Design And Evaluation Of Prednisone Pulsatile-release Pellets

Pulsatile delivery system also referred to as Time-Controlled Release system, can release the active ingredient timely according to the time attack regularity. Pulsatile delivery system releases the active ingredient after a scheduled lag-time and is unable to maintain a constant plasma concentration,which is different to the sustained or controlled release preparations. Thereby, pulsatile delivery system can guarantee the curative effect, reduce adverse reactions and improve the patients' compliance largely.Compared to the single-unit dosage forms, multiple-unit system has a good regulatory of the release and has become the focus in the pulsatile delivery system. At present, the release curve feature of the oral multiple-unit pulsatile delivery system is mostly achieved by the functional film coatings.Prednisone is one of the adrenal cortical hormone drugs commonly used to treat rheumatoid arthritis(RA). On July 31, 2013, a new preparation formulation of prednisone(Delayed Release Tablet)was approved by FDA. The trade name is Lodotra, which became the first-line medicines for chronopharmacology of rheumatoid arthritis. The AUC of the lodotra is roughly equal to the normal preparations, and the Cmax is delayed for 4~4.5 h, which can be taken before sleep and improve the patients' compliance largely, relieve the clinical symptoms of patients with RA.In this study, prednisone was chosen as model drug to prepare p H-dependent pulse-release pellets. The pellets were prepared by Glatt bottom-spray coating apparatus. The coating materials were Eudragit? RS-100 and Eudragit? L-100. The precise and reliable method to analysis in vitro prednisone coated pellets was established using HPLC.Pellets with prednisone were prepared by using suspension liquid medicine. The properties of the drug-loaded pellets were examined by yield, particle size distribution, roundness, friability, and all of them were very good. That is to say, the drug-loaded pellets could be used for the further coating procedure.The functional film coatings were also prepared by bottom-spray coating apparatus. According to the Eudragit user manual, TEC was selected as plasticizer and Talc as anti-adhesion agent. Eudragit?RS-100 and Eudragit? L-100 were selected as the best coating materials. By investigating the factors on the drug release, the coating level and the ratio of Eudragit? RS-100 to Eudragit? L-100 were confirmed as the major factors. The central composite design-response surface methodology was introduced to optimize the coating formulation, and obtained the best optimized range.The release of prednisone coated pellets was used to analyze release mechanism. The drug release of coated pellets was confirmed to the model of Hixson-Crowell and first order. Drug release is likely to be controlled by corrosion of the film and diffusion through the water-filled cracks. Stability studies of preparation were shown that light, moisture and temperature had little effect on the release of pellets coated with Eudragit? RS-100 and Eudragit? L-100.