Sustained release formulation of doxylamine-pyridoxine combination: a promising way to overcome nausea and vomiting of pregnancy

Background: Nausea and vomiting of pregnancy (NVP) are one of the most common complications affects up to 80% of future mothers.A phase III randomized clinical trial demonstrated the efficacy of the doxylamine-pyridoxine combination [under the trade names of Diclectin® in Canada].Doxylamine succinate-pyridoxine hydrochloride sustained release combination has been considered as a safe and welltolerated formulation by pregnant women.Due to the high prevalence of NVP in Iranian pregnant women, we aimed in this study to formulate this combination.Materials and methods: Direct compression method was used to prepare this formulation.First, tablets containing two active agents were prepared.Eudragit L100 and L10055 were used to coat the tablets.Then the coated tablets, were exposed to acidic conditions to ensure their stability in the stomach environment.All in-vitro evaluations were done.The analysis of the APIs was done using high-performance liquid chromatography coupled with ultraviolet detection, the HPLC method was developed and fully validated.Results: Based on the dissolution test and release profile, the formulation containing 3.5% croscarmellose in the core and Eudragit L100-55 as coating polymer showed optimum similarity to the famous brand.In the optimized formulation, no significant release was detected in pH equal to stomach and total release happened in the intestine pH, similarity and difference factors for pyridoxine and doxylamine were 78% and 3% ,71% and 4%, respectively.Conclusion: In this study, a comparable formulation of pyridoxine and doxylamine with famous brand was prepared for the management of NVP.