Of ranitidine

Therapeutics. Compounds containing the furan or tetrahydrofuran ring are biologically active and are present in a number of pharmaceutical products. Eurfurjdamine [617-89-0] is an intermediate in the diuretic, furosemide. Tetrahydrofurfurylamine [4795-29-3] may also have pharmaceutical applications. 5-(E)imethyiaininomethyi)furfuryi alcohol [15433-79-17 is an intermediate in the preparation of ranitidine, which is used for treating ulcers. 2-Acet5dfuran [1192-62-7] prepared from acetic anhydride and furan is an intermediate in the synthesis of cefuroxime, a penicillin derivative. 2-Euroic acid is prepared by the oxidation of furfural. Both furoic acid [88-14-2] and furoyl chloride [527-69-5] are used as pharmaceutical intermediates. 

Fig. 4. CPK rendering of ranitidine as in Fig. 3, although here illustrating the method of showing color-coded electronic charge data mapped onto the CPK surfaces, with red representing the highest density, blue the lowest density, etc (color not shown here).

Fig. 5. A representation of ranitidine displaying four layers of the Connolly solvent-accessible dot surface normally color-coded in this process to correspond with the energies of electrostatic potential (color not shown here). Thus, the highest charge density would be indicated by red dots representing points where the attraction to an atom is strongest, and conversely, purple points would signify regions of maximal positive charge.

Fig. 6. Two representations of ranitidine illustrating the electrostatic potential mapped onto (a) a soHd and (b) translucent constant-density surface (0.001...

Vigorito C, Russo P, Picotti GB, Chiariello M, Poto S, Marone G Cardiovascular effects of histamine infusion in man. J Cardiovasc Pharmacol 1983 5 531. Patterson LJ, Milne B Latex anaphylaxis causing heart block role of ranitidine. Can J Anaesth 1999 46 776. 

MF Williams, GF Dukes, W Heizer, Y-H Han, DJ Hermann, T Lampkin, LJ Hak. Influence of gastrointestinal site of drug delivery on the absorption characteristics of ranitidine. Pharmaceut Res 9 1190-1194, 1992. 

Gramatte, T., el Desoky, E., Klotz, U., Site-dependent small intestinal absorption of ranitidine, Eur. J. Clin. Pharmacol. 1994, 46, 253-259. 

Crystallization remains the primary means of controlling the polymorphic or solva-tomorphic state of a compound, and various groups have examined the influences of processing parameters on the identity and quality of the isolated form. Seeding was used to reduce the size of the metastable zone of eflucimibe, and thereby control the identity of the desired polymorphic identity of the product through a reduction in concomitant crystallization [16], Process improvements have been developed that were found to improve the filterability and enhance the bulk density of ranitidine Form-1 [17], while the variation of process parameters used in an oscillatory baffled crystallizer enabled better selection to be made between the metastable a- and /i-forms of (z.)-glutamic acid [18]. 

Secondary processing does not always lead to phase transformations, as was shown during studies of the polymorphs of ranitidine hydrochloride [92]. No solid-solid transformation could be detected during either the grinding or compression of metastable Form I, stable Form II, or of a 1 1 mixture of these forms. The dissolution rates of both forms were found to be equivalent, and the solution-mediated transformation of Form I to Form II was observed to be slow. 

Fig. 7.14. X-ray powder diffraction patterns of ranitidine hydrochloride, Form I (thick trace) and Form II (thin trace) [47].

Basit AW, Podczeck F, Newton JM, Waddington WA, Eli PJ, Lacey LF. Influence of polyethylene glycol on the gastrointestinal absorption of ranitidine. Pharm Res 2002 19 1368-1374. 

Gan, L.-S., Hysu, P.-H., Pritchard, J.F., and Thakker, D., Mechanism of intestinal absorption of ranitidine and ondansetron transport across Caco-2 cell monolayers, Pharm. Res., 10, 1722, 1993. 

Petersen LJ. Hansen U. Kristensen JK. Nielsen H. Skov PS. Nielsen HJ Studies on mast cells and histamine release in psoriasis the effect of ranitidine. Acta Derm Venereol 1998 78 190-193. 

Plate 8.2 Trace analysis of polymorphic form I of ranitidine. The RGB summary image highlights the distribution of sample components polymorphic form 2 of ranitidine in red, polymorphic form 1 of ranitidine in green and the excipients in blue. 

Toon S, Hopkins KJ, Garstang FM, et al. Comparative effects of ranitidine and cimetidine on the pharmacokinetics and pharmacodynamics of warfarin. Eur ] Clin Pharmacol 1987 32 165-72. 

Nizatidine Nizatidine is N-[2-[[[2-[(dimethylamino)methyl]-4-thiazolyl]methyl] thio] ethyl]-2-nitro-l,l-ethenediamine (16.2.15). According to its chemical structure, nizatidine is somewhat of a hybrid structure of ranitidine and famotidine, in which a side chain of ranitidine and carrying heterocycle, 2-aminothiazol, are used. Likewise, its synthesis also is a specific combination of pathways used for making both prototype drugs. 2-(Dimethyl-aminomethyl)-4-hydroxymethylthiazol serves as the initial compound, from which the desired nizatidine (16.2.15) is synthesized by subsequent reaction with 2-mercaptoethy-lamine hydrochloride and then with iV-methyl-l-methythio-2-nitroethenamine [71,72]. 

Children-The safety and effectiveness of ranitidine have been established in children from 1 month to 16 years of age. There is insufficient information about the pharmacokinetics of ranitidine in neonatal patients under 1 month of age to make dosing recommendations. Do not give OTC ranitidine to children under 12 years of age unless directed by physician. 

Clarithromycin/Ranitidine bismuth citrate-500 mg clarithromycin 2 times/day (every 12 hours) or 3 times/day (every 8 hours), and 400 mg ranitidine bismuth citrate given 2 times/day (every 12 hours) for 14 days. An additional 14 days of ranitidine bismuth citrate 2 times/day is recommended for ulcer healing and symptom relief. This combination is not recommended in patients with a creatinine clearance (Ccr) less than 25 mL/min. 

Chieng, N., Zujovic, Z., Bowmaker, G., Rades, T., and Saville, D. (2006). Effect of milling conditions on the solid-state conversion of ranitidine hydrochloride forrtnlt . J. Pharm. Sci., 327 36-44. 

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