Chemical engineering of a lipid nano-scaffold for the solubility enhancement of an antihyperlipidaemic drug, simvastatin; preparation, optimization, physicochemical characterization and pharmacodynamic study

Abstract

This project was designed to extract anti-hyperlipidaemic activity of simvastatin for the longer duration of time and the solubility enhancement of this BCS class II drug was also sought by preparing nanostructured lipid carrier (NLC). The method for NLC preparation involved melt-emulsification followed by ultrasonication. The developed formulation was optimized by 3-level, 3-factor Box-Behnken design. The independent variables were % lipid mixture, % surfactant and sonication time (minutes). The responses selected were particle size, PDI and entrapment efficiency. The optimized formulation had particle size 114.62 ± 5.65, PDI 0.210 ± 0.034 and entrapment efficiency 85.20 ± 7.98%. The optimized formulation was further characterized by TEM and SEM. Spherical shape and nano size distribution of the optimized formulation were confirmed by SEM and TEM, respectively. The DSC of optimized formulation hints for the loss of crystalline nature of drug whereas the FT-IR spectra reveal that there is no interaction between drug and excipients when incorporated in NLC. The drug release from the NLC was biphasic (burst release was followed by sustained release). The kinetic of drug release followed Fickian diffusion with Korsmeyer-Peppas model. When the antihyperlipidaemic activity of SMV-NLC was compared with SMVsuspension, it was found that SMV-NLC significantly decreased the total cholesterol and triglyceride level by 2.77 and threefolds, respectively.

Validated green spectroscopic manipulation of area under the curve (AUC) for estimation of Simvastatin: Application to nano-structured lipid carriers and niosomal systems

“…Quadrant "d" was left blank as the waste generated from the method will exceed 50g. The same assessment was observed for the reported method of NLC 47 . On the other hand, the reported method for niosomes 48 used 49% formic acid as a mobile phase; and that's why quadrant "c" was also left blank.…”

“…Therefore, the proposed AUCCM method was compared to two reported chromatographic method in terms of greenness assesment tools. The first method was reported for the analysis of NLC of SIM using a stationary phase C18 coulumn and a mobile phase at a mixture of acetonitrile and 0.1% phosphoric acid (85:15, v/v) at pH 4 at flow rate of 1.5 mL/min and UV detection at 238 nm 47 . The second method was reported for the analysis of niosomal system of SIM using a stationary phase C18 coulumn and a mobile phase of acetonitrile and formic acid 3 mM (51:49 v/v) at flow rate of 1 mL/min and UV detection at 238 nm 48 .…”

Assessment of implantable drug delivery technology: poly (3-hydroxybutyrate) / polypropylene glycol films containing simvastatin

“…Thus, the development of polymeric devices containing Simv. contributes to improving the bioavailability of this drug [38][39][40]. Moreover, statins are capable of promoting osteogenesis and contribute to bone fracture consolidation [41,42].…”

Development and Evaluation of Rizatriptan Benzoate-loaded Nanostructured Lipid Carriers for the Treatment of Migraine

“…1 gm of solid lipid (which was heated at 5°C above their melting point) and solubility was checked by adding RB in increments of 1mg until it failed to dissolve. The experiment was conducted in triplicate [7].…”