Preparation and in vitro release of dual-drug resinates containing equivalent content dextromethorphan and diphenhydramine

The dual-drug resinate containing equivalent content of dextromethorphan hydrobromide (DTM) and diphenhydramine hydrochloride (DPH) was developed and characterized. To achieve this specific resinate, a procedure of simultaneous dual-drug loading using loading solutions composed of different proportions of DTM and DPH was performed and a dual-drug loading diagram was constructed to determine the equivalent drug loading solution (ELS) and also the estimated equivalent drug content (EQC). The effects of resin crosslinkage, overall drug concentration of the loading solution, and temperature during drug loading on the values of ELS and EQC were assessed. The increased overall drug concentration from 0.25 to 1.0% w/v elevated the EQC values from 18 to 35% w/w for low crosslinked resins (Dowex 50W x 2 and x 4), and from 18 to 27% w/w for high crosslinked resin (Dowex 50W x 8). It also changed the values of ELS from 0.50 to 0.48 for the low crosslinked resins, and 0.50 to 0.55 for the high crosslinked resin. For the high crosshnked resin, the applied heat from 35 to 65 degrees C further increased the values of EQC from 27 to 32% w/w, and changed the values of ELS in the reverse direction from 0.55 to 0.48. However, the heat did not exert significant effects on the values of EQC and ELS for the low crosslinked resins. Different batches of dual-drug resinates prepared from the determined ELS provided the resultant resinates with equivalent contents of DTM and DPH which were very close to the estimated EQC. The drug release from the resinates was performed in 0.05, 0.1, 0.2, and 0.4 N of KCl solutions. The increased ionic strength generally accelerated the release of both drugs except for 0.4 N KCl solution in which the drug release from the resinates of high crosslinkage was decreased. The congestion on the outward movement of drugs through the high crosslinked matrix might cause the delay of drug release. In conclusion, the release study demonstrated that the dual-drug resinate using a suitable crosslinked resin could be used for extended delivery of two combined drugs with the equivalent therapeutic dose.