Stable hydrocortisone-based composition for use in local corticotherapy

A stable hydrocortisone-based composition comprises hydrocortisone solubilized in a mixture of an aliphatic alcohol, propyleneglycol and dimethyl coco-benzylammonium chloride.

The present invention relates to a new composition for use in local 
corticotherapy, said composition capable of containing in the solubilized 
state, a high concentration of hydrocortisone, thereby avoiding 
undesirable side-effects which generally are encountered in a prolonged 
usage of hydrocortisone-based compositions. 
Excessive and especially prolonged use of hydrocortisone-based lotions, 
ointments, creams or salves often is accompanied by certain secondary or 
side effects which cause, in the long run, a truly irreversible atrophy of 
the skin. 
Known hydrocortisone-based compositions generally contain hydrocortisone in 
amounts lower than about 2 weight percent and more often in amounts of 
about 1 weight percent. 
Compositions having a hydrocortisone concentration significantly less than 
this, i.e. in the order of 0.1 weight percent can be used principally to 
avoid the disadvantages attendant with the use of compositions having a 
higher hydrocortisone content. However, the duration of treatment is 
significantly longer and, consequently, the treatment requires medical 
supervision. 
With the view of reducing the duration of the treatment and thus avoid 
undesirable side effects, hydrocortisone-based compositions in the form of 
dispersions have also been proposed. These compositions, even if they have 
a higher hydrocortisone content, nonetheless they also have been found to 
be less effective since they lack acceptable skin penetration 
characteristics on the areas of the skin to be treated. 
Moreover, it has also been noted that these dispersion-type compositions 
exhibit poor storage stability characteristics, the hydrocortisone being 
degraded over a relatively short period of time which reduces to the same 
extent their activity. 
Until now it has not been possible to perfect stable compositions for use 
in local corticotherapy which contain hydrocortisone in high 
concentrations and which exhibit good skin penetration characteristics and 
which in turn are capable of reducing the treatment time, thereby avoiding 
an irreversible atrophy of the skin. 
This problem is resolved in accordance with the present invention by the 
use of a particular solvent mixture capable of solubilizing hydrocortisone 
in an amount greater than or equal to 2.5 weight percent based on the 
total weight of the composition. 
Moreover, stability tests carried out on the compositions made in 
accordance with the present invention have shown excellent results, the 
rate of degradation, measured by HPLC, after a period of 2 months at 
ambient temperature, being lower than 5%.

The present invention thus relates to a stable hydrocortisone-based 
composition for use in local corticotherapy containing, in the solubilized 
state, hydrocortisone in a solvent mixture comprising an aliphatic alcohol 
having 1-3 carbon atoms, propyleneglycol, dimethyl coco-benzylammonium 
chloride, and water. 
In accordance with the present invention, the aliphatic alcohol is 
methanol, ethanol or isopropanol, ethanol being more particularly 
preferred. 
The dimethyl coco-benzylammonium chloride is a quaternary ammonium salt of 
the formula 
##STR1## 
wherein 
R represents the coco (or copra) radical which is a mixture of alkyl and 
alkenyl radicals having 6 to 18 carbon atoms, principally alkyl radicals 
having 12 to 14 carbon atoms. 
In accordance with the present invention the solvent mixture comprises, 
preferably: 
15 to 60 weight percent aliphatic alcohol having 1-3 carbon atoms, 
15 to 60 weight percent propylene glycol, 
3 to 30 weight percent of dimethyl coco-benzylammonium chloride, and 
10 to 50 weight percent of water. 
The solvent mixture is generally present in the composition of the present 
invention in an amount ranging from 40 to 99.99 weight percent based on 
the total weight of said composition. 
The concentration of hydrocortisone in the compositions according to the 
present invention for use in local corticotherapy is generally not greater 
than 12 weight percent depending upon the solvent mixture employed. 
Preferably, however, the hydrocortisone is present in the compositions of 
the present invention in an amount between 0.01 and 5 weight percent, and 
more particularly between 0.5 and 4 weight percent, based on the total 
weight of the composition. 
The compositions according to the present invention can be provided in 
various forms, principally in the form of lotions, shampoos, ointments or 
gels and are employed in the treatment of all ailments or diseases 
requiring local corticotherapy. 
The lotions are essentially the hydrocortisone solubilized in said solvent 
mixture, to which optionally can be added conventional additives for this 
type of formulation. 
The gels are obtained using gelling agents such as silica, cellulose 
derivatives, carboxyvinyl polymers (Carbopols), natural or synthetic gums, 
said gelling agent being employed in an amount varying between 0.5 and 15 
percent by weight, relative to the total weight of the composition. 
The ointments are anhydrous compositions based, for example, on petrolatum, 
paraffin oil or waxes. 
The compositions according to the present invention are particularly useful 
in the treatment of eczema, psoriatic or eczematous erythrodermy, 
pruriginous lesions, chronic erythematous lupus, patch psoriasis and 
parapsoriasis, hyperthrophic cicatrix, and radiotherapic or solar 
erythema. 
These treatments require an application of the composition of the present 
invention to the affected area of the skin, on the average, twice each 
day, optionally with a massaging action in order to facilitate the 
penetration thereof into the skin. 
The following non-limiting examples are given to illustrate the 
compositions according to the present invention. 
EXAMPLE A 
Lotion for local corticotherapy 
Propylene glycol: 30 g 
Ethanol: 40 g 
50% aqueous solution of dimethyl coco-benzylammonium chloride, sold under 
the tradename "Arquad DMMCB 50" by Akzo: 10 g 
Hydrocortisone: 2.5 g 
Water, sufficient amount for: 100 g 
EXAMPLE B 
Gel for local corticotherapy 
Propylene glycol: 25 g 
Ethanol: 40 g 
50% aqueous solution of dimethyl coco-benzylammonium chloride: 10 g 
Aerosil (finely divided silica) sold by Degussa: 8.5 g 
Water: 14 g 
Hydrocortisone: 2.5 g 
EXAMPLE C 
Shampoo for local corticotherapy 
Propylene glycol: 20 g 
Ethanol: 20 g 
50% aqueous solution of dimethyl coco-benzylammonium chloride: 50 g 
Hydrocortisone: 
Water, sufficient amount for: 100 g 
Compositions A to C, above, are not only storage stable, but they also 
exhibit good skin penetration characteristics as well as good tolerance. 
Relative to conditions usual in the use of hydrocortisone-based 
compositions, the treatment time when using the compositions of the 
present invention can be reduced in an appreciable manner, thus avoiding 
prolonged usage and undue risk of skin atrophy.