Investigation of formulation variables and excipient interaction on the production of niosomes

Abstract

The aim of this study was to investigate the effects of formulation and process variables on the properties of niosomes formed from Span 40 as nonionic surfactant. A variety of formulations encapsulating Paclitaxel, a hydrophobic model drug, were prepared using different dicetyl phosphate (DCP) and Span 40-cholesterol (1:1) amounts. Formulations were optimized by multiple regression analysis to evaluate the changes on niosome characteristics such as entrapment efficiency, particle size, polydispersity index, zeta potential and in vitro drug release. Multiple regression analysis revealed that as Span 40-cholesterol amounts in the formulations were increased, zeta potential and percent of drug released at 24th hour were decreased. Besides, DCP was found to be effective on increasing niosome size. As a process variable, the effect of sonication was observed and findings revealed an irreversible size reduction on Span 40 niosomes after probe sonication. Monodisperse small sized (133 ± 6.01 nm) Span 40 niosomes entrapping 98.2% of Paclitaxel with a weight percentage of 3.64% were successfully prepared. The drug-excipient interactions in niosomes were observed by differential scanning calorimetry and X-ray powder diffraction analysis. Both techniques suggest the conversion of PCTs' crystal structure to amorphous form. The thermal analyses demonstrate the high interaction between drug and surfactant that explains high entrapment efficiency. After 3-month storage, niosomes preserved their stability in terms of drug amount and particle size. Overall, this study showed that Span 40 niosomes with desired properties can be prepared by changing the content and production variables.

Fig. 1

Response surface plots showing the effects of different amounts of Span 40, DCP, and cholesterol on following niosome properties: a zeta potential, b encapsulation efficiency, c % drug release at 24 h, d particle size, and e polydispersity index (DCP dicetyl phosphate, EE encapsulation efficiency)

Fig. 2

PCT release from FS1–FS9 niosomes prepared with different dicetyl phosphate and Paclitaxel: (Span 40-cholesterol) amounts (refer to Table I for formulation details)

Fig. 3

Effect of the sonication time on particle size of niosomes and changes on niosome sizes 24 h after probe sonication

Fig. 4

Particle size distribution of FS8 niosomes after probe sonication

Fig. 5

Transmission electron microscopy (TEM) micrographs of P6 niosomes

Fig. 6

X-ray powder diffraction (XRPD) diffractograms of a physical mixture of DCP + cholesterol + Span 40, b PCT, c physical mixture of DCP  +cholesterol + Span 40 + PCT, d P6 niosomes without PCT, e P6 niosomes (DCP dicetyl phosphate, PCT Paclitaxel)

Fig. 7

Differential scanning calorimetry (DSC) thermograms of a PCT, b DCP, c cholesterol, d Span 40, e physical mixture of DCP + cholesterol + Span 40 + PCT, f P6 niosomes (DCP dicetyl phosphate, PCT Paclitaxel)