Design and optimization of self-nanoemulsifying drug delivery systems of simvastatin aiming dissolution enhancement

Abstract

The aim of this work was to improve the in vitro dissolution of simvastatin through development of selfnanoemulsifying tablets. Various modified oils, surfactant and co-surfactant mixtures were used to prepare different self-nanoemulsifying drug delivery systems (SNEDDS) whose composition was optimized using drug-solubility, ternary phase diagram, system stability and droplet size distribution studies. Optimized SNEDDSs, with acceptable surfactant ratio, stability and particle size (nano-range) upon dilution with simulated gastric fluid (SGF, pH 1.2) under gentle agitation conditions, were loaded onto microcrystalline cellulose and nano-size colloidal silicon dioxide powders using loading factor (L f) = 0.2 and excipient ratio (R) = 20. Prepared powders were compressed into tablets and the in vitro performance of the prepared self-nanoemulsifying tablets was investigated. Results revealed that systems with 10% relatively polar oils (C 8), 60% Cremophore ® RH 40 (surfactant), and 30% Transcutol ® HP (co-surfactant), acquired good self-nanoemulsification properties either in liquid or tableted forms. Prepared self-nanoemulsifying tablets demonstrated significantly higher dissolution rates, compared to direct compression tablets (DCT) and marketed tablet (Zocor ®). In conclusion, self-nanoemulsifying tablets were able to introduce simvastatin successfully in a unique immediate-release solid dosage form.

In vitro/in silicoapproach in the development of simvastatin-loaded self-microemulsifying drug delivery systems

“…In contrast to SV poor water solubility (0.026 mg/ml experimentally determined), the drug displayed relatively high solubilities in the investigated excipients, which is in accordance with SV high log P value of 4.71 [31]. As depicted in Table 3, the experimental values were within or close to the wide range of values found in literature [8,9,11]. It was assumed that propylene glycol monocaprylate has greater capacity to solubilize poorly water soluble drugs due to certain polarity of caprylic acid, as discussed in the previous study with atorvastatin [47].…”

“…As one of the most promising formulation strategies, self-emulsifying drug delivery systems have been proposed to improve solubility and dissolution rate of SV [8][9][10][11]. The aforementioned approach is commonly used to resolve the issue of SV poor water solubility; however, none of the cited studies considered the extensive presystemic clearance of SV, which could in turn significantly decrease its systemic bioavailability if SV is delivered into the small intestine in a presolubilized form.…”

Oral nanoemulsions of candesartan cilexetil: formulation, characterization and in vitro drug release studies

“…This phenomenon could be attributed to the higher concentration of the Smix required to produce fine and stable NE due to the fact that smaller globule size, greater is the surface area and hence, the greater amount of Smix required to stabilize the cinnamon oil globules (Eid et al 2013). Results obtained for PDI values of formulations were found to be less than 0.5 which indicate the uniformity of droplet size distribution dispersed cinnamon oil globules within the formulation and affirm their homogeneity (Mahmoud et al 2013). …”

Limonene-based Self-nanoemulsifying System: Formulation, Physicochemical Characterization and Stability

“…Our results were less than 0.5 which indicates uniformity of droplet size distribution of limonene within the formulation and affirms its homogeneity. 28 29 The main advantage for using SNEDS is its stability, where the small size of the droplets act as Brownian particles and don't interact with each other, thus providing stability for months. Limonene-based SNEDS didn't change in visual appearance upon storage at different temperatures.…”