CZ2004161A3 - Method of preparing medicament formula containing zaleplon - Google Patents

Abstract

Drug form containing zaleplon for the treatment of serious insomnia in the tablet form or coating tablet containing zaleplon in an amount of 0.005 to 0.02 g and further containing microcrystalline cellulose having a middle particle size 10 to 1000 um in an amount of 60 to 90 % by weight, dry binder in an amount of 2 to 20 % by weight, disintegrant in an amount of 1.5 to 10 % by weight, agent regulating flow features in an amount of 0.1 to 2 % by weight, antiadhesive agent in an amount of 0.5 to 4 % by weight, colouring agent prohibiting misusing of the drug form in an amount of 0.5 to 5 % by weight and eventually film forming agents in an amount of 2 to 5 % by weight.

Description

The invention is in the field of pharmacy, solves the composition of a dosage form containing zaleplon in the form of tablets and film-coated tablets. It is used for the treatment of severe insomnia, which causes extreme stress to patients.

BACKGROUND OF THE INVENTION

Currently, the dose of zaleplon in the world's fast-acting oral formulations is in the range of 5 to 10 mg. Hard gelatin capsules are used as the dosage form.

For the preparation of the filling mixture into capsules, the usual excipients used in pharmacy are: cellulosum microcristallinum (microcrystalline cellulose), lactosum monohydricum (lactose monohydrate), maydis amylum pregelificatum (pregelatinized maize starch), sodium lauryl sulphate (sodium lauryl sulphate), silica anhydrous colloidal silica), indigocarmine E 132 (indigocarmine E 132) and magnesii stearas (magnesium stearate).

The powder mixtures are filled into hard gelatin capsules. The production of hard gelatine capsules is more expensive and the performance of the filling machines is less than the equipment for the production of coated tablets.

WO / 0178725 discloses the preparation of modified release pellets containing zaleplon. The pellets are prepared by wetting a mixture of the active ingredient and microcrystalline cellulose with water, which is evaporated from the mixture under increased temperature and vacuum.

EP 1005863 discloses capsules, tablets, multilayer tablets, zaleplon-controlled coated tablets which release about 40-70% of the active ingredient within 30 minutes, and about 90% of the active ingredient after 2 to 6 hours. The release control is ensured by the coating of the granules, pellets, resp. tablets with retardants consisting of hydrophilic or hydrophilic polymers.

Both of the above applications have not yet been applied in practice, or are not used to date.

««

Disadvantages of the prior art, i.e. the hard gelatine capsules produced include:

from the point of view of health care workers and patients, the impossibility of accurate dose titration; the capsule can only be emptied, but it is impossible to divide it into exact halves after spilling. Titration is particularly important at the beginning of therapy, in elderly and sick patients, as well as in patients with malnutrition or obesity. Technology requiring the use of hard gelatine capsules, which are more expensive and their production is usually time consuming, at the same time the use of gelatin, ie material of animal origin, is bound. The use of excipients of animal origin is also the reason why patients in some countries do not like these dosage forms.

According to the present state of the art, the capsules used are not equivalent in weight, i.e.. that each batch must be made separately to the degree prior to capsulation.

SUMMARY OF THE INVENTION

The present invention provides a dosage form comprising zaleplon, in the form of a tablet or film-coated tablet, comprising zaleplon in an amount of 0.005 to 0.02 g, and further comprising at least one excipient or mixture of excipients including microcrystalline cellulose, regulating the flow properties of the pulp, anti-adhesive, tablet disintegrating agents and coloring agents to prevent abuse of the dosage form and, if desired, film-forming agents. The structural formula of zaleplon is

CN

The dosage form in the form of a tablet or film-coated tablet comprises zaleplon in an amount of 0.005 to 0.02 g, and further microcrystalline cellulose with a mean particle size of 10 to 1000 µm in an amount of 60 to 90 wt. %, dry binder in an amount of 2 to 20 wt. % disintegrant in an amount of 1.5 to 10 wt. %, flow control agent in an amount

0.1 to 2 wt. 0.5 to 4.0 wt. 0.5 to 5% by weight of the dosage form and optionally 2 to 5% by weight of the film-forming agent; %.

