CS203846B1 - Hydrophilic unguent foundation - Google Patents

Description

The invention relates to a hydrophilic ointment base based on a water-washable oil-in-water emulsion containing non-ionic emulsifiers, especially for dermal pharmaceutical and / or cosmetic preparations.

Various oil-in-water emulsion bases appear in the literature and in practice. used for the preparation of externally applied preparations. Efforts have also been made to formulate a formulation for such a hydrophilic emulsion butter base which would allow the incorporation of as many lipophilic and hydrophilic active ingredients as possible. Some works deal with the recipe of foundations for skin creams (RL Goldenberg, Drug a. Cosmet. Ind., 104, 1969, δ. 1 ,, 54-58), other studies of the influence of emulsifiers on the emulsion system (E. Nurnberg, Pette, Seifen) , Anstrichmittel 71, 5, 386-394, 1969), others review the physicochemical, toxicological, and biopharmaceutical aspects of emulsions (BR Guillot, J. Cotte, finulsions in Pharmacy, Why.).

The efforts made to date to build an as versatile hydrophilic emulsion base as possible have largely failed to achieve unequivocal success. Therefore, research into the ointment base was undertaken, which would allow the technology to be simplified and, if possible, based on a small assortment of available raw materials. Systematic examination of samples of oil-in-water emulsions, in particular regarding their stability and possible interactions between the individual pharmacodynamically inert ingredients with respect to each other and / or with respect to each other. between inert and active ingredients, the formulation of a hydrophilic ointment base based on a water-washable oil-in-water emulsion containing non-ionic emulsifiers, especially for dermal pharmaceutical and / or cosmetic preparations, has been prepared according to the invention.

The essence of this base is that it contains 12 to 22 wt. % of the fat phase in which the weight ratio of liquid to solid is 1 to 3: 1.5 to 4, further 2 to 6 wt. mixtures of at least two non-ionic emulsifiers having a hydrophilic-lipophilic balance value of 4 to 16, one emulsifier having a hydrophilic-lipophilic balance value of 3-5 and the other of 16-18, and a weight ratio of a low hydrophilic-lipophilic balance emulsifier to a high hydrophilic emulsifier the lipophilic equilibrium is 2.5 to 6: 7.5 to 4, and preferably 5.5: 4.5, with the remainder up to 100 wt. form an aqueous phase,

The hydrophilic butter base of the present invention may comprise as a fat phase solid paraffin, cetyl stearyl alcohol, stearin, white wax and liquid paraffin and as an aqueous phase propylene glycol and demineralized or distilled water. Suitable non-ionic emulsifiers are, for example, the molecularly distilled monoglyceride of higher C14-C18 fatty acids and a mixture of ethoxylated higher C14-C10 fatty alcohols.

The beneficial properties of the hydrophilic butter base according to the invention are due to the content of a balanced amount of non-ionic emulsifiers of considerably different hydrophilic-lipophilic balance (HLB) values. The relationship between the solid and liquid paraffin wax, wax and cetylstearyl alcohol and the propylene glycol-water aqueous phase is given by the above-mentioned optimum emulsifier composition, as well as the solid-liquid phase relationship. In cases where it is desired to adjust the pH of the base and to strengthen the stability of the emulsion, triethanolamine may be added in an amount of 0.1 to 0.2% by weight.

The production of the hydrophilic butter base according to the invention can be carried out in conventional homogenizing boilers or on efficient continuous emulsifying machines.

The raw materials that form part of the hydrophilic butter base are nontoxic, pharmacodynamically indifferent and mostly commonly tolerated in pharmacopoeias. The hydrophilic butter base according to the invention is suitable for the incorporation of active substances soluble in both the fat and the aqueous phase or suspended in an emulsion.

In the clinical evaluation of the dermal irritability of the heparin ointment (Example 1), as a representative sample of the hydrophilic base and its butter-based preparations, no signs of adverse reactions were found.

The stability of the hydrophilic butter-based compositions of the invention was evaluated after storage in climatic cabinets for 3 months. The results are shown in the table.

Preparation 0 ° C Temperature +25 ° C +30 ° C rel. humidity 95% +25 ° C alternate +35 C after 12 hours Heparin ointment compliant compliant compliant hint lumpiness Hydrocortisone ointment compliant compliant compliant hint lumpiness Spermieidní vagin. cream compliant compliant compliant compliant

Further details of the hydrophilic butter base according to the invention and the possibilities of preparing various butter preparations are given in the following examples, which illustrate the invention but do not limit it in any way.

Examples

Example 1 Heparin ointment

Composition (in% by weight):

solid paraffin 3.50 cetylstearyl alcohol 3.00 stearin 2.00 white wax 1.00 paraffin liquid 9.50 methyl- and propylparaben 0.25 molecularly distilled monoglyceride t

higher fatty acids C16-Ctg (emulsifier A) 1.60 mixture of ethoxylated C14 - C18 higher fatty alcohols (emulsifier B) 1.40 propylene glycol 5.00 triethanolamine 0.15 demineralized water 72.40 heparinoid 100 j 0.20

Manufacturing process:

A mixture of solid, liquid, cetylstearyl alcohol, stearin and white wax is sterilized at 120 ° C for 30 minutes. Methyl- and propylparaben are dissolved in the melt. After cooling to 80 ° C, emulsifiers are added. The mixture is thoroughly mixed in a homogenization boiler and cooled longer. At 70 ° C, an aqueous phase formed by mixing propylene glycol with triethanolamine at 60 wt. water. The emulsification of the mixture occurs at an emulsifier speed of 1,400 rpm. The heparinoid is dissolved in the rest of the water. The solution was filtered and heated to 50 ° C. It is added to the emulsion at 50 ° C while stirring constantly. Stirring is continued until the ointment has cooled to room temperature (15-25 ° C).

