In developing Self Emulsifying Drug Delivery System (SEDDS) or Self Nano-Emulsifying Drug Delivery System (SNEDDS), optimization study of formulation is conducted and evaluated with the emulsified liquid.  However, in order to expand the dosage forms, the liquid SEDDS/SNEDDS needs to be converted into solid one.   With so many choices available for the conversion, the carrier adsorption may be the preferred method since it is energy-efficient and does not require special equipment.  
SNEDDS applications with Neusilin® have been introduced in our past technical newsletters (#27, #28, #29, #30, #31). In this newsletter, we introduce two more case studies with Berberine and Cilostazol from recently published papers.  

Background

Berberine is a plant-derived alkaloid.  Berberine extracts has been reported to have powerful effect against bacteria, viruses, fungi, etc., and used in traditional Eastern medicine. However, its hydrophobicity inhibited clinical uses for long time.
 The use of emulsion technique improves the solubility for many of these hydrophobic drugs.  Especially the Self Nano-Emulsifying Drug Delivery System (SNEDDS) improves the dissolution and permeability by achieving the micro/nano globule size of oil, in which the API is dissolved. In this study, the suitable liquid formulation was evaluated for Berberine. Then, the liquid formulation was adsorbed onto Neusilin® US2. 

Method 

The solubility studies conducted confirmed that the composition of Acysol K150 (modified oil), Capmul MCM (surfactant), and PEG 400 (co-solvent) in 1 : 0.33 : 0.66 ratio demonstrated the best result in terms of its globule size, Zeta potential, stability study by dilution, thermo-dynamic stability, and cloud point.  After the evaluation, the liquid SNEDDS was converted into a solid SNEDDS by adsorbing the solution onto Neusilin® US2 (1:1 ratio).  It was then sieved through (400 μm) to obtain free flowing powder and analyzed for angle of repose, true density, porosity, specific surface area, scanning electron microscope (SEM) and in vitro dissolution.

Results

Also, the surface study by SEM reveals that the adsorption without crystallization of API was attained. The Figure 1, A and B shows Berberine crystals at 10X magnification (A) and 40X magnification (B.)  The figure D shows the scanning electron microphotograph of solid SNEDDS of Berberine (Neusilin® US2 after the absorption of the liquid SNEDDS).  It is apparent by comparing the images that the Neusilin adsorbed the liquid SNEDDS without recrystallization.  
The dissolution studies of API alone (Berberine powder), liquid SNEDDS of Berberine and the solid SNEDDS were also conducted (900ml of pH 6.8 phosphate buffer using the USP dissolution apparatus I at 37˚C, 50 rpm). The liquid SNEDDS were filled in Flofit capsules while the solid SNEDDS and Berberine powder were filled in hard gelatin capsules for this study.    

Background

Cilostazol inhibits platelet aggregation and dilates arteries, and it is used for patients with peripheral vascular disease. However, it is categorized as class II in the biopharmaceutics classification system due to its poor solubility and high permeability. The lipophilic property makes the drug as an ideal candidate for self nano-emulsifying drug delivery system (SNEDDS).

 

Method 

The formulation study of self-emulsifying Cilostazol was carried out to determine the best suited excipients based on the solubility.  Campul MCM (oil), Tween 80 (surfactant), and Transcutol HP showed the optimum results, and were thus selected.    
Subsequently, the optimized formulation based on the study (Capmul MCM, Tween 80 and Transcutol HP; 3:5:5 parts by weight) was adsorbed onto Neusilin® US2 (1:1 by weight). A part of the mixture was diluted with water in order to analyze the globule size.  The scanning electron micrography was furthermore conducted to study the particle surface. The dissolution test was carried out for the comparison between the liquid SNEDDS (the optimized self-emulsifying solution) and the solid SNEDDS (the optimized self-emulsifying solution adsorbed onto Neusilin® US2).   

Results

After the reconstitution with water, the globule size of the solid SNEDDS showed 220nm, which illustrates that adsorption on to Neusilin® US2 did not have negative influence in the nano-emulsification.  The images by scanning electron micrograph surface revealed the surfaces of the liquid SNEDDS and Neusilin® US2 (shown in Figure 3. a and b).    

1. Pund, S et al.  Improvement of anti-inflammatory and anti-angiogenic activity of berberine by novel rapid dissolving nanoemulsifying technique. Phytomedicine. 2014 Feb 15; 21(3):307-14.
2. Pund, S et al.  Multivariate analysis of physicochemical characteristics of lipid based nanoemulsifying cilostazol--quality by design.  Colloids Surf B Biointerfaces. 2014 Mar 1; 115:29-36.