Said microcrystalline cellulose preferably has a mean particle size of 50 to 180 µm. Alternatively, the dosage form, based on the total weight of the formulation, is 10-15 wt. % microcrystalline cellulose with a mean particle size of 50 µm and 60 to 71 wt. % microcrystalline cellulose with a mean particle size of 180 µm.

According to another preferred embodiment, the dosage form, based on the total weight of the preparation, comprises 15 to 23% by weight. % microcrystalline cellulose with a mean particle size of 100 µm and 60 to 70 wt. % microcrystalline cellulose with a mean particle size of 180 µm.

In the case of a film-coated tablet, it comprises film-forming agents preferably in an amount of 3 to 4 wt. %.

The dry binder content is preferably 4 to 6 wt. %, a preferred representative is maydis amylum pregellificatum (pregelatinized maize starch). The disintegrant content is preferably 2 to 5 wt. %, preferably croscarmellosum natricum (croscarmellose sodium).

A preferred representative of the flow properties of the tablet is silica colloidalis anhydrica (anhydrous colloidal silica), preferably in an amount of 0.2 to 0.5% by weight. % of the substance.

Magnesium stearate is preferably used as the anti-adhesive and its content is preferably 0.7 to 1.5% by weight. % antiadhesive.

A preferred representative of the dye to prevent abuse of the dosage form is Indigocarmine (Indigocarmine) 85 E 132, preferably used in an amount of 0.7 to 1.5% by weight. %.

The essence of the method of manufacture of the dosage form consists in preparing the tablet by dry mixing, pressing the tablet and optionally coating the tablets with a film coating.

• * l l l l l l l l l

The preparation of the pulp is technologically simple, it is limited only to energy and time-saving technological steps. The preparation of the tablet does not involve stressful procedures such as the incorporation of a humectant into the mixture of the active ingredient and the excipients for the preparation of the tablet.

Dry blending of the pulp allows the preparation of cores that meet the parameters.

Film coating of the tablets is accomplished with an aqueous suspension of the finished film-forming concentrate, plasticizer, filler and color pigments without the use of organic solvents.

Other excipients such as: microcrystalline cellulose - as a filler and flow modifiers, anti-adhesive substances facilitating the tableting process, tablet disintegrants, colored substances to prevent drug abuse.

Film forming agents are the commonly used film forming agents available under the commercial name Sepifilm.

Microcrystalline cellulose is a pharmaceutical excipient known as Avicel and is used as a direct compression filler. For example, Avicel PH 101 is produced in powder form (mean particle size 50 µm); Avicel PH 102 granulate (mean particle size 100 µm) and Avicel PH 200 granulate (mean particle size 180 µm). It has good flow properties. Tablets have satisfactory strength and disintegration properties because microcrystalline cellulose in the compact ensures the maintenance of capillary openings through which water inhibits the binding force efficiency. They provide the product with very good stability. According to the present invention, the above properties have been repeatedly achieved by using combinations of microcrystalline cellulose with different mean particle sizes.

The essence of the technological process is the preparation of a tablet by mixing the active substance zaleplon with a corresponding amount:

microcrystalline cellulose having a particle size of 10 to 1000 µm of the above composition;

compressing a tablet of said composition;

coating the tablets with an aqueous suspension of the finished concentrates Sepifilm 752 White and Sepifilm 1015 Blue in a total amount of 2 to 5% by weight; Sepifilm 752 White and Sepifilm 1015 Blue are commercially available film coating compositions for cores. They are applied in the form of a 16% aqueous suspension in a total amount of 2 to 5% by weight. Sepifilm 752 White (Seppic, France) is a granular powder composed

From hydroxypropyl methylcellulose - Methocel E5 (film-forming substance), polyoxyl 40 stearate plasticizer) and titanium dioxide (white pigment). Sepifilm 1015 Blue (from Seppic, France) is a granular powder composed of hydroxypropyl methylcellulose - Methocel E5 (film-forming substance), microcrystalline cellulose (filler), polyoxyl-40 stearate (plasticizer), titanium dioxide (white pigment) and indigotine aluminum lacquer (colored) pigment).

and polishing the coated tablets with an aqueous solution of polyethylene glycol in an amount of 0.05 to 0.25% by weight, preferably 0.1 to 0.15% by weight.

