Development of protocol for screening the formulation components and the assessment of common quality problems of...

The present study investigates the screening of the formulation components as well as evaluates the quality issues of the nanostructured lipid carriers (NLCs) for the anticancer agent, CPT-11. The stepwise screening of the components for the preparation of NLCs requires the selection of liquid lipid or oil, based on the relative solubility of CPT-11 in different oils. Maximum solubility of the CPT-11 was found in capmul MCM-C8 (81±0.5 mg/ml). Hence, it was selected as the liquid lipid for the development of NLCs. Solid lipids gelucire 39/1, glyceryl mono stearate (GSM) and compritol ATO 888 were observed to have good affinity for the drug on systematic screening of different solid lipids. However, gelucire 39/1 and GSM were found to have lower physical compatibility (miscibility) with capmul MCM C-8. Hence, compritol ATO 888 was selected as the solid lipid phase for the preparation of NLCs. Ratio of liquid lipid (oil) to solid lipid was optimized with the intention of maximizing the oil concentration (as oil was found to have higher solubility of drug) as well as producing a lipid mix with sufficient melting point to maintain solid state. The liquid-solid lipid mixture in the ratio up to 30:70 was observed to have sufficient melting point (52.48±1.2 °C). Pluronic F-68 was selected as the main surfactant for the preparation of NLCs because of its good emulsification efficacy for the solid lipid liquid mix. The optimized formulation was also evaluated for the different quality issues. PXRD data revealed that the characteristic peaks of the compritol were present in the NLC samples and there was no appreciable polymorphic change when the formulation was stored for 6 months. Electron microscopic and DLS studies proved the absence of different colloidal species. Thermal analysis by DSC revealed that the lipid particles maintained sufficiently good melting point even after nanosizing. Absence of gelation on multiple syringing and resilience for the stress provided by autoclaving further established the quality of the developed NLCs.