Composition for the extemporary preparation of formulations for topical applications for pharmaceutical and cosmetic use

A composition for the extemporary preparation of gels and creams for topical application and for pharmaceutical and cosmetic use comprises, besides one or more ingredients active under the pharmacological and/or cosmetic point of view, a gum swellable in water and a permeation agent.

The present invention relates to a composition for the extemporary 
preparation of formulations for topical application, particularly gels and 
creams, for pharmaceutical and cosmetic use. 
The most widespread pharmaceutical and cosmetic forms for topical cutaneous 
application comprise: 
CREAMS OR MILKS 
These are emulsion of oil in water or water in oil containing emulsifiers 
of several types, fats, oils, waxes and water in different proportions. 
OINTMENTS AND FATTY STICKS 
They consist prevailingly of oils, waxes and fats with or without 
emulsifiers, characterized by a very reduced content or by the total 
absence of water. 
GELS 
These are usually transparent forms, the consistency of which varies from 
the gelatinous to a very fluid state, prevailingly consisting of vegetal 
polysaccharides such as arabic gum, tragacanth gum, carrageenin, alginic 
acids, etc, or synthetic polymers such as carboxyvinyl polymer (carbopol) 
variously salified and cellulose derivatives. 
All these polymers form gels with water, the consistency of which is 
proportional to the concentration and which are variously spreadable, 
acceptable for the skin and of pleasant feeling. 
LOTIONS 
These usually consist of a fluid solvent (water or water-alcohol mixtures, 
water-glycerin mixtures, etc.) which, owing to their fluidity, are 
generally applied onto the skin by means of a napkin or cotton flock. 
ASPERSING POWDERS, TALCS AND POWDERS 
These are based on talc, kaolin, silica, lactose, mannitol, waxes and 
micronized fats, etc. which upon being applied onto the skin form a thin 
film of protecting powder. 
All these vary common pharmaceutical and cosmetic forms show, 
alternatively, some drawbacks, which in some cases render their use 
difficult or even practically not possible. 
The emulsions of oil in water and of water in oil (creams and milks) are 
bases unsuitable as vehicles for substances not stable in the presence of 
water, such as antibiotics, enzymes or anyhow active principles readily 
degradable in solution. They are moreover of difficult storage and 
physically poorly stable. The presence of emulsifiers sometimes makes it 
not certain the skin compatibility, mainly for continuous and extended 
uses. It is also worth to note that in the emulsions the development of 
bacteria and mycetes takes readily place and the preservants which can be 
used are not always sufficient in order to inhibit any microbial growth. 
The use of ointments (without water) might partially solve these problems, 
but these fatty bases are of unpleasant application, and cause the 
garments to be smeared and soiled; moreover the fatty layer applied to the 
skin may constitute a barrier, both for the normal skin transpiration and 
for the absorption of the active principles, the latter being included in 
a vehicle of difficult permeation. 
Gels and lotions comprising water are affected by the same problems of 
stability of the substances degradable into contact with water and 
although exhibiting, mainly as regards gels, undeniable advantages over 
the emulsions from the point of view of both the physical stability and of 
ready and pleasant use, still show problems of degradation induced by 
microorganisms, even if in a reduced degree. 
The aspersing powders, which do not contain water, are undoubtedly the most 
adequate vehicle for the active compounds raising problems of chemical 
stability and also possess the undeniable advantage of not permitting, 
during the storage, any microbial growth. 
However their application is precarious and hardly quantitatively 
determinable; moreover it is easily foreseeable that the active 
substances, dispersed in solid state in the powder, shall not come into 
intimate contact with the skin and thus their activity is not exploited in 
a complete, exhaustive and above all constant manner as it occurs when the 
presence of a solvent leads not only to a more intimate contact with the 
skin but also to a better surface dispersion. 
As it can be noticed, none of the usual preparations for topical use is 
fully free from drawbacks, whereby it is necessary from time to time to 
choice that formulation seemingly most convenient for the requirements of 
stability, storage, functionality and practicalness related to the nature 
of the substances being used and, obviously, to the end purpose of the 
formulation. 
In order to obviate to the above mentioned drawbacks it would be necessary 
to be able to prepare extemporary pre-dosed creams or gels in which the 
solvent (water) can be added a few instants before the use on the skin or 
the mucosae. 
The attempts to date made for the preparation of these extemporaneously 
formulations for topical use did not lead to practical results since the 
time needed for the absorption of the solvent were very great so that the 
product was practically useless for the inteded use. Furthermore the gums 
usually used form with water unpleasant lumps the dissolution of which is 
very difficult. 
In the DE-PS 862,044 a process is described for the manufacturing of powder 
formulations to be used for the extemporary preparation of a base for 
ointments or directly of the ointment. 