The thus prepared film-coated tablets according to the invention guarantee the reproducibility of the manufacturing process. The preparation of the tablets is carried out in the same manner, in which the coating and polishing of the tablets is omitted in the final phase.

The advantage of the process according to the invention is lower energy and time consumption, especially preparation of tablet, simple technology, reduction of the use of capsules - use of materials of animal origin, possibility of dose titration.

Tablet dosage forms and coated tablets are accepted by virtually the entire population.

DETAILED DESCRIPTION OF THE INVENTION

The invention is illustrated by the following non-limiting examples.

Example 1

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Ingredients: core Weight in g Weight% Zaleplonum 0.00500 g 6,03% Avicel PH 101 0.00100 g 12.06% Avicel PH 200 0.05680 g 68.43% Maydis amylum pregelificatum 0.00400 g 4.82% Croscarmellosum natricum 0.00240 g 2.89% Silica colloidalis anhydrica 0.00020 g 0.24% Indigocarminum 85 El32 0.00080 g 0,96% Magnesii stearas 0.00080 g 0,96%

Composition: cover

Sepifilm 752 White 0.00210 g 2.53% Sepifilm 1015 Blue 0.00080 g 0,96% Macrogolum 6000 0.00010 g 0,12% Total: 0,08300 g 100,00%

· * ·

(b) method of preparation:

The active ingredient and Avicel PH 101 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. The homogenizer was charged with Avicel PH 200, maydis amylum pregeliftcatum, croscarmellosum natricum, silica coloidalis anhydrica and Indigocarminum 85 E 132. The mixture was stirred for 15 minutes (Stir II). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and screened mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). The finished tablets are compressed into a tablet press in the shape of 0.080 g. The tablets are coated on a horizontal or other suitable coating machine at a drying air temperature of 60 ° C with an aqueous suspension of Sepifil 752 White and Sepifil 1015 Blue. The coated tablets are polished with an aqueous solution of polyethylene glycol.

Example 2:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Ingredients: core Weight in g Weight% Zaleplonum 0.00500 g 6,03% Avicel PH 102 0.01600 g 19,28% Avicel PH 200 0.05080 g 61,21% Maydis amylum pregelificatum 0.00400 g 4.82% Croscarmellosum natricum 0.00240 g 2.89% Silica colloidalis anhydrica 0.00020 g 0.24% Indigocarminum 85 El32 0.00080 g 0,96% Magnesii stearas 0.00080 g 0,96% Composition: cover Sepifilm 752 White 0.00210 g 2.53% Sepifilm 1015 Blue 0.00080 g 0,96% Macrogolum 6000 0.00010 g 0,12% Total: 0,08300 g 100,00%

(b) method of preparation:

The active ingredient and Avicel PH 102 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. Add to the homogenizer Avicel PH 200, maydis amylum pregelificatum, croscarmellosum natricum, silica coloidalis anhydrica and Indigocarminum 85 E 132. Stir the mixture for 15 minutes (Stirring Π). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and screened mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). The lentil-shaped tablets are compressed from the finished tablet to 0.080 g in a tablet press. The tablets are coated on a horizontal or other suitable coating machine at a drying air temperature of 60 ° C with an aqueous suspension of Sepifilm 752 White and Sepifilm 1015 Blue. The coated tablets are polished with an aqueous solution of polyethylene glycol.

