Ticlopidine hydrochloride is a platelet aggregation inhibitor. When taken orally, ticlopidine hydrochloride causes a time and dose-dependent inhibition of both platelet aggregation and release of platelet granule constituents, as well as prolongation of bleeding time. Ticlopidine hydrochloride is marketed by Syntex under the trade name TICLID.RTM.. Detailed information on TICLID.RTM. is available in the Physicians' Desk Reference.
In order for ticlopidine hydrochloride, with or without diluents, to be made into solid dosage forms, tablets for example, with pressure, using available equipment, it is necessary that the ticlopidine hydrochloride, either in crystalline or powdered form, possess a number of physical characteristics.
These characteristics include cohesiveness, lubrication and the ability to flow freely. Since, most materials have none or only some of these properties, methods or formulations have been developed to impart these desirable characteristics to medicinal substances sought to be compressed into tablets.
The additional ingredients added to medicinal substances, to impart these desirable characteristics, are termed "excipients." Examples of excipients include diluents, binders, and lubricants.
The compressed tablets are also required to be stable through their shelf life. However, the addition of certain excipients can adversely effect other characteristics of the compressed tablets, including shelf life, and size.
U.S. Pat. No. 4,051,141 discloses a thieno-pyridine derived drug designated ticlopidine hydrochloride. However, it is subject to discoloration during normal storage. The discoloration has been associated with degradation of the ticlopidine. The initiating factor of the ticlopidine degradation was adjudged to be the presence of certain excipients such as gelatin, povidone and magnesium stearate.
U.S. Pat. No. 4,591,592 discloses that compositions containing ticlopidine hydrochloride can be stabilized by the addition of acidic compounds. However, the use of an acid as a stabilizer, in addition to the use of magnesium stearate as a lubricant, makes the composition more complex than desirable. However, use of magnesium stearate accelerates the decomposition of ticlopidine hydrochloride. Additionally, although the composition disclosed within U.S. Pat. No. 4,591,592 is more stable than that of U.S. Pat. No. 4,051,141, it is still less stable than desirable.
U.S. Pat. No. 5,520,928 discloses a pharmaceutical composition comprising an active ingredient with another acidic compound stearic acid, and other suitable pharmaceutical excipients, and which does not contain any organic acid other than stearic acid. The stabilization is achieved using stearic acid, which also serves as the lubricant. However, a tablet containing ticlopidine hydrochloride 250, microcrystalline cellulose 130, stearic acid 9.4 and croscarmellose sodium 0.6 mg, has a weight of 390 mg per tablet. Additionally, the typical composition has stearic acid as a stabilizer and croscarmellose sodium as a disintegrant, which also results in a composition more complex than desirable.
It is therefore an object of the invention to have a novel pharmaceutical composition with a fewer number of ingredients, without diluent, and with a smaller compressed tablet weight of 300 mg per 250 mg of ticlopidine hydrochloride.
It is a further object of the invention to have a stable pharmaceutical composition for ticlopidine hydrochloride containing no acid stabilizing agent alone or in combination with lubricant magnesium stearate.
And, it is yet a further object of the invention to have a pharmaceutical composition ticlopidine hydrochloride which uses hydrogenated vegetable oil as a lubricant, hydroxypropyl cellulose as a binder and corn starch as a disintegrant, all of which are substantially free of an effective amount of organic acid.