Formulation and Evaluation of Novel Drug Delivery System for Doxylamine Succinate and Pyridoxine Hydrochloride
Research Abstract
ABSTRTACT
The present work is concerned with tailoring and appraisal of a novel nano-cargo;
bilosomes (BLS) dual laded with doxylamine succinate (DAS) and pyridoxine hydrochloride
(PDH), the first treatment option against gestational nausea and vomiting, for intranasal delivery.
This bifunctional horizon could surmount constraints of orally-commercialized platforms both in
dosage regimen and pharmacokinetic profile. For accomplishing this purpose, DAS/PDH-BLS
were elaborated embedding phospholipid, sodium cholate and cholesterol applying thin-film
hydration method based on Box-Behnken design. Utilizing Design-Expert® software, the effect
of formulation variables on BLS physicochemical features alongside the optimal formulation
selection were investigated. Then, the optimum DAS/PDH-BLS formulation was incorporated
into a thermally-triggered in situ gelling base. The in vivo pharmacokinetic studies were
scrutinized in rats for intranasal DAS/PDH-BLS in situ gel compared with analogous intranasal
free in situ gel and oral solution. The optimized BLS disclosed particle size of 243.23 nm, ζ
potential of -31.33 mV, entrapment efficiency of 59.18 and 41.63%, accumulative % release
within 8 h of 63.30 and 85.52% and accumulative permeated amount over 24 h of 347.92 and
195.4 µg/cm2 for DAS/PDH, respectively. Following intranasal administration of the inspected
BLS in situ gel, pharmacokinetic studies revealed a 1.64- and 2.3-fold increment in the relative
bioavailability of DAS and a 1.7- and 3.73-fold increase for PDH compared to the intranasal free
in situ gel and oral solution, respectively besides significantly extended mean residence times for
both drugs. Thus, the intranasally harnessed DAS/PDH-BLS could be deemed as a competent
hybrid nanoplatform with auspicious pharmacokinetics and tolerability traits.
Keywords: Doxylamine succinate; Pyridoxine hydrochloride; Emesis gravidarum; Intranasal
delivery; Bilosomes; Pharmacokinetics.
Research Keywords
Formulation and Evaluation of Novel Drug Delivery System for Doxylamine Succinate and Pyridoxine Hydrochloride