Example 3:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Ingredients: core Weight in g Weight% Zaleplonum 0.01000 g 6,03% Avicel PH 101 0,02000 g 12.06% Avicel PH 200 0.11360 g 68.43% Maydis amylum pregelificatum 0.00800 g 4.82% Croscarmellosum natricum 0.00480 g 2.89% Silica colloidalis anhydrica 0.00040 g 0.24% Indigocarminum 85 E132 0.00160 g 0,96% Magnesii stearas 0.00160 g 0,96% Composition: cover Sepifilm 752 White 0.00420 g 2.53% Sepifilm 1015 Blue 0.00160 g 0,96% Macrogolum 6000 0.00020 g 0,12% Total: 0.16600 g 100,00%

• 4 ·· · · · · ·. i. í · · · ········ · * .. · · ·

(b) method of preparation:

The active ingredient and Avicel PH 101 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring Γ). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. Add Avicel PH 200, maydis amylum pregelificatum, croscarmellosum, cum, silica coloidalis anhydrica and Indigocarminum 85 E 132 to the homogenizer. Stir for 15 minutes (Stirring Π). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and quilted mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). The lentil-shaped tablets are compressed from the finished tablet to a weight of 0.160 g on a tablet press. The tablets are coated on a horizontal or other suitable coating apparatus at a drying air temperature of 60 ° C with an aqueous suspension of Sepifilm 752 White and Sepifilm 1015 Blue. The coated tablets are polished with an aqueous solution of polyethylene glycol.

Example 4:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Ingredients: core Weight in g Weight% Zaleplonum 0.01000 g 6,03% Avicel PH 102 0,03200 g 19,28% Avicel PH 200 0.10160 g 61,21% Maydis amylum pregelificatum 0.00800 g 4.82% Croscarmellosum natricum 0.00480 g 2.89% Silica colloidalis anhydrica 0.00040 g 0.24% Indigocarminum 85 E132 0.00160 g 0,96% Magnesii stearas 0.00160 g 0,96% Composition: cover Sepifilm 752 White 0.00420 g 2.53% Sepifilm 1015 Blue 0.00160 g 0,96% Macrogolum 6000 0.00020 g 0,12% Total: 0.16600 g 100,00%

• · ·

(b) method of preparation:

The active ingredient and Avicel PH 102 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. The homogenizer was charged with Avicel PH 200, maydis amylum pregelificatum, croscarmellosum natricum, silica coloidalis anhydrica and Indigocarminum 85 E 132. The mixture was stirred for 15 minutes (Stir II). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and screened mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). The lentil-shaped tablets are compressed from the finished tablet on a tablet press to a weight of 0.160 g. The tablets are coated on a horizontal or other suitable coating machine at a drying air temperature of 60 ° C with an aqueous suspension of Sepifil 752 White and Sepifilm 1015 Blue. The coated tablets are polished with an aqueous solution of polyethylene glycol.

Example 5:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Tablet composition Weight in g Weight% Zaleplonum 0.01000 g 6.25 Avicel PH 102 0,03200 g 20,00 Avicel PH 200 0.10160 g 63.50 Maydis amylum pregelificatum 0.00800 g 5.00 Croscarmellosum natricum 0.00480 g 3.00 Silica colloidalis anhydrica 0.00040 g 0.25 Indigocarminum 85 El32 0.00160 g 1.00 Magnesii stearas 0.00160 g 1.00 Total: 0.16000 g 100,00%

(b) method of preparation:

The active ingredient and Avicel PH 102 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. The Avicel is inserted into the homogenizer.

PH 200, maydis amylum pregelificatum, croscarmellosum natricum, silica coloidalis anhydrica and Indigocarminum 85 E 132. The mixture is stirred for 15 minutes (Stirring Π). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and sieved mixtures I and Π are placed in the homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). Lentil-shaped tablets are pressed from the finished tablet to a tablet weight of 0.160 g.

