Ketotifen hydrogen fumarate

In a separate container dissolve ketotifen hydrogen fumarate in ethanol until clear. 

The reaction sequence leading to ketotifen hydrogen fumarate is shown in sheme I. 

The IR absorption spectrum of ketotifen base, and that of ketotifen hydrogen fumarate with 2.5 molecules of water, are shown in Fig. 1. These spectra were recorded with KBr-pelleted samples using a Pye Unicam SP-2oo Infrared Spectrophotometer (5) Some of the major frequencies and band assignements are given in Tables 1. and,2. 

Fig. 2. shows the UV spectra (Pye-Unicam SP--8-loo Spectrophotometer) of ketotifen base (1) and ketotifen hydrogen fumarate with 2.5 molecule of crystal water (2). both compounds being in me-thanolic solution T5). 

Fig. 1. Infrared absorption spectra of ketotifen base (A) and ketotifen hydrogen fumarate with 2.5 HP0 (B). Instrumemt Pye-Unicam SP-2oo. ...

Fig. 3. Mass spectrum of ketotifen hydrogen fumarate. The electron energy was 70 eV and the temperature of the ion source was 250 C. Instrument mass spectrometer CEC-21-110 B.

Table 2. Characteristic IE bands of ketotifen hydrogen fumarate containing 2.5 molecules of crystal water...

The proton MR spectra (Jeol FX-loo Spectrometer) were recorded in different solvents that of ketotifen base in deuterated chloroform, and that of ketotifen hydrogen fumarate in deuterated dimethyl sulphoxide (in either case against TMS as internal standard) (5). These spectra are presented in Figs. 4. and 5. Characteristic features of the spectra are given separately in Tables 3 and 4. 

When ketotifen hydrogen fumarate was shaken with D 0, the carboxylic group protons of fumaric acid and the N+H protons were exchanged for deute-rons from D 0, as shown by the absence of the broad peak at 9.1 ppm (see Table 4.) (5). 

Fig. 5. H-Nuclear magnetic resonance spectrum of ketotifen hydrogen fumarate with 2.5 1 0. Instrument Jeol FX-100 at 100 mHz. 

Table 7. X-Ray diffraction data of ketotifen hydrogen fumarate...

Solubilities of ketotifen base and ketotifen hydrogen fumarate with 2.5..H2O in various solvents, at room temperature (18-2o°C7, are summarized in Tables 8. and 9 (5)... 

Table 9. Solubilities of ketotifen hydrogen fumarate hydrate (2.5 i O) ...

Ketotifen hydrogen fumarate was chromatographed on a glass capillary column 15 m x 0.32 mm I. D. with SE-3o. The carrier gas was H2, inlet pressure o.4-5 bar. The temperature program used in analysis was 12o-24o°C at 6°/min. rate. The concentration of ketotifen hydrogen fumarate (solvent ethanol) in the sample that gave the record shown in Pig. 8. was 1 mg/ml and the retention time was 12.3 min (5). 

Table 11. gives the HPLC conditions used for the analysis of ketotifen hydrogen fumarate (5). 

Potentiometric titration of fumaric acid fifty mg of ketotifen hydrogen fumarate with 2.5 HqO was weighed (io.l mg) into a titration vessel and dissolved in lo ml of ethanol and lo ml of water (5). The resulting solution was titrated potentiometrically with o.l M NaOH is equivalent with 5.8 mg of fumaric acid. The content of fumaric acid in the sample is calculated by using equation (2) ... 

Drug release can be modified incorporation of additives on microspheres cores or surfaces that would either control polymers degradation,or change the pH of the microsphere environment. For example, the release rate of a core material ketotifen hydrogen fumarate was modified by the use of an alkaline agent, for example, sodium hydroxide that was incorporated either in the water or in the oil phase. ... 

C-NMR spectra were recorded with a Jeol FX-—loo spectrometer at 25.o5 MHz. The sample of ketotifen base was dissolved in both CDC1, and DMSO-dg, and hydrogen fumarate only in DHSO-d (5). The samples were measured in 5 mm tubes with TMS as internal standard and using internal deuterium lock. 

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