Reformulation of a codeine phosphate liquid controlled-release product.
BACKGROUND
Ion-exchange resins have been successfully used to create drug formulations providing controlled drug release that are easy to swallow, are sufficiently stable, and have good taste-masking characteristics. The objective of the present study was to replace the ion-exchange resin in a proven delayed release codeine preparation with a new resin able to provide the beneficial properties of the original formulations without the need for Eudragit coating to comply with modern manufacturing regulations.


METHODS
Nine cationic exchangers with different particle meshes, form, and pore structures were optimally loaded with codeine and their respective in vitro codeine release profiles were compared using the USP XXIII paddle method.


RESULTS
The most favorable release profiles were obtained with Amberlite IR 69 F and with Dowex 50 × 8-100. The former was used to prepare the formulated drug-resin complexes as it was available in a pharmaceutically pure form. Both, the cough syrup and concentrate formulations exhibited drug release profiles equivalent to the nonformulated drug-resin complex. These profiles as well as initial free codeine levels, the purity, and the identity were moreover maintained for a storage period of at least 6 months.


CONCLUSIONS
The in vitro dissolution profiles demonstrated that the use of ion exchanger is most suitable for the development of sustained release codeine formulations.
Department of Pharmaceutical Technology, Institute of Pharmaceutical Sciences, Karl-Franzens University of Graz, Graz, Austria. eva.roblegg@uni-graz.at
Eva
E
Roblegg
Peter
P
Dittrich
Krista
K
Haltmeyer
Andreas
A
Zimmer
D000996:Antitussive Agents / Q000008:administration & dosage / Q000737:chemistry*; D002411:Cation Exchange Resins / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003061:Codeine / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D004355:Drug Stability; D007474:Ion Exchange; D012117:Resins, Synthetic / Q000737:chemistry; D012995:Solubility; D013649:Taste
D000996:Antitussive Agents; D002411:Cation Exchange Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D012117:Resins, Synthetic; C046797:amberlite; D003061:Codeine