Preparation and evaluation of colon targeted drug delivery systems for albendazole using kneading, extrusion and compaction technology

Albendazole is an orally administered broad-spectrum benzimidazole anthelmintic used against helminthiasis, hydatid cyst disease and neurocysticercosis. The objectives of this investigation are to develop a sustained release drug delivery system for albendazole, and to target its delivery to colon. Albendazole matrix tablets containing varying proportions of single and binary blends of four polymers; polyacrylic acid (carbopol 971), ethylcellulose (Etcell), eudragit L100-55 (EUD), and sodium carboxymethyl cellulose (CMC) were prepared by a modified wet granulation technique of kneading, extrusion and compaction. In vitro release profiles of albendazole was sequentially determined in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) without enzymes and in rat caecal content medium (RCCM) at 37℃. The in vitro drug release from matrix tablets containing CMC and Etcell as single polymers showed initial burst effect in the first 2 h (>20% and 50% respectively), followed by a slow release in SIE However, matrix tablets containing polymer blends showed that no appreciable drug release occurred up to 5 h. Drug release from tablets containing polymer blends in the dissolution medium containing rat caecal material suddenly increased to ≥30% after 5 h (RCCM), and reaching up to 90% in 24 h. Albendazole matrix tablets containing carbopol 971, Etcell, EUD, and CMC as single polymers and as blends were formulated for oral use. Drug release from the tablet matrices containing carbopol alone, binary blends of carbopol/Etcell, and CMC/EUD were found to be very slow and dependent on polymer concentration. Matrix tablets containing blends of these polymers formulated using kneading, extrusion and compaction technique could provide sustained drug release and can be utilized in the colonic delivery of albendazole.

Objective　To test the immunosuppressive effect of cyclosporine (Cs) in a polymer placed in the anterior chamber of corneal allograft recipients. Methods　Wistar inbred rats with vascularized corneas were recipients of corneal allografts from Sprague-Dawley donor rats. Rats underwent penetrating keratoplasty and were divided randomly into four groups: untreated control animals (UCA); Cs-polymer anterior chamber recipients (CPA); co-polymer subconjunctival recipients (CPS); and Cs-olive oil drop recipients (COO). Grafts were examined by slit lamp every 3 days and clinical conditions were scored. Cs concentration in the aqueous humor was assayed at 1, 2, and 4 weeks. At 1, 2 and 4 weeks after transplantation, the operated eyes were collected for histopathological evaluation of the grafts.Results　The median survival time of the allografts was 8.2±1.48 days for the UCA group, 11.4±2.50 days for the CPS group, and 17.0±2.00 days for the CPA group. There was a statistically significant difference (P<0.05) between survival time of the allografts in the animals of the CPA group compared to the other groups of graft recipients. Significantly higher concentrations of Cs were found in the eyes given an anterior chamber implant of Cs-polymer, compared to other treatment groups or untreated rats. A transient inflammatory response in the anterior chamber was observed in the CPA group. Conclusions　Cs-polymer placed in the anterior chamber significantly prolongs corneal allograft survival time in a high risk corneal graft rejection model. This intraocular delivery system may be a valuable adjunct for the suppression of immune graft rejection.