Journal of Drug Delivery Science and Technology 43 (2018) 113e121

Contents lists available at ScienceDirect

Journal of Drug Delivery Science and Technology

journal homepage: www.elsevier.com/locate/jddst

Spray bandage strategy in topical drug delivery

Arun Radhakrishnan , Gowthamarajan Kuppusamy *,
Veera Venkata Satyanarayana Reddy Karri
Department of Pharmaceutics, JSS College of Pharmacy, Ootacamund, Jagadguru Sri Shivarathreeswara University, Mysuru, India

a r t i c l e i n f o a b s t r a c t

Article history: Pharmaceutical spraying technology is an amplified method of delivering aseptic medication. The
Received 25 July 2017 improved version of spray bandage contains either liquid or solid particle in a container that can be
Received in revised form delivered via fine spray nozzle once activated by actuator. In other words, a bandage film formed in situ
11 September 2017
on a skin surface by actuating a hydrophilic polymer and a low volatile plasticizer with the solvent
Accepted 25 September 2017
Available online 28 September 2017
system. They are commonly used to guard and prevent infection of topical abrasion and cut which exist
in minor level. By changing the spray drug concentration it can also be considered as a drug delivery film
on the skin to the systemic circulation. This review deals with the preparation and evaluation methods of
Keywords:
Spray bandage
spray-on bandages, their existing problem and strategies to overcome the issue, there by summarizing as
Topical delivery a future novel drug delivery system with huge market potential and also details current schemes (market
Film and research) in spray on bandages.
Polymer © 2017 Elsevier B.V. All rights reserved.
Propellant
Skin

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
2. Skin and topical delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
2.1. Disadvantage of existing topical delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
3. Need for spray bandage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
4. History of spray bandage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
5. Spray bandage technical composition [14] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
5.1. Polymeric bases [11e13] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
5.2. Dissolved medicaments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
5.3. Plasticizers [18] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
5.4. Antifoaming agent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
5.4.1. Mechanism of antifoaming agents [19] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
5.4.2. Foam-inhibitor classification [20] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
5.5. Preservatives [21] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
5.6. Propellant [22,23] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
5.6.1. Compressed gas propellant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
5.6.2. Liquefied gas propellant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
6. Spray containers and its filling methods [24] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
6.1. Cold filling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
6.2. Pressure filling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
7. Applied strategies on spray bandage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
8. Spray bandage preparation approach [25] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
9. Evaluator parameter of the spray film [31,32] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
9.1. Film strength . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

* Corresponding author.
E-mail address: gowthamsang@gmail.com (G. Kuppusamy).

https://doi.org/10.1016/j.jddst.2017.09.018
1773-2247/© 2017 Elsevier B.V. All rights reserved.
114 A. Radhakrishnan et al. / Journal of Drug Delivery Science and Technology 43 (2018) 113e121

9.2. Folding endurance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119

9.3. Tear resistance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
9.4. Tackiness [55] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
9.5. Water resistance time . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
9.6. Drug release . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
10. Formulative hurdles in spray bandage-industrial perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
11. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120

