Variation in moisture content of the capsule shells either due to the change of storage conditions or the moisture transfer between the capsule shell and its contents may lead to undesired physical properties, such as capsule brittleness and stickiness. DMP 504, a developmental bile-acid sequestrant, is a strongly basic anion-exchange polymer which contains randomly distributed primary, secondary, tertiary, and quaternary amine groups in their hydrochoride salt form. The alkylammonium groups which comprise this polymer form a random network containing a high level of branching and a low level of cross-linking. DMP 504 is very hygroscopic and has a tendency to gain or lose moisture with ease. The transfer of moisture from the capsule shell to DMP 504 powder contained in a hard gelatin capsule can be expected, and if a low water content of the capsule shell is achieved, the capsules become brittle and fracture easily. The sorption isotherm for DMP 504 was generated by storing the drug substance under various relative humidity conditions. After equilibrium, the moisture contents for the samples of individual isotherm points were measured by thermogravimetric analyses. This report applies the sorption-desorption moisture transfer (SDMT) model to predict the equilibrium relative humidity in a system containing DMP 504 in hard gelatin capsules and to establish target loss on drying values for DMP 504 and the capsule shell. Application of this SDMT model resulted in finding a solution to the brittleness problem. The moisture levels of capsule shells and contents for two formulations in a 12-month stability program are also reported here. Results of this study further demonstrate that the SDMT model can be used as a tool to guide the formulator to select optimal initial moisture contents for the empty capsule shell and the formulation to avoid the incidence of brittle capsule problems.