DE2546371A1 - Solid digitalis glycoside medicaments - contg. polyalkylene glycol and/or a vinyl pyrrolidone (co)polymer - Google Patents

Abstract

Digitalis glycoside medicaments contain a solid mixt. of the glycoside and a polyalkylene glycol and/or polyvinylpyrrolidone (PVP) and/or a copolymer of vinylpyrrolidone and vinyl acetate (VP/VA). The medicaments give rapid release and good resorption of the glycoside. The glycoside is pref. acetyldigoxin (I), digoxin or lanatoside A, B or C. The other component is pref. a mixt. of a polyethylene glycol, a polypropylene glycol or a polyoxythylene/polyoxypropylene copolymer (mol. wt. 200-20,000, esp. 600-13,000) with PVP (mol. wt. 10,000-100,000, esp. 25,000) and/or a VP/VA copolymer (mol. wt. 30,000-100,000, esp. 40,000-90,000). The glycoside/polymer wt. ratio can be between 0.1:99.9 and 20:80 (esp. 5.95).

Description

New galenic forms

The invention relates to new galenic forms of digitalis glycosides with accelerated release and improved absorption of the active ingredients that make one solid substance consisting of the active ingredient and pharmaceutically safe polyalkylene glycols and / or polyvinylpyrrolidone and / or copolymers of vinylpyrrolidone and vinyl acetate contain.

According to the invention one arrives at the new galenic forms for digitalis glycosides, idem one digitalis glycosides together with pharmaceutically safe polyalkylene glycols and / or polyvinylpyrrolidone and / or copolymers of vinylpyrrolidone and vinyl acetate processed into a solid substance and then combined with known additives A well-known way produces galenic forms. The method according to the invention is carried out as follows: digitalis glycosides, iosbesonders Acetyldigoxin, Digoxin sawie Lanatosid A, B and C, are used together with an or several pharmaceutically acceptable polyalkylene glycols, for example polyoxyethylene or polyoxypropylene polymers or their copolymers with a molecular weight from 200 to 20,000, preferably from 4000 to 15,000, in particular from 6000 to 13,000, for example polyethylene glycol, polypropylene glycol and polyoxyethylene / polyoxypropylene mixtures of the molecular weights given above, either alone or by preference in Form of their mixtures are used and / or Pplyvinylpyrrolidon in the form of Poly-N-vinylpyrrolidone-2 (uncrosslinked) with molecular weights between 10,000 and 100,000, in particular 11,500 to 40,000, preferably 25,000, and / or copolymers of vinyl pyrrolidone, and vinyl acetate with average molecular weights of 30,000 to 100,000, preferably 40,000 to 90,000, the copolymer expediently consists of 50 parts by weight of vinyl pyrrolidone and 40 parts by weight of vinyl acetate, optionally together with pharmaceutically harmless additives, for example Surfactants, such as sodium lauryl sulfate, polyethylene glycol solid esters, in particular Polyethylene glycol stearate mixed. In these mixtures the weight ratio is from digitalis glycosides to the polyethylene glycols and / or polyvinylpyrrolidone used and / or copolymers of vinyl acetate and vinyl pyrrolidone and optionally also the Other additives expediently from 0.1: 99.9 to 20:80, in particular from 5:95. When using mixtures of polyethylene glycols, polyvinylpyrrolidone and copolymers The mixing ratio of vinyl acetate and vinyl pyrrolidone is not critical per se; however, it is preferred that one or three of these components be the same Parts used. The weight ratio of the remaining pharmaceutically acceptable ones Additions to the amount of active ingredient used should be from 95: 5 to 50:50, with all the weight ratio of the surfactants to the amount of active ingredient used of 1:45 should be up to 10: 1.