1. Introduction 2.1. Disadvantage of existing topical delivery

The skin is an organ of the integumentary system with the Most of the topical delivery system such as cream, paste, oint-
surface area of 1.5e2.0 square meter, which in turn make it as a ment etc. suffers serious drawback in case of specific infectious or
easy assessable route to deliver the drug either for local action or wound that are characterized by localized eruptions or damage on
systemic effect. As per field analysis, topical drug delivery market skin surfaces which are generally painful on touch results in un-
worth's about USD 92.40 Billion in 2016 and expected to reach USD acceptable difficulties on applying ointment in the wounded area
125.88 Billion by 2021 [1]. Even Physicians indicated in a survey for both adult and children. If the localized infection is produced by
about their interest of switching into topical delivery compared virus or bacteria, transude from that infection also highly enriched
with conventional system [2]. Topical delivery has multipoint with microorganisms. This on touch may lead to cross-
advantage they can either deliver therapeutic agent or act as contamination for example viral agents such as Herpes will cause
emollient, soothing and protective agent. As on date various con- small localized infection on specific area of skin. Further all these
ventional and specialized systems are developed to deliver the drug mean of formulation requires physical contact for application
topically. Conventional topical delivery includes lotion, liniment, which may lead to cross-contamination. In case of burnt wound
cream, gel, foam, ointment suspension, emulsion etc., which manually applying topical medicaments like silver sulphadiazine
generally follows first order kinetic release [3]. But the specialized cream, gel or ointment will cause undesirable pain [9]. Musculo-
topical delivery systems has the advantage of proceeding zero order skeletal disorder leads to pain in many regions of the body such as
kinetic release behavior example microemulsion based hydrogel, upper and lower back, neck, shoulders, arms, hamstrings and
Topical microsponge delivery etc [4,5]. Formulative researchers quadriceps, being this kind of large region it's difficult to spread
extensively involved in developing transdermal films with incor- medicaments and the gripping sensation cannot be provided by the
porated medicaments for cosmetic and therapeutic effect, which available formulation. As per chronopharmacology most of the pain
will be considered as a convenient way of administration. The will be occurring in evening and early morning [10], but the mar-
techniques of forming a film or a bandage on the skin by spraying keted topical analgesic fails to provide the sustained release profile,
are known as spray bandage that consist of either blank or medi- which is necessary for effective therapy.
cine incorporated polymeric base [6]. This review contains detailed
description about the advantage and formulative aspects of spray 3. Need for spray bandage
bandage as a superior system to overcome the drawbacks of
existing topical drug delivery system. The current scenario ready to accept the product which can
overcome the drawback of available topical delivery and should
possesses advantages like compact package, easy to apply, easy to
2. Skin and topical delivery wash, non cross contaminating on applying to topical microbial
infections, painless application on burnt wounds, and in case of
Drug content in the topical system, penetrates through the skin musculoskeletal disorder easy way of spreading in large surface
by three main mechanisms that happens based on the physio- with gripping sensation is necessary. In Industrial point of view,
chemical character of drug molecule. Primary mechanism in- developing smart delivery system which can be economically
volves movement of drug through keratin embedded corneocytes feasible, easy to commercialize the technology and exclusive
and the secondary pathway involves movement through the aseptic packing will also be needed for next generation wound care
intercellular space of the corneocytes and in some case shunt materials. Most of the medicated semisolid such as lotions, cream
transport takes place through topical pores such as hair follicles, etc., maintaining long term stability is also a commercial issue
sweat gland and sebaceous gland and this pathway is termed as when compared with medicated aerosol preparations. All these
transappendageal [7]. Which was explained in Fig. 1. requirements and urges can be fulfilled by developing the Spray
Epidermis consist of keratinocytes about 95% and minor level of bandage technology, which has the potency to commute the cur-
other cells such as melanocytes, merkel and langerhans cells. They rent topical drug delivery market.
are the most vital and large organ of the body that provide thermal
regulation, microbial protection and helps in vitamin D synthesis. 4. History of spray bandage
The outer most layer of epidermis known as Stratum corneum
which offers the main structural barrier for the drug absorption The first article of spray bandage was dated about 1966 pub-
form the topical or transdermal formulations. They are dead cells lished in Journal of society of cosmetic chemists [11] and later 1969
made up of proteins and lipids arranged like bricks and mortar. The US patent was filed on the title of “Preparation of Spray on
extracellular space of stratum cornea consists of hydrophobic bandage” [6]. After a gap again on 1990's spray technology devel-
lipids, where this lipid-enriched matrix is dispersed into lamellar oped results in initiation of research in spray bandage and various
membrane that covers the corneocyte [8]. patents like “Spray on wound dressing composition” in 1990 [12],
 A. Radhakrishnan et al. / Journal of Drug Delivery Science and Technology 43 (2018) 113e121
Fig. 1. Skin Structure and penetration mechanisms.
“Aerosol composition containing a film-forming hydroxycarboxylic
acid polymer” in 1993 [13], and “Sprayable topical pharmaceutical
compositions” in 1995 [9] were patented. But due to formulative
complications, commercialization of this technology became real
hurdle for pharmaceutical company. After 2000's some companies
like nexcare product, newskin, elastoplasts etc, started actively
introducing spray bandage and many more companies are involved
in developing upgraded version of spray bandage to uphold the
commercial market.
5. Spray bandage technical composition [14]
Technical composition of any spray bandage includes resinous
polymeric base (film former/drug loaded vehicle), solvent system
either organic or inorganic (solubilising medium), dissolved me-
dicaments (for therapeutic action), plasticizer (maintains flexi-
bility), antifoaming agent, preservative (optional) and propellant
(exhale the content from container) where filled with required
composition in aerosol container the structure of the container
given in Fig. 2.
5.1. Polymeric bases [11e13]
Polymer occupies major volume of the composition, they should
have the property such as compatible with most of the medica-
ments, non-toxic/non-irritant to skin, stable in pressurized condi-
tion, should have a extensive film forming ability, should be
economical, should be stable at body temperature, some base
should be easily washed by water (used for topical delivery) and in
some case base should not be easily washed by water (Used for
open wound to prevent bleeding and further infection) for opti-
mized formulation development. Based on the source polymeric
base can be classified in two categories natural and synthetic.
Natural polymeric base includes chitosan, alginate, starch, collagen,
gelatine, cellulose, dextran, (1-3)-b-D glucans, alginic acid, hyal-
uronic acid, heparin, chondroitin, dermatan and keratin sulphates,
115
C-P02 polymer (water base polymer obtained from bacterium, is
non-cytotoxic and biodegradable), fibrin, nitrocellulose. Polymer
obtained from synthetic route includes polyvinyl alcohol, polyvinyl
acetate, polyvinyl pyrolidone, polyvinyl methyl ether, acrylic poly-
mer, ethylene oxide polymer, acrylate terpolymer, polyphenyl
methyl siloxane, pyroxylin, polyacrylate, dipropylene glycol, prop-
nendiol, polylactic acid, poly-ε- caprolactone, polyethylene alcohol,
octanyl cyano acrylate, poly lactic co-glycolic acid, hydroxyl ethyl
acrylate. Hydroxyl ethyl methacrylate and hydroxyl propyl acrylate.
5.2. Dissolved medicaments
Pharmaceutically active medicaments are incorporated in the
polymeric base. So, that it can produce either localized topical effect
or concentration based systemic effect. Release rate of the drug can
be modified based n the formulative requirements. Most commonly
incorporated drugs in spray bandage are local anaesthetic [6], non-
steroidal anti-inflammatory drugs [14], anti-septic [15], anti-
bacterial [15], topical steroids [16], counter irritant [17], etc.,
5.3. Plasticizers [18]
Most of the bases commonly used in the film forming phar-
maceutical formulation on losing moisture will become brittle and
rigid. Inorder to prevent this condition plasticizers are incorporated
which can enhance the mechanical property and flexibility of the
spray bandage. The major advantage of plasticizer in spray bandage
is that they can reducing the brittleness, improve flow, ensure
flexibility, enhance the resistance and tear strength of the polymer
film formed after spraying.
Commonly used plasticizers can be classified into two categories
namely hydrophyllic and lipophyllic types. The hydrophyllic plas-
ticizer includes glycerine, glycerine triacetate, glyceriyltributyrate,
propylene glycol, oleil oleate, sorbitol, triethyl citrate, tributryl
citrate and the examples of lipophilic plasticizers are dibutryl
pthtalate, diethyl phthalate, dibutyl sebacate, diethyl sebacate,
116 A. Radhakrishnan et al. / Journal of Drug Delivery Science and Technology 43 (2018) 113e121
Fig. 2. Component of Spray container.
diethyl tartarate, butanediol-1,3, butanediol-1,4, haxanediol-2,5,
heptanediol-2,4 and 2-ethyl-1,3-hexanediol.
5.4. Antifoaming agent
Antifoaming agents or defoamers are components that are used
to inhibit foam formation in the formulation during agitation or
occasional shaking that generally happens during transportation.
5.4.1. Mechanism of antifoaming agents [19]
5.4.1.1. Bridging estretching mechanism. This mechanism states
that, on the foam lamella, with the flimsy region in the centre
biconcave oil bridge will be developed. Due to uncomparable
capillary pressure at oil-water-gas respective interfaces continuous
stretching will take place in radical direction will leads to rupture of
oil films and finally entire foam lamella gets damaged.
