FOME 2

ORIGINAL
43/MUM/2000

THE PATENTS ACT, 1970
(39 of 1970)
COMPLETE SPECIFICATION
[See section 10]
TOPICAL MEDICINAL SPRAY
COMPOSITIONS FOR
TRASDERMAL DRUG DELIVERY.
CIPLA LIMITED, A COMPANY
INCORPORATED UNDER THE
INDIAN COMPANIES ACT, 1913,
WHOSE ADDRESS IS 209,
BELLASIS ROAD, MUMBAI
CENTRAL, MUMBAI-400 008, IN THE STATE OF MAHARASHTRA, WITHIN THE UNION OF INDIA.
THE FOLLOWING SPECIFICATION DESCRIBES THE NATURE OF THIS INVENTION.

1

The present invention relates to a topical medicinal spray composition and their preparation, which compositions can be used to treat a variety of disorders.
Many delivery systems for the topical application of pharmaceutical compounds are currently available and include lotions, creams, gel, 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 many 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 is that the percutaneous penetration of the drug is often poor.
Topical spray formulations can help reduce the problem of skin irritation 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 foam which is effective in the control of Pseudomonas aeruginosa at the site of a burn or scald. US patent specification No. 4, 534, 958 describes and claims "a sprayable aerosol foam treatment composition which is a liquid in the aerosol container and foams 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 includes a burn treatment agent and one or more adjutants. The composition is used "for treating living skin".
However problem with conventional topical spray formulation 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 is only available transiently. By contrast, medicament in a transdermal patch is potentially available for as long as the patch remains in place.
2

We have now found a way of combining 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 films remains stable and in place over a period of days. In this way, medicament can be delivered transdermally over a period of time. Since the film is non-bcclusive, the problem for 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.
According to the present invention there is 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 polymer or combination of polymers which when sprayed on the surface of the skin forms a film on skin. The components of this invention are not restricted to, but preferably comprise of (w/w) from 0.1% to 10% of one of one or more medicaments, from 0.1% to 10% of film - formers, from 0.1% to 10% solubilizer, from 0.1% to 8% permeation enhancer, from 0.1% to 10% plasticizer, 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 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-former(s) may remain in a solubilised 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 release over a period of time or immediately.
Accordingly, the present invention also provides a dispenser containing the spray composition of the invention, which dispenser dispenses the composition as a spray.
Preferably, the composition is dispensed from a pump dispenser or from an aerosol dispenser. In the latter case, the composition additionally comprises from 10% to 90% of propellant in order to provide a suitable pressure within the aerosol dispenser. Generally propellant is not required for compositions

dispensed from a pump dispenser. However, if desired, such composition may also comprise from 10% to 90% of a propellant which is liquid at room temperature, for example trichloromonofluromethane (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 ingredient 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 ingredient, 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.
The medicament can be any medicinal compound which is stable in mixing with the Other ingredient of the rnmnnsitinn and pffpr.tivp nn tnninal administration- nr

a combination of any two or more such compounds. Preferably the medicament is a drug which is ant-emetic, anti-anginal, anti-inflarrnmatory, a steroid, or a steroid horrnone, 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 is scopolamine. "Preferred anti-anginals include nitroglycerine, clon]dine, isosorbide dinitrate, propanolol HCI. timolol maleate, clonazepam or verapamil. Preferred anti-inflammatory drugs include diclofenac sodiumr alendronate sbdium, ibuprofen, ketoprofen, indomethacin. piroxicam, ketorolac, tromethiamine or nimesulide. Preferred steroids include hydrocortisone and esters thereof, dexamethasone, fluocinolone acetonide or betamethasone and salts thereof
Preferred hormonal steroids include estradiol or noethisterone or a combination thereof, testosterone or progesterone. Preferred bronchodilators include salbutamol base and it's salts and bambuterol, salmeterol xinafoafe, fluticasone propionate, mometasone furoate, budesonide, be'clomethasone 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 antimigraine 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/obessive compulsive disorder include fluoxetine and paroxetine. Preferred ACE inhibitors include lisirpprir. trahdolapril and captoprit. Preferred calcium channel blockers include amlodipine 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 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 dimethylamine ethyl methacrylate and a neutral methacrylic add ester (Eudragit E100®), 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 breathabilityof thefilm is achieved t)y,the .absence of any occlusive backing membrane together with the generally hydrophinc properties of the Tilm-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 include a copolymer of dimethylamine ethyl methacrylate and a neutral methacrylic acid ester (Eudragit E100®, USP/NF); surfactants, for example, sodium lauryl sulphate; polyhydric alcohols, for example, 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 penetration of drug and/or act as humectants.
Preferred plasticisers include triethyl citrate, dimethyl isosorbide, acetyltributyl citrate, castor oil, propylene glycol, and polyethylene glycol, or any two or more of the above in combination.
-The permeation enhancer is preferably a lyophilic solvent, for example, dimethyl sulfoxide, dimethyl formamide or isopropyl myristate; a surfactant, for example, Tween 80 or sodium lauryl sulfate or menthol; a two-component system, for example, oleic acid and octyl dimethyl paraamino benzoin-acid (Padimate O); 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 can be water or a non-aqueous solvent. Preferred nonaqueous vehicle include acetone, isopropyl alcohol, methylene chloride, methyl-ethyl-ketone, absolute alcohol, ethyl acetate and trichloromonofluoromethane (p11); or any two or more of the above combination
The aqueous or non-aqueous vehicle may additionally comprise (weight /weight of vehicle) from 1% to 20% of one or more humectants. Preferred humectants include polyhydric alcohols and polyvinyl pyrrolidone. Preferred polyhydric alcohols are propylene glycol, butylenes glycol, polyethylene glycols, glycerol and sorbitol.
The water soluble additives is preferably propylene glycol, sodium lauryl sulphate, one or more polaxomers, polyoxyl 35 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 10% to 90 % (w/w) of the composition The propellant can be any pharmaceutically acceptable propellant which provides a pressure from 20 psig (pound(s) per square inch gauge) to 130 psig within an aerosol dispenser. Preferred propellant includes hydrocarbons, for example, propane, butane, isobutene, or dimethylether; hydrofluorocarbons and hydrochlorofluorocarbons for example dichlorodifluoromethane (P12), trichloromonofluoromethane (P11), dichlorofluoroethane, dichlorofluoroethane, monochlorodifluoromethane (P22), dichlorotetrafluoroethnane (P114). difluoroethane (P152a), tetrafluoroethane (P134a), heptafluroropropane (P227b); or compressed gases, for example, nitrogen or carbon dioxide. The topical compositions of the present invention are quick drying, non-occlusive formulations which cause marked enhancement of the skin penetration 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 compressed to existing transdermal patches.
The present compositions are 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 film-forming spray itself. The topical films formed by the present compositions show excellent stability and peelability and can be easily removed from the site of application by washing with water.
The composition are generally prepared by mixing the ingredient without liquefied propellant at a temperature of from 0° to 100° 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 pressurised 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.
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 thin 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.
In general, 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 solubiliser(s) along with the permeation enhancer, together with any water-soluble additives required, in the solution formed in step 1.

