Abstract
The short term stability of efavirenz-loaded solid lipid nanoparticle and nanostructured lipid carrier dispersions was investigated. Hot High Pressure Homogenization with the capability for scale up production was successfully used to manufacture the nanocarriers without the use of toxic organic solvents for the first time. Glyceryl monostearate and Transcutol® HP were used as the solid and liquid lipids. Tween® 80 was used to stabilize the lipid nanocarriers. A Box-Behnken Design was used to identify the optimum operating and production conditions viz., 1100 bar for 3 cycles for the solid lipid nanoparticles and 1500 bar for 5 cycles for nanostructured lipid carriers. The optimized nanocarriers were predicted to exhibit 10% efavirenz loading with 3% and 4% Tween® 80 for solid lipid nanoparticles and nanostructured lipid carriers, respectively. Characterization of the optimized solid lipid nanoparticle and nanostructured lipid carrier formulations in relation to shape, surface morphology, polymorphism, crystallinity and compatibility revealed stable formulations with particle sizes in the nanometer range had been produced. The nanocarriers had excellent efavirenz loading with the encapsulation efficiency >90%. The optimized nanocarriers exhibited biphasic in vitro release patterns with an initial burst release during the initial 0–3 h followed by sustained release over a 24 h period The colloidal systems showed excellent stability in terms of Zeta potential, particle size, polydispersity index and encapsulation efficiency when stored for 8 weeks at 25 °C/60% RH in comparison to when stored at 40 °C/75% RH. The formulations manufactured using the optimized conditions and composition proved to be physically stable as aqueous dispersions.
Highlights
Pharmaceutically-relevant colloidal systems consisting of small molecules, with sizes typically ranging between 10 nm and 1 μm, are being used to achieve different therapeutic outcomes
The optimum operating production conditions were established by Box-Behnken Design (BBD) through numerical optimization viz., 1100 bar for 3 cycles for the solid lipid nanoparticles (SLN) and 1500 bar for 5 cycles for nanostructured lipid carriers (NLC)
A hot high pressure homogenization method was successfully used for the manufacture of efavirenz-loaded solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC)
Summary
Pharmaceutically-relevant colloidal systems consisting of small molecules, with sizes typically ranging between 10 nm and 1 μm, are being used to achieve different therapeutic outcomes. No reports in which a comparison of formulation and stability of EFV-loaded SLN and NLC manufactured using Hot High Pressure Homogenization (HHPH) have been published This technique avoids the use of toxic organic solvents and can be readily adapted for scale up production. EFV levels in the CNS are generally high due to “dose-dumping” that is associated with the use of conventional dosage forms and can lead to severe psychiatric side effects Innovative lipid carriers such SLN and NLC have the potential to sustain and modulate release of EFV into brain tissues and may reduce or limit the incidence of adverse psychiatric effects. The LC and EE of the SLN and NLC for EFV was investigated using a validated reversed-phase high performance liquid chromatography (RP-HPLC) method [39] following filtration of the aqueous dispersion using Centrisart® filter tubes (Satorius AG, Goettingen, Germany).
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