5.4.1.2. Bridging-dewetting mechanism. Oil drop (Defoaming agent)
that reaches the foam film surface and develop a geometrical lense
shape because of the hydrodynamic and gravity force. On contin-
uous action of these force thinning of the film will proceed and the
drop reaches opposite film surface in the foam, the bridge is
developed but it is unstable due the action of capillary force that
dewet the film from the bridge results in film rupture.
5.4.1.3. Spreading efluid entrainment mechanism. In this mecha-
nism the foam film destruction will happen due to the oil spreading
along the gas -foam film interface. This is based on the concept of
Marangoni-driven flow (Fluid entrainment) that if the monolayer of
oil covers the film surface, it will take up the subsurface liquids,
leads to thinning of film and finally the foam will break down.
5.4.2. Foam-inhibitor classification [20]
Nonpolar oil, polar oil and solid inorganic particles are the types
of foam inhibitors available for aerosol compositions. Nonpolar oil
includes mineral oil and silicone oil. Polar oil includes fatty acid,
fatty alcohol, alkyl amide and tributyl phosphate. Solid inorganic
particle includes silica, aluminum oxide, titanium dioxide and
magnesium stearate.
5.5. Preservatives [21]
Preservatives are used in spray bandage to prevent the microbial
contamination of the ingredients of the aerosol container. Most of
the synthetic base are highly resistant to the micro-organisms and
in addition organic volatile solvent will also provide undesirable
condition for microorganism multiplication. But incase of natural
polymeric base such as gelatin, collagen, plant polysaccharides etc.
in aqueous solvent system can readily act as suitable platform for
the growth of micro-organisms to prevent this contamination
antimicrobial agents are added in optimum quantity. Some exam-
ples of commonly used preservatives include benzalkonium chlo-
ride, cetrimonium bromide, benzethonium chloride, methyl
paraben, propyl paraben, butyl paraben, benzoic acid, chlorhexi-
dine, bronopol, sorbic acid etc., The preservative should be selected
based on several criteria such that the selected preservative should
be capable of exhibiting broad spectrum antimicrobial activity even
in low concentration and should be stable and effective throughout
the shelf-life of product. The antimicrobial agent should be topi-
cally safe, non-irritant in nature and should not affect the product
performance and storage container.
5.6. Propellant [22,23]
Atomisation of formulated composition from container through
valve opening only happens due to the pressure increment gener-
ated by propellant. The propellant must be dynamic enough to
overcome surface tension and coherent force of the liquid with
sufficient dispersive energy. Should have vapour pressure greater
than atmospheric pressure at 40
C (105
F) and should also have
ability to develop pressure of normal range 0.7e9.8 bars at 21.1
C.
High dispersive efficiency are generally exhibited by low molecular
weight propellant except in some case may due to interaction with
the content. The propellant should be nontoxic, non irritant and
environmental friendly. Generally two types of propellants are
commonly used in aerosol preparations and they are compressed
 A. Radhakrishnan et al. / Journal of Drug Delivery Science and Technology 43 (2018) 113e121
gas and liquified gas.
5.6.1. Compressed gas propellant
Gases which are insoluble in nature and cannot be liquefied at
room temperature are come under this category of compressed
gases. Some common examples are nitrogen, nitrous oxide, and
carbon dioxide. Compressed gases are used to disperse foams,
semisolid and mist. The common disadvantage of these propellants
is on spraying, wet and unstable foams are production due to low
expansion and dispersion ratio. In spite of this disadvantage, it
bears a greater advantage of maintaining the product as same
without interacting or solubilizing in it.
The compressed gas occupies the headspace above the product
which on spray it emits out with the product in desired force. In this
type they carry no propellant reservoirs. On comparing with liq-
uefied gas propellant it requires high-pressure and there is a fall in
pressure on reduction of product. Compressed gases are most
commonly used in hair sprays, dental cream, food preparation,
ointment etc.
5.6.2. Liquefied gas propellant
In Liquefied types the propellant gas either alone or as admix-
ture with other propellants is sealed in the aerosol container along
with the ingredients of spray bandage. These propellant will be
uniformly distributed in liquid phase and also as a gases in the head
space in the container, perfect equilibrium is maintained in both
phase. Based on atmospheric temperature there is a chance of
change in internal vapour pressure. The main advantage of lique-
fied gas propellants are the dispersion pressure is independent of
the quantity of liquefied phase present. The pressure applied on the
content f the container and direct towards dip tube when it is
actuated. On expose in atmosphere fall in pressure and increase in
surface area leads to evaporation of the propellant leaving the dry
particle of the medicaments. After this first phase ejection of
product through dip tube again the equilibrium within the
container is re-established and so it maintains the constant
dispersion ratio throughout its operation. The hydrocarbons are
commonly used because of their character of nonreactivity and
environmental friendly. Because of their low density they can be
used in three phase (Two layers) aerosol system. It will remain on
the top of the aqueous phase in which hydrocarbons are immiscible
and also will never hydrolysis the water base, helps in ejection of
content. The only drawback of these category propellants is flam-
mable when exposed to high temperature. Commonly used hy-
drocarbon propellants are propane, butane and isobutane they can
be used alone or mixed with Chlorofluorocarbon (CFC) propellants.
The chlorofluorocarbon (CFC) propellants are safe and low toxic,
various types of CFC propellants were used P-11, P-12 and P-114
etc., but due to the investigational finding of its contribution to-
wards ozone depletion further usage of these propellants were
restricted. P-12 propellant was replaced by recently developed P-
134a and P-227, but in minor quantity CFC propellants are used in
the Asthma and Chronic Obstructive Pulmonary Disease (COPD). In
spite of their inert behavior P-11 exhibit the property of hydrolysis
in the presence of water and results in hydrochloric acid which
leads to corrosion of containers and also irritate the area of appli-
cation. P-12 or P-114 is the choice of priority for water containing
spray bandage formulation. The Physical property of Hydro-
ChloroFluoroCarbons (HCFC) and HydroFluoroCarbons (HFC) are
not similar to chlorofluorocarbons. They will be depleted easily in
atmosphere and would not because damage to ozone. Some of the
propellants used in topical formulae are P-22, 142b, and 152a, and
they have greater miscibility with water but slightly high flam-
mable than chlorofluorocarbons.
117
6. Spray containers and its filling methods [24]
Spray container must have the ability to withstand high pres-
sure about 140e180 psig at 130
F and should be inert with the
loaded ingredients. Based on the requirement, various types of
containers are commercially available such as Tinplated steel,
Aluminum, Stainless steel, Glass, coated uncoated etc., and various
types of filling methods are available, which includes cold filing and
pressure filling.
6.1. Cold filling
The device is made up of insulated box fitted with metal copper
tubes which consist of dry ice or acetone. These tubes are used to
increase the surface area that results in rapid cooling. Content can
be filled into container by two methods. Either the product
concentrate and propellant cooled one by one at 30 to 40
F and
filled into the cooled can or both the product concentrate and
propellant were mixed and cooled then filled into the cooled can
and sealed. Then finally passed through the heated water bath of
temperature 130
F.
6.2. Pressure filling
In this apparatus either single propellant or the mixture of
propellants can be filled the inlet valve of the can in their own
vapour pressure from the metered burette that has the capacity to
measure the quantity of propellant. It consists of compressed gas
such as nitrogen gas which helps the propellant to flow into the
inlet valve through the metered burette. This process will come to
an end when the internal container pressure is equal to the external
flowing propellant pressure.
7. Applied strategies on spray bandage
The first work on spray bandage was carried out with polyvinyl
alcohol along with poly ethylene glycol as a gel base in which the
film strength was increased by propylene glycol and triethanol-
amine to increase viscosity of the composition. 1.6e3.2% V/V
formaldehyde that can act as plasticizer and also helps in improved
film strength, reduces the drying time. Commercial product like
Gleva aqueous emulsion which made possible to form a uniform
film from the water insoluble polyvinyl acetate 54.5% diluting with
water but the solution formed were not stable for long time. Pol-
yvinylpyrrolidone were too soluble in water and exhibit very less
water resistance, on addition of plasticizers tackiness of the film
gets increased. Solution formed by polyvinyl methyl ether in water
was sticky and not suitable for bandage films. Spray Bandages made
from polyvinyl methyl ether maleic anhydride copolymer were
brittle on addition of plasticizer low tensile and tacky film were
formed which cannot be used as spray bandage. Acrylic polymers
such as polyacrylic acid, polymath acrylic acid including their salts
and copolymers showed pH depended viscosity variation in the
solution of water. Good tensile and acceptable water-resistance
spray bandage can be formed by the acrylic polymer. High molec-
ular weight ethylene oxide cannot be easily solubilized without
strong agitation. Even after that the film formed is not superior as
the film formed by admixture of ethyl oxide with polyvinyl acetate
or acrylic polymer [11]. Then opacifying agents such as ungelat-
nized starch derivative, calamine, micronized cellulose, titanium
dioxide, magnesium stearate, zinc oxide and silica were tried in the
spray bandage formulation [6]. Polymer such as Hydron S with
sufficient hydrophilic character of vapour permeability, at least
200 g/sq. Meter/2 h/mill and generally insoluble in water but sol-
vated into plastisol by interaction with polar plasticizer-solvents
118 A. Radhakrishnan et al. / Journal of Drug Delivery Science and Technology 43 (2018) 113e121

