BG66010B1 - Medicamentous form of sildenafil - Google Patents

Abstract

The invention relates to a new medicamentous form of sildenafil, in particular of sildenafil-citrate. It is a stable film-tablet, convenient for pharmaceutical manufacturing, of high strength and lowerasure. It is suitable for filming both with an organic and with an aqueous film coating. The film-tablet has a quick degree of dissolution of the medicamentous substance of sildenafil citrate. The lactose, included as an auxiliary substance, is not hygroscopic, has low humidity content and has no abrasive effect. The medicamentous form comprises lactose monohydrate, binder selected from povidon, hydroxypropylcellulose or hydroxypropylmethylcellulose, decaying auxiliary substance selected from crosscaramelosis sodium, sodium glycolate starch, crosspovidon, lubricant û sodium stearyl fumarateor magnesium stearate, preferably sodium stearyl fumarate, microcrystalline cellulose, siliconized microcrystalline cellulose and film-forming coating containing water soluble or water insoluble polymer.

Description

Technical field

The invention relates to an oral dosage form containing sildenafil nitrate for use in men with erectile dysfunction.

BACKGROUND OF THE INVENTION

There is a known dosage form of sildenafil citrate - film-coated tablets containing 25.50 and 100 mg of sildenafil in the form of sildenafil citrate and excipients-microcrystalline cellulose, calcium hydrogen phosphate, croscarmellose sodium, magnesium stearate, titroxytose, tiproctose, and colorants (Viagra - Patient Information). The use of calcium hydrogen phosphate as the main filler creates manufacturing problems as it has a strong abrasive effect on metal surfaces and results in high-abrasion tablets making it difficult to film (1).

Sildenafil citrate dosage form (EP 1301186) is known as a fast-dissolving tablet containing highly water-soluble sugar as an excipient. It is obtained by melting the drug together with xylitol at a temperature of 195 ° C and after cooling it is formed as a powdery solid dispersion which is mixed with mannitol and croscarmellose sodium and tableted to obtain rapidly dissolving tablets. This dosage form requires special apparatus for producing the soluble dispersion, allowing the resulting mass to be melted and milled.

Also known is the dosage form of sildenafil (patent application BG 103541), which is a pellet containing sildenafil citrate, providing a quick release and masking of the bitter taste of the drug through the use of a two-layer coating. The core contains sildinafil citrate, microcrystalline cellulose and hydroxypropyl cellulose. The inner covering layer is made up of a water-soluble polymer and the outer layer is made up of a polymer insoluble in saliva. The production of these pellets is complex and requires special equipment that is not typical for tablet production.

SUMMARY OF THE INVENTION

The problems that need to be addressed with the new sildenafil citrate-based dosage form are to ensure that the drug dissolves quickly while masking the unpleasant taste and good stability of the dosage form, using excipients with good flowability, guaranteeing the production of healthy, low-abrasion-resistant tablets suitable for the film, indifferent to the drug substance and the apparatus used.

The problems are solved by a dosage form of the invention containing sildenafil 25 to 100 mg in the form of sildenafil citrate and excipients: lactose monohydrate at a concentration of 10 to 45 wt. % binder selected from: povidone from 3 to 8 wt. %, hydroxypropylcellulose or hydroxypropylmethylcellulose from 2 to 7% by weight. % disintegrant selected from: croscarmellose sodium, starch glycolate sodium, crospovidone - from 1 to 10 wt. %, preferably croscarmellose sodium, glidant sodium stearyl fumarate or magnesium stearate in an amount of from 0.5 to 3% by weight. %, preferably sodium stearyl fumarate, microcrystalline cellulose from 10 to 65% by weight. % and / or silica microcrystalline cellulose from 5 to 50 wt. % and a film-forming coating of 1 to 4 wt. % containing a water-soluble or water-insoluble polymer.

