Role of medium-chain fatty acids in the emulsification mechanistics of self-micro-emulsifying lipid formulations

Abstract

Potential SMEDDS formulations for the bioavailability enhancement of poorly water-soluble compounds were developed by mixing blends of {Miglyol 812/Imwitor 988} and Tagat TO as a non-ionic surfactant. 'Diffusion and stranding' appears to be the dominant mechanism of emulsification.

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

“…These systems upon mild agitation in aqueous media form fine oil-in-water emulsions of droplet size of<5 µm in the case of SEDDS [1] or droplets with diameters between 5 and 140 nm in the case of SMEDDS [2]. It is proposed that enhancement in the water solubilisation region (L2) and the formation of interfacial liquid crystal on dilution with water are important to the mechanistic processes [3][4]. Furthermore, it is important in order to maximize the rate of absorption and thus bioavailability of oily formulations; one must maintain the drug in solution and avoid crystallization of the drug on dilution in the lumen of the gut [3,5,6].…”

“…Self-emulsifying technology for oral delivery use has recently witnessed the introduction of many self-emulsifying microemulsion formulations [7] including; Neoral ® , originally marketed as 'Sandimmune™' (Cyclosporin A, calcineurin inhibitor; new drug application year NDA 1999), Norvir ® (Ritonavir, protease inhibitor; NDA 1996), Targretin ® (Bexarotene, protease inhibitor; NDA 1999), Rapamune ® (Sirolimus, mTOR kinase inhibitor: NDA 1999), Avodart ® (Dutasteride, 5 alpha-reductase inhibitor; NDA 2001, Aptivus ® (Tipranavir, protease inhibitor; NDA 2005), Amitiza ® (Lubiprostone, chloride channel activator; NDA 2006), Xtandi ® (Enzalutamide, androgen receptor inhibitor; NDA 2012) and Rayaldee ® (Calcifediol, vitamin D analog; NDA 2016). However, the design for effective selfmicro-emulsifying drug delivery systems (SMEDDS) needs through an understanding of the various key elements which influence emulsification and how these factors interplay to affect absorption [3][4]. Pouton [8][9] has suggested a classification system for lipidic formulations based on their dispersions characteristics, digestibility and the physicochemical characteristics of the formulation components; principally the HLB of the surfactants and % glycerides content.…”

Smedds Tablet: Compatability of Solid Smedds Using Various Pharmaceutical Tablet Excipients

“…According to the method developed by Hasan et al, [11,12], blends of various oils, co-surfactants and surfactants were accurately weighed into glass test tubes and then wrapped by cling film. Test tubes were heated in a water bath at 50 °C for 2 min before lipid mixtures were thoroughly vortexed.…”

“…In order to maximize the bioavailability of lipophilic drugs, key elements in the lipid composite have to be optimized which include; type of oil (LCT or MCT), oil-cosurfactant ratio and type of surfactant (HLB value) [11,37]. Fig.…”

“…In order to facilitate formulation design of lipid systems, they were classified by Pouton [10] into type I, II and III and IV according to the hydrophilicity of oil mixture, oil droplet size after aqueous dispersion and digestion by bile salts. One advantage which, both SEDDS and SMEDDS have over solid dosage formulations is, the avoidance of slow and incomplete drug dissolution as they can facilitate the formation of solubilised phases from which absorption may occur [11,12]. Nonetheless, formulation design of self-emulsifying lipid technology has some disadvantages including; possible interaction between the filling and the capsule shell, precipitation of either active ingredient and/or oil constituents as influenced by storage temperature, besides high manufacturing cost [13,14].…”