DE4333190C2 - Bite-coated tablet with delayed release of active ingredient - Google Patents

Description

The invention relates to a novel chewing tablet the basis of a chewable mass.

In the case of oral prolonged-release pharmaceutical forms, the Active ingredient in matrix tablets, film-coated tablets or prolonged-release tablets pellets incorporated, the pellets then in Capsules filled or compressed into swallowing tablets the. The tablets or capsules are naturally in theirs Size limited to a weight of approximately 0.6 g. Already for tablets or capsules that enter its weight difficulties in swallowing. Either Tablets as well as capsules can be used before swallowing  not be chewed, because in this way the pellets and Matrices would be destroyed and the retard effect would be lost would go.

DE 37 27 615 A1 describes a pharmaceutical preparation device for the delayed release of fluoride and Calcium ions for the treatment and prevention of bones loss of substance known. This registration affects everyone but no chewable tablets.

The invention is therefore based on the object, a new to provide like chewing tablet, the one Delayed drug release enables.

According to the invention, this task is performed in a generic manner Bite tablet by the in the mark of claim 1 listed features solved.

Preferred embodiments result from the sub claims.

The measures according to the invention are the first Mouthguard provided, in which the active ingredient substance or the combination of active ingredients is released in a delayed manner becomes. A particular advantage is that the active ingredient contained in the microparticles so dosed can be, as has been the case with familiarization with previously oral retard systems was not possible.

In an alternative of the chewing tablet according to the invention te is the active ingredient or combination of active ingredients eventually present in the microparticles. Especially high-dose active ingredients according to the state of the art not or only partially applied in delayed form could be in the form of a chewing tablet  to be taken. By incorporating the active ingredient or the active ingredient combination in the invention formed microparticles occurs when the Ta is chewed blette no impairment of the retarding property because of their elasticity and strength when biting is not destroyed. Each after the microparticle retard system has been built up a delayed release at a later time, for example in the gastrointestinal tract after the gastric pass legend.

In a further alternative it is possible, in addition to the in the active ingredient contained in the microparticles, which delays to be released into the chewable mass incorporate further active ingredient that immediately, d. H. at the Biting the tablet, can and should be released. A combination preparation would be an example of this Treatment of osteoporosis to name the sodium fluoro phosphate or sodium fluoride in the form of retarding Microparticles embedded in a calcium-containing kaumas se.

In a further alternative the Zer bite tablet can also be provided that the effect substance or the combination of active ingredients both in the micro particles as well as contained in the chewable mass, the quantities can then be adjusted so that the active ingredient in the chewable mass, which immediately, d. H. when the tablet is chewed, is released - as an initiation aldosis works while the amount of active ingredient in the Mi croparticles, which is only released later than He maintenance dose works.

In the drawings  

. Figure 1 shows the in-vitro liberation of phosphate from Natriumfluoro Zerbeißtabletten invention; and

Fig. 2 shows the in vitro liberation of diclofenac from chewable tablets according to the invention.

To illustrate the invention are in the following games for the different alternatives of the invention according chewable tablet specified in more detail.

Examples example 1 MFP chewable tablets

The following (Table 1) are composition and retar duration of different cerations according to the invention bite tablets listed as an active ingredient in the micro particles of sodium fluorophosphate (= monofluorophosphate, MFP) included. The elastic retard matrix is off Cellulose derivatives or cellulose derivatives in combination constructed with Eudragit® compositions. The one in this Context used terms Avicel, Methocel and Eudragit are registered trademarks for mikrokri stalline cellulose, methyl cellulose (derivatives) or Polymethacrylate copolymers.  

Table 1

Example 2 Combined MFP chewable tablets

As already explained, bites are also according to the invention tablets provided, in which, as an initial dose, a Part of the active ingredient in the chewable mass and an on the part, as a maintenance dose, in the microparticles is present. In addition, according to the invention in the chewable Ren mass calcium salts may be provided to a Kombina preparation for the treatment of osteoporosis len.

The following combinations, for example, can be used see his:

To further illustrate the invention, reference is made to FIG. 1, in which the in vitro liberation of MFP from combined chewable tablets according to composition 1 indicated above is shown.

Example 3

For similar uses as in Examples 1 and 2 Written MFP chewing tablets can also fiction chewable tablets with the active ingredient sodium fluoride are used in the microparticles, wherein in Table 2 below shows an example of a possible Zu composition is specified.

Table 2

Example 4 Bite tablets with naftidrofuryl hydrogen oxalate as an active ingredient material

The ones shown in more detail below (Table 3) Composition of a chewing tablet according to the invention contains naftidrofuryl hydrogen oxalate as the active ingredient promotes blood circulation and vasodilator. The ela Retic matrix in which this active ingredient in the Mi croparticles is based on an Eudragit® Composition while the chewable tablet base (as Darge represents) can be composed differently.  