Example 6:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Tablet composition Weight in g Weight% Zaleplonum 0.01000 g 6.25 Avicel PH 102 0,03200 g 20,00 Avicel PH 200 0.11064 g 69.15 Maydis amylum pregelificatum 0.00320 g 2.00 Croscarmellosum natricum 0.00240 g 1.50 Silica colloidalis anhydrica 0.00016 g 0.10 Indigocarminum 85 El32 0.00080 g 0.50 Magnesii stearas 0.00080 g 0.50 Total: 0.16000 g 100,00%

(b) method of preparation:

The active ingredient and Avicel PH 102 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. The homogenizer was charged with Avicel PH 200, maydis amylum pregelificatum, croscarmellosum natricum, silica coloidalis anhydrica and Indigocarminum 85 E 132. The mixture was stirred for 15 minutes (Stir II). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and screened mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). Lentil-shaped tablets are pressed from the finished tablet to a tablet weight of 0.160 g.

Example 7:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Tablet composition Weight in g Weight% Zaleplonum 0.01000 g 6.25 Avicel PH 101 0.01600 g 10.00 Avicel PH 200 0,10600 g 64.25 Maydis amylum pregelificatum 0.01600 g 10.00 Croscarmellosum natricum 0.00800 g 5.00 Silica colloidalis anhydrica 0.00080 g 0.50 Indigocarminum 85 E132 0.00160 g 2.00 Magnesii stearas 0.00160 g 2.00 Total: 0.16000 g 100,00%

(b) method of preparation:

The active ingredient and Avicel PH 101 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. Add to the homogenizer Avicel PH 200, maydis amylum pregelificatum, croscarmellosum natricum, silica coloidalis anhydrica and Indigocarminum 85 E 132. Stir the mixture for 15 minutes (Stirring Π). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and screened mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). Lentil-shaped tablets are pressed from the finished tablet to a tablet weight of 0.160 g.

Example 8:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Tablet composition

Zaleplonum Avicel PH 102

Weight h

0.01000 g 0.02400 g

Weight%

6.25

15.00

Avicel PH 200

Maydis amylum pregelificatum Croscarmellosum natricum Silica colloidalis anhydrica Indigocarminum 85 E132 Magnesii stearas

(b) method of preparation:

13 0.09640 g 60.25 0.00640 g 4.00 0.01200 g 7.50 0.00160 g 1.00 0.00480 g 3.00 0.00480 g 3.00 0.16000 g 100,00%

The active ingredient and Avicel PH 102 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. Add to the homogenizer Avicel PH 200, maydis amylum pregelificatum, croscarmellosum natricum, silica coloidalis anhydrica and Indigocarminum 85 E 132. Stir the mixture for 15 minutes (Stirring Π). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and screened mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). Lentil-shaped tablets are pressed from the finished tablet to a tablet weight of 0.160 g.

Example 9:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Tablet composition Weight in g Weight% Zaleplonum 0.01000 g 6.25 Avicel PH 101 0.01600 g 10.00 Avicel PH 200 0.09640 g 60.25 Maydis amylum pregelificatum 0.01840 g 11.50 Croscarmellosum natricum 0.00800 g 5.00 Silica colloidalis anhydrica 0.00320 g 2.00 Indigocarminum 85 El 32 0.00320 g 2.00 Magnesii stearas 0.00480 g 3.00 Total: 0.16000 g 100,00%

(b) method of preparation:

The active ingredient and Avicel PH 101 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. The homogenizer is charged with Avicel PH 200, maydis amylum pregelificatum, croscarmellosum natricum, silica coloidalis anhydrica and Indigo carmine 85 E 132. The mixture is stirred for 15 minutes (Stirring Π). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and screened mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). The lentil-shaped tablets are compressed from the finished tablet to a tablet weight of 0.160 g.

Example 10:

(a) a pharmaceutical preparation containing, in the composition of a tablet:

Tablet composition Weight in g Weight% Zaleplonum 0,02000 g 6.25 Avicel PH 101 0,03200 g 10.00 Avicel PH 200 0.19200 g 60,00 Maydis amylum pregelificatum 0.05680 g 17.75 Croscarmellosum natricum 0.00640 g 2.00 Silica colloidalis anhydrica 0.00320 g 1.00 Indigocarminum 85 El32 0.00640 g 2.00 Magnesii stearas 0.00320 g 1.00 Total: 0,32000 g 100,00%

(b) method of preparation:

The active ingredient and Avicel PH 102 are placed in a homogenizer. The mixture is stirred for 15 minutes (Stirring I). The mixed premix is poured into a container and subsequently passed through a sieve with a mesh size of 1.0 mm. The homogenizer is charged with Avicel PH 200, maydis amylum pregelificatum, croscarmellosum natricum, silica coloidalis i. . ··. ....