The advantages of the dosage form according to the invention are:

- the dosage form is a film tablet suitable for pharmaceutical production;

- the inclusion of the diluent excipient lactose monohydrate, avoids the use of anhydrous calcium hydrogen phosphate;

- lactose monohydrate is not hygroscopic, has low moisture content and has no abrasive properties;

- the combination of lactose monohydrate,

66010 B1 a suitable binder (povidone, hydroxypropylcellulose, hydroxypropylmethylcellulose) and siliconized microcrystalline cellulose and / or microcrystalline cellulose, permits the production of healthy tablets with low abrasion; suitable for filming;

- the inclusion in the composition of sodium stearin fumarate as a gliding agent further favors the rapid dissolution of the drug substance;

- the tablet core obtained is suitable for filming with both organic and aqueous film coating;

- a stable dosage form with rapid dissolution of the drug sildenafil citrate is obtained.

Embodiments of the invention

The invention is illustrated, without limitation, by the following exemplary embodiments.

Example 1. Sildenafil citrate / eq. 100.00 mg sildenafil / 140.45 mg Lactose monohydrate 200,00 mg Povidone 20,00 mg Croscarmellose sodium 36,00 mg Magnesium stearate 9,00 mg Microcrystalline cellulose 80.00 mg Silicon microcrystalline cellulose 120,00 mg Film coverage 18,00 mg

Sildenafil citrate and lactose monohydrate were granulated using aqueous povidone. After granulation and drying, the resulting dry granulate is dusted with the remaining excipients and tableted. The filming is done with water film coating.

Example 2

Sildenafil citrate / eq. 50 mg sildenafil / 70.225 mg Lactose monohydrate 120.00 mg Hydroxypropylcellulose 17.00 mg Croscarmellose sodium 15.00 mg Magnesium stearate 3.00 mg Microcrystalline cellulose 75.00 mg

Film coating 9,00 mg Sildenafil citrate and lactose monohydrate were granulated using aqueous povidone. After granulation and drying, the resulting dry granulate is dusted with the remaining excipients and tableted. The filming is done with an organic film coating.

Table 1 gives the stability data of the finished tablets.

The dissolution test shows:

Active ingredient tablet 50 mg - over 80% release rate over 5 min.

Active substance content tablet 100 mg - 5 min 68.5%, 10 min 91.8%, 15 min 96.3%.

Norm - up to 30 min. Not less than 75%.

66010 Bl

Table # 1

STABILITY STUDY TABLE for Sildenafil 50 mg tablets

Observed batches Terms of storage: Packaging:

Method of analysis:

6 and 8B

4 (PC and (25 ± 2) ° CJ (60 ± 5)% OB aluminum foil / PVC no. EJ.2.

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CONCLUSION: As a result of the studies on Sidenaft 50 mg tablets, the shelf life is estimated to be 1 (one) year.

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CONCLUSION: As a result of the juvenile fever test, 50mg tablets are predicted for a viability average of 1 mg ($ 1 per year). The study continues.

Claims (1)

Claims What is claimed is: 1. A dosage form comprising 25 to 100 mg of sildenafil in the form of sildenafil citrate comprising microcrystalline cellulose and hydroxypropyl cellulose, characterized in that it also contains lactose monohydrate at a concentration of 10 to 45 wt. %, a binder selected from the group: povidone - from 3 to 8 wt. % and / or hydroxypropylcellulose or hydroxypropylmethylcellulose from 2 to 7% by weight. % disintegrant selected from: croscarmellose sodium, starch glycolate sodium, crospovidone - from 1 to 10 wt. %, preferably croscarmellose sodium; glidant - sodium stearyl fumarate or magnesium stearate in an amount of 0.5 to 3 wt. %, preferably sodium stearyl fumarate; microcrystalline cellulose from 10 to 65 wt. and / or silicified microcrystalline cellulose from 5 to 50 wt. % and a film-forming coating of 1 to 4 wt. % containing a water-soluble or water-insoluble polymer.