The Development of Self-nanoemulsifying Liquisolid Tablets to Improve the Dissolution of Simvastatin

Abstract

The aim of this work was to develop self-nanoemulsifying liquisolid tablets (SNELT) to enhance the dissolution profile of poorly water-soluble simvastatin. SNELT present a unique technique of incorporating self-nanoemulsifying drug delivery systems (SNEDDS) into tablets. Optimized SNEDDS containing different oils, Cremophor RH 40 (surfactant) and Transcutol HP (co-surfactant), at different ratios, were used as liquid vehicles and loaded on carrier material, microcrystalline cellulose (MCC), and coating material, Cab-o-sil H-5 (nanosize colloidal silicon dioxide) powders at different loading factors (L ) and fixed excipient ratio (R = 20). The effect of using different carrier materials, granulated mannitol, crystalline mannitol, and maltodextrin with MCC at different ratios, and different coating materials, Aeroperl 300 (granulated silicon dioxide) at different excipient ratios (R), was also emphasized. Liquisolid powders with acceptable flowability, compressibility, and tablet weight were compressed into tablets. Results revealed that powders with L = 0.2 possessed the most preferable properties to be tableted. SNELT with MCC and Cab-o-sil H-5 were able to generate nanoemulsions and to enhance the cumulative percent of drug dissolved at 60 min significantly to reach up to 90%. Furthermore, using carrier material (granulated mannitol/MCC at ratio 3:1) enabled SNELT to disperse into nanoemulsion (Z-average = 25.7 nm) and improved the dissolution profile significantly to reach 99% at 60 min. Cab-o-sil H-5 proved to be a better coating material compared to Aeroperl 300. In conclusion, developed SNELT were promising in enhancing in vitro dissolution of simvastatin and excipients highly affect SNELT's performance.

Improvement of the Dissolution Profile of Simvastatin Tablets With the Addition of Cremophor-El Using Wet Granulation Method

“…The result of the resting angel test was 26.10 α (°). This result showed that simvastatin-cremophor EL tablets meet the requirements because it has an angle of repose between 25-30° [14] Comparison of Hausner's ratio is derived from mammoth weight and real weight. The higher the Hausner's ratio, the poorer the granule flow properties.…”

Cardioprotective Efficacy of Silymarin Liquisolid in Isoproterenol Prompted Myocardial Infarction in Rats

“…The capsules containing either SM free-flowing liquisolid powder or pure SM (26,27) were placed at the bottom of the cell using a capsule sinker to avoid its floating in 500 mL medium at 37 ± 0.5°C compared to SM free drug of the same concentration. At appropriate intervals (5,10,15,20,25,30,35,40,45,50,55, 60 min), 5 mL samples were withdrawn and filtered through 0.2 μm Millipore filter and replaced with fresh medium. The samples were measured spectrophotometrically at the predetermined wavelength λ max = 285.8 nm (16).…”

“…The solubility of SM liquisolid formulae in the dissolution medium was increased in spite of the small amount of liquid vehicle, which was sufficient to increase the solubility of SM liquisolid particles by acting as a co-solvent with the dissolution medium. Consequently, the concentration gradient of SM liquisolid and its dissolution rate were increased (39,45).…”

Nanoporous Silica Entrapped Lipid-Drug Complexes for the Solubilization and Absorption Enhancement of Poorly Soluble Drugs

“…It has been used as a drug delivery system to improve the solubility and increase the bioavailability of poorly water-soluble drugs [44][45][46][47][48][49][50][51][52]. In this study, a nanoporous silica entrapped lipid-drug complex (NSC) was prepared to maximize the oral absorption of the poorly water-soluble drug, DUT.…”