The mixture is dissolved in a suitable solvent such as a lower one Alcohol such as methanol or ethanol, at an elevated temperature, especially from 30 to 800C, preferably from 40 to 700C. After complete dissolution (clear solution) the solvent is at temperatures of 50 to 80 C, preferably from 40 to 700C, initially under normal pressure and then evaporated in vacuo. It is possible here for only part of the polyalkylene glycol to be used in the preparation of the solution or the other additives is used and the addition of the remaining polyalkylene glycol or the other additives, takes place during the evaporation of the solution. The after completely sm Evaporation of the solvent remaining residue will be at room temperature. (15 up to 250C) in the usual white to a fine powder and this during approx. 12 hours in vacuo at approx. 30 ° C. nachgetrocknut, the powder obtained is together with known additives in a manner known per se, as described below processed into tablets, coated tablets, hard or soft gelatine capsules.

In the manufacture of tablets, organic additives can also be used or anoraanic aids such as binders, lubricants, fillers and wetting agents be used. In addition, the pharmaceutical preparation can also contain dyes, Contains flavorings, sweeteners, etc. As auxiliary materials for the manufacture of tablets Calcium carbonate, sodium carbonate, lactose, talc and starches, can be used as granulating agents and disintegrants starch and alginic acid, as bindersl starch, gelatin, and as Talc can be used for example. The tablets can be coated or uncoated, the coating being applied in a manner known per se will.

The above is used to make soft gelatin capsules mentioned solid substance in a manner known per se with a mixture of e.g. glycerine, Sorbitol, water and a preservative and, if appropriate, coloring agent, and for the production of hard gelatine capsules the above is processed mentioned solid substance in a manner known per se with, for example, milk sugar, storks and Any dyes and other pharmaceutical aids used.

Dragees are produced in a manner known per se Coating of tablet cores, for example.

A suitable tablet composition consists of 4.0 mg of the according to solid obtained by the above procedure, 78.0 mg of lactose, 30.0 mg of corn starch, and 7.5 mg talc and 0.5 mg silicon dioxide, suitable mixture for filling soft gelatine capsules obtained by mixing 4 mg of the solid obtained by the above procedure Substance, 88 mg polyethylene glycol 400, 8 mg glycerine.

A suitable mixture for filling hard gelatine capsules is obtained by mixing 4.0 mg of the solid substance obtained according to the above procedure, 71 mg lactose, 0.1 mg silicon dioxide, Example: In a round bottom flask of 4 1 volume, 12.6 g of acetyldigoxin and 182.6 g of polyethylene glycol are added with stirring 6000 dissolved in 915 ml of methanol. When the reflux condenser is in place, the solution becomes heated to the boil in a water bath at 700 ° C. and at this temperature for 30 minutes left.

The flask and its contents are connected to a rotary evaporator. At a bath temperature of 700 ° C., 185 ml of methanol are used within 24 minutes distilled off under reduced trick (about 400 torr), under normal pressure to the hot, clear solution 54.8 g of polyoxyethylene-polyoxypropylene (mol. wt. 13,300) added, which dissolves in the rotating flask within a minute.

The resulting solution is used on a rotary evaporator at a Bath temperature of 700 C under reduced pressure (about 250 torr) the remaining methanol distilled off within 6 minutes. The flask is left for another 10 minutes Rotate the evaporator at a bath temperature of 70 ° C and reduced pressure (50 Torr).

The resulting clear melt is allowed to solidify at room temperature, and then dry in a vacuum drying cabinet at 300 C and about 1 Torr overnight.

The mass is powdered and again as described above post-dried.

The powder produced is used with commonly used pharmaceuticals Processing aids into dosage forms.

Claims (2)

Claims Nsue galenic forms for digitalisgiykoside, the a solid substance consisting of the active ingredient and pharmazautiech harmless Polyalkylene glycols and / or polyvinylppyrrolidone and / or Capoöymerisaten van Vinyl pyrrolidone and vinyl acetate containing. 2. Process for the production of never-gaenischer forms for digitalis glycosides, characterized in that one digitalis glycosides together with pharmaceutically acceptable Polyalkylene glycols and / or polyvinylpyrrolidone and / or copolymers of vinylpyrrolidone and vinyl acetate processed into a solid substance and collected from it with known Additives produces galenic forms in a manner known per se.