The composition of said powder is as follows: 
carboxymethylcellulose 30-45% 
clay swellable in water (bentonite, Fuller's earth, etc.) 30-45% 
wetting agent (aliphatic or aromatic sulfonic acids) 3-6% 
buffer agent, to adjust pH in the range 6-6.5, from 0.4 to 0.8% 
bacteriostatic agent 3-7% 
diluent (preferably lactose or similar carbohydrates) 8% at maximun 
active compound 1-25%. 
In the examples of the preparation of the extemporary cream the stirring of 
the initial water suspension is carried out to promote the dissolution. 
Said operation may have a duration of 30 minutes (ex. 1) or of 0.5 to 1 
minute (ex. 2). 
In turn French Pat. No. 2.311.530 discloses a powder or granule composition 
for the extemporary preparation of ointments. 
The composition is characterized in that it contains a carboxyvinylpolymer, 
having molecular weight of between 860,000 and 1,000,000, insoluble but 
swellable in water, in a concentration of 1 to 10% by weight. 
The other components for the formulation are the following: 
alkalinizing agents (e.g. ammonium or potassium carbonate) 2-5% 
emulsifier of the type oil in water (e.g. sodium stearate, sodium 
dioctylsulfosuccinate, etc., preferably sodium laurylsulfate) 0.5-2% 
fatty substances (e.g. liquid paraffin, triglycerides, decyl ester of oleic 
acid, cetyl alcohol, isopropyl miristate) 1-30%. 
To the said composition other thickening agents can be added such as 
starch, celluloses, colloidal silica, etc. in an amount of 10 to 90%. The 
ointment is readily prepared by admixing one part of granules or powder 
having the above composition with 8 parts of water and mixing for a time 
of 1 to 2 minutes. 
The French Pat. No. 2,068,447 relates to compositions permitting an aqueous 
preparation for dermatological or cosmetic use to be obtained as well as 
to their preparation method. 
Said compositions are in form of a lyophilizate directly obtained from an 
emulsion of the oil in water type essentially containing: 
one or more active principles for dermatological or cosmetic use; 
a lipidic phase containing fatty acids and their derivatives, fatty 
alcohols and their derivatives, natural and synthetic fats; 
a hydrophilic phase consisting of a thickening agent and of an emulsifier 
in water. As thickeners natural gums, cellulose derivatives, pectines, 
bentonite and colloidal silica, polysaccharides, synthetic macromolecules 
and starches can be used. As emulsifiers use can be made of anionic, 
cationic, non ionic surface active compounds, or salts of organic acids or 
fatty alcohols oxyethylene derivatives. 
In the specification of this patent it is stated that the granules as such 
must not be put directly into contact with the water, since they tend to 
soften thus hindering the dissolution process. 
In order to eliminate this drawback these granules are wrapped up in a bag 
of wide weft cloth, so as to permit the free passage of the water as well 
as of the emulsion, once it is reconstituted. 
Said bags are in turn enclosed in paper or aluminum bags, possibly combined 
with plastic material. 
In the French Pat. No. 2,101,044 a like composition is disclosed but 
particularly directed to shampooing, hair lotion and tooth paste 
formulations. 
A modification is described of the preparation of the dry residue to be 
later dissolved in water to reconstitute the emulsion. In this case the 
solution, before the lyophilization, is absorbed in a poliurethane foam 
"sponge". 
In this case the emulsion reconstitution takes place by simple immersion of 
the sponge in water; however the residue part contained in the innermost 
part of the sponge shall start to dissolve only when that of the outermost 
parts of the sponge are already dissolved. 
U.S. Pat. No. 2,484,637 relates to a base for the extemporary preparation 
of ointments, in form of an anhydrous powder comprising methylcellulose 
and sorbitol in the proportion of 10 to 40 parts of sorbitol for 100 parts 
of methylcellulose. 
The powder dissolution in water takes about one minute. 
Such a preparation does not swell, since methylcellulose is a water soluble 
polymer. 
It has now been surprisingly found and is the subject of the present 
invention that compositions comprising a gum capable of fixing water or 
swellable in water, i.e. carboxymethylstarch, provided that it is combined 
with a cellulose as a permeating agent, when put into contact with water 
form almost istantaneously gels and creams of easy and ready applicability 
to the skin. 
It has been furthermore found that the compositions according to the 
present invention can be suitably dosed in form of tablets having a 
predetermined water absorption and thus an adjustable viscosity or 
consistency. 
Of course the compositions according to the present invention contain one 
or more active compounds having the desired topic effect. 
As regards the carboxymethylstarch, the content thereof in the composition 
of the invention may range from 10 to 50% by weight, whereas as regards 
the celluloses, as permeating substance, their content in the composition 
of the invention is of between 1 and 50% by weight. 