which was taken in separate slayable container [25]. Spray spun
bandage was developed by using composition of nonelastomeric
polymer such as polystyrene and elastomeric polymer such as
polyisoprene with the crosslink regulator to get desirable character
[26]. Spray on wound dressing is developed by using anti-bacterial
quaternary ammonium salt incorporated in a synthetic film form-
ing polymer namely polyvinylpyrolidone polymer (PVP-K30) which
is solublized in high vapour pressure, low boiling solvent eg:
Methanol, ethanol, methylene chloride etc [27]. Later developed
hydroxycarboxylic acid film forming polymer such as polylactic
acid,polyglycolic acid and polylactic-co-glycolic acid etc. in a sol-
vent (ethanol, isopropyl alcohol) to form a spray film [28]. Biode-
gradable spray wound dressing were developed by using
pharmaceutically accepted thermoplastic polymer in a solvent
which on application will form a film. The thermoplastic polymer
includes polylactides, Polyglycolides, polycaprolactones, poly-
anhydrides, Polyamides, polyurethanes, polyesteramides, Poly-
orthoesters, polydioxanones, polyacetals and the solvent includes
N-methyl-Z-pyrrolidone, 2-pyrrolidone [29]. The fluid composition
consist of tacky adhesive and non-tacky film forming polymer
formulated by emulsion polymerization examples of the polymer
used: ethyl cellulose, nitrocellulose, silicone polyureas, silicone
polyurethanes, polyvinylacetate, polymethyl (meth)acrylate, sty-
rene, butadiene rubbers, polyurethanes, vinyl copolymers, poly-
amides, polyimides, polyamideimides etc [30].
8. Spray bandage preparation approach [25]
Polymeric base of suitable characteristic ability were selected
for intended formulation such as hydrophilic base for easy wash
topical spray bandage and for open wounds the base must critically
prevent the entry of water. Active pharmaceutical ingredient
should be incorporated in the formulation to produce required
pharmacological effect. Active pharmaceutical ingredient can be
loaded by three methods that include impregnation, physical
mixture, temperature dependent dissolving or dispersing in the
polymer. Selected and categorized drug loaded base solublized in
suitable plasticized solvent. The consistency of the content should
be ready to form a thin film on the topical region once on spraying.
Some case propellants are used to prevent the agglomeration and

Table 1
Marketed spray bandages.

