FI63671B - FOERFARANDE FOER BILDANDE AV EN DOSERINGSENHETSFORM AV EN HJAERTMEDICIN - Google Patents

Description

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England-England (GB) 1U265 (71) R.P. Scherer Limited, 216-222 Bath Road, Slough, Buckinghamshire,

The present invention relates to a method of administering a cardiac drug dosage form. This invention relates to a method of administering a cardiac drug dosage unit form. f to form a unit form, wherein the cardiac drug contains digoxin as an active ingredient.

Cardiac glucosides are widely used cardiac drugs and are generally formed into oral tablets. Each tablet should contain a very small amount of active ingredient (e.g., 250 micrograms or less) as these specific active ingredients are administered in such very small doses, almost always less than 0.5 mg. The fact that each tablet must contain so little active ingredient causes problems in preparation and makes it particularly difficult to ensure complete mixing of the tableting mixture so that each tablet contains the same amount of active ingredient with varying ranges (see e.g.

Thomas et al., The Lancet, December 1, 1973, pp. 1267-8; Fraser et al., 5, Pharm. Pharmac., 1973, 25, pages 268-973; and Shaw et al., British Medical Journal, 1973, 4, pages 763-766).

2 63671

The method of the present invention provides an improved dosage unit useful for oral administration of cardiac glucoside.

The dosage unit form comprises a soft gelatin capsule containing a liquid cardiac drug preparation comprising a) digoxin b) dimethylformamide or preferably dimethylacetamide; and c) liquid polyethylene glycol, and optionally also d) propylene glycol or glycerol.

The process according to the invention is characterized in that (a) the digoxin is dissolved in dimethylformamide or dimethylacetamide in a weight ratio of dimethylformamide or dimethylacetamide to digoxin of at least 5: 1, (b) the resulting solution is mixed with an amount of polyethylene glycol containing at least 75% by weight. -% polyethylene glycol and (c) encapsulating the mixture in a gelatin capsule.

The weight ratio of dimethylacetamide or dimethylformamide to digoxin is usually 5: 1 to 15: 1.

The digoxin solution is mixed with polyethylene glycol (optionally containing propylene glycol or glycerol), the polyethylene glycol being the main component of the dosage unit form and present in an amount of at least 75% by weight, preferably 80-95% by weight of the total soft gelatin capsule mixture.

The gelatin capsule should be one formed from gelatin containing a plasticizer such as glycerol, propylene glycol, diethylene glycol or hexanetriol. Furthermore, the plasticizer may consist of one of the above-mentioned substances together with sorbitol, which improves the durability of the capsule when exposed to air humidity. The amount of sorbitol is preferably approximately equal to the amount of glycerol or other plasticizers.

Thus, a preferred capsule consists of gelatin softened with about 8-15% by weight, preferably about 12.5% by weight, glycerol and 12.5-15% by weight, preferably about 13% by weight. , 5% sorbitol, based on the total weight of gelatin, glycerol and sorbitol.

The total weight of the ingredients contained in the gelatin capsule of the dosage unit form is preferably about 100-300 mg, and thus the weight of digoxin contained in each capsule is that generally required for a unit dose, e.g. 50-300 micrograms.

63671

The dosage unit form is prepared in the liquid phase so as to provide an accurate and uniform dispersion of the active ingredient (digoxin) throughout the liquid phase. Thus, it is possible to ensure that each dosage unit (i.e., capsule) contains the same amount (within ranges) of active ingredient.

It has also been found that the unit dosage form according to the invention provides a better or faster release of the active ingredient (as demonstrated in experiments with artificial gastric fluids) than the corresponding tablets. It has been found that not only do capsules release their contents more quickly but also that this occurs more completely than in the case of tablets, which often release only about 50% or less of their contents.

Thus, the capsules prepared according to the invention form a much more reliable dosage unit form than many tablets, since it can be relied on that the capsules release substantially all of their active ingredient content in a relatively short time, which is not the case with tablets.

The following examples illustrate the invention. PEG means polyethylene glycol.

Example 1 140 mg capsule containing 131 micrograms of digoxin

Digoxin 0.131 mg

Dimethylacetamide 0.75 mg PEG 400 140.119 mg

Example 2 140 mg capsule containing 66 micrograms of digoxin

Digoxin 0.066 mg

Dimethylacetamide 0.75 mg PEG 400 140.559 mg

Example 3 140 mg capsule containing 263 micrograms of digoxin Digoxin 0.263 mg

Dimethylacetamide 4.500 mg PEG 400 139.237 mg