ABSTRACT
The physicochemical properties of crystals can vary with the crystallization procedure employed in their isolation and purification. Moreover, the success of any direct-tableting procedure is directly effected by the quality of the crystals used in this process. We examined the conventional crystallization method employed in the isolation and purification of octotiamine crystals, the active component of the pharmaceutical compound Neuvita. Our objective was to determine under what crystallization conditions (i.e., supersaturation ratio [pH], temperature, impeller speed) octotiamine crystals with excellent direct-tableting potential could be obtained. Our results indicated that modifications in pH level (from 4.3 to 4.0), i.e., a reduction in the supersaturation ratio, and in impeller speed (from 100 to 78 rpm) are necessary to obtain octotiamine crystals with superior flowability and compressibility compared to the use of the conventional crystallization method. Thus, with these modifications in the conventional crystallization method, octotiamine crystals can be made that show dissolution rates similar to those of the conventionally made crystals, yet which can be manufactured into tablets using a simpler method (i.e., direct tableting). Also, the tableting powder made from the new crystal type proved to be less adhesive than the conventionally made crystal powder. This property attributed to the new crystal type will allow for more stable automated manufacturing than the conventional crystal type would allow.
Subject(s)
Chemistry, Pharmaceutical , Clofibrate/chemistry , Nicotinic Acids/chemistry , Nicotinyl Alcohol/chemistry , Pemoline/chemistry , Vitamins/chemistry , Caprylates , Chemical Phenomena , Chemistry, Physical , Crystallization , Disulfides , Drug Combinations , Powders , Pyrimidines , Solubility , Tensile StrengthABSTRACT
We report two case histories of previously healthy patients who both developed persistent dyskinetic syndromes (spasmodic torticollis and cranial dystonia, respectively) following the intake of norpseudoephedrine (NPE) as an appetite suppressant. The symptoms took a chronic course even after NPE intake was discontinued. Similar drug-induced dyskinesias have been described for amphetamine and neuroleptic drugs. This side effect has, however, not yet been reported for NPE, which is pharmacologically related to amphetamine. One of the patients may also have had multiple sclerosis. Structural lesions in the basal ganglia area might predispose the development of such a movement disorder. The potential relationship between NPE intake and the development of dyskinesia is discussed. Appetite suppressants, often taken without the neurologist's knowledge, may be the cause of dyskinetic syndromes.
