| dc.description.abstract | Although pharmaceutical excipients are considered pharmacologically inert, some excipients in dosage forms have shown an effect on the pharmacokinetics of certain drugs. This could be due to different mechanisms such as opening of tight junctions, inhibition of efflux transporters or interactions with the drug molecules. The presence of P-gp in the different regions of the gastrointestinal tract (GIT) is an important factor that may influence the absorption of drugs. Furthermore, the regions of the gastrointestinal tract have physiological differences that may have an impact on drug absorption, which is the reason why certain drugs have a limited absorption window after oral administration.
The aim of this study was to investigate whether selected excipients, Ac-di-sol® (ADS) and Pharmacel® (PC), at different concentrations would have an effect on the transport of the model compound, Rhodamine 123 (Rho123), across excised sections of different regions from the pig gastrointestinal tract (i.e. the duodenum, proximal jejunum, medial jejunum, distal jejunum and ileum).
The apical-basolateral transport of Rho123 over a period of 2 h across the different excised pig intestinal regions was measured in the absence (control group) and presence of ADS (0.005% w/v, 0.01% w/v and 0.02% w/v) and PC (0.015% w/v, 0.03% w/v and 0.06% w/v) respectively, using the Sweetana-Grass diffusion chamber technique. All the test solutions were prepared in Krebs-Ringer bicarbonate (KRB) buffer. Samples of 200 μl were withdrawn from the acceptor chamber at 20 min intervals for analysis by means of a flourometric analysis method.
Statistically significant (p < 0.05) differences were obtained in the transport of Rho123 for the different concentrations of the selected excipients in the duodenum, medial jejunum and ileum. Although enhanced transport of Rho123 was observed when applied with the selected excipients, the Rho123 transport was also reduced by certain concentrations of the excipients in some of the gastrointestinal tract regions. The reduction in the transepithelial electrical resistance (TEER) could indicate that the tight junctions opened, which explained the increase in Rho123 transport. The reduction in the transport of Rho123 could be explained by possible interactions between the excipients and the active ingredient molecules or interactions of the excipients with the intestinal tissue such as blocking of the paracellular spaces.
The results indicated that the addition of ADS and PC in certain concentrations had statistically significant effects on the intestinal transport of Rho123 across some of the regions of the gastrointestinal tract.
Farmaseutiese hulpstowwe word beskou as farmakologies inert, maar sommige hulpstowwe in doseervorms het ‘n effek op die farmakokinetika van verskeie geneesmiddels getoon. Dit kan toegeskryf word aan die verskeie meganismes wat betrokke is, soos die opening van digte aansluitings, inhibisie van effluks transporters of die interaksies met geneesmiddelmolekules. Die teenwoordigheid van P-glikoproteïen (P-gp) in die verskeie gedeeltes van die gastrointestinale kanaal is ‘n belangrike faktor wat moontlik die absorpsie van geneesmiddels kan beïnvloed. Daar is fisiologiese verskille tussen die verskillende gedeeltes van die gastrointestinale kanaal wat ‘n groot impak kan hê op geneesmiddelabsorpsie, wat dus die rede is waarom sekere geneesmiddels beperkte absorpsie toon na orale toediening.
Die doel van die studie was om die invloed van die hulpstowwe Ac-di-sol® (ADS) en Pharmacel® (PC), te ondersoek by verskillende konsentrasies op die transport van die modelgeneesmiddel Rhodamine 123 (Rho123). Uitgesnyde gedeeltes van die vark se gastrointestinale kanaal (duodenum, proksimale jejunum, mid jejunum, distale jejunum en ileum) was gebruik om die effek van die hulpstowwe op Rho123 transport te toets.
Die apikale tot basolaterale transport van Rho123 oor ‘n periode van 2 h oor die uitgesnyde weefsel van die verskillende gedeeltes van die vark se gastrointestinale kanaal was in die afwesigheid (kontrolegroep) en die teenwoordigheid van ADS (0.005% m/v, 0.01% m/v en 0.02% m/v) en PC (0.015% m/v, 0.03% m/v en 0.06% m/v) gemeet met behulp van die Sweetana-Grass diffusie-apparaat. Die toetsoplossings was voorberei in Krebs-Ringer bikarbonaatbuffer. Monsters van 200 μl was onttrek uit die ontvangerkant van die diffusiesel tydens 20 min intervalle, waarna dit geanaliseer was met behulp van ‘n fluorometriese analitiese metode.
Statisties betekenisvolle (p < 0.05) verskille was waargeneem met die transport van Rho123 in kombinasie met die hulpstowwe by verskeie konsentrasies in die duodenum, mid jejunum en ileum. Verhoogde transport, maar ook verlaging in transport van Rho123 was waargeneem in die verskillende gedeeltes van die gastrointestinale kanaal. Die afname in die transepiteel elektriese weerstand (TEEW) was ‘n moontlike aanduiding dat die digte aansluitings oopgemaak het, wat dus die verhoogde transport kan verduidelik. Die afname in die transport van Rho123 kan moontlik verduidelik word deur interaksies wat kan voorkom tussen die hulpstowwe en die aktiewe bestanddeel, asook die hulpstowwe se interaksies met die intestinale weefsel soos om die parasellulêre spasies te blokkeer.
Die resultate dui daarop dat die byvoeging van ADS en PC in sekere konsentrasies ‘n statistiese betekenisvolle effek toon op die transport van Rho123 oor sekere intestinale gedeeltes. | en_US |