S. Name of the Ingredients Polymers used Category Advantage Remarks

No spray bandage

1 3M-Nexcare Hexamethyl disiloxane, isooctane Acrylate terpolymer, Anti -microbial Waterproof, soothing, Not for larger areas
liquid bandage polyphenylmethylsiloxane breathable, alcohol free.
spray
2 Mistdress Cetrimide, lidocaine Polyvinyl polymer Antiseptic,anti- Waterproof, bacteria Not for large areas, Do not restrict
spray bandage bacterial proof, flexible, controls blood supply.
blood loss.
3 Medtech labs 8 e hydroxyquinoline 1%, alcohol 4.2%, Pyroxylin solution Anti septic, anti Waterproof, flexible, Not for large areas, Do not store above
New-skin isobutane propane, oil of clove bacterial, breathing. 120F
liquid bandage
spray 1oz
4 Medique Medi Benzethonium chloride 0.2% w/w, Anti e septic, Blood clotting, fights Flammable, Fast acting spray, not for
e First pain Lidocaine 4% w/w. disinfectant infection, stops superficial larger areas
relief blood bleeding
coating spray
5 New skin 8 - Hydoxyquinoline 1%, amyl acetate, Nitrocellulose Anti e Waterproof, breathable, Do not apply over larger areas,
liquid bandage benzalkonium chloride, castor oil, bacterial, anti for larger affected areas. Flammable above 120 F
e spray clove bud oil, ethyl alcohol, isobutane- eseptic
propane, n- butyl acetate
6 Kericure Polyacrylate Antiseptic Waterproof, prevents Suitable for all ages and With
natural seal infection, seals bleeding sensitive skin, water based spay
spray bandage
7 Medical Sod. Tetraborate, ascorbic acid Propanediol Anti infective Wound dressing, repairing
adhesive spray and healing
bandage
8 Nexcare no Hexamethyldisiloxane Acrylate terpolymer, Anti infective For minor scrapes and Not for large, deep, puncture wounds,
sting liquid Polyphenylmethylsiloxane abrasions, waterproof serious bands or animal bites, Not for
bandage spray use in chronic skin conditions.
9 Banda- sil Silver (silver oxide) Chitosan Anti infective, For minor cuts, abrasions, Not for major cuts
liquid bandage protectant lacerations, flexible, long
spray, silver 1 lasting, non toxic, alcohol
oz and triclosan free
10 JUC spray Water soluble macromolecular Anti microbial Wound (cut/burn), rapid Solves acute leg abrasion & has no
dressing 30 ml cationic active agent, i.e, 2% of healing, physical, drug resistance, Substitutes local
organosilicon quarternary ammonium antimicrobial. antibiotics in treatment of leg
salt & 98% of distilled water abrasion as it avoids drug resistance.
11 Elastoplast ethanol, water, dimethylether Acrylic copolymer, Wound Easy to apply, flexible,
first aid spray polyurethane polymer dressing water proof, multiday
plaster protection
12 Swift Aerosol Benzocaine 1.92%, Benzethonium Anti infective Provides coating for minor Water soluble, flammable contents
spray chloride 0.012% injuries, minor insect under pressure
bandage, 3 oz bites.
13 Medi e First 0.05%, cetyl trimethyl ammonium 40.5% Dipropylene glycol Anti septic and Wound care, for cuts and Provides a fast & easy way to
antiseptic Bromide, 4.5%, Benzocaine anti infective abrasions, minor cuts disinfectant, helps minimize pain.
spray, 3 oz
14 First Aid Only, Benzocaine 3.2%, Benzethonium Anti infective Protects cuts and Water soluble, washable, contains no
Aerosol Spray chloride 0.2% abrasions, prevents fluorocarbons, environmentally safe,
Bandage, 3 0z infection, assists healing, extremely flammable under pressure.
 A. Radhakrishnan et al. / Journal of Drug Delivery Science and Technology 43 (2018) 113e121 119

antifoaming agents will restrict the foam formation in the aerosol
content. Selection suitable propellant is necessary that can be
either compressed gas of liquefied gas either alone or mixture can
be used and filled in the container by the applicable filling tech-
nique. Propellant should contain adequate amount of volatile ma-
terial boils at below 20
C and boils below 50
C. Various marketed
product, Research aspects and patents where mentioned in
Tables 1e3.
9.2. Folding endurance
Folding endurance test will give details about the flexibility of
the film formed by spraying. This is very important character of the
film to retain on skin without breaking for long time. Folding
endurance test is carried out by repeated folding of the film at 180

angle of the plane at the same place till it breaks. Folding endurance
value of 300 or more shows perfect flexible nature [35].

9.3. Tear resistance

9. Evaluator parameter of the spray film [31,32]
Tear resistance is the basic property of withstanding the rupture,
by applying various deformations this tear resistance can be
9.1. Film strength
measured. Then the maximum force required to tear out the film is
measured [36]. The unit of tear resistance is Newton or pound.
Texture analyzer is the common method for evaluating the film
Based on the data generated stress stain curve is plotted and the
strength. The system starts measuring force and displacement of
area under this curve can be directly related to the toughness of the
the probe when they are in contact with the sample. Based on the
film formed on spraying.
size of film various sample holders are available in which the films
were attached and the holder is stabilized to prevent the move-
ment of film. Then he probe is allowed to pass through the film in a 9.4. Tackiness [55]
constant speed and pressure till the film gets detached. There is an
individual sample holder to aid measurement of small-sized film By using digital polyken probe tack tester the degree of tacki-
samples. The applied force and the displacement should be ness can be measured. This device consists of flat, circular probe
measured in room temperature and humidity [33,34] generally made up of stainless steel or aluminium alloy with

Table 2
Research status for spray bandages.

