving a novel mouth sensation.
 FOAMBURST™ has attracted interest from food and
confectionary manufacturers as a means of carrying and
releasing flavours.
33

34. 4) XGEL™ film is at the heart of Meldex International's
intellectual property, used in all its film systems and its
ingestible dosage delivery technologies.
 XGEL™ film provides unique product benefits for
healthcare and pharmaceutical products:
 it is nonanimal-derived, approved on religious grounds
and is suitable for vegetarians; the film is GMO free and
continuous production processing provides an economic
and competitive manufacturing platform.
34

35.  XGEL™ film can be taste masked, coloured, layered, and
capable of being enteric properties whilst also having the
ability to incorporate active pharmaceutical ingredients.
 The XGEL™ film systems can be made to encapsulate
any oral dosage form, and can be soluble in either cold or
hot water.
 XGEL™ film is comprised of a range of different water-
soluble polymers, specifically optimised for the intended
use.
35

36. TABLE 1. LIST OF DRUGS CAN BE GIVEN IN FILM/STRIP
FORM
36

37. TYPES OF FILM/STRIP
• Made to dissolve in mouth in
fraction of seconds
• E.g. Benzocain wafers
Oral fast
dissolving
• Releases drug for 4-5 hr in mouth
• E.g. Salbutamol sulphate buccal
patch
Buccal slow
release
• Sustain release films for prolong
action
• E.g. Papverin transdermal patches
Transdermal
37

38. 38

39. ORODISSOLVING FILM
 Involves characteristics such as taste masking, fast
dissolving, physical appearance, mouth-feel etc.
 From the regulatory perspectives, all excipients used
in the formulation of film should be Generally
Regarded as Safe (i.e. GRAS-listed) and should be
approved for use in oral pharmaceutical dosage
forms.
39

40. Active pharmaceutical ingredient
 Generally 5%w/w to 30%w/w of active
pharmaceutical ingredients can be incorporated in
the film.
 Water soluble APIs are present in the dissolved state
in the films or in the solid solution form, the water
insoluble drugs are dispersed uniformly in the strip.
 Milled, micronized or in the form of nanocrystals,
liposomes, niosomes or particles.
 Taste masking for bitter drugs, E.g. MonosolRx
technology utilizes particulate technology for taste
masking. 40

41. Sweetening agents
 More important in case of paediatric films
 Used in the concentration of 3 to 6 %w/w either alone or in
combination
 Sucrose, dextrose, fructose, glucose, liquid glucose and
maltose
 Polyhydric alcohols such as sorbitol, mannitol, isomalt and
maltitol can be used in combination
 The artificial: Saccharin, cyclamate and aspartame are the
first generation of the artificial sweeteners followed by
acesulfame-K, sucralose, alitame and neotame which are
second generation artificial sweeteners
41

42. Flavoring agents
 Age
 Up to 10%w/w flavors are added
 Initial flavor quality
 Natural flavors include Peppermint oil, cinnamon oil,
spearmint oil, oil of nutmeg are examples of flavor oils while
vanilla, cocoa, coffee, chocolate and citrus are fruity flavors.
Apple, raspberry, cherry, pineapple
 Synthetic flavor oils, oleo resins, extract derived from
various parts of the plants like leaves, fruits and flowers and
can be used alone or in the combination
 Cooling agents like monomethyl succinate, WS3, WS23 and
Utracoll II
42

43. Colouring agents
 Pigments such as titanium dioxide or FD&C approved coloring
agents in not exceeding concentration levels of 1%w/w.
Saliva stimulating agent
 Used alone or in combination between 2 to 6%w/w of weight
of the strip.
 Generally acids used in the preparation of food can be utilized
like citric acid, malic acid, lactic acid, ascorbic acid and
tartaric acid.
 Synthetic sugars like glucose, fructose, xylose, maltose,
lactose .
43

44. Stabilizing and thickening agents
 Improve the viscosity and consistency of dispersion
or solution .
 Natural gums: Xanthan gum, locust bean gum,
carrageenan and cellulosic derivatives in the
concentration up to 5%w/w as thickening agents and
stabilizing agents.
 Surfactants and emulsifying agents are also added in
small amount.
44

