Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-12-15
1997-09-09
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514 58, A61K 3134, A61K 31715
Patent
active
056657676
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP94/00645 filed Mar. 4, 1994.
The present invention relates to a novel type crystalline cyclodextrin inclusion complex of ranitidine hydrochloride, to the process for the preparation thereof, and to pharmaceutical compositions containing the same.
Ranitidine.HCl, i.e. N-[2(5-dimethylamino)methyl-2-furanylmethyl thio]ethyl-N-methyl-2-nitro-1-ethenediamine hydrochloride has been widely used as a histamine H.sub.2 receptor atagonist for the treatment of gastric and duodenal ulcers, as well as for treating hyperacidic conditions. The substance inhibits the normal and stimulated secretion of gastric acid, thus it reduces the amount of gastric juice and its acid and pepsine content.
Two types of polymorphic crystalline forms of ranitidine.HCl, "Form 1" and "Form 2" have been described.
The basic form or "Form 1" can be obtained from the ethanolic solution of ranitidine base by salt formation with hydrochloric acid. The filtration and drying characteristics of "Form 1" are known to be unfavourable, moreover, it exhibits considerable hygroscopicity. "Form 2" is obtained upon the isopropanolic recrystallization of "Form 1".
The preparation of "Form 2" is described in U.S. Pat. No. 4,672,133. The two above crystalline forms of ranitidine.HCl are well distinguishable by X-ray powder diffraction patterns, as their characteristic reflection peaks appear at different 2 theta angle values.
From a technological standpoint "Form 2" is more advantageous, consists of larger crystals, is easy to filter, to dry, and less sensitive to moisture,
Upon storage "Form 1" slowly gets converted into "Form 2".
The existence and spontaneous transformations of polymorphic forms of drug substances are of disadvantage, because they cause difficulties to fulfill exacting pharmaceutical requirements and specifications. The physicochemical properties of products with such polymorphics change according to the actual ratios of polymorphic forms.
Surprisingly, it has been found that strongly hydrophilic, in water freely soluble ranitidine hydrochloride formed a well defined crystalline inclusion complex with cyclodextrins, preferably with .beta.-cyclodextrin.
According to one embodiment the invention concerns complexes of ranitidine hydrochloride as guest substance with cyclodextrin as host substance.
.alpha.-, .beta.- and/or gamma-cyclodextrin and/or their alkylated and/or hydroxy alkylated derivatives are examples of cyclodextrin.
Further, ranitidine.HCl "Form 1" or ranitidine.HCl "Form 2" can be used as guest substance.
The molecular ratio of host substance: guest substance is normally .gtoreq.1.
According to another embodiment the invention concerns a process for the production of complexes of ranitidine hydrochloride as guest substance with cyclodextrin as host substance, wherein an aqueous solution or suspension of the guest substance and the host substance is formed and the formed solution is brought to dryness, i.e. the water is removed. The aqueous solution of suspension has, for example, a content of 5 to 70 and especially 20 to 40% .beta.-cyclodextrin. Ranitidine.HCl "Form 1" or ranitidine.HCl "Form 2" can be used as guest substance, or ranitidine base can be used as starting material for ranitidine hydrochloride as guest substance.
The water of the formed solution is, for example, removed by lyophilization, spray-drying, low temperature vacuum evaporation or vacuum drying.
Finally, according to one embodiment the invention concerns a pharmaceutical composition comprising as active ingredient their complex of ranitidine hydrochloride as guest substance with cyclodextrine as host substance beside usual ingredients and/or additives.
The above observation is surprising, since cyclodextrins have long been reputed to form crystalline inclusion complexes with guest molecules of a polar character, and of poor water solubility.
Both thermoanalytical studies (DSC: Differential Scanning Calorimetry) and X-ray powder diffractometry proved the existence of a novel solid phase and thus the formation of an inclusio
Fischer Wilfried
Klokkers Karin
Henley III Raymond
Hexal Pharma GmbH
LandOfFree
Crystalline cyclodextrin complexes of ranitidine hydrochloride, does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Crystalline cyclodextrin complexes of ranitidine hydrochloride, , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Crystalline cyclodextrin complexes of ranitidine hydrochloride, will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-70611