Film-Forming Sprays for Topical Drug Delivery

Figures & data

Figure 1 Flowchart of the methodology.

Figure 2 Mechanism of film-forming spray.

Table 1 Natural and Semisynthetic Polymers Used in Film-Forming Spray Systems

No	Polymer	Concentration (% b/v)	API	Sprayer	Ref
1.	Chitosan	0.5–1.5	–	ES	[^Citation25,Citation26]
2.	Cyclodextrin derivate (RAMEB)	5	Testosterone	Ordinal	[^Citation68]
3.	Ethyl cellulose	0.1–10	Ethanolic extract solution of Psoralea corylifolia seeds, ketoprofen, fluconazole, voriconazole, and clotrimazole	Ordinal	[^Citation35,Citation41^–^Citation43,Citation45]
4.	HPC (Klucel^® EF)	5	Testosterone	Ordinal	[^Citation68]
5.	HPMC^® E5	1–5	Piper nigrum L. oil	Ordinal	[^Citation43]
6.	HPMC phthalate (HPMCP^® 50)	5	Testosterone	Ordinal	[^Citation68]
7.	GG (Kelcogel^®)	0.25–0.9	–	Ordinal	[^Citation69,Citation70]
8.	Methylcellulose (Methocel^® E5)	5	Testosterone	Ordinal	[^Citation68]
9.	Na-CMC	0.5–2	Immunoglobulin	Ordinal	[^Citation31]
10.	Xanthan gum	<0.5	-	Ordinal	[^Citation71]

Table 2 Synthetic Polymers Used in Film-Forming Spray Systems

No	Polymer	Concentration (% b/v)	API	Sprayer	Ref
1.	Carbopol^® 940	0.05–1	Ketoprofen and oxybutynin	Ordinal and MDS	[^Citation42]
2.	Carbopol^® 971P	0.25–0.5	Beta-1,3/1,6-glucan	Ordinal	[^Citation79]
3.	Eudragit^® EPO	5	Ropivacaine	MDS	[^Citation20,Citation32]
4.	Eudragit^® E100	2–10	Clotrimazole, methylphenidate, ropivacaine and testosterone	Ordinal and MDS	[^Citation20,Citation32,Citation34,Citation80]
5.	Eudragit^® L100-55	5	Testosterone	Ordinal	[^Citation68]
6.	Eudragit^® RSPO	5	Ropivacaine	MDS	[^Citation20]
7.	Eudragit^® RS100	5–15	Fluconazole, clotrimazole, methylphenidate, and testosterone	Ordinal and MDS	[^Citation34,Citation40,Citation80]
8.	Eudragit^® RLPO	5–15	Voriconazole, clotrimazole, and dexketoprofen	Ordinal and MDS	[^Citation33,Citation34,Citation41]
9.	Eudragit^® RL100	5	Ropivacaine	MDS	[^Citation20]
10.	Eudragit^® S100	9–11	Ethanolic extract solution of Psoralea corylifolia seeds, ropivacaine and clotrimazole	Ordinal and MDS	[^Citation20,Citation34,Citation44]
11.	Lutrol^® F-127	0.05–0.2	Oxybutynin	MDS	[^Citation30]
12.	PDDA + SiO2	10 (mM) + 0.2	-	Ultrasonic	[^Citation49]
13.	PEO (Polyox^® WSR N-10)	5	Testosterone	Ordinal	[^Citation68]
14.	Plasdone^® S630	5	Testosterone and dexketoprofen	MDS	[^Citation32,Citation33]
15.	Poloxamer^® 407	0.05–1	Ketoprofen	Ordinal	[^Citation42]
16.	PVP (Kollidon^® 30)	0.5–5	Ibandronate sodium, testosterone, dexketoprofen, betamethasone 17-valerate, and piper nigrum l. Oil	Ordinal and MDS	[^Citation32,Citation33,Citation43,Citation81,Citation82]
17.	PVP (Kollidon^® PF12)	5	Dexketoprofen	MDS	[^Citation33]
18.	VA (Kollidon^® VA64)	5	Testosterone	Ordinal	[^Citation68]

