Development of self-microemulsifying drug delivery system for oral delivery of poorly water-soluble nutraceuticals

Abstract

The objective of the study was to develop a self-microemulsifying drug delivery system (SMEDDS), also known as microemulsion preconcentrate, for oral delivery of five poorly water-soluble nutraceuticals or bioactive agents, namely, vitamin A, vitamin K2, coenzyme Q, quercetin and trans-resveratrol. The SMEDDS contained a 1:1 mixture (w/w) of Capmul MCM NF (a medium chain monoglyceride) and Captex 355 EP/NF (a medium chain triglyceride) as the hydrophobic lipid and Tween 80 (polysorbate 80) as the hydrophilic surfactant. The lipid and surfactant were mixed at 50:50 w/w ratio. All three of the SMEDDS components have GRAS or safe food additive status. The solubility of nutraceuticals was determined in Capmul MCM, Captex 355, Tween 80, and the SMEDDS (microemulsion preconcentrate mixture). The solubility values of vitamin A palmitate, vitamin K2, coenzyme Q, quercetin, and trans-resveratrol per g of SMEDDS were, respectively, 500, 12, 8, 56, and 87 mg. Appropriate formulations of nutraceuticals were prepared and filled into hard gelatin capsules. They were then subjected to in vitro dispersion testing using 250 mL of 0.01 N HCl in USP dissolution apparatus II. The dispersion test showed that all SMEDDS containing nutraceuticals dispersed spontaneously to form microemulsions after disintegration of capsule shells with globule size in the range of 25 to 200 nm. From all formulations, except that of vitamin K2, >80-90% nutraceuticals dispersed in 5-10 min and there was no precipitation of compounds during the test period of 120 min. Some variation in dispersion of vitamin K2 was observed due to the nature of the material used (vitamin K2 pre-adsorbed onto calcium phosphate). The present report provides a simple and organic cosolvent-free lipid-based SMEDDS for the oral delivery of poorly water-soluble nutraceuticals. Although a 50:50 w/w mixture of lipid to surfactant was used, the lipid content may be increased to 70:30 without compromising the formation of microemulsion.

Role of Hydrophilic Surfactants in the Emulsification Mechanistics of Type Iii Self-Micro-Emulsifying Drug Delivery Systems (Smedds)

“…In contrast to oil mixtures containing Crillet 4, Miglyol 812/Imwitor 988-Crillet 1 has shown no potential for pre-microemulsion formulations hence it has produced dispersions with high MEDD values at all Miglyol 812/Imwitor ratios (data not shown). This was also observed by Kawakami et al [24] whereby Tween 80 (equivalent to Crillet 4) was able to solubilise 23% w/w of oil mixture composed of 1: (15) and more importantly similar chemical structure, yet with the lack of sorbitan ring in the case of Tagat O2. This suggests that the sorbitan nucleus structure in the case of polyoxyethylene monoalkyl esters is not the major factor to determine good self-emulsification with triglyceride oils.…”

“…Type II formulations are often referred to as SEDDS which comprise water-insoluble components; blends of glycerides and non-ionic surfactants with HLBs less than 12 such as; polysorbate 85 (Tween 85) or polyoxyethylene 25glyceryl trioleate (Tagat TO). Type III systems contain blends of glycerides (oils), hydrophilic surfactants with HLB>12 such as; Cremophor RH40 [10,11], Cremophor EL [12,13], Tween 80 [14,15], Tween 20 [14] or Tagat O2 [16] and/or hydrophilic co-solvents such as, ethanol, propylene glycol or polyethylene glycol. Type III formulations which include water-soluble components are referred to as self-micro-emulsifying systems (SMEDDS) as they can lead to the production of a microemulsion on dispersion in GI tract (particle size ≈ 50 nm).…”

Gelatin-Graphene Oxide Nanocomposite Hydrogels for Kluyveromyces lactis Encapsulation: Potential Applications in Probiotics and Bioreactor Packings

“…The efficient oral administration and subsequent absorption of different bioactive compounds such as drugs, proteins, peptides, hormones, and antibodies by the human body have been widely studied due to various challenges to preserve their functionality and structural integrity as they transit through harsh environments in the gastrointestinal (GI) tract [1][2][3]. Similarly, nutraceuticals, which generally are poorly soluble in water, have low bioavailability by this route of administration [4]. This is also the case of whole cells, including lactic acid bacteria (LAB), Bifidobacteria, Escherichia coli Nissle 1917, and beneficial molecules such as bivalent fusion protein r-BL with recombinant protein U-Omp19, Garcinia mangostana L. ethanolic extract, and insulin [5][6][7][8][9][10][11].…”

Topical Delivery of Coenzyme Q10-Loaded Microemulsion for Skin Regeneration

“…Previously, a self-emulsifying drug delivery system (SMEDDS) has been reported for oral administration of CoQ10. However, the SMEDDS still showed a low solubility of CoQ10 [37]. A nanoemulsion containing CoQ10 using Tween 80 was developed for alleviating the formation of wrinkles [38].…”