Isosorbide mononitrates pharmaceuticals

Novakovic, J. Nova, H. Filka, K. In-process control and process parametric assessment of isosorbide 5-mononitrate pharmaceuticals. J. Planar Chromatogr.Mod. TLC 1999, 12, 161-164. 

The double dehydration of sorbitol yields D-isosorbide (l,4 3,6-dianhydrohexitol), a white, biodegradable, nontoxic solid. It is used in medicine to treat glaucoma. Other medications are derived from isosorbide, including isosorbide dinitrate and isosorbide mononitrate used to treat angina pectoris. The high thermal stability makes isosorbide interesting as a monomeric building block for thermoplastic polymers such as polyester and polycarbonates. The electrophilic alkylation of isosorbide with dimethyl sulfate yields dimethyl isosorbide, a colorless liquid which is used as a plasticizer for vinyl polymers and as a solvent in pharmaceutical and cosmetic preparations. 

A high-performance, liquid chromatography (h.p.l.c.) assay (reversed phase, C lg column, methanol - water- acetate buffer) for isosorbide dinitrate along with the two mononitrates in pharmaceutical formulations has been described.45 A similar method can be found in Ref. 44. 

Differential scanning calorimetry can be used to detect isosorbide dinitrate in the presence of various proportions of other isohexide mononitrates in pharmaceutical formulations81 and for testing its hazardous characteristics.82 A complete analytical profile for isosorbide dinitrate, detailing spectroscopic and other physical properties, as well as useful analytical methods, has been reported.83... 

The continuous worldwide application of isosorbide dinitrate and, since the early eighties, of isosorbide 5-mononitrate also, has given rise to a very great number of publications on different aspects of these drugs. It would be beyond the scope of this report to include all of the work on these two important compounds. The present synopsis is therefore restricted to other novel isohexide derivatives and to some new pharmaceutical applications of known compounds. 

D. Agbaba, V. Janjic, D. Zivanov Stakic, and S. Vladimirov, HPLC assay for isosorbide 5-mononitrate and Impurities of inorganic nitrates in pharmaceuticals, J. Liquid Chromatogr., 77 3983 (1994). 

For certain substances it is generally accepted that in conventional orcil pharmaceutical formulations they do not cause bioequivalence problems. That is why the MEB does not consider it necessary to perform and submit bioequivalence research for the following 19 substances amoxicilline, dextromethorfan, diazepam, doxycycline, potassiumfenoxymethylpenicillin, flunarizine, indometacine, isosorbide-5-mononitrate, lorazepam, lormetazepam, metoprolol, naproxen, nitrazepam, oxprenolol, paracetamol, pindolol, piroxicam, salbutamol, temazepam. According to the MEB there is enough evidence present in literature to prove that there is no problem with the bioequivalence. 

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