S. Title Researchers Chemicals & polymers Purpose Remarks

No. used

1 Intra operative use of the
absorbable fibrin adhesive
bandage: long term effects [38]
2 The effect of new tissue
adhesive wound dressing on
the healing of traumatic
abrasions [39]
3 Spray on bandage wound
healing product in development
[40]
4 Norwalk, conn. Plant helps
cured launch advanced bandage
[41]
5 Invivo method for determining
effectiveness of spray on
bandages containing anti-
infectives [38].
6 Physical evaluation of Haruan
spray for wound dressing &
wound healing [43].
7 Nanoscale biological coating
instantly stops bleeding [44].
8 Evaluation of wound healing
potential of b e chitin hydrogel/
nano zinc oxide composite
bandage [45]
9 ‘Spray on skin’ -Treatment for
leg ulcers [46]
10 Smart spray on bandage reports
healing progress by lighting up
[47]
11 Gelatin based sprayable foam as
a skin substitute [48]
Brooke Army Medical Fibrin Hemostasis effect Reduces acute blood loss in experimental trauma
Centre, Texas, USA. models
University of Michigan, Octylcyanoacrylate Healing of traumatic Well tolerated & did not show any signs of
USA (medical grade abrasions histotoxicity or adverse wound healing.
adhesive with
antimicrobial
properties)
Surrey, UK. (British Ethanol & polylactic Heals wound and skin too
company) acid (biodegradable
polymer).
Wilton e based Curad silver Heals wound with
Beiersdorf, USA impregnated with a antibacterial property
natural antibacterial
treatment
St. John's University, Neomycin sulfate and Reduces degree of Till now done with guinea pig.
Jamaica triclosan infection
School of Pharmaceutical Haruan extract (active Evaluation of wound It can minimize pain and emotional trauma.
Sciences, Penang, ingredient) & the healing & dressing for
Malaysia aerosol concentrate haruan spray using
different propellents.
MIT researchers Tannic acid & thrombin Halts bleeding within
seconds and heals
Amrita Centre for B- chitin powder, To heal wounds faster Showed blood coating ability & platelet activation &
Nanosciences and methanol, CaCl2, dist. antibacterial activity against S.aureus & E. coli.
Molecular Medicine Water, ZnO
nanoparticles
Researchers from the Combination of Treats venous leg ulcers Trial was promising, further trials done for testing
University of Miami & donated skin cells and safety & effectiveness in larger group of people.
other institutions in UK. proteins
Researchers from USA, Phosphorescent Healing progress by
South Korea & Germany. material reacts with lighting up
Later by Harvard Medical oxygen
School
P.M. Neumann, B. Zur & Gelatin Antimicrobial properties Physical & antimicrobial properties of newly
Y. Enhenreich developed gelatin based spray- on foam bandage for
use on skin wounds. The foam possesses
antimicrobial properties against gram þ ve, -ve &
fungal contaminants.
120 A. Radhakrishnan et al. / Journal of Drug Delivery Science and Technology 43 (2018) 113e121

Table 3
Spray bandage related patent analysis.

Patent number Title Date of issue

EP0521455 A2 [13] Aerosol composition containing a film-forming hydroxycarboxylic acid polymer 07.01.1993
EP0679390 A2 [9] Sprayable topical pharmaceutical compositions 02.11.1995
US 3305511 A [49] Pressure-sprayable water-soluble alkyl acrylate polymer solutions 02.02.1967
US3476853 [50] Sprayed opaque bandage composition 04.11.1969
US3577516 A [51] Preparation of spray on bandage 04.05.1971
US3880158 [26] Spray-spun bandage composition 29.04.1975
US 3987000 A [52] Sprayable polymer composition 19.10.1976
US4921691 [27] Spray on wound dressing composition 01.05.1990
US5632727A [53] Biodegradable film dressing and method for its formation 27.05.1997
US5725491A [29] Method of forming a biodegradable film dressing on tissue 10.03.1998
US5792469 [54] Biodegradable in situ forming film dressing 11.08.1998
US 6627216 B2 [55] Spray on bandage and drug delivery 30.09.2003
US 6962691 B1 [56] Topical spray compositions 08.11.2005

contact surface of 0.5 or 0.7 cm. This flat probe will come to contact medicaments like NSAIDs, anti-bacterial, anti-septic, steroids etc.,
with the sprayed content. also applicable to cover minor cuts and burn wounds. Further
optimizing the formulation strategy to get quick dry non sticky
9.5. Water resistance time spray bandage will have a tremendous potency to shift the current
topical drug delivery market.
Weight of the formed films was taken and then they were
subjected to expose with water spray and again their weight were Conflict of interest
taken (final weight). The films were then examined by,
None.
initial weight  final weight
% Moisture content ¼  100
final weight References

