DD262530A5 - PROCESS FOR PREPARING A PHARMACEUTICAL WAFEREN GEL PREPARATION - Google Patents

Abstract

The invention relates to a process for the preparation of a pharmaceutical aqueous gel preparation. The pharmaceutical aqueous gel preparation for topical application contains as traegerstoff for the active pharmaceutical ingredients a C1-C6-alkyl-hydroxy-C1-C6-alkylcellulose or a hydroxy C1-C6-alkylcellulose, preferably methylhydroxyethylcellulose.

Description

Field of application of the invention

The invention relates to a process for the preparation of a pharmaceutical aqueous gel preparation for topical application.

Characteristic of the known state of the art

For the development of topically applicable, wound healing gel preparations, it is important to provide a carrier material which exerts a positive effect on the course of wound healing, but at least physiologically no irritant effect or has a healing process delaying effect.

This is not easy because in open wounds the tissue is extremely sensitive and is also irritated by non-aggressive foreign substances, which delays the healing process and causes pain to the patient.

Object of the invention

The aim of the invention is to provide an improved pharmaceutical aqueous gel preparation for topical application.

Explanation of the essence of the invention

The invention has for its object to provide a carrier for topical gel preparations, which exerts no irritating effect on injured tissue of humans and warm-blooded animals and thus promotes the healing of wounds.

It has been found that oxyalkylcellulose is such a carrier which exerts no irritating effect on the tissue in the form of an aqueous gel preparation (hydrogel) and may even exhibit a healing-promoting effect even without active ingredients.

Appropriately, however, a healing-promoting agent is added to the hydrogel according to the invention, which in turn should have no irritating effect on the tissue, so as not to negate the advantages of the carrier material.

For example, this is outstandingly suitable mixtures of active ingredients according to DE-PS 34 16 777, since these have in isotopic composition both a wound healing strong promotional effect and are tolerated simultaneously by the tissue without any irritation.

As oxyalkylcellulose such celluloses are understood to mean the lower alkyl radicals, i. H. those which each have 1 to 4, preferably 1 to 2 carbon atoms or hydrogen and a lower alkyl radical.

These include ζ. Β.

Methylhydroxymethylcellulose

Methylhydroyxpropylcellulose

Butylhydroxymethylcellulose

Ethylhydroxypropylcellulose

hydroxymethyl

hydroxyethyl

hydroxypropyl

hydroxybutyl

and preferably methylhydroxyethylcellulose.

Celluloses are understood to mean those having a polymerisation number of from 120 to 1,200, such as e.g. sold under the trade name "Tylose" ®.

These form clear gels with water, which are spreadable and can be applied to wound surfaces in sterile and as isotonic form readily together with appropriately dosed active ingredients.

The gels can be prepared by slowly adding the oxyalkylcellulose to warm water with stirring and allowing it to swell to homogeneity. The water may optionally beforehand means for adjusting the isotonic, z. As sodium chloride, glycerol or sorbitol, and preservatives such. B. PHB esters are added.

The invention thus relates to a pharmaceutical aqueous gel preparation for topical application, which is characterized in that it is a carrier for the active pharmaceutical ingredients a C ₁ to Ce-alkylhydroxy-C ₁ to C ₆ alkylcellulose or a hydroxy-C ₁ to C ₆ alkyl cellulose contains.

The gel preparation can, of course, depending on the application with other preparations, such. For example, oil in water

or water in oil emulsions, for example, to give the formulation a degree of lipophilicity preventing, for example, the caking or crusting of the wound surface.

Care must also be taken to ensure that during preparation a pH range which is favorable for wound healing of about 3.5 to 7.5, preferably 4-7, is not exceeded or exceeded. In first experiments, a sorbitol-containing gel with pH 4 has been found to be very well tolerated.

The viscosity should be adjusted based on the ratio cellulose / water so that the gel on the warm skin surface does not dissolve too easily and on the other hand can be easily distributed. A viscosity of 30 to 60 Pa.s seems to be favorable here.

embodiment

The invention is explained in more detail below with reference to some examples. example 1

Production of the drug-free gel

75 g 70% by weight sorbitol solution are dissolved in 883 ml of water with 2 g of PHB ester as preservative. This solution is heated to 60 ⁰ C and slowly added with stirring with 40g Methylhydroxyethylcelluiose. The mixture is stirred for 1 to 2 hours to homogeneity and cooled over this period to room temperatures.

This gives a transparent gel of pH 4 and a viscosity of 50 Pa.s. (at 20 ⁰ C) of the following composition:

Methylhydroxyethylcelluiose 4.00%

Sorbitol solution 70% 7.50%

Preservative 0.20%

Purified water ad 100.00%

Example 2 Pharmaceutical preparation with a K ⁺ / Ca ⁺ ~ mixture as active ingredient (according to OE-PS 3416 777)

According to Example 1, a 60 ° C aqueous solution with 30mmol CaCl ₂ , and 40mmol KCI prepared as a drug mixture and with sorbitol to adjust the isotonic and PHB esters as a preservative and treated with methylhydroxyethylcelluiose to obtain a gel having a pH of 4, 0 and a viscosity of 40 Pa.s.

The gel has the following composition:

calcium chloride

potassium chloride

Methylhydroxyethylcelluiose

sorbitol

preservative

Purified water

Example 3 Pharmaceutical preparation with a K ⁺ / Ca ⁺⁺ mixture as active ingredient (according to DE-PS 34 16 777)

According to Example 1, a 60 ⁰ C warm aqueous solution with 30mmol CaCl ₂ , and 40mmol KCl as a drug mixture and one prepared with sorbitol to adjust the isotonic and PHB esters as a preservative, with Methylhydroxyethylcelluiose added hydrochloric acid and cooled with stirring. This gives a gel with a pH of 4.0 and a viscosity of 35 Pa.s.

The gel has the following composition:

Calcium chloride 30mmol ... 0,44%

Potassium chloride 40mmol ... 0,30%

Methylhydroxyethylcelluiose (Tylopur®) 4.00%

Hydrochloric acid 0.01 N 4.00%

Sorbitol solution 70% 2.80%

Preservative 0.20%

Purified water ad 100.00%

30 mmol ... 0.44% 40 mmol ... 0.30% 4.00% 2.80% 0.20% ad 100.00%

Claims (2)

1. A process for the preparation of a pharmaceutical aqueous gel preparation for topical use, characterized in that a C ₁ to Ce-alkyl-hydroxy-CVCe-alkylcellulose or a hydroxy C ₁ to Cg-alkylcellulose slowly and with stirring in optionally pharmaceutical active ingredients containing warm Water enters and swells to homogeneity. 2. The method according to claim 1, characterized in that one uses methylhydroxyethylcellulose.