F0RM-3A
THE PATENTS ACT, 1970
COMPLETE SPECIFICATION
SECTION 10

TITLE

A PROCESS FOR PREPARING A TOPICAL MEDICINAL SPRAY COMPOSITION.

APPLICANTS

CIPLA LIMITED, 289, BELLASIS ROAD, MUMBAI CENTRAL, MUMBAI: 400 008.' MAHARASHTRA, INDIA.

The following Specification particularly describes and ascertains the nature of this invention and the manner in which it is to be performed:

The present invention relates to topical medicinal spray compositions and their preparation, which compositions can be used to treat a variety of disorders.
Many delivery system for the topical application of pharmaceutical compounds are currently available and include lotions, creams, gels, ointments, transdermal patches and sprays. The choice of delivery system usually depends upon the desired pharmacokinetic profile of the drug, for example whether immediate - or sustained - release is required. Many of these systems suffer from occlusion problems and may cause skin irritation. For example, many compounds, including hormonal drugs, are conventionally delivered using a transdermal patch. These patches comprise an occlusive backing membrane which often results in local skin irritation. A further disadvantage of transdermal patches in that percutaneous penetration of the drug is often poor.
Topical spray formulations can help reduce the problem of skin irritation associated with transdermal patches. For example, British Patent specification No. 1,372,721 discloses a container of antiseptic for the topical treatment of burns and scalds, containing a topically acceptable antiseptic active agent against Pseudomonas aeruginosa, a pressuring agent and at least one surfactant admixed with water. The container comprises an outlet, and valve means operable to allow discharge of the contents of the container through the outlet in the form of a foam which is effective in the control of Pseudomonas aeruginosa at the site of a burn or scald and a container of antiseptic for the treatment of burns and scalds by topical application, comprising a first compartment containing a pressuring agent and at least one surfactant admixed with water, a second compartment
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containing a topically acceptable antiseptic active against Pseudomonas aeruginosa or a substance which will -react with a substance contained in said first compartment to form a desired antiseptic, said second compartment containing a pressuring agent and/or being collapsible under the pressure of the pressurizing agent contained in said first compartment, an outlet from the container, and valve means operable to put both compartments in communication with the out Jet, operation of said valve means resulting in discharge from said outlet of a foam containing an antiseptic which is effective in the control of Pseudomonas aeruginosa at the site of a bum or scald. US Patent specification No. 4,534,958 describes a pressurized composition in an aerosol container and adapted to form a spray upon release of pressure therefrom which composition is a liquid inside the container and forms a gel on contact with living tissue comprising water, propellant, volatile solvent and a polyoxyethylene-polyoxypropylene copolymer. The preferred composition may also advantageously include a skin treating agent, and conventional skin treatment additives and claims "a sprayable aerosol foam treatment composition which is a liquid in the aerosol container and forms a gel upon application to the skin", which composition comprises water, propellant, volatile solvent, and a polyoxyethylene-polyoxypropylene copolymer whose function is not described and optionally including a burn treatment agent and one or more adjuvants. The composition is used "for treating living skin".
However, a problem with conventional topical spray formulations is that they tend to remain for only a short time at the application site-for example they are easily rubbed off. In consequence the medicament to be absorbed through the skin in only available transiently. By contrast, medicament in a
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transdermal patch is potentially available for as long as the patch remains in place.
We have now found a way of combination the advantages offered by transdermal patches and topical sprays, whilst minimizing the disadvantages associated with each. We have devised a topical spray composition which can be sprayed on to the skin to form a breathable film or patch, which film remains stable and in place over a period of days. In this way medicament can be delivered transdermal^ over a period of time. Since the film is non occlusive the problem of local skin irritation associated with transdermal patches is thereby substantially reduced. Moreover, the composition as per the invention is not restricted for human use alone, it may be used for veterinary applications too.
