Preparation and In Vitro Release of Dual-Drug Resinates Containing Equivalent Content Dextromethorphan and Diphenhydramine

Abstract

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 50 W x 2 and x 4), and from 18 to 27% w/w for high crosslinked resin (Dowex 50 W 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 crosslinked 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.

Effect of a Pharmaceutical Cationic Exchange Resin on the Properties of Controlled Release Diphenhydramine Hydrochloride Matrices Using Methocel K4M or Ethocel 7cP as Matrix Formers

“…DPH was very soluble in water (1 g/ml), dissolving very fast (<1 min) (23). Without the resin, development into matrices using either HPMC or EC retarded in-vitro release of DPH (HPMC/0 in Fig.…”

“…In regard to ion exchange resin-based dosage forms, ions played an important role in drug release (23,28). Therefore, DPH release from matrices containing 20% resin (HPMC/20 and EC/20) were further investigated in 0.005-0.4 M KCl solutions.…”

Preparation of Codeine-Resinate and Chlorpheniramine-Resinate Sustained-Release Suspension and its Pharmacokinetic Evaluation in Beagle Dogs

“…Drug release from resinate relies on the ionic environment and should therefore be less susceptible to other conditions, such as enzyme content, at the site of absorption. Therefore, many formulation studies for peroral DDSs based on IERs have been reported recently, and IERs have imparted flexibility in designing peroral DDSs, such as complexes (Agarwal et al, 2000;Akkaramongkolporn, 2001Akkaramongkolporn, , 2006, microcapsules (Sriwongjanya & Bodmeier, 1997;Sprockel & Price, 1989;Fundueanu et al, 2005), floating systems (Atyabi et al, 1996;Kouchak & Atyabi, 2004) and liquid suspensions (Raghunathan, 1980;Sprockel & Price, 1989;Pongpaibul et al, 1990;Cuna et al, 2000).…”

Wet granulation as innovative and fast method to prepare controlled release granules based on an ion‐exchange resin

“…2 In literature different approaches have been reported to prepare oral pharmaceutical forms based on IER. Agarwal et al 3 complexed chloroquine phosphate with a polyacrylic acid ionexchange resin by the batch method to mask the bitterness of the drug.…”

“…IER have been used as an effective carriers for oral drug delivery; in fact in the digestive system, the resinate releases the bound drug on exposure to the like-charge ions present in the gastrointestinal tract, acting as an ideal system for the extended release of drugs. 2 In literature different approaches have been reported to prepare oral pharmaceutical forms based on IER. Agarwal et al 3 complexed chloroquine phosphate with a polyacrylic acid ionexchange resin by the batch method to mask the bitterness of the drug.…”