Development of microemulsion of mitotane for improvement of oral bioavailability

Abstract

This SMEDDS can now be considered as a very good candidate to optimize the administration of mitotane.

Selection of oral bioavailability enhancing formulations during drug discovery

“…Physical form modification approaches, such as pharmaceutical co-crystals, have been recently explored as promising approaches to modify the compound properties such as stability, dissolution rate and bioavailability [15][16][17][18][19] . In addition to nanoparticles and salt/co-crystals, lipid-based formulations have been shown to increase the oral bioavailability of lipophilic compounds by improved drug solubility, increased membrane permeability and lymphatic transport [20][21][22][23][24][25][26][27] . Solid dispersions in water-soluble polymers have attracted considerable interest as a means of improving bioavailability of poorly water-soluble compounds.…”

Preparation and evaluation of bicyclol microemulsions for enhanced oral bioavailability

“…Thus, the enhanced bioavailability found in this study cannot be directly compared with other prior arts of bicyclol formulations. However, the increased oral absorption in this study may be compared with those of previous reports of microemulsions [12][13][14][15][18][19][20][21][23][24][25][26][27] and those of noisome 37 , wet grinding 38 , β-cyclodextrin inclusion complex prepared by liophilization 39 , solid dispersions by spray drying 40 and by hot melting 41 of other drugs. The relative biovailailabilities to conventional/immediate release formulation of noisome, grinding, inclusion complex, spray drying, and hot melting techniques are approximately 255, 133, 353, 176 and 177%, respectively in the literature [37][38][39][40][41] .…”

“…Microemulsion formulations or self-microemulsifying drug delivery systems (SMEDDSs) have been utilized to overcome problems associated with the poor solubility and low oral absorption of drugs [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] , including dimethyl dicarboxylate biphenyl (DDB) [28][29][30] . Microemulsions are thermodynamically stable and isotropically clear dispersions of two immiscible liquids such as oil and water, stabilized by an interfacial film of surfactant molecules.…”

A Micellar Mitotane Formulation with High Drug‐Loading and Solubility: Physico‐Chemical Characterization and Cytotoxicity Studies in 2D and 3D In Vitro Tumor Models

“…Accordingly, the solubilization of MT, which exhibits an extremely low water solubility, zero H‐bond donor groups, and higher aromatic character, was tested using five different ABA triblock copolymers including the most commonly investigated ABA triblock amphiphile, that is, A‐pBuOx‐A, and A‐pPrOzi‐A, A‐pBuOzi‐A, A‐pPrOx‐A, and A‐pBzOx‐A ( Figure 1 c and Table ). The polymers with short linear side chain (which have been shown to optimally solubilize various hydrophobic drugs) or with the aromatic content (inspired by a potential benefit of π‐π stacking between drug and carrier) were specifically selected to find a good MT solubilizer, for which only very few formulations are reported to date . Using the thin‐film approach (Figure b), we prepared micellar formulations of MT with the aforementioned amphiphilic triblock copolymers (Table S1, Supporting Information).…”

“…The solubility of MT in individual vehicle was maximal with 409 g L −1 in cremophore EL. The relative bioavailability in rabbits at a dose of 100 mg kg −1 body weight was increased by a factor of 3.4 for the MT emulsion . Battung and coworkers filed a patent about the development of an oily formulation (SMEDDS) of MT (based on propylene glycol monocaprylate, propylene glycol dicaprate and polyoxyethylene sorbitan monooleate).…”