Evaluation of Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) for Poorly Water-Soluble Talinolol: Preparation, in vitro and in vivo Assessment

Abstract

Objective The aim of this study was to investigate the in vitro and in vivo performance of self-nanoemulsifying drug delivery systems (SNEDDSs) of talinolol (TAL), a poorly water-soluble drug. Methods Self-nanoemulsifying drug delivery systems of TAL were prepared using various oils, non-ionic surfactants and/or water-soluble co-solvents and assessed visually/by droplet size measurement. Equilibrium solubility of TAL in the anhydrous and diluted SNEDDS was conducted to achieve the maximum drug loading. The in vitro dissolution experiments and human red blood cells (RBCs) toxicity test, ex vivo gut permeation studies, and bioavailability of SNEDDS in rats were studied to compare the representative formulations with marketed product Cordanum ® 50 mg and raw drug. Results The results from the characterization and solubility studies showed that SNEDDS formulations were stable with lower droplet sizes and higher TAL solubility. From the dissolution studies, it was found that the developed SNEDDS provided significantly higher rate of TAL release (>97% in 2.0 h) compared to raw TAL and marketed product Cordanum ® . The RBC lysis test suggested negligible toxicity of the formulation to the cells. The ex vivo permeability assessment and in vivo pharmacokinetics study of a selected SNEDDS formulation (F6) showed about four-fold increase in permeability and 1.58-fold enhanced oral bioavailability of TAL in comparison to pure drug, respectively. Conclusion Talinolol loaded SNEDDS formulations could be a potential oral pharmaceutical product with high drug-loading capacity, improved drug dissolution, increased gut permeation, reduced/no human RBC toxicity, and enhanced oral bioavailability.

Bioactive Self-Nanoemulsifying Drug Delivery Systems (Bio-SNEDDS) for Combined Oral Delivery of Curcumin and Piperine

“…The anhydrous SNEDDS samples were visually evaluated for homogeneity and appearance. As a preliminary screening, drug-free SNEDDS formulations were mixed with deionized water at 1:100 w/w ratio to provide fast evaluation of formulation appearance, homogeneity and spontaneity upon aqueous dilution [62][63][64]. Furthermore, SNEDDS formulations were loaded with CUR and PP at ≈80% of their equilibrium solubility and were then subjected to 1:1000 w/w aqueous dilution prior to formulation evaluation.…”

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

“…Similar results were reported by Kazi et al where droplet size was found to be around 150 nm having spherical shape. 27 Another crucial parameter is polydispersity index (PDI), which reflected positively on formulation physical stability. Our results were less than 0.5 which indicates uniformity of droplet size distribution of limonene within the formulation and affirms its homogeneity.…”

Development of Topical/Transdermal Self-Emulsifying Drug Delivery Systems, Not as Simple as Expected

“…The interfacial tension between the lipophilic and hydrophobic components of SEDDSs are reduced by surfactants. They create an interfacial film between the two immiscible phases for the purpose of generating a dispersion [3][4][5][6][7][8]72]. During formulation of SEDDSs, higher emulsification properties are achieved by including surfactants with HLB values exceeding a value of 12.…”

“…Self-emulsifying drug delivery systems (SEDDSs) are isotropic blends of an active compound with a mixture of lipids, surfactants, and co-surfactants that produce spontaneous oil-in-water emulsions (dispersions) during moderate agitation in an aqueous phase, such as the upper gastrointestinal tract. A highly solubilised, thermodynamically stable phase of drug for improved drug absorption is subsequently formed [3][4][5][6][7][8]. SEDDS, however, is a comprehensive term for selected lipid-based drug delivery systems and can rather be differentiated into three categories in terms of droplet size.…”

“…SMEDDSs and SNEDDSs, however, have some disadvantages compared to SEDDS that include higher production costs, lower drug loading, and often, irreversible drug/excipient precipitation that may also be challenging. More significantly, the high amounts of surfactants included in these formulations may induce gastrointestinal irritation, which may also be problematic if topical/transdermal drug delivery is to be deliberated [3,6,11]. On the other hand, the smaller average oil droplet size enhances drug bioavailability, which is due to an increased surface area [12,13].…”