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-

Inqredients Percent w/w
Active ingredient - 0.5-10.0
Plastoid B 2.25
EudragitElOO 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
Inqredients "Percent w/w
Active ingredient 15
Povidone 3
Povidone VA-64 2
Vitamin E 0.5
PEG 400 1.0
Propylene glycol 1.5

15 15
Ethanol Acetone
Propellant q.s.
More specific examples of compositions for use in an aerosol dispenser include: Example 3

Example 4

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

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

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
Ingredients 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
E_xample 8
Ingredients Percent w/w
Active ingredient 15
PVP K 30 6
PVP VA 4
Vitamin E TPGS 0.5

Dimethyl isosorbide 5
Ethanol 20
Tnchloromonofluoromethane . q.s
(P11)
Example 9
Ingredients Percent w/w
Active ingredient 0.5-10
PVP VA 10
Vitamin E 0.5
Propylene glycol 3
Acetone 15
Ethanol 25
Tnchloromonofluoromethane q.s.
(P11)
More specific examples of compositions use in a pump dispenser include.
Example 10
Ingredients Percent w/w
Estradiol 2
PVP K-30 6
PVP VA 4
Vitamin E 1
PEG 6000 2
Polyethylene glycol 3
Acetone 27

Methylene chloride 27
Ethanol 28
Example 11
Ingredients Percent w/w
Estradiol 1
PVP K-30 6
PVP VA 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 glycoj 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

Propellants are very stable compounds and relatively non-toxic, inert and non¬flammable.
Sodium lauryl sulfate acts as a solubiliser for the drug.
The composition 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 atleast 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.

WE CLAIM
1. A topical, medicinal spray composition comprising 0.1% to 10% (w/w) of one or more medicaments, 0.1% to 10% of film formers, 0.1% to 10% solublizers, 0.1% to 8% permeation enhancer, 1% to 10% plasticisers, 1% to 7% of one or more water-soluble additives and a vehicle q.s. 100%, wherein the composition forms a stable, breathable film when sprayed on a topical site making the medicaments available transdermally.
2. A composition as claimed in claim 1, wherein said medicament is released from the said film either immediately or over a period of time.
3. A composition as claimed in claims 1 or 2, wherein the medicament is anti-inflammatory, a steroid, or a steroid hormone, and erectile dysfunctions.
4. A composition as claimed in claims 1,2 or 3, wherein the medicament is, scopolamine, nitroglycerine, clonidine, isosorbide dinitrate, verapamil, diclofenac sodium, alendronate sodium, naproxen sodium, ibuprofen, ketoprofen, indomethacin, piroxicam, ketorolac, tromethamine, nimesulide, hydrocortisone or esters thereof, dexamethasone, fluocinolone acetonide, or betamethasone or salts thereof, estradiol, or norethisterone or a combination thereof, testosterone, or progesterone, fluticasone propionate, mometasone furoate, budesonide, beclomethasone dipropionate, sodium cromoglycate or isoprenaline sulphate; alendronic acid, pamidronic acid, etidronic acid or salts thereof, vasopressin, oxybutynin, imipramine, mirtazapine, desipramine, nicotine, loperamide, misoprostol, atropine, trihexyphenidyl, fluoxetine, paroxetine, amlodipine, felodipine, prazosine, amiloride, leuprolide acetate, insulin, growth hormone and analogues thereof, doxazosin, tamsulosin, terazosin finasteride, alprostadil, sildenafil

