New Crystalline Form of Pemirolast

Abstract

There is provided a hemihydrate form of the sodium salt of pemirolast.

Description

FIELD OF THE INVENTION[0001]This invention relates to new solid state forms of a drug, to pharmaceutical compositions containing them, and to processes for obtaining them.BACKGROUND TO THE INVENTION[0002]In the formulation of drug compositions, it is important for the drug substance to be in a form in which it can be conveniently handled and processed. This is of importance, not only from the point of view of obtaining a commercially viable manufacturing process, but also from the point of view of subsequent manufacture of pharmaceutical formulations comprising the active compound.[0003]Chemical stability, solid state stability, and “shelf life” of the active ingredients are also very important factors. The drug substance, and compositions containing it, should be capable of being effectively stored over appreciable periods of time, without exhibiting a significant change in the active component's physico-chemical characteristics (e.g. its chemical composition, density, hygroscopici...

AI Technical Summary

Benefits of technology

[0027]We have found that it is possible to obtain compounds of the invention via crystallisation advantageously following at least partial dissolution and / or suspension of a sodium salt of pemirolast.

[0120]The compounds of the invention may also have the advantage that, in the treatment of the conditions mentioned hereinbefore, they may be more convenient for the physician and / or patient than, be more efficacious than, be less toxic than, have a broader range of activity than, be more potent than, produce fewer side effects than, or may have other useful pharmacological properties over, similar compounds known in the prior art for use in the treatment of inflammatory disorders (such as atherosclerosis and associated cardiovascular conditions) or otherwise.

Problems solved by technology

Amorphous, or semi-amorphous materials may present significant problems in this regard.

For example, such materials are typically difficult to handle and to formulate, provide for unreliable solubility, and are often found to be unstable and chemically impure.

It is to be noted, however, that this goal is not always achievable.

Indeed, typically, it is not possible to predict, from molecular structure alone, what the crystallisation behaviour of a compound will be.

Commercial pemirolast potassium has the disadvantage that it is known to give rise to sharp plasma concentration peaks in humans (see, for example, Kinbara et al, “Plasma Level and Urinary Excretion of TBX in Humans”, Japanese Pharmacology &Therapeutics, 18(3) (1990), and “Antiallergic agent—ALEGYSAL tablet 5 mg—ALEGYSAL tablet 10 mg—ALEGYSAL dry syrup”, Pharmaceutical Interview Form (IF), Revised in October 2007 (7th version), Standard Commodity Classification No.

The latter document also reports that the potassium salt of pemirolast is hygroscopic, which is believed to give rise to chemical instability, and possesses a bitter taste.

As described herein, this technique produces a sodium salt that is physically unstable.

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