Study On Oral Pulased Release Pellet Drug Delivery System Of Diclofenac Sodium

The predominant physiological and pathological periodic variations are related to alternation between day and night (activity and rest). To fulfill the specific therapeutic needs of such diseases, which depend on circadian rhythmicity new drug delivery devices are required or anyway desirable for the time-programmed administration of the active ingredients. Because of the early morning symptoms of arthritis disease, the assumption in the evening of a dosage form by starting release the dose some hours after ingestion could be a suitable therapeutic regimen. Diclofenac sodium(DS) was chosen as a model drug.Ultraviolet spectrophotomatry method was developed for assay during the study of content and drug release. Precise and reliable HPLC method was developed for assay in vivo.The core pellets of were prepared by extrusion-spheronization. Pulsed release pellets (PRP) of DS were prepared by using low-substituted hydroxyprolcellulose (L-HPC)as inner swelling layer and aqueous ethycellulose dispersion-Surelease as outer controlled membrane on a mini-fluidized bed spray coater. The effect of factors on the release of PRP was investigated. The results showed that the release behavior was influenced by the types and the amount of the swelling layer, the size of pellets and the amount of the controlled layer. For the pellets with the core pellet between 20 and 26 mesh , a 11% L-HPC coating level and 14% Surelease coating level, the release in vitro was initiated after a lag time of 4h in water or 3h in 0.1%SDS and the accumulative percent released more than 80% within the following 1.5h, which showed better pulsed release when compared to core pellets.The scintigraphic trace evaluation demonstrated that the DS-PRP coulddisintegrate at intestine and release completely from jejunum to ileum. It would be reasonable and suitable for the DS-PRP with 3~4h lag time in vivo after oral administration.The behaviour in vivo of the pellets has been evaluated in eight volunteer after a single oral administration of core pellets or pulsed release pellets. The result demonstrated that the pulsed pellets could be released after 2.96h lag time and that the relative bioavailability would be more than 80%. Obvious correlation existed between absorption fraction in vivo and the release percentage in vitro.A new drug delivery system useful to reduce the early morning symptom of arthritis was prepared.