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According to the present invention there Js provided a topical, medicinal spray composition comprising of a drug or combination of drugs as solution or suspension in a volatile carrier containing a polymer or combination of polymers which when sprayed on the surface of the skin forms a film on the skin. The components of this invention are not restricted to, but preferably comprise of (w/w) from about 0.1% to 10% of one or more medicaments from about 0.1% to 10% of film-formers, from about 0.1% to 10% solubilizer, from about 0.1% to 8% permeation enhancer, from about 1% to 10% plastictser, and a vehicle q.s100%, wherein the composition can be sprayed on a topical site to form a stable breathable film on said site, from which film the medicaments are transdermal^ available. Preferably, the composition further comprises from 1% to 7% (w/w) of one or more water-soluble additives. The drug or combination of drugs so deposited in the matrix of the film-formers(s) may remain in a solubillised form or may be in a form of suspension. The composition can be dispensed from any dispenser which provides the composition as a spray and may be used for systemic action or topical action. The drug from the composition may be released over a period of time or immediately. The details of all the above ingredients are given in the following paragraphs.
Preferably, the composition is dispensed from a pump dispenser or from an aerosol dispenser. In the latter case, the composition additionally comprises from about 10% to 90% of propellant in order to provide a suitable pressure within the aerosol dispenser. Generally, propellant is not required. Generally propellant is not required for compositions dispensed from a pump dispenser. However, if desired, such compositions may also comprise from about 10% to 90% of a propellant which is liquid at a room temperature, for example trichloromonofluoromethane,(P11).
In another aspect, the invention provides a method of preparing a pump dispenser containing the spray composition of the invention, which method comprises mixing the ingredients of the composition with or without liquid propellant, and then placing the mixed ingredients in a pump dispenser.
In a further aspect, the invention provides a method of preparing an aerosol dispenser containing the spray composition of the invention, which method comprises mixing the ingredients, of the composition without propellant, and then charging the mixture together with propellant into an aerosol dispenser. The composition is preferably dispensed from the chosen dispenser in a metered dose.
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The medicament referred above can be any medicinal compound which is stable on mixing with the other ingredients of the composition and effective on topical administration; or a combination of any two or more such compounds. Preferably medicament is a drug which is anti-emetic, anti-anginal, anti-inflammatory, a steroid ,or a steroid hormone, a bronchodilator or a drug used to treat osteoporosis. Additional preferred -medicaments include drugs .used to treat incontinence, antidepressants/anxiolytics , antimigraine agents, agents used in smoking cessation therapy.antidiarroheas, anticholinergics, anticonvulsants, drugs for mood disorders/obessive compulsive disorder. ACE inhibitors, calcium channel blockers, antihypertensives/diuretics, antiobesity drugs, hormonal peptides and analogues , drugs for benign prostatic hyperplasia/urinary retension and erectile dysfunctions, antiparkinson agents such as dopamine agonists and MAO inhibitors, drugs for sleep disorders and antidiabetic agents.
One preferred anti-emetic referred above is scopolamine. Preferred anti-anginals include nitroglycerine, clonidine, isosorbide dinitrate, propanoiol HCI, timolol maleate, clonazepam or verapamil. Preferred anti-inflammatory drugs include diclofenac sodium, alendronate sodium, ibuprofen, ketoprofen, indomentacin, piroxicam, ketorolac, tromethamine or nimesulide. Preferred steroids include hydrocortisone and esters thereof, dexamethasone, fluocinolone acetonide or betamethasone and salts thereof.
Preferred hormonal steroids referred above include estadiol or noethisterone or a combination thereof, testosterone or progesterone. Preferred bronchodilators include salbutamol base and its salts and bambuterol, salmeterol xinafoate, fluticasone propionate, mometasone furoate, budesonide, beclomethasone, dipropionate,sodium cromoglycate or isoprenaline sulphate . Preferred drugs used in case of osteoporosis include alendronic acid, pamidronic acid , etidronic acid and their pharmaceutically acceptable salts. Preferred drugs used to treat incontinence include vasopressin and oxybutynin. Preferred antidepressants/anxiolytics include imipramine, mirtazapine and desipramine. Preferred antimigramine agents include naratriptan, zolmitriptan and sumatriptan. One preferred antidiarrhoeal is loperamide. One preferred antiulcerant is misoprostol. Preferred anticholinergics include hyoscyamine, atropine and trihexyphenidyl. Preferred anticonvulsants include lorazepam, diazepam and tiagabine. Preferred drugs for antimood disorders/obsessive compulsive disorder include fluoxetine and paroxetine. Preferred ACE inhibitors include lisinopril,
