Effects of polymeric surfactants with low HLB values on drug and excipient release from self-emulsifying drug delivery systems

Abstract

In this study, we evaluated the effects of polymeric surfactants with low hydrophile–lipophile balance values (PSLH) lauryl PEG-8 dimethicone (LP8D) and Pluronic L121 (P121) on drug and excipient release from self-emulsifying drug delivery systems (SEDDS). Valsartan (logKOW 1.5) was used as a model drug, whereas oleic acid (logKOW 7.64) was loaded in SEDDS as a model excipient. Diffusion of valsartan from oil phase to aqueous phase was significantly reduced when adding 5 % LP8D or P121 into the oil phase consisting of isopropyl myristate:Capmul MCM 4:1 m/m. Drug diffusion reached plateau phases after 72 h compared to 3 h in case of the non-PSLH oil phase. Adding 10 % either LP8D or P121 further decreased drug diffusion to aqueous phase. P121 showed a more controlled drug diffusion profile than LP8D at the same loading level. PSLH were loaded in SEDDS preconcentrates at different concentrations in the ranges of 0–15 % LP8D and 0–10 % P121 m/m to yield emulsion with size ∼200 nm and polydispersity index <0.3 upon dilution. The burst release phases from PSLH loaded SEDDS were suppressed and better controlled with higher PSLH loading ratios. The presence of PSLH in the oil phase could increase intermolecular interactions such as hydrogen bonding and London dispersion forces between PSLH and drug or excipient molecules as shown by FTIR difference spectra. Furthermore, PSLH can accumulate at the oil-water interfacial barrier and increase the activation energy level for solute molecules diffusion, i.e. adding 10 % LP8D led to a 3-fold increase in activation energy for oleic acid. Therefore, incorporation of PSLH in SEDDS formulation could be a potential approach to reduce drug diffusion coefficients, enhance drug affinity to oil phase and control drug release rate.