Self-nanoemulsifying Drug Delivery Systems: Formulation Insights, Applications and Advances

Abhijit A Date; Neha Desai; Rahul Dixit; Mangal Nagarsenker

Disclosures

Nanomedicine. 2010;5(10) 

In This Article

Solid SNEDDS

The researchers realized that it may be possible to obviate disadvantages associated with liquid SNEDDS handling, manufacturing and stability should one convert them to solid state. Hence, the concept of solid SNEDDS was developed. Solid SNEDDS in the form of dry, solid powders would help in overcoming the limitations associated with liquid SNEDDS. Solid dosage forms are most stable and are convenient for handling; therefore, attempts are made to convert the liquid systems into solid SNEDDS. Various techniques, such as spray drying, freeze drying and adsorption on carriers, can be employed to convert liquid SNEDDS into solid SNEDDS compressed into tablets. The selection of a particular process for preparation of solid SNEDDS would depend on the content of oily excipient of the formulation, properties of active pharmaceutical ingredients, such as solubility, heat stability and compatibility with other ingredients.

The simplest technique to convert liquid SNEDDS to solid SNEDDS is by adsorption onto the surface of carriers or by granulation using liquid SNEDDS as a binder. This technique is uncomplicated, cost effective, easily optimized and industrially scalable. It can be used for heat- and moisture-sensitive molecules, thus providing an advantage over other techniques, such as spray drying and freeze drying. Various excipients utilized for the preparation of solid oral dosage forms can be employed for adsorption. The excipients should possess large surface areas to adsorb sticky and sometimes viscous oily SNEDDS formulation.

We have studied the ability of different excipients, such as dibasic calcium phosphate, lactose, microcrystalline cellulose, colloidal silicon dioxide and Neusilin, to adsorb cefpodoxime proxetil SNEDDS. Neusilin was found to give free-flowing powder with high bulk density [Date AA, Unpublished Data]. Conversion to solid form did not significantly alter the dissolution profile. In another study, we successfully developed and evaluated self-nanoemulsifying granules (SNG) of ezetimibe and ezetimibe–simvastatin combination. In both cases, Aerosil 200 was utilized for adsorption of SNEDDS. X-ray diffraction studies indicated loss of crystallinity and/or solubilization of drug in the SNGs. This result was supported by scanning electron microscopy studies, which showed no evidence of drug precipitation on the surface of the carrier. A remarkable improvement was observed in dissolution of the drug from SNGs compared with pure drug. In vivo evaluation in rats showed a significant decrease in total cholesterol levels compared with the drug suspension.[53,82] The percentage protection offered by the combination of simvastatin and ezetimibe is depicted in Figures 5 & 6.

Figure 5.

Percentage changes in the levels of total cholesterol and triglyceride of experimental groups at different time intervals.
(A) Percentage changes in the levels of total cholesterol. (B) Percentage changes in the levels of triglycerides. Ezetimibe and simvastatin were used in the concentration of 10 mg in the formulation.
SNG: Self-nanoemulsifying granule; TC: Triglyceride.
Reproduced with permission from [53].

Figure 6.

Percentage changes in the levels of total cholesterol and triglycerides of experimental groups at different time intervals.
(A) Percentage changes in the levels of total cholesterol. (B) Percentage changes in the levels of triglycerides. Ezetimibe and simvastatin were used in the concentration of 10 and 40 mg in the formulation.
SNG: Self-nanoemulsifying granule; TC: Triglyceride.
Reproduced with permission from [53].

Taha et al. adsorbed vitamin A SNEDDS on microcrystalline cellulose and compressed the powder to obtain tablets.[104] The self-nanoemulsifying tablet exhibited a higher relative bioavailability of 143.68% when compared with tablets in which vitamin A oily solution was incorporated. The peak plasma concentration and area under the curce of vitamin A self-nanoemulsifying tablet was found to be higher in comparison with tablets of vitamin A oily solution. Lutein SNEDDS were adsorbed on Aerosil 200 to obtain solid SNEDDS by Yoo et al..[64] Dissolution of lutein from the solid SNEDDS was effected in less than 5 min in distilled water and no signs of precipitation or aggregation of the drug were observed. Mahmoud et al. have identified the use of superporous hydrogel as a solid carrier for carvedilol SNEDDS.[105] The same group of scientists have reported self-nanoemulsifying tablet formulation of carvedilol, where granulated aerosil and microcrystalline cellulose were used as adsorbents and processed into liquisolid tablets.[106] These tablets retained the nanoparticle size of the nanoemulsion. The self-nanoemulsifying tablet possessed drug release properties similar to that of immediate-release dosage form.

Few reports have been published in the literature where solid self-emulsifying systems are formulated using techniques such as spray drying, freeze drying and extrusion spheronization.[107–111] Patil and Paradkar have employed polystyrene beads to deposit self-emulsifying loratidine.[112] In a similar manner, solid self-nanoemulsifying formulations can be developed utilizing these techniques.

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