Table 3

Example 5 Chewing tablet with the active ingredient Diclofenac Na

In the following (Table 4) is a Zer according to the invention Bite tablet shown in which the microparticles Active ingredient contain diclofenac, the anti-inflammatory and has an anti-rheumatic effect. The elastic matrix into which the ser active ingredient is embedded in the microparticles, be is also from the cellulose derivative Avicel®.

Table 4

In correspondence to Fig. 1 2 is shown in-vitro Libe ration of the active ingredient diclofenac from the above-described NEN Zerbeißtabletten in Fig..

As further application examples for combined bitters the following combinations are possible, whereby the active ingredient in the indicated indication in the microparticles are incorporated and the remaining sub punch combined components in the chewable Represent mass.

• 1. H₂ blocker z. B.
  Cimetidine + sucralfate
  Cimetidine + calcium carbonate + magnesium oxide.
• 2. Vasodilatants e.g. B.
  Pentoxyfylline + magnesium asparate or magnesium citrate
• 3. Antiallergica e.g. B.
  Loratadine + calcium salts + tricalcium citrate
• 4. Antihypertonica e.g. B.
  β-blockers such as propranolol, atenolol + magnesium salts
  α-blockers such as clonidine + magnesium salts + potassium salts.
• 5. Diuretic e.g. B.
  Furosemide, hydrochlorothiazide + magnesium salts + potassium salts.

Claims (17)

1. Biting tablet on the basis of a chewable mass, characterized in that active substance-containing microparticles with retarding properties are present in a conventional chewable mass, which are not destroyed due to their elasticity and strength when the tablet is chewed. 2. Biting tablet according to claim 1, characterized net that the chewable mass at least one additional Lichen active ingredient.   3. Biting tablet according to one of claims 1 and 2, there characterized in that the chewable mass (the) same active ingredient (s) as the microparticles ent holds. 4. Biting tablet according to claim 3, characterized net that the amount of active ingredient in the chewable Mass is set so that it is the initial dose acts, and the amount of active ingredient in the microparties is set so that it is a maintenance dose works. 5. Biting tablet according to one of the preceding claims che, characterized in that the microparticles a retarding, elastic active ingredient Matrix and a retarding and also elastic exist. 6. Biting tablet according to claim 5, characterized net that the matrix from a Endragit® derivative (polymer of acrylic / methacrylic acid or their esters) or a combination of different Endragit® Derivatives, cellulose derivatives, preferred Methyl cellulose, hydroxyethyl cellulose or Hydroxypropyl cellulose, or other usual, retar auxiliary materials with a high proportion of pla constituent components.   7. chewing tablet according to one of claims 5 or 6, characterized in that the polyacryla ten, preferably Endragit® or Endragit® compositions, or from Cellu Loose derivatives, preferably ethyl cellulose, cellulose acetate pht halate or hydroxypropylmethyl cellulose phthalate, if necessary with the addition of plasticizing auxiliaries. 8. Biting tablet according to one of the preceding claims che, characterized in that the microparticles have a diameter between 0.3 and 3.0 mm. 9. chewing tablet according to claim 8, characterized net that the microparticles have a diameter of 0.3 up to 1.0 mm. 10. Biting tablet according to one of the preceding claims Containing sodium fluorophosphate or natri umfluorid in the microparticles and optionally at least one calcium salt or calcium complex in the chewable mass, especially for prevention or therapy of osteoporosis. 11. Biting tablet according to one of claims 1 to 9, with a content of naftidrofuryl salt, preferably naftidro furyl hydrogen oxalate in the microparticles, to pass through promoting bleeding and / or vasodilation.   12. Bite tablet according to one of the speech 1-9, with egg content of diclofenac or its salt in the Mi croparticles, as an anti-inflammatory and / or anti rheumatic. 13. Biting tablet according to one of the speech 1-9, with egg nem content of cimetidine or ranitidine or their sal zen in the microparticles, as an H₂ blocker. 14. Biting tablet according to one of the speech 1-9, with egg content of pentoxyfylline in the microparticles, as Vasodilatans. 15. Bite tablet according to one of the claims 1-9, containing loratadine in the microparties as an anti-allergy. 16. Biting tablet according to one of the claims 1-9, containing β-blockers, preferably propanolol and Atenolol, or α-blocker, preferably clonidine, in the microp articles, as an antihypertensive. 17. Biting tablet according to one of claims 1-9, with egg content of furosemide or hydrochlorothiazide in the Microparticles, as a diuretic.