FR2789589A1 - Storage stable coated ticlopidine hydrochloride tablets containing synergistic lubricant mixture of sodium benzoate and magnesium stearate - Google Patents

Abstract

Pharmaceutical coated tablets contain a homogeneous mixture of ticlopidine hydrochloride (I), a polyvidone binding agent, and a synergistic lubricant mixture of sodium benzoate and magnesium stearate.

Description

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  PROCESS FOR PACKAGING PHARMACEUTICAL COMPOSITIONS

  AND TICLOPIDINE COMPOSITIONS OBTAINED BY THIS PROCESS.

  The present invention relates to a process for packaging pharmaceutical compositions of ticlopidine hydrochloride. It also relates to the tiplopidine hydrochloride compositions obtained by this process. Ticlopidine, especially in the form of the hydrochloride, has long been known for its properties as an anti-platelet aggregating agent. However, heretofore, its packaging, in particular in the form of tablets, has not been satisfactory, since it occurs, after a certain period of storage, degradation and yellowing of the tablet. A number of methods advocate the use of compounds having free acid radicals. However, such methods have a certain number of drawbacks, in particular in the metering and

choice of acid to use.

  The main object of the present invention is to provide a packaging of ticlopidine hydrochloride, making it possible to obtain, thanks to the synergistic action "in situ" of several compounds, acting concomitantly with an appropriate film coating, therefore avoiding all

  disintegration and yellowing of the tablet.

  The present invention therefore relates to a process for packaging pharmaceutical compositions of ticlopidine hydrochloride, characterized in that, with a view to preventing the degradation, yellowing and aging of said compositions, the latter are packaged in the form of tablets, by mixing, using a suitable granulation technique, the active compound, triclopidine hydrochloride in the presence of polyvidone as a binding agent, with a synergistic composition consisting of two lubricants, namely sodium benzoate, and magnesium stearate, by getting a mixture

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  homogeneous, which is transformed into tablets before subjecting them to an operation

filming.

  The packaging method of the present invention is further remarkable by the following points: Pharmaceutical compatible fillers and excipients are incorporated into the mixture; The agent used for the film-coating of the tablets is a product sold under the name

OPADRY (OY.L.

  A subject of the invention is also the pharmaceutical compositions obtained from

process specified above.

  i 0 It particularly targets an embodiment of tablets made up of 62.50% of ticlopidine hydrochloride, 1.75% of polyvidone, 9.75% of corn starch, 22% of microcrystalline cellulose, 1% of benzoate sodium, 0.50% magnesium stearate, and

  2.5% OPADRY OY.L, as a film-coating agent, combined with triethyl nitrate.

  The invention will be further illustrated by the following example of the preparation of a composition

  i 5 pharmaceutical according to the invention in the form of tablets.

Example

  250 grams of ticlopidine hydrochloride are introduced into the tank of a mixer, for example of the Turbula type, in the form of grains previously bound with 7 grams of

  polyvidone is calibrated to 1.0 millimeters, then 88 grams of micro- cellulose are added

  crystalline and 39 grams of corn starch and the whole is mixed thoroughly, after which 2 grams of magnesium stearate and 4 grams of sodium benzoate are introduced into the resulting mixture. 390 grams of a homogeneous powdery mixture are thus obtained which are transformed into 100 bare tablets of 0.39 grams each. These tablets are then subjected to a film coating by means of a film-coating agent of the OPADRY type (D OY.I., associated with

  triethyl citrate, applied in aqueous phase.

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  The aqueous coating guarantees a good coating of the surface of each tablet, which does not

  in no way changes the dissolution parameters of the tablets.

  The tablets obtained each have a theoretical mass of 400 milligrams, a hardness of 70 N, a disintegration in 30 seconds for a thickness of 5.08 millimeters and a diameter of 10.13 millimeters.

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Claims (4)

  1 - Process for conditioning a pharmaceutical composition based on ticlopidine hydrochloride, characterized in that, in order to avoid degradation, yellowing and aging of said compositions, the latter are packaged in the form of tablets, by mixing, using a granulation technique of the active compound, ticlopidine hydrochloride, in the presence of polyvidone as a binding agent, is a synergistic composition consisting of two lubricants, namely sodium benzoate and magnesium stearate, thereby obtaining a homogeneous mixture , which we transform, by   techniques known per se, in tablets which are subjected to a film-coating operation.   2 - Method according to claim 1, characterized in that one incorporates into the mixture of   pharmaceutically compatible fillers and excipients.   3 - Process according to claim 1, characterized in that the agent used for the film coating corresponds to a product sold under the trade name (OPADRY (OY.L.), in   combination with a sufficient amount of triethyl citrate.   4 - The pharmaceutical composition obtained according to the process of claims 1, 2 and 3.   - Pharmaceutical composition obtained according to the process of claims 1, 2 and 3,   characterized in that it contains 62.50% of ticlopidine hydrochloride, 1.75% of polyvidone, 9.75% of corn starch, 22% of microcrystalline cellulose, 1.0% of sodium benzoate, 0.5% magnesium stearate and 2.5% type film-coating agent (OPADRY OY. L.).