The interaction between polyelectrolytes (PE) and oppositely charged drugs (D) results in complexes (PE-D) that can be exploited in controlled release drug delivery systems. The aim of this work is to better understand the relevance of some preparative parameters such as moisture content and particle size on the performance of two PE-D complexes to be used in oral controlled release tablets. PE-D complexes containing diltiazem HCL (DTZ) or metoprolol tartrate (MTP) and lambda carrageenan were obtained at two particle size levels (<45 microm and 75-105 microm), maintained at different values of relative humidity (RH) (11, 52, 75, and 93%), and compressed. The tablets were characterized for porosity, hardness, moisture content, and contact angle. Drug release profiles were fitted to the Weibull equation, and a factorial design was used to understand the relevance of particle size and RH% on release rate as a function of medium pH. The results indicated that the hydrophobic character of the complex between PE and D depended on the drug and in the present case was more pronounced for DTZ than for MTP. This in turn affected the possible release mechanism and therefore the importance of particle size and RH%.