CZ8935U1 - Dosage form of sildenafil-citrate - Google Patents

Description

The dosage form of sildenafil citrate

Technical field

The invention relates to a suitable dosage form of 5- [2-ethoxy-5- (4-methylpiperazin-1-ylsulfonyl) phenyl] -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3- d] pyrimidin-7-one (generically named sildenafil) in the form of citrate.

BACKGROUND OF THE INVENTION

The active ingredient sildenafil and its pharmaceutically acceptable salt of sildenafil citrate are applied for disorders of, in particular, male erection and impotence. Said active substance has so far been administered in the form of coated tablets (see for example WO 98/30209). Emphasis is placed on a film-coated tablet composition that masks the unpleasant taste of the active ingredient. Indeed, the bitter taste of many pharmaceutical preparations causes a number of problems in their oral administration. The most common problems are swallowing these preparations, which then lead to the development of a negative attitude of the patient to the administered preparation.

Another problem is the rate of release of the active ingredient from the dosage form, which is closely related to the rate of onset of action. For coated tablets containing sildenafil citrate as active substance, onset of action is registered on average only one hour after ingestion of the tablet. Because patients are often unwilling to wait long for the effect or feel that the ingested dose of the active substance has been low, there is often an overdose.

The film-coated tablets used so far allow only oral administration of sildenafil citrate.

There are references to the development of nasal spray in the literature where the onset of action should be faster. In summary, commonly used film-coated tablets suffer from the above-mentioned disadvantages and the nasal sprays considered are technologically complicated and hence economically demanding. Therefore, there is still a need for suitable dosage forms for the administration of sildenafil citrate which are economically acceptable and do not have the above-mentioned disadvantages.

The essence of the technical solution

Disadvantages of the prior art are largely eliminated by the disclosed dosage form for the administration of sildenafil citrate, which is a gelatin capsule in which the active ingredient is contained in a certain proportion to the gelatin from which the capsule is formed.

It is known that a number of active substances are now administered in the form of capsules, in which the active substance is usually contained in a carrier. Various oily substances and / or polymer blends are often used as suitable carriers, as described, for example, in U.S. Patent 4,690,823.

However, in the case of sildenafil citrate, this dosage form has not yet been used. Surprisingly, however, it has now been found that the capsule form is particularly suitable when the weight ratio of the sildenafil citrate contained in the capsule to the gelatin from which the capsule is formed ranges from

1: 0.2 to 1: 9.5, preferably from 1: 0.6 to 1: 5.2. The application of such capsules brings significant advantages, as will be discussed below.

Sildenafil citrate may be present as such in the capsule, but it is generally preferred to suspend the active ingredient in a liquid or semi-liquid mixture containing various combinations of polyvinylpyrrolidones, polyalkylene glycols, monomers and vegetable oils thereof. In addition, various adjuvants and preservatives such as glycerol, sorbitol, water, methylparaben, ethylparaben, propylparaben, as well as lubricants and vitamins may also be present. Said capsule may be either hard or soft.

The dosage form of the proposed solution has a number of advantages over existing dosage forms. First, the unpleasant bitter taste of the active substance is practically completely covered and is guaranteed,

There is no premature release of sildenafil in the oral cavity. However, an essential advantage of the present dosage form is that the release of the active ingredient occurs within 5 minutes, and the complete dose of the active ingredient is released within no more than 30 minutes, resulting in a much faster onset of action. undesirable and often dangerous overdose of the active substance. The production of capsules according to the proposed solution is technologically and economically undemanding and already well mastered in the pharmaceutical field. Last but not least, this dosage form extends the possibilities of administration by rectal or vaginal administration.

The composition of the dosage forms of the proposed solution is described in the following examples and embodiments. These examples show the weights of the individual components from which the entire dosage form is made; both the capsule-forming components and the capsule-containing components of the mixture so that the ratios of the active ingredient to the gelatin are immediately visible. Distinguishing the individual components will not cause any difficulty to the average practitioner.

Examples

Example 1 component sildenafil citrate 25 mg gelatin 44 mg glycerol 15 mg sorbitol 5 mg propylene glycol 70 mg water 18 mg

Example 2 Component Content of Sildenafil Citrate 30 mg Gelatin 80 mg Glycerol 12 mg Sorbitol 6 mg Polyvinylpyrrolidone 9 mg Water 18 mg

EXAMPLE 3 Component Content of Sildenafil Citrate 30 mg Gelatin 40 mg Glycerol 17 mg Sorbitol 9 mg Propylene Glycol 10 mg Polyethylene Glycol 70 mg Ethyl Paraben Na 0.2 mg Yellow Dye (E 110) 0.1 mg Water 5 mg

-2GB 8935 Ul

Example 4 component content sildenafil citrate 50 mg gelatine 35 mg 5 glycerol 13 mg sorbitol 5 mg polyvinylpyrrolidone 5 mg polyethylene glycol 70 mg propylparaben Na 0.2 mg 10 dye Orange 0.1 mg water 12 mg Example 5 component content sildenafil citrate 20 mg 15 Dec gelatine 125 mg glycerol 20 mg sorbitol 8 mg polyethylene glycol 70 mg propylparaben Na 0.2 mg 20 May ethylparaben Na 0.2 mg titanium dioxide 0.5 mg Example 6 component content sildenafil citrate 50 mg 25 gelatine 155 mg glycerol 20 mg sorbitol 6 mg polyvinylpyrrolidone 70 mg olive oil 15 mg 30 vitamin E 5 mg methylpyrabene Na 0.2 mg water 9 mg Example 7 component content 35 sildenafil citrate 40 mg gelatine 38 mg glycerol 10 mg sorbitol 4 mg polyethylene glycol 120 mg 40 olive oil 15 mg vitamin E 5 mg methylparaben Na 0.2 mg water 7 mg

-3 CZ 8935 Ul

Example 8 component sildenafil citrate 40 mg gelatin 85 mg glycerol 10 mg sorbitol 4 mg polyethylene glycol 120 mg olive oil 15 mg vitamin E 5 mg i propylparaben Na 0.2 mg water 9 mg

Example 9 component sildenafil citrate 30 mg gelatin 90 mg glycerol 16 mg sorbitol 7 mg polyvinylpyrrolidone 80 mg olive oil 22 mg vitamin E 15 mg propylparaben Na 0.2 mg water 10 mg.

Industrial applicability

The dosage form of the invention is suitable for the industrial manufacture of a medicament for both clinical and outpatient administration.

Claims (6)

PROTECTION REQUIREMENTS A dosage form of sildenafil citrate, comprising a gelatin capsule containing sildenafil citrate in a sildenafil citrate: gelatin ratio by weight of from 1: 0; 2 to 1: 9.5. The dosage form of claim 1, wherein the weight ratio of sildenafil citrate to gelatin ranges from 1: 0.6 to 1: 5.2. A dosage form according to claims 1 to 2, characterized in that the capsule comprises a suspension of sildenafil citrate in a liquid or semi-liquid mixture containing one or more substances selected from the group consisting of polyvinylpyrrolidones, polyalkylene glycols, monomers thereof. 35 substances and natural vegetable oils. A dosage form according to claims 1 to 3, wherein the capsule comprises excipients and preservatives selected from the group consisting of glycerol, sorbitol, water, methylparaben, ethylparaben, propylparaben, lubricants and vitamins. -4GB 8935 Ul « A dosage form according to claims 1 to 4, characterized in that it is a hard gelatin capsule. A dosage form according to claims 1 to 4, characterized in that it is a soft gelatin capsule.