9.6. Drug release
The films formed by spraying at constant time (5sec) [36] were
cut into 1 cm2 and placed on the commercial semi-permeable
membrane (cellophane membrane) or stratum cornea were fixed
to the diffusion cell in such a way that the drug releasing surface of
the film towards the receptor compartment. Receptor compart-
ment contains phosphate buffer solution of pH 7.4 at 37 ± 0.5
C.
The elution medium was stirred magnetically. The sample of 1 ml
from receptor compartment was withdrawn at regular time in-
tervals and replaced with same volume of phosphate buffer pH 7.4.
Then the samples were analyzed for drug content. Drug release can
studied even through dissolution test apparatus [37].
10. Formulative hurdles in spray bandage-industrial
perspective
Organic solvents are generally used in formulation, drugs and
polymers which can be solublized only by aqueous solvent face
challenge in formulation. Non-aqueous solvent possibly may cause
skin irritation. Spray films are not immediately dried as soon as
sprayed, which in turn become a spot for accumulation of atmo-
spheric. Being hydrophobic in nature, Film formed on skin is not
easily washed off. Some market research shows the sticky nature
during drying adsorbs atmospheric dust. Cost of manufacturing is
high leads to reduction in commercial flow. In this recent scenario
many research work of altering the resinous base and solvent are
proceeding forward to achieve better spray bandage formulation.
11. Conclusion
Topical film or bandage that can be formed by spraying makes
the new scenario in pharmaceutical drug delivery, thus research
towards this direction initiated from 1966. Many companies and
researchers have taken this to next level by incorporating
[1] Topical Drug Delivery Market by Product Type Formulation (Solid, Cream,
Lotion, Paste, Liquid), Transdermal (Patch, Gel), Route of Administration (Skin,
Ophthalmic, Rectal, Vaginal, Nasal), & Facility of Use (Hospital, Clinic, Home
Care, Research) - Global Forecast to 2021, Markets and Markets Research
Private Ltd, Maharashtra, 2017 March. Available from: http://www.
marketsandmarkets.com/Market-Reports/topical-drug-delivery-market-
124871717.html.
[2] Christi Bird, MARKET brief e sequestratio n haunts life science research tool
market into 2014, Drug Dev. Deliv. 14 (2014) 26e29.
[3] Stefan C. Weiss, Conventional topical delivery systems, Dermatol. Ther. 24
(2011) 471e476.
[4] Huabing Chen, Xueling Chang, et al., Microemulsion-based hydrogel formu-
lation of ibuprofen for topical delivery, Int. J. Pharm. 315 (2006) 52e58.
[5] M. Jelvehgari, M.R. Siahi-Shadbad, S. Azarmi, et al., The microsponge delivery
system of benzoyl peroxide: preparation, characterization and release studies,
Int. J. Pharm. 308 (2006) 124e132.
[6] Bernard Jatul, North Caldwell, Christopher Costello, Colgate-Palmolive Com-
pany, Sprayed Opaque Bandage Composition, 1965 Apr 13. United State Pat-
ent US 3476853.
[7] Nikhil Sharma, Geta Agarwal, A.C. Rana, et al., A review: transdermal drug
delivery system: a tool for novel drug delivery system, Int. J. Drug Dev. Res. 3
(2011) 70e84.
[8] Mark R.P. rausnitz, Peter M. Elias, Thomas J. Franz, Matthias Schmuth, et al.,
Barrier and transdermal drug delivery, Med. Ther. 19 (2012) 2065e2073.
[9] Ernest Arthur, Robert John David, S.A. Zyma, Sprayable Topical Pharmaceutical
Compositions, 1995 Apr 19. European Patent EU0679390 A2.
[10] A. Reinberg, F. Le
vi, Clinical chronopharmacology with special reference to
NSAIDs, Scand. J. Rheumatol. 16 (1987) 118e122.
[11] Winthrop E. Lange, Victor S. Fang, Aqueous topical adhesives II, spray-on
bandage, J. Soc. Cosmet. Chem. 17 (1966) 115e122.
[12] Richard F. Stockel, Spray on Wound Dressing Composition, 1990 May 1.
United States Patent US4,921,691.
[13] masayuki Yamada, Satoshi Mekata, Takeda Chemical Industries, Aerosol
Composition Containing a Film-forming Hydroxycarboxylic Acid Polymer,
1993 Jun 30. European Patent EU 0 521 455 A2.
[14] S. Derry, T. Massey, R.A. Moore, et al., Topical NSAIDS for chronic musculo-
skeletal pain in adults, Cochrane Libr. 4 (2009) 1e6.
[15] B.S. Atiyeh, S.A. Dibo, S.N. Hayek, Wound cleansing, topical antiseptics and
wound healing, Int. Wound J. 6 (2009) 420e430.
[16] E. Charles, Crutchfield, Topical Steroid Spray, 2003 Jun 17. United States
Patent US 6579512 B2.
[17] P. Matthews, S. Derry, R.A. Moore, et al., Topical rubefacients for acute and
chronic pain in adults, Cochrane Libr. 4 (2008) 1e5.
[18] Sevgi Güngo €r, M. Sedef Erdal, Yıldız Ozsoy, Recent advances in plasticizers,
Plasticizers Transdermal Drug Deliv. Syst. (2012) 91e112.
[19] Farzad Abdolahi, A. Mohammad, Moosavian, et al., The mechanism of action of
antifoams, J. Appl. Sci. 5 (2006) 122e1129.
[20] Rainer Ho € fer, Franz Jost, Milan J. Schwuger, et al., Foams and Foam Control,
 A. Radhakrishnan et al. / Journal of Drug Delivery Science and Technology 43 (2018) 113e121
Ullmann's Encyclopedia of Industrial Chemistry, 2000, 2.4-3.
[21] David P. Elder, Patrick J. Crowley, Antimicrobial Preservatives Part One:
Choosing a Preservative, American Pharmaceutical Review, 2012. Available
from: http://www.americanpharmaceuticalreview.com/Featured-Articles/
38886-Antimicrobial-Preservatives-Part-One-Choosing-a-Preservative-Sys-
tem/.
[22] Lahkar Sunita, An overview on :pharmaceutical aerosols, Int. Res. J. Pharm. 23
(2012) 68e75.
[23] An Introduction to Aerosol Propellants Diversified CPC International, Inc;
Available from: www.diversifiedcpc.com/PDF/intro.pd.