The function of the cellulose is that of absorbing the solvent (water) 
without being dissolved and permit it to reach in every part of the tablet 
the gum which is thus almost istantaneously swelled. 
From the field experiments it was found that: 
(a) the tablet according to the invention is swelled in water in a maximum 
time of one minute forming a soft, voluminous gel, which can be easily 
topically applied; 
(b) the amount of absorbed water varies from 5 to 10 times the weight of 
the tablet and gives place to an increase, in about the same ratio, of the 
gel volume with respect to the initial one of the tablet, 
(c) the addition of a hydrophilic but water insoluble polymer, i.e. the 
cellulose, permits the almost instantaneous absorption of the water, which 
otherwise, in the presence of only carboxymethylstarch, would take place 
much more slowly. 
With the compositions according to the invention it is possible to prepare 
any pharmaceutical formulation for topical use and any cosmetic and more 
precisely: 
gels with active compounds not stable in water solution (e.g. some 
antibiotics); 
antiacne, hair detergent, after-shave, skin protecting, anti-cellulitis, 
anti-transpirant, deodorizing, hair-removing, nutrient and hydrating, skin 
detergent, intimate hygiene preparations. 
Among the advantages of the present invention, apart from the stability and 
from the practicalness of use, the elimination of water is to be 
mentioned, the latter being usually the prevailing part of the product 
sold to the customers. 
Some examples of compositions and formulations according to the invention 
are given hereinafter, clearly of having exemplifying but non limiting 
purpose.

EXAMPLE 1 
Tablets for an anti-acne extemporary gel 
25 g of carboxymethylstarch, 50 of zinc oxide, 5 g of colloidal sulfur, 50 
g of microgranular cellulose and 0.05 g of Triclosan are precisely 
weighted and then sieved through a 40 mesh sieve; thereafter the powders 
are admixed in a laboratory mill for 15 minutes. 
The said mixture is then charged in the tank of a manual press having a 7.5 
mm punch. There are obtained about 500 tablets, each of the weight of 270 
mg, with a hardness of between 3 and 4 kg. 
On a watch glass placed onto a laboratory balance 8 tablets as above 
prepared are positioned in sequence. 
On each tablet, by means of a pipette, water is added in form of a thin 
stream with a constant flow rate of 100 microliters/second. It is seen 
that the tables are fully swelled up in an average time of 24.+-.3 
seconds. The amount of water absorbed is about 8 to 9 times the initial 
weith of the tablet. 
The corresponding volume of the gel thus obtained is of between 2.5 and 3 
ml. 
Upon the water feeding is continued, the water is no longer absorbed and 
collected onto the glass. 
EXAMPLE 2 
Tablets for extemporary gel containing penicillin 
Carboxymethylstarch: 0.100 g 
microgranular cellulose: 0.100 g 
penicillin: 250,000 U.I. 
EXAMPLE 3 
Tablets for extemporary cream containing tetracyclin 
carboxymethylstarch: 0.150 g 
microgranular cellulose: 0.200 g 
polyoxyethylensorbitan monostearate: 0.010 g 
cetylstearyl alcohol: 0.100 g 
tetracyclin: 0.046 g 
EXAMPLE 4 
Tablets for extemporary vaginal gel with trichomonacidal activity 
carboxymethylstarch: 0.350 g 
cellulose: 0.200 g 
metronidazole: 0.500 g 
EXAMPLE 5 
Tablets for extemporary vaginal hormonal cream 
carboxymethylstarch: 0.100 g 
microgranular cellulose: 0.200 g 
polyoxyethylenated castor oil: 0.050 g 
spermaceti: 0.100 g 
conjugated estrogens: 0.002 g 
EXAMPLE 6 
Tablets for extemporary hair shampooing gel 
carboxymethylstarch: 0.150 g 
sodium laurylsulfate: 0.100 g 
acylglutamate: 0.050 g 
microgranular cellulose: 0.200 g 
EXAMPLE 7 
Tables for extemporary after-shave gel 
carboxymethylstarch: 0.100 g 
cellulose: 0.100 g 
azulene: 0.001 g 
allantoin: 0.010 g 
EXAMPLE 8 
Tablets for extemporary cream 
carboxymethylstarch: 0.100 g 
microgranular cellulose: 0.070 g 
saccharose monopalmitate: 0.050 g 
hydrogenated coconut oil: 0.020 g 
bees wax: 0.050 g 
EXAMPLE 9 
Tablets for extemporary nutrient and hydrating cream 
Carboxymethylstarch: 0.050 g 
microgranular cellulose: 0.200 g 
bees wax: 0.050 g 
lanolin: 0.050 g 
carob oil: 0.070 g 
sodium piroglutamate: 0.005 g