The preparation can also be produced by so-called cold emulsification or continuously using a compact line.

In cold emulsification, the process differs from the previous one in that an aqueous phase of 20 ° C is sucked into a fat phase of 70 ° C by means of a special ring nozzle.

In continuous emulsification, the fat phase is prepared as above. The aqueous phase is prepared by mixing propylene glycol with triethanolamine and water in which the heparinoid has been previously dissolved and heated to 50 ° C. The fat and aqueous phases are metered by a volumetric pump into a continuous machine where the components are homogenized, emulsified and cooled.

Example 2

Hydrocortisone ointment

Composition (in% by weight):

solid paraffin 3.50 cetylstearyl alcohol 3.00 stearin '2.00 white wax 1.00 paraffin liquid 9.50 methyl- and propylparaben 0.25 emulsifier A 1.10 emulsifier B 0.90 propylene glycol 5.00 triethanolamine 0.15 demineralized water 72.60 hydrocortisone acetate 1.00

Manufacturing process:

It is identical to the procedure of Example 1, except that trituration is prepared from the hydrocort, isonacetate by mixing the compound with the prepared emulsion at 45 ° C warm. The mixture is refined in a collagen mill and fed back into the homogenization boiler, where it is stirred slowly for at least 45 minutes.

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203846 4

Example 3

Spermicidal vaginal shop

Composition (in% by weight):

solid paraffin 3.50 ethyl alcohol 3.00 stearin 2.00 white wax 1.00 liquid paraffin 4.50 methyl and propylperaben '0.25 propylene glycol 5.00 mercuric phenylborate 0.03 perfume 0.03 emulsifier A 1.00 emulsifier B 3.00 lactic acid 0.01 demineralized water 76.68

Manufacturing process:

It is the same as in Example 1, except that mercury phenylborate is dissolved in water instead of heparinoid.

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Neutral dry cream (for cosmetic products)

Composition (in% by weight):

solid paraffin 3.50 cetylstearyl alcohol 3.00 stearin 2.00 wax white 1.00 liquid paraffin 9.50 methyl- and propylperaben 0.25 emulsifier A .1,60 emulsifier B 1.40  propylene glycol 5.00 trletanolamine 0.15 demineralized water 72.60 The manufacturing process is the same as in example 1. Example. 5 Dry vitamin cream Composition (% w / w); solid paraffin 3.50 e tyls tearyl alcohol 3.00 stearin 2.00 white wax 1.00 liquid paraffin 9.50 methyl- and propylparaben 0.25 exeroftoacet 0.05 tocopherol acetate 0.10 tocoparol 0.10 emulsifier A 1, 60 emulsifier B 2.40

propylene glycol 5.00 demineralized water 71.50

The manufacturing process is the same as in Example 1 except that the lipophilic vitamins are dissolved in the fat phase at 70 ° C, which is then emulsified with the aqueous phase.

Example.6

Purcelin cream

Composition (in% by weight):

liquid peat (blend of branched chain fatty acid esters) 2.00 solid pail (long chain fatty acid blend) 3.50 ce tyls tearyl alcohol 3.00 stearin 2.00 white wax 1.00 paraffin liquid 7.50 methyl- and propylparaben 0.25 emulsifier A 1.60 emulsifier B 2.40 propylene glycol 5.00 demineralized water 71.75

The production process is the same as in Example 1. The solid and liquid porcine is dissolved in the fat phase at 70 ° C and emulsified with the aqueous phase.

Claims (4)

A hydrophilic butter base based on a water-washable oil-in-water emulsion comprising non-ionic emulsifiers, characterized in that it contains 12 to 22 wt. a fat phase in which the weight ratio of liquid to solid components of Sine 1 to 3: 1.5 to 4, further 2 to 6 wt. mixtures of at least two non-ionic emulsifiers having a hydrophilic-lipophilic balance value of 4 to 16, one emulsifier having a hydrophilic-lipophilic balance value of 3-5 and the other of 16-18, and a weight ratio of a low hydrophilic-lipophilic balance emulsifier to a high value emulsifier the hydrophilic-lipophilic balance is 2.5 to 6: 7.5 to 4, preferably 5.5 to 4.5, with the remainder up to 100 wt. form an aqueous phase. 2. Hydrophilic butter base according to claim 1, characterized in that it comprises solid paraffin, cetyl stearyl alcohol, starch, white wax and liquid paraffin as the fat phase. 3. Hydrophilic butter base according to claim 1, characterized in that it comprises propylene glycol and demineralized or distilled water as the aqueous phase. 4. A hydrophilic butter base according to claim 1, characterized in that it contains, as non-ionic emulsifiers, the molecularly distilled monoglyceride of higher fatty acids C18 to C18 and a mixture of ethoxylated higher fatty alcohols C14 to C18.