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trandolapril and captopril. Preferred calcium channel blockers include arnlodipine and felodipine. Preferred antihypertensives/diuretics include prazosin and amiloride. Preferred antiobesity drugs include methamphetamine and sibutramine hydrochloride. Preferred hormonal peptides and analogues include GnRH analogues such as nafarelin; leuprolide acetate, insulin and growth hormone and analogues thereof. Preferred drugs for benign -prostatic hyperplasia /urinary retention include doxazosin, tamsulosin, terazosin and finasteride. Preferred drugs for erectile dysfunction include alprostadil and sildenafil citrate. Preferred antiparkinson agents include dopamine agonists such as bromocriptine and cabergoline and MAO inhibitors such as selegiline HCI. One preferred agent for sleep disorders is melatonin. Preferred antidiabetic agents include 1st and 2nd generation sulphonyl ureas such as glimepiride.rosiglitazone.glyburide and glipizide. Also the chiral forms of all the drugs mentioned above can be used to make the Topical Spray Composition of the present invention.
The film-formers referred above preferably include any acrylic polymers or copolymers. Preferred film-formers include a non-ionic copolymer of methyl methacrylate and butyl methacrylate (Plastoid B®) , a copolymer of dimethyiamine ethyl methacrylate and a neutral methacrylic acid ester (Eudragit E 100 ®), ammonio methacrylate copolymer type B (Eudragit RS®, USP/NF), ammonio methacrylate copolymer type A (Eudragit RL®, USP/NF), methacrylic acid copolymer type A (Eudragit L100®, USP /NF), methacrylic acid copolymer type B (Eudragit S100®, USP/NF), polyvinyl acetate, cellulose acetate, polyvinyl alcohol, povidone, povidone vinyl acetate, hydroxypropyl methyl cellulose, hydroxy ethyl cellulose and methyl cellulose.
The bteathability of the film is achieved by the absence of any occlusive backing membrane together with the generally hydrophilic properties of the film -forming polymer(s) . These polymers can partially dissolve on exposure to moisture (from the skin or air), which dissolution results in the development of a porous film. This porosity can be enhanced by including further water-soluble additives, such as those detailed below.
Preferred solubilizers referred above include a copolymer of dimethyiamine ethyl methacrylateand a neutral methacryclic acid ester (Eudragit E 100®, USP/NF); surfactants , for example , sodium lauryl sulphate; polyhydric alcohols, for example,
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propylene glycol or polyethylene glycols: vitamin E, vitamine E TPGS (tocopheryl polyethylene glycol 1000 succinate) and labrasol: or any two or more of the above in combination. Preferably, the solubiliser is a copolymer of dimethylamine ethyl methacrylate and a neutral methacrylic acid ester (Eudragit E100®) in combination with, a non-ionic copolymer of methyl methacrylate and butyl methacrylate (Plastoid B ®). The solubilisers serve to dissolve the drug in the chosen vehicle. Many of the solubilisers also enhance percutaneous pernetration of drug and/or act as humectants.
Preferred plasticisers referred above include triethyl -citrate, dimethyl ispsorbide, acetyltributyl citrate, castor oil, propylene glycol and polyethylene glycol or any two or more of the above in combination.
The permeation enhancer referred above is preferably a lyophilic solvent, for example, dimethyl sulfoxide, dimethyl formamide or isopropyl myristrate; a surfactant, for example. Tween 80 or sodium lauryl sulfate or menthol; a two-component system, for example , oleic acid and octy! dimethyl paraamino benzoic acid (Padimate 0); or a polyhydric alcohol for example, propylene glycol or diethylene glycol monoethyl ether EP (transcutol): or any two or more of the above in combination.
The vehicle referred above can be water or a non- aqueous solvent. Preferred nonaqueous vehicles include acetone, isopropyl alchol, methylene chloride , methyl -ethyl - ketone, absolute alcohol, ethyl acetate and trichloromonofluromethane (P11): or any two or more of the above in combination.
The aqueous or non-aqueous vehicle may additionally -comprise (weight/weight of vehicle) from about 1% to 20% of one or more humectants. Preferred humectants include polyhydric alcohols and polyvinylprrolidone. Preferred polyhydric alcohols are propylene glycol, butylenes glycol, polyethylene glycols, glycerol and sorbitol.
The water-soluble additive referred above is preferably propylene glycol, sodium lauryl sulphate, one or more polaxomers, polyoxyl 34 castor oil, polyoxyl 40 hydrogenated castor oil, cetomacrogol, polyethylene glycol or transcutol; or any two or more of the above in combination.
When the composition is dispensed as an aerosol, the vehicle partly comprises a propellant in an amount to provide from about 10% to 90% (w/w) of the composition.
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The propellant can be any pharmaceutical^ acceptable propellant which provides a