Table 3 Excipient Commonly Used in Film-Forming Sprays

No	Excipient	Function	Concentration (% b/v or v/v)	Sprayer	Ref
1.	Azone	Permeation enhancer	1–5	MDS	[^Citation32,Citation33]
2.	Camphor:menthol (1:1)	Permeation enhancer	4–10	Ordinal	[^Citation34,Citation40,Citation41,Citation81]
3.	Cyclomethicone	Co-solvent	0.5	MDS	[^Citation30]
4.	Dimethyl ether	Propellant	39–59.8	MDS	[^Citation80]
5.	Ethanol	Volatile solvent	7.5–50	MDS	[^Citation80,Citation82]
6.	Ethanol:acetone (8:2)	Solvent	Ad. 100	Ordinal	[^Citation40^–^Citation42]
7.	Ethanol:acetone:methylal (2:1:2)	Solvent	Ad. 100	MDS	[^Citation30]
8.	Ethanol:PG:water (4:1:1)	Solvent	Ad. 100	Ordinal	[^Citation68]
9.	Ethanol:water (1:1)	Solvent	Ad. 100	Ordinal	[^Citation43]
10.	Glycerol	Stabilising agent and plasticiser	10–30	Ordinal and electrospray	[^Citation25,Citation26,Citation79]
11.	Hydrofluoroalkane	Propellant	76.7–87.2	MDS	[^Citation82]
12.	IPA	Volatile solvent	30	MDS	[^Citation80]
13.	IPA:water (8:2)	Solvent	90	Ordinal	[^Citation81]
14.	IPA:ethanol (1:1)	Solvent	Ad. 100	MDS	[^Citation20]
15.	IPM	Permeation enhancer	2.5–5	MDS	[^Citation32,Citation33,Citation82]
16.	LA	Permeation enhancer	5	MDS	[^Citation33]
17.	Myristyl lactate	Penetration enhancer	0.5	MDS	[^Citation30]
18.	NaCl	Cross-linker	0.1–0.5 (Molar)	Ordinal	[^Citation69]
19.	NMP	Permeation enhancer	5	MDS	[^Citation32]
20.	PEG-200	Plasticiser	0.25	Ordinal	[^Citation44]
21.	PEG-400	Plasticiser	0.45–10	Ordinal	[^Citation34,Citation41,Citation43,Citation82]
22.	PG	Plasticiser and permeation enhancer	0.25–9	Ordinal and MDS	[^Citation32^–^Citation34,Citation42,Citation43,Citation68,Citation80,Citation81]
23.	Tween 80	Surfactant	5	Electrospray	[^Citation25,Citation26]

Figure 3 Thixotropic in pseudoplastic, plastic, and dilatan systems.

Notes: Reprinted from Journal of Controlled Release, 136(2), Lee CH, Moturi V, Lee Y. Thixotropic property in pharmaceutical formulations:88–98, Copyright 2009, with permission from Elsevier.¹¹³

Figure 4 Measurement of spray angle and observation of spray patterns.

Figure 5 Illustration of ex-vivo permeation testing.

Table 4 Skin Irritation Scale

Grading	Description of Irritant Response
0	There is no reaction
+	A weak positive reaction (characterised by moderate erythema on the part where the drug is applied)
++	A moderate positive reaction (characterised by erythema which may spread in the application part of the drug)
+++	A strongly positive reaction (strong, characterised by erythema which may be accompanied by oedema)

Notes: Reprinted from Acta Pharmaceutica Sinica B, 3(6), Lee CH, Moturi V, Lee Y. Lu W, Luo H, Wu Y, Zhu Z, Wang H. Preparation and characterization of a metered dose transdermal spray for testosterone: 392–399, Copyright 2013, with permission from Elsevier.³²

Table 5 The Product of FFS

Trade Names	Manufacturer	Polymer	Application
Cavilon^®	3M^TM Health Care	Acrylate terpolymer and polyphenylmethylsiloxane	Skin protector from irritation
OpSite^®	Smith & Nephew Healthcare	Acrylic polymer	Wound cover and protector
Cutimed^® PROTECT	Essity	Unknown	Wound cover and protector
SKIN-PREP* Protective Dressing	Smith & Nephew Healthcare	Unknown	Wound cover and protector
No-Sting Skin Barrier Film Spray	Safe n’ Simple^TM	Diglycol/CHDM/isophthalates/SIP copolymer	Sensitive-skin protector
Sensi-Care^®	ConvaTec	Siloxane copolymers	Adhesive-releaser
SurePrep^® Rapid Dry	Medline Industries, Inc.	Unknown	Damaged or intact skin protector

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