··· ··. I · · · ··· ::

···· ·· *. .j. · Anhydrica and Indigocarminum 85 E 132. Stir the mixture for 15 minutes (Stirring Π). The mixed mixture is poured into a container and then passed through a sieve with a mesh size of 0.80 mm. Mixed and screened mixtures I and II are placed in a homogenizer. and stirred for 30 minutes. Magnesia stearas is added to the mixture in the homogenizer. The mixture was stirred for 15 minutes (Finish). Lentil-shaped tablets are compressed from the finished tablet to a tablet weight of 0.320 g.

Results from dissolution of the active substance

The in vitro dissolution of zaleplon is monitored for:

Equipment used: Ph.Eur. Dissolution apparatus, paddle, 100rpm

Medium: 0.1HCl, 900ml

Temperature: 37 ° C ± 0.5 ° C

Time: 30 minutes

Determination of drug dissolution: HPLC at 230 nm

The dissolution of the active compound is illustrated by the embodiment 4 used in the clinical trials and the dissolution results are shown in the table.

Table:

Dissolution of the active substance:

Time Amount of active substance released (%) 5 minutes 10 minutes 20 minutes 30 minutes 45 minutes 81.88 88.63 92.04 93.35 93.74

Dissolution results show that more than 95% of the drug is released within 10 minutes.

Industrial applicability of the invention

The invention is useful in the pharmaceutical manufacture of tablets and film-coated tablets.

The film-coated tablets can be used therapeutically in the treatment of severe insomnia.

Claims (8)

PATENT CLAIMS A zaleplon-containing dosage form, characterized in that it is in the form of a tablet or film-coated tablet containing zaleplon in an amount of 0.005 to 0.02 g, further comprising microcrystalline cellulose with a mean particle size of 10 to 1000 µm in an amount of 60 to 90 wt. %, dry binder in an amount of 2 to 20 wt. % disintegrant in an amount of 1.5 to 10 wt. 0.1 to 2 wt. 0.5 to 4.0 wt. %, a dye to prevent abuse of the dosage form in an amount of 0.5 to 5 wt. 2 to 5 wt. %. Pharmaceutical form according to claim 1, characterized in that the microcrystalline cellulose has a mean particle size of 50 to 180 µm. Pharmaceutical form according to claims 1 and 2, characterized in that it comprises, based on the total weight of the preparation, 10 to 15 wt. % microcrystalline cellulose with a mean particle size of 50 µm and 60 to 71 wt. % microcrystalline cellulose with a mean particle size of 180 µm. A dosage form according to claims 1 and 2, characterized in that it comprises, based on the total weight of the preparation, 15 to 23% by weight. % microcrystalline cellulose with a mean particle size of 100 µm and 60 to 70 wt. % microcrystalline cellulose with a mean particle size of 180 µm. 5. A dosage form according to claim 1 comprising 4 to 6 wt. % dry binder, preferably maydis amylum pregellificatum. A dosage form according to claim 1, characterized in that it comprises 2 to 5 wt. % disintegrant, preferably croscarmellosum natricum. A dosage form according to claim 1 comprising 0.2 to 0.5 wt. % of a flow regulating agent, preferably silica colloidalis anhydrica. · · * * * * * * * * * * * * * * * * * * * * * Pharmaceutical form according to claim 1, characterized in that it contains 0.7 to 1.5 wt. % antiadhesive, preferably magnesii stearas. it. Dosage form according to claim 1 or 2, characterized in that it contains 0.7 to 1.5 wt. % dye to prevent abuse of the dosage form, preferably Indigocarminum 85 E 132. 1®. A dosage form according to any one of claims 1 to 10 comprising film-forming agents in an amount of 3 to 4% by weight. %.