45. TRANSDERMAL FILM
 This formulation also includes the same basic
ingredients for film formation like, film forming
polymers, film stabilizers, thickening agents and
plasticizers while avoids organoleptic ingredients
and saliva stimulating agents.
45

46. Active pharmaceutical ingredient
 Potent
 5%w/w to 30%w/w of active pharmaceutical ingredients
can be incorporated in the film however now upto 62.5%
API may also be incorporated
 t1/2 should be short
 Must not induce cuteneous irritant or allergic response
 Tolerance must not develop under the near zero-order
release
 Molecular weight less than 1000 dalton
 Both water soluble and organic solvent soluble drugs can
be used
46

47. Permeation Enhancer
 Promote skin permeability by altering the skin as a barrier to
the flux of a desired penetrant.
 Affect one or more of skin layers to achieve penetration
enhancement.
 E.g. 23-lauryl ether, Aprotinin, Azone, Benzalkonium
chloride,Cetylpyridiniumchloride,Cetyltrimethylammonium
bromide, Cyclodextrin, Dextran sulfate, Lauric acid
47

48. Pressure sensitive adhesives
 Maintaining an intimate contact between
transdermal system and the skin surface.
 In case of drug in adhesive matrix selection will be
based on the rate at which the drug and the
penetration enhancer will diffuse through
adhesives.
 Polyacrylates, polyisobutylene and silicon based
adhesives are widely used.
Backing layer
 Flexible and provide a good bond to the reservoir,
prevent drug from leaving the dosage form through
the top. 48

49. CONT..
 Metallic plastic laminate, plastic backing with
absorbent pad and occlusive base plate (aluminium
foil), adhesive foam pad (flexible polyurethane) with
occlusive base plate (aluminium foil disc) etc.
49
Patch designed for Unidirectional drug release

50. Release Liner
 During storage the patch is covered by a protective liner that
is removed and discharged immediately before the
application of the patch to skin
 Composed of a base layer which may be non-occlusive (e.g.
paper fabric) or occlusive (e.g. polyethylene,
polyvinylchloride) and a release coating layer made up of
silicon or teflon
Solvents
 For matrix: Chloroform, methanol, acetone, isopropanol and
dichloromethane
 Plasticizer: Dibutylpthalate, triethylcitrate, polyethylene
glycol and propylene glycol
50

51. MANUFACTURING OF FILM
 Films can be prepared following technique:
1. Solvent casting
2. Semi-solid casting
3. Hot-melt extrusion
4. Solid dispersion extrusion
5. Rolling
 From above methods mainly solvent casting and hot-melt
extrusion methods are widely used for making films. Rolling
technique is used in industries for commercial scale
production.
51

52. EXTRUSION TECHNIQUE:
 API and other ingredients are mixed in dry state, subjected
to heating process and then extruded out in molten state.
 Here solvents are completely eliminated.
 Strips are further cooled and cut to the desired size.
 The high temperature may degrade thermolabile APIs.
52

53. SOLVENT CASTING TECHNIQUE
 Preparation of the base material involves the mixing of strip
forming excipients and the API in a suitable solvent or solvent
system
 The solution is subjected to continuous mixing to keep the
viscosity and concentration unchanged under controlled
temperature condition to achieve desired viscosity.
 Once this solution is prepared, casting process is performed
wherein a strip of desired thickness is cast onto a inert
substrate like glass or teflon plates
 The formed strip is then subjected to drying process (critical
step)
 High dosing accuracy essentially depends on micrometer
accuracy of film casting and accuracy in cutting
53

54. ROLLING TECHNIQUE
54

55. EVALUATION OF FILM
1. Thickness
2. Dryness test/tack tests
3. Tensile strength
4. Percent elongation
5. Tear resistance: Basically very low rate of loading 51 mm
(2 in.)/min is employed and is designed to measure the force
to initiate tearing. The maximum stress or force required to
tear the specimen is recorded as the tear resistance value in
Newtons 55

56. 56
INSTRON universal testing instrument

57. 57
6.1. PEELADHESION TEST
BACKING LAYER
ADHESIVE LAYER
Adhesion test
• The force required to remove an adhesive coating from
a test substrate is referred to as peel adhesion
• The force is expressed in ounces (or grams) per inch
width of tape.
• If higher value then it indicates greater bond strength

