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V sklopu magistrske naloge smo opazovali in vrednotili sproščanje natrijevega diklofenakata (Na-DF) iz ogrodnih tablet v medijih z različnimi viskoznostmi ter pri različnih hidrodinamskih obremenitvah. Kot medij za sproščanje natrijevega diklofenakata smo uporabili 4x redčen Mcllvainov pufer s pH vrednostima 5 ali 6,8, v katerega smo za povečanje viskoznosti dodali hidroksipropilmetilcelulozo (HPMC). HPMC smo izbrali na podlagi pregleda člankov, v katerih so ponazarjali viskoznost želodčne vsebine po jedi z dodatkom HPMC. Polimer smo v medije dodali v koncentracijah od 0% (m/V) pa do 1,4% (m/V). Poleg HPMC smo pri nekaterih poskusih v medij namesto HPMC dodali natrijev klorid (NaCl) v različnih koncentracijah. Teste sproščanja smo izvedli na napravi II pri različnih hitrostih vrtenja vesel ter v pretočnem sistemu s steklenimi kroglicami, s čimer smo spreminjali hidrodinamsko oziroma mehansko obremenitev na tablete. Koncentracijo sproščenega Na-DF iz ogrodnih tablet smo izračunali s pomočjo umeritvenih premic iz absorbanc, ki smo jih izmerili z UV-VIS spektrofotometrom. Med poskusi sproščanja smo opazovali tudi čase razpadnosti tablet, prav tako smo razpadnost tablet testirali tudi na napravi za testiranje razpadnosti. Iz rezultatov poskusov sproščanja smo ugotovili, da ima povečana viskoznost medija vpliv na sproščanje, saj je bilo sproščanje Na-DF v viskoznejših medijih počasnejše, tako v medijih s pH 6,8, kot tudi v medijih s pH 5. Tudi tablete so v poskusih sproščanja in v testu razpadnosti na napravi za testiranje razpadnosti v bolj viskoznih medijih razpadle počasneje. Pri primerjavi sproščanja v medijih s pH 5 in pH 6,8 smo ugotovili, da je v mediju s pH 5 sproščanje pri določenih koncentracijah HPMC potekalo počasneje kot pri pH 6,8, prav tako so bili tudi časi razpadnosti tablet daljši v mediju s pH 5. Iz rezultatov sproščanja v mediju z NaCl smo ugotovili, da je upočasnitev sproščanja v medijih z NaCl pri določenih koncentracijah podobna upočasnitvi v medijih s HPMC. Pri poskusih, v katerih smo proučevali vpliv hidrodinamskih obremenitev na sproščanje Na-DF v viskoznih medijih, smo ugotovili, da so pri večji mehanski obremenitvi razlike v sproščanju Na-DF manjše med različno viskoznimi mediji. Prav tako smo ugotovili, da so pri večji viskoznosti medijev profili sproščanja pri različnih hidrodinamskih obremenitvah med seboj bolj različni, kot pri manjši viskoznosti medijev. In this thesis, we observed and evaluated the release of diclofenac sodium (Na-DF) from matrix tablets in media with different viscosities and at different hydrodynamic conditions. We used 4x diluted Mcllvaine buffer pH 5 and pH 6.8 as media for diclofenac sodium release, to which a hydroxypropyl methylcellulose (HPMC) was added to increase medium viscosity. HPMC was selected based on a literature review where the viscosity of gastric contents after a meal was simulated by adding HPMC into the medium. In our experiments the polymer was added to the media in concentrations from 0% (w/V) to 1.4% (w/V). Instead of HPMC, we also added different concentrations of sodium chloride (NaCl) in some media. Dissolution tests were performed on an apparatus II at different speeds of paddle rotations and in a glass-bead flow-through system, thereby we assessed the effect of distinctive hydrodynamic or mechanical load on the tablets. The concentration of diclofenac sodium released from matrix tablets was calculated from absorbances measured with a UV-VIS spectrophotometer. During the dissolution experiments, we also observed the disintegration times of the tablet. Additionally, we also tested the disintegration time of the tablet on the disintegration tester apparatus. From the dissolution experiments, we observed that the increased viscosity of the media impacts on the release, as Na-DF release was slower in more viscous media, at both pH medium pH values 6.8 and 5. Also, the tablets disintegrated more slowly in viscous media in dissolution tests as well as in a test performed on the disintegration tester apparatus. In comparison to the release of Na-DF in the media with pH 5 and pH 6.8, we observed that the release in media with pH 5 at certain concentrations HPMC was slower than at pH 6.8. Additionally, the tablet disintegration times were also slower at pH 5. From dissolution tests in media with NaCl, we observed that at particular NaCl concentrations, Na-DF release was slowed similarly as in media with added HPMC. In experiments where we studied the influence of hydrodynamic loads on Na-DF release in viscous media, the differences in Na-DF release in media with different viscosities were smaller at higher mechanical loads. We also observed that at higher media viscosities, the differences between the release profiles at different hydrodynamic loads are greater than at lower media viscosities. |
