PubMed · 2274959
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C N Ab, L Gatenbeck, O Olsson. 1990-11-30. [Acetazolamide].. https://pubmed.ncbi.nlm.nih.gov/2274959/
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Since the nitric oxide (NO) and cyclooxygenase pathways have been suggested to have important roles in most vasodilations, our aim was to study the influence of cyclooxygenase inhibitors and nitrovasodilators on cerebrovascular reserve capacity. Corticocerebral blood flow was measured by hydrogen polarography during hypercapnia and acetazolamide stimuli in conscious rabbits. The measurements were repeated in the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME) and indomethacin as nitric oxide synthase (NOS) and cyclooxygenase inhibitors. The effects of nitroglycerin and isosorbide-5-nitrate were also tested. L-NAME completely, while indomethacin markedly inhibited the hypercapnic corticocerebral blood flow response. Nitroglycerin and isosorbide-5-nitrate significantly attenuated hypercapnia elicited corticocerebral blood flow increase. The different treatments reduced only moderately the acetazolamide-induced corticocerebral blood flow response. These results lend support to the hypothesis that antithrombotic and antiinflammatory medication (cyclooxygenase inhibitors) and nitrovasodilator treatments could interfere with the measurement of cerebrovascular reactivity resulting in underestimation of the cerebrovascular reserve capacity in patients taking these drugs.
Acetazolamide shows a very poor compression ability and tablets must usually be produced through a wet granulation process. However, the possibility to obtain pure acetazolamide for direct compression could be interesting for industrial application. With the scope to obtain a material for direct compression, three different crystallisation methods were chosen, with respect to acetazolamide solvent solubility. (a) Acetazolamide was dissolved in an ammonia solution and then spray dried. It was possible to characterise the spherical particles as a mixture of two polymorphic forms, I and II by Powder X-ray diffraction study. (b) Pure form I was obtained by slowly cooling to room temperature a boiling water solution. (c) Pure form II, the marketed form, was obtained by neutralisation of an ammonia solution. Their compression behaviour was investigated firstly by a rotary press. Whilst pure polymorphic forms I and II could not be compressed, the spray dried particles showed very good compression properties. In fact, tablets were obtained only by spray dried particles, which show very good properties under compression and the absence of capping tendency. On the other hand, it was impossible to obtain tablets from polymorphic forms I and II, whatever compression pressures were used. In order to explain their densification mechanism, a single-punch tablet machine, equipped for the measurement of the upper punch displacement in the die, was used. From calculated Heckel's parameters, it was demonstrated that the spray dried material shows a greater particle rearrangement in the initial stage of compression due to its spherical habit and minor wrinkledness of particle surface. The crystalline structure due to the presence of polymorphic forms I and II concur to lowering the intrinsic elasticity of the material. This fact avoids the risk of the rupturing the interpaticulate bonds, which are formed during the compression, concurring to the consolidation of the tablet.
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