[24] Naseeb Basha Shaik, Manufacturing or Formulation and Filling of Aerosols.
Pharmaceutical Information. Available from: http://www.pharmainfo.net/
book/pharmaceutical-aerosols/manufacturing-or-formulation-and-filling-
aerosols.
[25] Francis E. Gould, Thomas H. Shepherd, Nat Patent Dev Corp, Preparation of
Spray on Bandage, 1971 May 04. United States Patent US 3,577,516.
[26] John A. Gurney, Johnson & Johnson, Spray-spun Bandage Composition, 1975
Apr 29. United States Patent US 3,880,158.
[27] Richard F. Stockel, F. Stockel Richard, Spray on Wound Dressing Compositions.
Spray on Wound Dressing Composition, 1990 May 01. United States Patent US
4,921,691.
[28] Masayuki Yamada, Satoshi Mekata, Takeda Chemical Industries, Ltd.,Osaka
Aerosol Industries Corporation, Aerosol Composition Containing a Film-
forming Hydroxycarboxylic Acid Polymer, 1993 Jan 07. European Patent EP
0,521,455A2.
[29] Arthur J. Tipton, Shawn M. Fujita, Richard L. Dunn, Atrix Laboratories, Inc,
Method of Forming a Biodegradable Film Dressing on Tissue, 1998 Mar 10.
United States Patent US 5,725,491.
[30] Patricia J. Andolino Brandt, Charles M. Leir, David J. Wirtanen, 3M Innovative
Properties Company, Spray On Bandage and Drug Delivery System, 2005 Oct
25. United Sates Patent US 6,958,154 B2.
[31] K. Gowthamarajan, Thinley Tsomu, Spray-on bandage; an overview, World J.
Pharm. Pharm. Sci. 9 (2016) 2209e2220.
[32] Sandeep Karki, Seon-Jeong Na, et al., Thin films as an emerging platform for
drug delivery, Asian J. Pharm. Sci. 11 (2016) 559e574. http://www.
sciencedirect.com/science/article/pii/S1818087616300368.
[33] M. Preis, K. Knop, J. Breitkreutz, Mechanical strength test for orodispersible
and buccal films, Int. J. Pharm. 461 (2014) 22e29.
[34] C.F. Wong, K.H. Yuen, K.K. Peh, An in-vitro method for buccal adhesion
studies: importance of instrument variables, Int. J. Pharm. 180 (1999) 47e57.
[35] D. Mukherjee, S. Bharath, Design and characterization of double layered
mucoadhesive system containing bisphosphonate derivative, ISRN Pharm.
(2013) 1e10.
[36] R.P. Dixit, S.P. Puthli, Oral strip technology: overview and future potential,
J. Control Release 139 (2009) 94e107.
[37] C.F. Wong, K.H. Yuen, K.K. Peh, An in-vitro method for buccal adhesion
studies: importance of instrument variables, Int. J. Pharm. 180 (1999) 47e57.
[38] Rhonda Cornum, James Bell, Vincent Gresham, et al., Intraoperative use of the
absorbable fibrin adhesive bandage: long term effects, J. Urol. 162 (1999)
121
1817e1820.
[39] James Quinna, Laurie Loweb, Michelle Mertza, The effect of a new tissue-
adhesive wound dressing on the healing of traumatic abrasions, Derma-
tology 201 (2000) 343e346.
[40] Kevin Wilson, 'Spray-on bandage' wound healing product in development,
Dermatol. Times 11 (2000). Available from: https://www.highbeam.com/doc/
1P3-52742331.html.
[41] Richard L. Norwalk, Conn, Plant Helps Cured Launch Advanced Bandage,
Knight Ridder/Tribune Business News, 2004. Available from: https://www.
highbeam.com/doc/1G1-116126726.html.
[43] Noor AM. Febriyenti, S. Bin Bai, Physical evaluations of Haruan spray for
wound dressing and wound healing, Int. J. Drug Deliv. 3 (2011) 115e124.
Available from: http://www.arjournals.org/index.php/ijdd/article/view/75/69.
[44] A. Trafton, Nanoscale Biological Coating Instantly Stops Bleeding, SciTech
Daily, 2012. Available from: https://scitechdaily.com/nanoscale-biological-
coating-instantly-stops-bleeding/.
[45] P. Sudheesh Kumar, V. Lakshmanan, M. Raj, R. Biswas, et al., Evaluation of
wound healing potential of b-chitin hydrogel/nano zinc oxide composite
bandage, Pharm. Res. 30 (2012) 523e537. Available from: https://link.
springer.com/article/10.1007/s11095-012-0898-y.
[46] States News Service, 'Spray-on-Skin' Treatment for Leg Ulcers, 2012. Available
from: https://www.highbeam.com/doc/1G1-298505919.html.
[47] Kendall Costello, "Smart" Spray on Bandage Reports Healing Progress by
Lighting up. DOGOnews, 2014. Available from: https://www.dogonews.com/
2014/10/23/smart-spray-on-bandage-reports-healing-progress-by-lighting-
up.
[48] P. Neumann, B. Zur, Y. Ehrenreich, Gelatin-based sprayable foam as a skin
substitute, J. Biomed. Mater. Res. 15 (1981) 9e18.
[49] Robert J. Gander, Johnson & Johnson, Pressure-sprayable Water-soluble Alkyl
Acrylate Polymer Solutions, 1967 Feb 21. United States Patent US 3,305,511.
[50] Costello Christopher, Jatul Bernard, Colgate Palmolive Co, Sprayed Opaque
Bandage Composition, 1969 Nov 04. United States Patent US 3,476,853.
[51] F.E. Gould, Preparation of Spray on Bandage, 1969 Dec 2. United states Patent
US3,577,516.
[52] Peter Gleichenhagen, Dietrich Schulte, Gunther Bonitz, Beiersdorf Aktienge-
sellschaft, Sprayable Polymer Composition, 1976 Oct 19. United States Patent
US 3,987,000 A.
[53] Arthur J. Tipton, Shawn M. Fujita, Richard L. Dunn, Atrix Laboratories, Inc,
Biodegradable Film Dressing and Method for its Formation, 1997 May 27.
United States Patent US 5,632,727.
[54] Arthur J. Tipton, Shawn M. Fujita, Richard L. Dunn, Atrix Laboratories, Inc.,
Biodegradable in Situ Forming Film Dressing, 1998 Aug 11. United States
Patent US 5,792,469.
[55] Patricia J. Andolino Brandt, Charles M. Leir, David J. Wirtanen, 3M Innovative
Properties Company, Spray on Bandage and Drug Delivery, 2003 Sept 30.
United States Patent US 6,627,216.
[56] Amar Lulla, Geena Malhotra, Preeti Raut, U & I Pharmaceuticals Ltd, Topical
Spray Compositions, 2005 Nov 08. United States Patent US 6,962,691 B1.