Physicochemical interactions between drugs and superdisintegrants

Abstract

We have evaluated the interactions between superdisintegrants and drugs with different physicochemical characteristics, which may affect the in-vivo absorption e.g. after mucosal administration. The binding of sodium salicylate, naproxen, methyl hydroxybenzoate (methylparaben), ethyl hydroxybenzoate (ethylparaben), propyl hydroxybenzoate (propylparaben), atenolol, alprenolol, diphenhydramine, verapamil, amitriptyline and cetylpyridinium chloride monohydrate (CPC) to different superdisintegrants (sodium starch glycolate (SSG), croscarmellose sodium (CCS) and crospovidone) and one unsubstituted comparator (starch) was studied spectrophotometrically. An indication of the in-vivo effect was obtained by measuring the interactions at physiological salt concentrations. SSG was investigated more thoroughly to obtain release profiles and correlation between binding and ionic strength. The results showed that the main interactions with the anionic hydrogels formed by SSG and CCS were caused by ion exchange, whereas the neutral crospovidone exhibited lipophilic interactions with the non-ionic substances. The effect of increased ionic strength was most pronounced at low salt concentrations and the ion exchange interactions were almost completely eradicated at physiological conditions. The release profile of diphenhydramine was significantly affected by the addition of salt. It was thus concluded that the choice of buffer was of great importance for in-vitro experiments with ionic drugs. At physiological salt concentrations the interactions did not appear to be strong enough to influence the in-vivo bioavailability of any of the drug molecules.

Effects of Functional Biomaterials on the Attributes of Orally Disintegrating Tablets Loaded with Furosemide Nanoparticles: In Vitro and In Vivo Evaluations

“…In contrast, the lowest IDR value (3.87 ± 0.11%) of FUR from the ODT formulations was recorded with ODT formulation F8, which was prepared by using the lowest level of both CPV (B), 2%, and thymol (A), 10%. The presence of superdisintegrants in the tablet formulations enhanced the initial dissolution rate due to the high permeability of the tablet that could be obtained [ 33 , 34 ].…”

ICH M9 Guideline in Development on Biopharmaceutics Classification System-Based Biowaivers: An Industrial Perspective from the IQ Consortium

“…with a physiologically relevant ionic strength. Further, these interactions have not been observed to produce an in vivo effect. − Other factors such as variability from the source of water due to differences in dissolved gases, ionic strength, etc. The Japanese Guideline describes a process to select the appropriate population for an in vivo BE study based on dissolution comparison . If the test and reference show a difference at pH 6.8 (between pH 3.0 and 6.8 for basic drugs) tested in the compendial buffer, the decision should be made to conduct a study in achlorhydric patients.…”

“…with a physiologically relevant ionic strength. Further, these interactions have not been observed to produce an in vivo effect. − …”