citrate, bromocriptine, selegiline, melatonin, glimepiride, glyburide or glipizide; any of the chiral forms of the above medicaments; pharmaceutically acceptable salts of any of the above; or any two or more of the above, including their chiral forms, in combination.
5. A composition as claimed in any preceding claim, wherein the film-former is any acrylic polymer or copolymer, preferably a nonionic copolymer of methyl methacrylate and butyl methacrylate, copolymer of dimethylamine 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 , methyl cellulose or ethyl cellulose.
6. A composition as claimed in any of the preceding claims, wherein the solubilizer is a copolymer of dimethylamine ethyl methacrylate and a neutral methacrylic acid ester; a surfactant, preferably a Tween, Span, sodium lauryl sulphate; a polyhydric alcohol, preferably propylene glycol or a polyethylene glycol; vitamin E, vitamin E TPGS (tocopheryl polethylene 1000 succinate), or labrasol; propylene carbonate; or any two or more of the above in combination.
7. A composition as claimed in any of the claims 1 to 6, wherein the film former polymer is a non-ionic copolymer of methyl methacrylate and butyl methacrylate and the solubilizer is a copolymer of dimethylamine ethyl methacrylate and a neutral methacrylic acid ester.
8. A composition as claimed in any of the claims 1 to 7, wherein the plasticiser is triethyl citrate, dimethyl isosorbide, acetyltributyl citrate, castor oil, propylene glycol or polyethylene glycol or any two or more of the above in combination.

9. A composition as claimed in any of the claims 1 to 8, wherein the permeation enhancer is a. lyophilic solvent, preferably dimethyl sulfoxide, dimethyl formamide or isopropyl myristate; a surfactant, preferably Tween 80, menthol, or sodium lauryl sulfate; a two component system, preferably oleic acid and octyl dimethyl paraamino benzoic acid (PadimateO); menthol; mixed esters of capric or caprylic acids ; or a polyhydric alcohol, preferably propylene glycol or transcutol; or any two or more of the above in combination.
10. A composition as claimed in any of the claims 1 to 9, 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.
11. A composition as claimed in any of the claims 1 to 10, wherein the vehicle is aqueous or non-aqueous vehicle .
12.. A composition as claimed in claim 11, wherein the vehicle
comprises water or a non-aqueous solvent, wherein said solvent is
preferably acetone, isopropyl alcohol, methylene chloride, methyl-
ethylketone, absolute alcohol, ethyl acetate,
trichloromonofluoromethane(P11) or methylene dimethyl ether.
13. A composition as claimed in claims 11 or 12 wherein the vehicle is volatile.
14. A composition as claimed in any of the claims 1-13, wherein the vehicle comprises from 1% to 20% (w/w) of one or more humectants.

15. A composition as claimed in claim 14, wherein each humectant is a polyhydric alcohol, preferably propylene glycol, butylene glycol, a polyethylene glycol, glycerol or sorbitol; or is polyvinylpyrrolidone.
16. A composition as claimed in any of the preceding claims, wherein the vehicle comprises a propellant in an amount to provide from 10 to 90% of the composition.
17.A composition according to claim 16, wherein the propellant is a
hydrocarbon, preferably propane, butane, isobutane, or
dimethylether; a hydroflurocarbon or a hydrochloroflurocarbon,
preferably dichlorodifluromethane (P12),
trichloromonofluromethane(P11), dichlorofluroethane, monochlorodifluromethane (P22), dichlorotetrafluroethane(P 114), difluroethane(P 152 A), tetrafluoroethane(P 134 A) or
heptafluoropropane (P227 B); or a compressed gas, preferably
nitrogen or carbon dioxide.
18.A composition as claimed in claim 1, wherein the medicament or combination of medicaments so deposited in the matrix of the film former(s) remains in a solubilised form or in the form of a suspension.
19. A dispenser containing a composition as claimed in any of claims 1 to 18, which dispenser dispenses the composition as a spray.
20.A dispenser as claimed in claim 19, wherein the composition is dispensed as a metered dose.
21.A dispenser as claimed in claims 19 or 20, which is a pump dispenser containing the composition as claimed in any of claims 1 to 15.
22.A dispenser as claimed in claims 19 or 20, which: jis an aerosol dispenser containing a composition as claimed in claim 16 or 17.

23. An aerosol dispenser as claimed in claim 22, wherein the propellant provides a pressure of from 20 p. s. i. g. to 130 p. s. i. g. inside the dispenser.
24. An aerosol dispenser as claimed in claims 22 or 23, wherein the valve of the dispenser is an all position valve.
25. An aerosol dispenser according to any of claims 22 to 24, wherein the dispenser has a mechanical break-up actuator.
Dated this 13th day of January 2000
FOR CIPLA LIMITED By Their Agent
(UMA BASKARAN)