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

High level of gentamicin resistance (HLGR) among enterococcus strains isolated from clinical specimens

SummaryBackgroundEnterococci are pathogens that can cause nosocomial infections and acquire resistance properties via several molecular mechanisms. The aac (6′)Ie-aph(2″)Ia gene plays a significant role in the emergence of high-level gentamicin-resistant (HLGR) strains. The screening of resistant strains and the provision of appropriate antibiotic therapy can decide the outcome of serious nosocomial infections.MethodsIn the present study, 142 enterococci were isolated from patients, and the species were identified using standard methods. An antimicrobial susceptibility test was performed using the disc diffusion method, and the minimum inhibition concentration (MIC) of gentamicin was determined according to the broth micro-dilution method. Additionally, PCR was utilized to detect the aac(6′)Ie-aph(2″)Ia gene, the presence of which was confirmed by digestion with Sca1 and sequencing.ResultsOf the 142 isolates, 62 (43.7%) were found to exhibit the HLGR phenotype. All except one of the HLGR isolates contained the aac(6′)Ie-aph(2″)Ia gene. The prevalence of resistance to other antibiotics and multi-drug resistance (MDR) was higher among the HLGR isolates compared to the non-HLGR isolates.ConclusionsOur results indicate that high prevalence rates of MDR and HLGR enterococci are an important problem associated with medical treatment. Furthermore, the presence of the aac(6′)Ie-aph(2″)Ia gene was shown to correspond to the presence of the HLGR phenotype among enterococci