Doxylamine Succinate

Doxylamine succinate (10 mg) and pyridoxine hydrochloride (10 mg) delayed-release combination (Diclegis) is the only medication approved by the US FDA for nausea and vomiting in pregnancy (NVP), with Pregnancy Category A status indicating no fetal risk in controlled studies. A randomized controlled trial showed significantly greater improvement in NVP symptoms with Diclectin versus placebo based on validated PUQE scores (4.8 vs. 3.9 points, P=0.006). Pyridoxine alone also demonstrates efficacy. Due to its robust safety profile, doxylamine-pyridoxine is recommended as first-line pharmacologic therapy for NVP when conservative measures fail.

Glutaraldehyde cross-linked chitosan microspheres were developed via spray-drying for sustained nasal delivery of doxylamine succinate and pyridoxine hydrochloride. Cross-linking with 0.1–1.0 mg/mL glutaraldehyde produced spherical microparticles with high drug entrapment efficiency, though loading decreased at higher glutaraldehyde concentrations. FTIR confirmed cross-linking via C=N bond formation without drug interactions. XRPD showed that both drugs became amorphous after processing. Cross-linking significantly reduced particle swelling in a concentration-dependent manner and prolonged in vitro drug release to 5 hours (non-crosslinked released fully within 3 hours).
Release followed Korsmeyer-Peppas kinetics with Fickian diffusion. Although mucoadhesion decreased with increased cross-linking, all formulations retained high mucin adsorption. These cross-linked chitosan microparticles offer a promising platform for sustained-release nasal administration of doxylamine and pyridoxine, potentially reducing dosing frequency and systemic toxicity.

Fig. 1 SEM images of non-cross-linked (A) and cross-linked chitosan microparticles (B-D). (Katsarov P.; et al. 2018)