58. 58
6.2. TACK PROPERTY
6.2(a) THUMB TACK TEST
Qualitative test.
 The thumb is simply pressed on the adhesive and relative tack
property is detected
2(b) ROLLING BALL TACK TEST
2(c) QUICK-STICK (PEEL TEST) TEST

59. 59
6.2(d) PROBE TACK TEST
 Polyken probe tester: The tip of clean probe is
brought into contact with adhesive, and when a
bond is formed between probe and adhesive. The
force required to pull the probe away from the
adhesive at fixed rate is recorded as tack (Grams).
6.3. SHEAR STRENGTH TEST
Stainless steel plate
Adhesive coated tape
Weight

60. Folding endurance: Folding endurance is determined
by repeated folding of the strip at the same place till
the strip breaks. The number of times the film is
folded without breaking is computed as the folding
endurance value.
Disintegration time: The disintegration time limit of 30
sec or less for orally disintegrating tablets described in
CDER guidance can be applied to fast dissolving oral
strips. Pharmacopoeial disintegrating test apparatus
may be used for this study. Typical disintegration time
for strips is 5–30 sec.
60

61. Dissolution test: Dissolution testing can be performed using
the standard paddle over disk (USP type 5) and cylinder
(USP type 6) apparatus or as described in any of the
pharmacopoeia. The dissolution medium will essentially
be selected as per the sink conditions and highest dose of
the API
Diffusion test:
 In vitro diffusion test: It is being performed for the
transdermal films. To check the drug release amount and
time using FRANZ diffusion cells
 In vivo diffusion test: It is being performed on rats. Patch is
applied on shaved rat skin and the drug release is checked by
suitable way as per the nature of drug
61

62. 62
DESIGN OF FRANZ DIFFUSION CELL

63. Assay/drug content and content uniformity
Moisture content
% Moisture content = Initial weight – Final weight X 100
Final weight
Moisture Uptake
% moisture uptake = Final weight – Initial weight X 100
Initial weight
Flatness
% constriction = I1 – I2 X 100
I1
I1 = Initial length of each strip
I2 =Final length of each strip 63

64. Organoleptic evaluation
 For evaluation of psychophysical evaluation of
the product, special controlled human taste
panels are used.
 In vitro methods of utilizing taste sensors,
specially designed apparatus and drug release
by modified pharmacopoeial methods are
being used for this purpose.
64

65. CONCLUSION
 It is consumer-friendly alternative, many of the
pharmaceutical companies are moving towards thin
films. This technology option can also provide a good
platform for patent non-infringing product
development. Compared to some of the complicated
and expensive process (like lyophilization) used to
manufacture other dosage forms, the film is relatively
easy to fabricate;
hus reducing the overall cost of the therapy. The
application of film has not only been limited to buccal
fast dissolving system, but also expands its horizon to
other applications like gastroretentive, topical,
implantable, sublingual delivery options.
65

66. REFERENCES
 N.K.Jain, Controlled and Novel Drug Delivery, CBS PUBLISHERS &
DISTRIBUTORS, New Delhi, page 61-71, 105-122
 R.P. Dixit, S.P. Puthli, Oral strip technology: Overview and future
potential, Journal of Controlled Release, vol. 139 ,2009, page 94–107
 Rakesh P. Patel, Grishma Patel, Ashok Baria , Formulation and
evaluation of transdermal patch of Aceclofenac, International Journal of
Drug Delivery vol. 1,2009, page 41-51
 Geeta Aggarwal, Development, Fabrication and Evaluation of
Transdermal Drug Delivery System - A Review, pharmainfo.net, Vol. 7,
Issue 5, 2009
 A Gupta, AK Mishra, V Gupta, P Bansal, R Singh, AK Singh, review
article: Recent Trends of Fast Dissolving Tablet - An Overview of
Formulation Technology, International Journal of Pharmaceutical &
Biological Archives, vol.1(1), page 1 – 10
 P.D. Shah, Formulation development and evaluation of terbutaline
sulphate quick dissolving oral film (thesis)
66

67. 67