pressure of from about 20 p.s.i.g. to about 130 p.s.i.g. within an aerosol dispenser.
Preferred propellants include hydrocarbons, for example, propane, butane, isobutene,
or dimethylether; hydrofluorocarbons and hydrochlorofluorocarbons, for example
dichlorodiflucromethane (P12), trichloromonofluoromethane (P11),
dichlorofluoroethane, monochlorodifluoromethane (P22), dichlorotetrafluoroethane (P114), difluoroethane (P152a), tetrafluoroethane (P134a), heptafluoropropane (P227b), or compressed gases, for example, nitrogen or carbon dioxide.
The topical compositions of the present invention are quick drying, nonocclusive formulations which cause marked enhancement of the skin permeation of the drug both in vitro and in vivo when compared with transdermal patches. They offer the advantages of lower skin irritation, greater ease of use, increased dosage flexibility and a simpler method of manufacture when compared to existing transdermal patches.
The present compositions are a significant advance over conventional medicinal aerosol compositions, since they permit the application of a medicament by a method whereby no physical contact on the area of application is required, except by the film-forming spray itself. The topical films formed by the present compositions show excellent stability and peelability and can be easily removed from the side of application by washing with water.
The compositions are generally prepared by mixing the ingredients without liquefied propellant at a temperature of from 0°C to 100°C and at ambient pressure and then charging the resulting mixture together with the liquefied propellant into an aerosol dispenser to achieve the final composition. Mixing is preferably carried out at a temperature of from 10 C to 25°C. Alternatively, the mixed composition is placed in a pump dispenser, for example, a metered dose pump, which dispenses the composition typically without liquefied propellant since a pressurized atmosphere is not required. Propellant which is liquid at room temperature may, however, be included in a pump dispenser composition as part of the non-aqueous vehicle. The composition so prepared is sprayed from the dispenser on to a topical site, at which site it forms a stable, plastic film or patch.
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The aerosol dispenser is preferably a conventional aerosol can having a conventional metered spray aerosol valve. The pump dispenser is preferably a conventional can or bottle having a conventional metered spray pump. Preferably, the aerosol dispenser has an all position valve having a shroud that permits spraying when the dispenser is held at any angle. In this way, horizontal bottom surfaces as well as horizontal top surfaces and vertical surfaces can be sprayed. The valve actuator can be any actuator which produces a spray and not a foam at the nozzle. A preferred valve actuator is a mechanical breakup actuator, which employs mechanical forces rather than expansion and evaporation of the propellant to produce a spray. A typical mechanical breakup actuator has a conical or cylindrical swirl chamber with an inlet channel oriented perpendicular to the axis thereof. This structure imparts a swirling motion to the aerosol mixture upon discharge. The swirling motion occurs around the axis of the swirl chamber forming a then conical film of discharged mixture, which breaks into droplets as it leaves the swirl chamber and travels in the direction of the axis thereof. The result is a fine, soft, dispersed spray which can be easily controlled to produce a stable thin film of even thickness completely contacting the application site. In dispensing a composition of the invention the dispenser is typically held about 1 to 2 inches (2.5 to 5cm) from the application site and produces a film of even thickness. The dispensers used in the present invention are preferably compact units. They can be conveniently used for quick and easy application of a medicament over a large surface area. Typically, the area is not more than 50cm2; and is more preferably from 10cm2- to 25cm2-.
The following Examples illustrate the preparation of compositions according to the present invention, in order that the invention may be more fully understood.
A composition according to the present invention suitable for use in an aerosol dispenser can be prepared as follows :
1. Dissolve the film former in the chosen vehicle under stirring to form a clear solution.
2. Dissolve or suspend the active ingredient and solubilisers(s) alongwith the permeation enhancer, together with any water-soluble additives required, in the solution formed in step 1.
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3. Add the plasticiser to the solution and fill a conventional aerosol can with the mixture.
4. Charge the filled can with liquefied propellant.
Examples of partly generalised formulas which can be used with any suitable medicament to prepare compositions according to the present invention for use in an aerosol dispenser include-

