In vitro / In vivo correlation for erythropoietin implantable dosage forms applied in treatment of anemia associated with renal failure induced in rabbits

Abstract

This work involved the fabrication, optimization, and evaluation in vitro and in vivo of Erythropoietin (EPO) from implantable film dosage forms prepared by two different methods (casting method and more modern method in industrial pharmacy preparation which is 3D printing techniques) that may be a usefully used for treatment of anemia related with chronic renal failure for six months upon single implantation under skin and can be adjusted according to personal need. Through this study, two types of implantable films were prepared; one of these films was prepared by 3D printing film, and the other films prepared by casting method using PVA/glycerol base film. Each film contains a certain amount of our previously prepared sustained-release EPO (equivalent to 100,000 IU) as well as pure EPO powder (10,000 IU). In vitro evaluation was performed and in-vivo evaluation for both films in comparison to the routinely applied treatment. Both films successfully passed in-vitro evaluation and the folding endurance of the casting films was 66 times more than 3D printing films. In addition, both films gave biphasic drug release where 10% of EPO was released within the first week and continued for 6 months to reach 98.73% for casting film and 88.79% for 3D printing film. The in-vivo evaluation of both types of film showed normal Hb-level within the first two weeks of implantation associated with correction of EPO level to the normal level in both films and both Hb/EPO levels continued normally for 6 months in comparison to repeated Sc injection of EPO which showed normal Hb level with high EPO (much more than normal) that may increase happening of cardiac disorders. This work succeeded in preparing implantable films of EPO that can adjust both Hb and EPO to the normal level and continued normally for six months upon a single simple implantation under the skin with good links between in-vitro as well as in vivo evaluation. Such preparation might be used as alternative to the routinely applied repeated subcutaneous injection to improve patient compliance with less possibility to produce tangible side effects.