Silymarin Glyceryl Monooleate/Poloxamer 407 Liquid Crystalline Matrices: Physical Characterization and Enhanced Oral Bioavailability

Abstract

Abstract. Silymarin, a mixture of flavonolignans extracted from the seeds of milk thistle, is used clinically as a hepatoprotector to treat liver injuries and chronic hepatitis. However, its therapeutic effect is compromised by its poor oral bioavailability due to the poor solubility and low permeability across intestinal epithelia. The main purpose of this study was to prepare silymarin glyceryl monooleate/ poloxamer 407 liquid crystalline matrices (GMO/P407 LCM) to improve the oral bioavailability of silymarin. GMO/P407 LCMs were prepared by a melting/congealing method. The isotropic phenomenon observed under polarized light microscope confirmed the liquid crystalline structure at the junction of LCM and water. Both differential scanning calorimetry and X-ray diffraction analysis confirmed disappearance of silymarin crystallinity after incorporation into the LCMs. In vitro release of silymarin from LCMs was limited, whereas LCMs were readily degraded by lipase and released silymarin quickly and completely. Pharmacokinetic study in beagle dogs showed significantly increased peak concentration for silymarin GMO/P407 LCM, and, most importantly, a 3.46-fold increase in oral bioavailability as compared with Legalon®, a commercial silymarin formulation.

Binary lipids-based nanostructured lipid carriers for improved oral bioavailability of silymarin

“…[3][4][5][6] However, its clinical efficacy is compromised by its poor oral bioavailability due to poor water solubility and low permeability. 7,8 In order to improve the oral bioavailability of SM, several delivery systems have been explored such as self-microemulsifying drug delivery systems, [9][10][11] porous silica nanoparticles, 12 solid dispersions, 13 glyceryl monooleate/poloxamer 407 liquid crystalline matrices, 14 proliposomes, 15 silybinphospholipid complexes, 16 and solid lipid nanoparticles. 17 It seems that lipid-based drug delivery systems are more promising in improving the oral absorption of SM owing to their specific absorption-enhancing mechanisms.…”

Formulation and characterization of Liquid Crystalline Hydrogel of Agomelatin: In vitro and Ex vivo evaluation

“…Donor compartment consisted of a boiling tube which was cut open at one end and tied with dialysis membrane (Lian et al, 2011) at the other end into which 1 mL of cubosomal dispersion was taken for release study. Receptor compartment consisted of a 250 mL beaker which was filled with 100 mL of release medium and the temperature was maintained at 37 ± 0.5°C.…”

Enhanced oral absorption and therapeutic effect of acetylpuerarin based on D-α-tocopheryl polyethylene glycol 1000 succinate nanoemulsions

“…[25][26][27] Briefly, 50 mg nanoemulsions or an ethyl linoleate-containing drug was dispersed in 20 mg digestion medium containing a mixture of 50 mM tris-maleate (pH, 7.5), 150 mM sodium chloride, 5 mM calcium chloride, 5 mM sodium taurocholate, and 1.25 mM soy phosphatidylcholine. The reaction was initiated by dispersing 1 mL porcine pancreatic lipase solution (4,000 tributyrin units/mL) into the digestive system.…”

“…A solution of sodium hydroxide (1M) was added into the digestive system to maintain the pH at 7.5. [25][26][27] At the end of the experiment, the lipolysis was terminated by the addition of 1 mL lipase inhibitor (1 M 4-bromophenylboronic acid in methanol). Two milliliters of the postdigestion mixtures were withdrawn and ultracentrifuged at 310,000 g for 30 minutes at 4°C (Optima L-80XP ultracentrifuge; Beckman Coulter Inc., Brea, CA, USA) to separate the mixtures into both an aqueous phase, containing the drug solubilized in micellar structures making up endogenous bile salts and phospholipid and exogenous lipid digestion products, and a pellet phase containing precipitated drug and insoluble (calcium) soaps of fatty acid.…”