Ingredients Percent w/w
Active ingredient 0.5-10.0
Plastoid B 2.25
EudragitEl00 0.25
Propylene glycol 3.0
Sodium lauryl sulfate 3.5
Acetone 20
Propellant q.s.
Vitamin E 0.1
Transcutol 1.0
Example 2
Ingredients Percent w/w
Active ingredient 15
Povidone 3
Povidone VA-64 2
Vitamin E 0.5
PEG 400 1.0
Propylene glycol 1.5
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15 15
Ethanol
Acetone
Propellant q.s.

More specific examples of compositions for use in an aerosol dispenser include: Example 3
Ingredients Percent w/w
Estradiol 1
PVP K-30 6
PVP VA 4
Vitamin E 1
PEG 6000 2
Polyethylene glycol 3
P12 58.1

P 11

24.9

Example 4

Inqredients Percent w/w
Estradiol 2
PVP K-30 6
PVPVA 4
Vitamin E 1
PEG 6000 2
Polyethylene glycol 3
P12 24.9
12
P11

57.1

Example 5

Ingredients Percent w/w
Alendronate sodium 1
PVP K-30 6
PVPVA 4
Vitamin E 0.5
Menthol 0.05
Dimethyl isosorbide 3.0
Acetone 10
Ethanol 10
Tetrafluoroethane 25.45
(P134)
Dichlorodifluoromethane 40
(P12)
To prepare a composition according to the present invention suitable for use in a pump dispenser the same general method of Example 1 can be used except that it is not necessary to charge the pump dispenser with liquefied propellant to provide a pressurised atmosphere. The mixture itself may contain propellant which is liquid at room temperature as part of the vehicle.
Examples of partly generalised formulas, which can be used with any suitable medicament to prepare compositions according to the present invention for use in a pump dispenser include:
Example 6
Ingredients Percent w/w
Active ingredient 0.5-10.0
Plastoid B 5.6
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Eudragit E 100 0.6
Propylene glycol 4.0
Sodium lauryl sulfate 3.0
Acetone 20
Isopropyl alcohol q.s.
Vitamin E 0.2
Transcutol 2.0
Example 7
Inqredients Percent w/w
Active ingredient 25
Povidone 6
Povidone VA-64 4
Vitamin-E 1.0
Polyethylene glycol 3
Ethanol 27
Acetone q.s.
Methylene chloride 27
Example 8
Ingredients Percent w/w
Active ingredient 15
PVP K 30 6
PVP VA 4
Vitamin E TPGS 0.5
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Dimethyl isosorbide 5
Ethanol 20
Trichloromonofluoromethane (P11) q.s
Example 9
Inqredients Percent w/w
Active ingredient 0.5-10
PVP VA 10
Vitamin E 0.5
Propylene glycol 3
Acetone 15
Ethanol 25
Trichloromonofluoromethane (P11) q.s.
More specific examples of compositions use in a pump dispenser include: Example 10
Ingredients Percent w/w
Estradiol 2
PVP K-30 6
PVPVA 4
Vitamin E 1
PEG 6000 2
Polyethylene glycol 3
Acetone 27
15
Methylene chloride 27
Ethanol 28

