Dextromethorphan Hydrobromide Drug Resin Sustained Release Suspensions

Oral sustained-release suspension (SRS) is a novel liquid prolonged-release dosage form which is a two-phase composed of sustained-release drug micro-particles and suspending medium. As a multi-units drug delivery system , it presents several advantages except for steady release rate, little stomach-empty effect on absorption, easier dosage-divided process. Currently, the most successful SRS in the market is based on ion-exchange resin technology which minimized the amount of drug leaking out.In this paper, the sustained-release suspension was made of dextromethorphan with gel-type strong acidic cationic exchange resin as carrier, the research work was composed of preparation and properties.In order to get the shorter exchange time, complete availability and higher drug-loading, the best preparation condition would be set up: length of resin bed(8cm), cross-section area (1cm2), concentration (2mg/ml) and flow rate (4ml/min) to obtain 515mg/g drug-loading.It was proved by SEM, solid-liquid contact angle and DSC test that there was no physical absorption on resin particle surface or crystallition.Sustained-release pellets were prepared by taking 4% Eurdrugit RS100, 10%PEG-400, 20%DEP, The loading formulation was optimized by orthogonal experiment and the accumulation release amount of 2hr,6hr and 10 hr as the evaluation target. Methods of improving its stabilities in water were proposed:(1)Coating drug-resin after swelling. (2)Improving property of coating film through large amount of plasticizer.Suspending ability of HPMC, MC, PVP K90. Avicel RC 591 was investigated with sedimentation volume and redispersability as indicia. It had been should showed that the use of Avicel RC 591 or carbopol 934p could form flocculated suspensions. For microcapsule, No interaction between Avicel RC 591 and sustained-release pellets while strong interaction between carbopol 93 4p and sustained-release pellets were proved by rheological flow curve. The result of stability test showed that the suspensions were stable when exposed to strong light, high temperature and low temperature.Using HPLC with UV detection to determinine DP concentration inplasma and using commercial conventional tablets as the reference, the relative bioavailability and pharmacokinetics study of DMH SRS was performed in three healthy dogs. The AUC of reference tablets (90mg) and DMH SRS (90mg) were 7988.35ng.h/ml and 7787.54 ngh/ml respectively. The Cmax and Tmax of reference tablets were 1467. 1ng/ml and 2h; the Cmax and Tmaxof DMH were 750.5ng/ml and 4h. The two formulations were bioequivalent. DMH SRS had good correlation between absorption in vivo and release in vitro.\...