Film-ovojnica smjese pektina, kitozana i Eudragita® RS za bimodalno oslobađanje lijeka iz peleta s teofilinom: Priprava i evaluacija

Pellets containing theophylline as a model drug and microcrystalline cellulose, in a ratio of 6:4, were prepared by extrusion-spheronization method. The pellets were coated with Eudragit® RS aqueous dispersions, containing various amounts of pectin-chitosan complex and different coating mass gains, using a fluidized-bed apparatus. Twelve formulations were developed, which differed in two factors: coating mass gain (10, 15 and 20%, m/m) and amount of pectin-chitosan complex (5, 10, 15 and 20%, m/m). Drug release studies were conducted using the USP apparatus Ι (basket) in dissolution media, mimicking the conditions pertaining in the stomach, small intestine and colon, respectively. Studies have shown that drug release rate and pattern were dependent on both two mentioned factors. Some formulations showed bimodal and burst drug release, being triggered in the colonic medium by the action of pectinolytic enzymes. In formulations with 15 or 20% (m/m) of coating mass gain and 5 or 10% (m/m) of pectin-chitosan amount, the burst drug release was eliminated and replaced by lag phase of drug release. In viewpoint of burst drug release in the colonic medium, formulations with 20% (m/m) of coating mass gain and 15 or 20% (m/m) of pectin-chitosan amount were found to be better than the other formulations. Studies on the surface SEMs of uncoated and coated pellets show that after coating, coated pellets became smoother and exposure to pectinolytic enzymes in the colonic medium may result in surface erosion.Pelete s teofilinom kao modelnim lijekom i mikrokristaliničnom celulozom u omjeru 6:4 pripravljeni su metodom ekstruzije i sferonizacije. Pelete su presvučene vodenom disperzijom Eudragita® RS koja sadrži različite količine kompleksa pektina i kitozana i različite mase ovojnice, koristeći uređaj za fluidizaciju. Pripravljeno je 12 peleta koji se razlikuju po masi ovojnice (10, 15 i 20%, m/m) i udjelu kompleksa pektina i kitozana (5, 10, 15 i 20%, m/m). Oslobađanje ljekovite tvari proučavano je u USP aparaturi Ι (s košaricama) u medijima koji odgovaraju pH probavnog sustava. Dobiveni rezultati ukazuju da brzina i način oslobađanja lijeka ovisi o oba spomenuta parametra. Iz nekih pripravaka oslobađanje je bimodalno, a posljedica je djelovanja pektinolitičkih enzima iz kolona. U pripravcima u kojima je udio ovojnice 15 ili 20% (m/m), a udio pektin-kitozana 5 ili 10% (m/m) oslobađanje je bilo polagano. Najbolji pripravci za naglo oslobađanje u pH mediju područja kolona sadržavali su 20% (m/m) ovojnice i 15 ili 20% (m/m) pektin-kitozana. Proučavanje obloženih i neobloženih peleta SEM metodom pokazuje da obložene pelete imaju glatkiju površinu, koja erodira djelovanjem pektinolitičkih enzima

Priprava i ex vivo evaluacija TEC kao promotora apsorpcije tvari u kolonu

In previous studies, it was established that chitosan and its quaternized derivatives are potent enhancers of hydrophilic compounds absorption across intestinal epithelia. The aim of this study was to evaluate the application of a new quaternized chitosan, triethyl chitosan (TEC), in pharmaceutical approaches. TEC was synthesized by a one step process via a 22 factorial design to optimize the preparation conditions. In ex vivo experiments, everted rat colon sac was used to determine the effect of TEC on the penetration of hydrophilic compounds of different molecular masses (e.g., sodium fluorescein and brilliant blue) through colonic epithelia in comparison with chitosan at pH 7.4. These studies indicated a significant increase in absorption of sodium fluorescein and brilliant blue in the presence of TEC compared to chitosan. TEC bearing positive charge is able to interact with the tight junctions of colon epithelia and hence increase the permeation of sodium fluorescein and brilliant blue through the tight junctions. This investigation has shown that triethyl chitosan could be used as a penetration enhancer for poorly absorbable compounds in the colon drug delivery system.U ranijim istraživanjima utrđeno je da su kitozan i njegovi kvartenizirani derivati snažni promotori apsorpcije hidrofilnih spojeva kroz intestinalnu sluznicu. Cilj rada bio je evaluirati novi kvartenizirani kitozan, trietil kitozan (TEC ).TEC je sintetiziran u jednom stupnju. U ex vivo eksperimentima na kolonu štakora praćen je učinak tog polimera na penetraciju hidrofilnih spojeva različitih molekulskih masa (fluorescein natrija i briljant plavila). Rezultati su uspoređivani s učinkom kitozana na pH 7,4. Primjećeno je da TEC značajno povećava apsorpciju ispitivanih tvari u odnosu na nemodificirani kitozan. TEC svojim pozitivnim nabojem dolazi u interakciju s epitelom kolona i tako povećava njegovu permeabilnost. Ispitivanja ukazuju da se trietil kitozan može upotrijebiti kao promotor penetracije za spojeve koji se slabo apsorbiraju u kolonu