Example 11
Ingredients Percent w/w
Estradiol 1
PVP K-30 6
PVPVA 4
Vitamin E 1
PEG 6000 2
Polyethylene glycol 3
Acetone 27
Methylene chloride 28
Ethanol 28
With reference to the specific compounds of the above Examples, the following explanation is given. Eudragit E 100 is a self-adhesive, hydrophilic matrix system. It also acts as a solubilizer for the drug Estradiol.
Plastoid B is a film-former. When used together, Eudragit E 100 and Plastoid B give better peelability and water washability than when either is used alone.
Acetone is a volatile, quick-drying, non-occlusive vehicle which helps to dispense the contents of the spray over a large surface area.
Propylene glycol acts as a humectant to prevent the excessive drying of the application site after application of the medicament. It also acts as a plasticiser for the film formed after application. Propylene glycol additionally acts as a solubilizer for the drug and a permeation enhancer.
Propellant is necessary for developing proper pressure within the container and for expulsion of the composition when the valve is open. It is also responsible, together with the valve, for dispensing the product as a fine spray. The preferred
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propellants are very stable compounds and relatively non-toxic, inert and nonflammable.
Sodium lauryl sulfate acts as a soulbiliser for the drug.
The compositions in the above Examples were discharged from the dispenser as a fine, soft dispersed spray which could be easily controlled to produce a stable thin film of even thickness on a target surface, for example a laboratory cover glass. The films have been observed to last for at least 24 hours. The concentration of the film-formers in the composition can be varied as required to obtain a patch which can deliver the drug in a sustained manner for a period of upto 1 to 15 days. The film is easily removable from the application site by water in preparation for reapplication of the film or other treatment.
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We Claim :
1. A process of preparing a topical medicinal spray composition comprising
following steps:
a. Dissolving the film former in the chosen vehicle under stirring to form
a clear solution;
b. Adding active ingredient and solubiliser(s) along with the permeation
enhancer, together with any water-soluble additives required, in the
solution formed in step 1;
c. Adding the plasticiser to the solution and fill a conventional aerosol
can with the mixture.
d. Charging the filled can with liquefied propellant 10% to 90% of
composition w/w.
2. A process of preparing a topical medicinal spray composition claimed in
claim i, wherein the medicament is scopolamine, nitroglycerine, clonidine
isosorbide dinitrate, propanolol hydrochloride, timolol maleate, clonazepan,
verapamil, diclofenac sodium, alendronate sodim, ibuprofen, ketoprofen,
indomethacin, piroxicam, ketorolac, tromethamine, nimesulide,
hydrocortisone or esters thereof, dexamethasone, fluocinolone acetonide or
betamethasone or salts thereof, estradiol or noethisterone or a combination
thereof, testosterone or progesterone, salbutamol or salts thereof,
bambuterol, salmeterol xinafoate, fluticasone propionate, mometasone
furoate, budesonide, beclomethasone dipropionate, sodium cromoglycate or
isoprenaline sulphate, alendronic acid, pamidronic acid, ethdronic acid or
salts thereof, vasopressin, oxybutynin, imipramine, mitrazapine,
desipramine, naratriptan, zolmitriptan, sumatriptan, nicotine, loperamide,
misoprostol, hyoscyamine, atropine, trihexyphenidyl, lorazapam, diazepam,
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tiagabine, fluoxetine, paroxetine, lisinopril, trandolapril, captoprii, amlodipine, felodipine, prazosin, amiloride, methamphetamine, sibutramine hydrochloride, nafarelin, leuprolide acetate, insulin growth hormone and analogues thereof, doxazosin, tamsulosin, terazosin, fanasteride, alprostadil, sildenafil citrate, bromocriptine, cabergoline, selegiline or melatonin, glimepiride, rosiglitazone, glyburide or glipizide; any of the chiral forms of the above medicaments; or any two or more of the above, including their chiral forms, in combination.
3. A process of preparing a topical medicinal spray composition claimed in the preceding claim, wherein the filmformer is any acrylic polymer of copolymer, preferably a non-ionic copolymer of methyl methacrylate and butyl methacrylate, copolymer of dimethylarnine ethyl methacrylate and a neutral methacrylic acid ester, ammonio methacrylate copolymer type B, ammonio methacrylate copolymer type A, methacrylic acid copolymer type A, methacrylic acid copolymer type B, or is polyvinyl acetate, cellulose acetate, polyvinyl alcohol, povidone, povidone vinyl acetate, hydroxypropylmethyl cellulose, hydroxyethyl cellulose or methyl cellulose.
4. A process of preparing a topical medicinal spray composition as claimed in any of the preceding claim, wherein the solubilizer is a copolymer of dimethylarnine ethyl methacrylate and a neutral methacrylic acid ester; a surfactant preferably sodium lauryl sulphate; a polyhydric alcohol, preferably propylene glycol or a polyethylene glycol; vitamin E. vitamin E TPGS (tocopheryl polyethylene 1000 succinate) or labrasol; or any two or more of the above in combination.
5. A process of preparing a topical medicinal spray composition as claimed in claims 1 to 4 wherein the filmformer is a non-ionic copolymer of methyl
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methacrylate and butyl methacrylate and the solubiliser is a copolymer of dimethylamine ehyl methacrylate and a neutral methacrylic acid ester.
6. A process of preparing a topical medicinal spray composition as claimed in claims 1 to 5, wherein the plasticisers is| triethyl citrate, dimethyl isosorbide, acetyltributyl citrate, castor oil, propylene glycol or polyethylene glycol or any two or more of the above in combination.
7. A process of preparing a topical medicinal spray composition as claimed in claims 1 to 6, wherein the permeation enhancer is a lyophilic solvent, preferably dimethyl sulfoxidfe, dimethyl formamide or isopropyl myristate; a surfactant, preferably Tween 80 or menthol, or sodium lauryl sulfate; a two components system, preferably oleic acid and octyl dimethyl paraamino benzoic acid (Padimate 0); or a polyhydric alcohol, preferably propylene glycol or transcutol.
8. A process as claimed in claims 2 to 7 wherein the water soluble additive is propylene glycol, sodium lauryl sulphate, one or more polaxomers, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, cetomacrogol, polyethylene glycol or diethylene glycol monoethyl ether EP (transcutol); or any two or more of the above in combination.
9. A process of preparing a topical medicinal spray composition as claimed in claims 1 to 8 wherein the vehicle comprises water or a non-aqueous solvent, wherein said solvent is preferably acetone, isopropyl alcohol, methylene chloride, methyl-ethyketone, absolute alcohol, ethyl acetate or trichloromonofluroethane (P11).
10. A process of preparing a topical medicinal spray composition as claimed in
claims 1 to 9 wherein the vehicle comprises from about 1% to about 20%
(w/w) of one more humectants.

