title: Preparation and in vitro release of dual-drug resinate complexes containing codeine and chlorpheniramine.
abstract: OBJECTIVE
  To develop the dual-drug resinate complexes containing codeine and chlorpheniramine with a novel batch processing, characterize the dual-drug resinate complexes, and study its drug release behavior in vitro.
  
  
  METHODS
  A procedure of simultaneous dual-drug loading using combination solutions composed of different proportions of codeine phosphate and chlorpheniramine maleate was performed to achieve the specific resinate, and the dual-drug loading content was determined by high-performance liquid chromatography method. The dual-drug resinate complexes were characterized by a scanning electron microscope, and the formation mechanisms were confirmed with X-ray diffraction analyses and differential scanning calorimetric analyses. The release behavior of the two drugs from the dual-drug resinate complexes in vitro was studied in the media simulating in vivo environments (simulated gastric fluid: pH = 1.2 HCl, simulated in vivo ionic strength: 0.15 M NaCl, and simulated intestinal fluid: pH = 6.8 buffer solution containing KH2PO4-NaOH).
  
  
  RESULTS
  Scanning electron microscopic analyses proved that the dual-drug resinate complexes had the same appearance and characters as the initiative ion exchange resins (IERs). Via X-ray diffraction and differential scanning calorimetric analyses, it is found that the two drugs in dual-drug resinate complexes were combined with IERs by chemical bond. The drug-resinate complex, like IER, was in amorphous state. More than 90% of codeine phosphate was released in 15 minutes in three different media, whereas little amount of chlorpheniramine maleate was released in all the release time in the medium pH = 1.2 HCl, and the release equilibrium time was about 5 minutes, only 40% was released in the medium 0.15 M NaCl, and the equilibrium time was 40 minutes, and about 90% was released in the medium pH = 6.8 KH2PO4-NaOH. The increased ionic strength generally accelerated the release of the two drugs from the dual-drug resinate complexes.
  
  
  CONCLUSIONS
  The dual-drug resinate complexes were formed through the reaction between the drugs and the IERs by chemical bond. The release behavior of the drug from the dual-drug resinate complexes in vitro was mainly correlated with the drug molecular structure, the eluting ionic strength, composition, and ionic strength of the release media. The novel dual-drug resinate complexes could be used to deliver two drugs in one therapeutic dose.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, PR China. zenghxg@yahoo.com
authors.forename: Huan-Xiang
authors.initials: HX
authors.lastname: Zeng
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Jia
authors.forename: Su-Jing
authors.initials: SJ
authors.lastname: Lin
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
authors.forename: Wei-San
authors.initials: WS
authors.lastname: Pan
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D002744:Chlorpheniramine / Q000008:administration & dosage* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003061:Codeine / Q000008:administration & dosage* / Q000737:chemistry; D004338:Drug Combinations; D005750:Gastric Juice / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000378:metabolism; D007475:Ion Exchange Resins; D008855:Microscopy, Electron, Scanning; D009994:Osmolar Concentration; D013997:Time Factors; D014961:X-Ray Diffraction
chemical_list: D000701:Analgesics, Opioid; D004338:Drug Combinations; D006634:Histamine H1 Antagonists; D007475:Ion Exchange Resins; D002744:Chlorpheniramine; D003061:Codeine