SOLID AND SEMI-SOLID GALENIC PREPARATIONS WITH MODIFIED RELEASE OF THEIR ACTIVE INGREDIENTS, FROM THE "DRY EMULSIONS" PROCESS

Abstract

The present invention relates to a new method for formulating and preparing modified- and delayed-release solid dosage forms of active ingredients. This solid dosage form is characterized by being composed of particles of varying fineness prepared from conventional base emulsions and comprising at least two inert supports: one hydrophilic and the other hydrophobic. This delayed-release dosage form is intended for oral and cutaneous administration.

Description

The present text relates to an improvement for the invention (previously described in the text of French patent no. 8602694) and which concerns small, more or less fine solid particles called "dry emulsions" obtained by drying a conventional W / O or H / E type emulsion. This invention relates to particles containing, in particular but not exclusively, an active pharmaceutical substance. The particles according to the invention may also contain other substances such as vitamins, etc. Thus obtained, these particles offer the possibility of delaying and prolonging the release of active ingredients in physiological environments after administration via both oral and cutaneous routes. In the text of the patent cited above, these particles are obtained by transforming a "water in oil" (W / O) type emulsion into a "dry emulsion", through the use of inert supports such as silicas and their derivatives. The present text follows the same process described in the patent cited above, but it applies to other types of emulsions such as "oil-in-water" (O / W) and uses other inert supports such as: silicone polymers, natural polymers, semi-synthetic polymers derived from cellulose and synthetic polymers derived from acrylic acid, hydrogenated oils... According to the claims of patent no. 8602694, the solid particles obtained by the process comprise two inert supports made of two types of silica: hydrophilic and hydrophobic. In the present text, the solid particles of the finished product are still characterized by the two inert supports, hydrophilic and hydrophobic, except that one or both of the two silicas have been totally or partially replaced by other inert supports mentioned in the preceding paragraph, or even: polymers and their derivatives, hydrogenated oils, etc. MATERIAL The vertical propeller mixer comprising two superimposed paddles (described in patent no. 8602694). MANUFACTURING PROCESS It consists of a single operation, carried out in two stages which are not separate and follow each other continuously until a solid or semi-solid product divided into fine particles is obtained (patent n- 8602694). OPERATING CONDITIONS - For the base emulsion (first step) temperature between 45 and 70°C Agitation at 6000 to 8000 rpm - For the dry emulsion (2nd step) ambient temperature Agitation speed: 12,000 to 14,000 rpm SIEVING THE FINISHED PRODUCT The product is sieved, and particles larger than 2000 microns are separated, ground, and reduced to a smaller size. The final particle size ranges from 100 to 2000 microns. EXAMPLES Prepared according to the characteristics of the invention in patent no. 8602694 and the present text, using the various types of inert supports already mentioned, the following examples illustrate the feasibility and application of the process on other types of supports. It is understood that the implementation examples described below do not in any way constitute a limitation. The aim, however, is to vary the types of supports used, as well as the lipid phase of the base emulsion and subsequently the type of emulsion, in order to obtain significant results for delayed release. Example 1 Particles prepared from a basic emulsion and using methyl cellulose as a hydrophilic support (n1) and collold hydrophobic silica as a hydrophobic support (n2), according to the proportions Castor oil 60 Stearic acid 20 Lime water 20 10% sodium salicylate Support ne 1 nl 5 8 - 9 8 Support n 2 n2 = 22 Z The particles of this formula are obtained by following the instructions of the process described in patent ns 8602694. They are white in color and the release of Na salicylate is delayed. Example 2 This is the same formula as example 1, but methyl cellulose has been replaced by an acrylic acid polymer as the hydrophilic support n 1, and a colloidal hydrophobic silica has been retained as the hydrophobic support n 2, according to the proportions Castor oil 60 Stearic acid 20 Lime water 20 10% sodium salicylate Support n' 1 nl = 7 - 9 Z Support ns 2 n2 = 22% The particles are white and the release of Na salicylate is greatly delayed. Example 3 Particles prepared from the same basic emulsion as in Example 1 and using methyl cellulose, but this time the colloidal hydrophobic silica has been replaced by another solid hydrophobic support such as hydrogenated oils, thus conforming to the following formula Castor oil 60 Stearic acid 20 Lime water 20 10% sodium salicylate Support ne 1 nl = 8 - 9% Support n 2 n2 = 18% The particles are white and shiny and the release of Na salicylate is greatly delayed. Example 4 The particles in this example are prepared from a different base emulsion than the others (silicone oil base); the hydrophilic support #1 is methyl cellulose, and the hydrophobic support #2 is hydrophobic colloidal silica. Silicone oil 60 Calcium Stearate 20 Water 20 20% sodium salicylate Support n 1 nl = 10% Support n 2 n2 = 21% The particles are white, the release and delayed effect of the release of Na salicylate are very marked. It should be noted that the preparation process for this formula is the same as the process of the invention described in patent no. 8602694 as well as for all the other examples. CONCLUSION It follows from the detailed description of these cited examples, which are the subject of this text, and from the studies carried out within the framework of the in vitro availability of the active ingredient, that new pharmaceutical forms are obtained, using the so-called "dry emulsion" process, presented as more or less fine solid particles; this form has the following advantages: delayed release and release of the active ingredient compared to... time, - protection and stability of the active ingredients included, - presentation in oral and cutaneous forms, with adjustable consistency semi-solid and solid.

Claims

CLAIMS 1) New process for preparing a solid pharmaceutical dosage form delayed and progressive release, characterized in that it is constituted by small solid particles comprising two inert supports one one hydrophilic and the other hydrophobic, both belonging to the class silicas, silicates and their derivatives, polymers and their derivatives. 2) Method for manufacturing solid particles according to claim 1 characterized by First step: obtaining a basic emulsion at a temperature between between 45" and 70°C A second step: obtaining a dry emulsion at room temperature The mixer's rotation speed varies between 5,000 and 15,000 rpm, in depending on the size of the particles required 3) Manufacturing process, according to claims 1 and 2, characterized by the possibility of modulating the consistency of the emulsions according to the quantity of inert supports incorporated. 4) A method according to any one of claims 1 to 3, characterized in that that the two inert supports are introduced in a proportion by weight calculated with respect to the mass of the two respective phases of the emulsion of base 5) Solid particles obtained by the process according to any one of the following Indications 1 to 4 are characterized in that they include both supports inert materials as defined in claim 1 and in that the size is included between 100 and 2000 microns. 6) Solid particles according to any one of claims 1 to 4, characterized in that they contain at least one active ingredient produced in either of the two phases of the base emulsion. 7) Solid particles according to any one of claims 1 to 5, characterized in that they offer a delayed release of principles included assets. 8) Solid particles according to any one of claims 1 to 6, intended for oral or cutaneous use.