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11. A process of preparing a topical medicinal spray composition as claimed in claim 10, wherein the each humectant is a polyhydric alcohol, preferably propylene glycol, -butylene glycol, a polyethylene glycol, glycerol or sorbitol; or is polyvinylpyrrolidone.
12. A process of preparing a topical medicinal spray composition as claimed in any preceding claim, wherein the vehicle partly comprise a propellant in an amount to provide from 10% to 90% of the composition.
13. A process of preparing a topical medicinal spray composition as claimed in claim 12, wherein the propellants is a hydrocarbon, preferably propane, butane, isobutene, or dimethylether, hydrofluorocarbonor a hydrochorofluorocarbons, preferably dichlorodifluoromethane (PI 2), trichloromonofluoromethane (P11), dichlorofluroethane, monochlorodiuorometha ne (P22), dichloroietrafluroethane (P114), difluoroethane (P152A), tetrafluoroethane (P134A), heptafluoropropane (P227B), or compressed gases, preferably nitrogen or carbon dioxide.
14. A process of preparing a topical medicinal spray composition as claimed in
claim 1, wherein the drug or combination of drugs so deposited in the matrix
of the film-former(s) may remain in a solubillised form or may be in a form of
suspension.
Dated this 13th day of January, 2000.

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ABSTACT
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A topical, medicinal spray composition comprises of a drug or combination of drug as solution or suspension in a volatile carrier containing a polymer or combination of polymers which when sprayed on the surface of the skin forms a film on the skin. The components of this invention are not restricted to, but preferably comprise of (w/w) from about 0.1% to 10% of one or more medicaments, from about 0.1% to 10% of film formers, from about 0.1% to 10% solubiliser, from about 0.1% to 8% permeation enhancer, from about 1% to 10% plasticiser, and a vehicle q.s. 100% wherein the composition can be sprayed on a topical site to form a stable, breathable film on said site, from which film the medicaments are transdermally available. Preferably, the composition further comprises from 1% to 7% (w/w) of one or more water-soluble additives. The drug or combination of drugs so deposited in the matrix of the film-formers) may remain in a solubillised form of suspension. When sprayed on a topical site, the composition forms a stable breathable film from which the medicaments are transdermally available. The invention includes a spray dispenser containing the topical composition.