Initial characterization of D-cycloserine for future formulation development for anxiety disorders

Abstract

The purpose of this study is to characterize D-cycloserine (DCS) physicochemical properties to facilitate future formulation development of DCS for anxiety disorders. A stability-indicating HPLC assay method for the quantitation of DCS was developed and calibrated to be used for this study. The partition coefficient was determined and compared with the predicted value. The solution stability of DCS was studied under various pH (2.0-11.5) and ionic strengths of 10 and 20 mM at physiological temperature of 37°C. The 250 mg capsule was compounded to the nominal strength of 50 mg used for anxiety disorders. These capsules were then put under stability. The in vitro dissolution was also carried out at 37°C as per the United States Pharmacopeia (USP) guidelines. The partition coefficient value (Kp) determined for the DCS was log Kp = -2.89 ± 0.06 (n = 6). The pH-solution stability profile shows that DCS has maximum stability under alkaline conditions. The maximum rate of degradation was seen at pH of 4.7. The mean percent recovery of DCS from the capsules compounded to strength of 50 mg was 100.3 ± 1.4. The stability study of the reformulated capsules concluded that reformulated DCS is stable for at least one year at room temperature. The in vitro dissolution illustrates that all the DCS is released from the capsules in 10 min. The present characterization of DCS study will serve as guidance for the future directions regarding the reformulation of DCS in order to be used in anxiety disorders.