Formulation development and pharmacokinetic investigation of self-assembled hybrid niosomes for oral delivery of 17-Hydroxyprogesterone caproate

17-Hydroxyprogesterone caproate (HPC) is an approved efficacious drug for reducing the incidence of a preterm birth defect by intramuscular (I.M.) injection. Oral administration of HPC encounters challenges given by slow absorption and low bioavailability. Thus, the objective of this study was to explore the feasibility of delivering HPC through the oral route using niosomes. Niosomes were prepared with different non-ionic surfactants having permeation enhancing properties (NSPEs) in combination with Span 60 and cholesterol to form hybrid niosomes and later screened for the lead formulation by variability studies. All the formulations were characterized in terms of entrapment efficiency, particle size. Results indicated that 1:2:2 M ratio of Brij 76: cholesterol: Span 60 (N2-c) demonstrated optimal characteristics with entrapment efficiency (92.2 +/- 1.05%), particle size (62.9 +/- 0.65 nm), PDI (0.2 +/- 0.003) and zeta potential (-22.2 +/- 0.85 mV) and was chosen as the lead formulation. Ex vivo intestinal permeation study showed significantly high permeation of HPC. In vivo pharmacokinetics in rats showed an increase in oral bioavailability (AUC(0-t)) by niosomes (1.8-fold, 802.4 +/- 273.84 h*ng/mL) compared to the oral suspension and better efficacy than intramuscular injection. Overall, results showed hybrid niosomes enhanced the bioavailability of HPC by increasing the intestinal permeation, which may be a better approach to minimize side effects of administration associated with intramuscular injection.

Automated summary

The study explored the feasibility of delivering 17-hydroxyprogesterone caproate (HPC) through the oral route using hybrid niosomes. The lead formulation, N2-c, demonstrated optimal characteristics and significantly increased oral bioavailability of HPC, showing better efficacy than oral suspension and intramuscular injection. Results indicate that hybrid niosomes enhance the bioavailability of HPC by increasing intestinal permeation, potentially minimizing side effects associated with intramuscular injection.