Title:
AEROSOL COMPOSITION CONTAINING A VASOCONSTRICTOR
United States Patent 3608065


Abstract:
An aerosol composition containing phenylephrine as the vasoconstrictor is made exceptionally uniform by using dipropylene glycol as a cosolvent.



Inventors:
Lover, Myron J. (Mountainside, NJ)
Rodon, Maria C. (Elizabeth, NJ)
Application Number:
04/857229
Publication Date:
09/21/1971
Filing Date:
09/11/1969
Assignee:
MERCK & CO. INC.
Primary Class:
International Classes:
A61K9/00; A61K9/12; A61K31/135; A61K31/16; C09K3/30; (IPC1-7): A61K27/00
Field of Search:
424/45
View Patent Images:



Other References:

Chem. Abst. (1), 33, 46599 (1939). .
Chem. Abst. (2), 33, 94419 (1939)..
Primary Examiner:
Friedman, Stanley J.
Claims:
What is claimed is

1. In an aerosol composition for confining in a valved sealed container and comprising up to 1 percent phenylephrine as an active ingredient and a nontoxic halohydrocarbon volatile propellant, the feature involving the inclusion therein of dipropylene glycol as a cosolvent to solubilize the phenylephrine.

2. The aerosol composition of claim 1 in which the glycol constitutes from 50 to 70 percent by weight thereof.

Description:
This invention relates to aerosol preparations for the topical application of a medicament and particularly to a self-propelling composition containing phenylephrine as the active therapeutic agent.

Numerous aerosol preparations have been devised to propel a therapeutic agent against an exposed surface such as the skin and eyes or into a body orifice such as the mouth, lungs and nose. For instance, the U.S. Pat. No. 3,014,844 to Thiele et al. describes several aerosol compositions for dispensing various medicaments but all of them contain a surfactant such as sorbitan trioleate to maintain the medicament in a suspension. Several of the examples incorporate a vasoconstrictor as the medicament.

While they are serviceable, the compositions of the Thiele et al. patent are open to the objection that the surfactant is irritating to sensitive body surfaces and tissues. This is true even though this patent utilizes a small relative amount of the surfactant. To reduce this irritation the U.S. Pat. No. 2,868,691 to Porush et al. teaches the use of ethanol as a solvent or suspending agent for the medicament but as large relative amounts of this alcohol are necessary to accomplish its intended purpose these compositions have also proved to be irritating.

An effort to minimize this irritation and still maintain a constant intermix in the aerosol container so that all the individual dispensed doses will have a uniform amount of medicament in them, is disclosed in U.S. Pat. No. 3,282,781 to Macek et al. That patent reduces the amount of ethanol which is necessary by including a glycol in the composition. The glycol serves the additional function of inducing dispersion of the medicament into the lungs on inhalation.

The problem of preparing an aerosol composition in which the medicament is a vasoconstrictor has been particularly troublesome. These vasoconstrictors are usually to be applied to the nasal orifice in instances of head colds and allergies, at which time the mucosa is already in an inflamed, irritated state. This calls for an aerosol composition which is especially nonirritative.

In accordance with the present invention it has been found that dipropylene glycol not only is nonirritating but that it serves as an excellent cosolvent with the conventional aerosol propellents to keep the vasoconstrictor in solution. This function of serving to codissolve the drug with the volatile propellant results in a single liquid phase composition under the pressure conditions in the container. Accurate metering is thereby obtained so that from the first to the last spray dose there is uniformity in the spray content, varying only by the proportion of liquid propellent evaporating into the headspace.

The composition is a true solution throughout and consequently it is exceptionally uniform in its entirety and there are no localized zones within the container where the concentration is higher or lower. If it is put in a pressure-sustaining glass container it will be found to be water clear and this accounts for its uniformity and free passage through the discharge nozzle.

A further advantage of this composition is that the spray is an exceptionally fine mist which penetrates well and is nonirritating. These advantages are achieved because there are no solid particles of drug substance to cause locally high concentrations, and because the glycol is a demulcent. The glycol may also provide a reservoir effect for sustained action.

The propellant may be any of the ones described in the above mentioned patent and these propellants are incorporated herein by reference. They are halogenated hydrocarbons and although a single entity may be used, it has been found that mixtures of the halogenated hydrocarbons are especially effective as they provide a better solvent action and give lower, more desirable pressures. These mixtures are described in the above patents and also in U.S. Pat. Nos. 3,320,125 and 3,282,791.

The dipropylene glycol preferably should constitute about 60 percent by weight of the total composition but it may be from 50 to 70 percent. The remainder will be tee propellant except for the vasoconstrictor which will constitute 1 percent of the composition at most.

The composition is made by the conventional methods well-known in the art.

Representative example are: --------------------------------------------------------------------------- EXAMPLES 1

Phenylepherine HCL 0.60% by wt. Dipropylene glycol 59.40$%by wt. Propellant 40.00% by wt. Dichlorofluoromethane 30.00% by wt. Dichlorotetrafluoro ethane 70.00% by wt. __________________________________________________________________________ --------------------------------------------------------------------------- EXAMPLE 2

Phenylepherine HC1 0.60% by wt. Dipropylene glycol (approximately) 50.00% by wt. Propellant (same) 50.00% by wt. __________________________________________________________________________ --------------------------------------------------------------------------- EXAMPLE 3

Penylepherine HCL 0.60% by wt. Dipropylene glycol (approximately) 70.00% by wt. Propellant (Same) 30.00% by wt. __________________________________________________________________________ --------------------------------------------------------------------------- EXAMPLE 4

Phenylepherine HCL 0.60% by wt. Dipropylene glycol 59.40% by wt. Propellant 40.00% by wt. Dichlorofluoromethane 40.00% by wt. Dichlorotetrafluoro ethane 60.00% by wt. __________________________________________________________________________

In the above examples the propellant is a mixture of specific halohydrocarbons but although this is a preferred propellant, the composition of the invention is not limited to it. As is stated above, the various halohydrocarbon propellants are known in the art as is represented for instance by the patents mentioned above; these propellants are incorporated herein by this reference. The essential feature of this invention is the combination of dipropylene glycol and phenylephrin in an aerosol propellant as this particular glycol acts as a cosolvent for this particular vasoconstrictor. Thus the aerosol propellant may be of the nontoxic kind described in lines 15 to 51 of column 4 of the above-mentioned U.S. Pat. No. 3,014,844.

The invention also contemplates the inclusion in the composition of other active therapeutic agents which are completely soluble therein.