Enhanced oral bioavailability of valsartan using a polymer-based supersaturable self-microemulsifying drug delivery system

Abstract

A novel, supersaturable self-microemulsifying drug delivery system (S-SMEDDS) was successfully formulated to enhance the dissolution and oral absorption of valsartan (VST), a poorly water-soluble drug, while reducing the total quantity for administration. Poloxamer 407 is a selectable, supersaturating agent for VST-containing SMEDDS composed of 10% Capmul ® MCM, 45% Tween ® 20, and 45% Transcutol ® P. The amounts of SMEDDS and Poloxamer 407 were chosen as formulation variables for a 3-level factorial design. Further optimization was established by weighting different levels of importance on response variables for dissolution and total quantity, resulting in an optimal S-SMEDDS in large quantity (S-SMEDDS_LQ; 352 mg in total) and S-SMEDDS in reduced quantity (S-SMEDDS_RQ; 144.6 mg in total). Good agreement was observed between predicted and experimental values for response variables. Consequently, compared with VST powder or suspension and SMEDDS, both S-SMEDDS_LQ and S-SMEDDS_RQ showed excellent in vitro dissolution and in vivo oral bioavailability in rats. The magnitude of dissolution and absorption-enhancing capacities using quantity-based comparisons was in the order S-SMEDDS_RQ > S-SMEDDS_LQ > SMEDDS > VST powder or suspension. Thus, we concluded that, in terms of developing an effective SMEDDS preparation with minimal total quantity, S-SMEDDS_RQ is a promising candidate.

Enhanced Lymphatic Delivery of Methotrexate Using W/O/W Nanoemulsion: In Vitro Characterization and Pharmacokinetic Study

“…Taking into account the molecular weight of the drug and the characteristics of the emulsion type, we expected the release to occur within a short period of time, and thus, this short period was our focus. In the previously reported studies [ 13 , 54 ], drug release from formulations, such as emulsions, proceeded quickly within a relatively short time (about 60 min). Therefore, in this study, in vitro release test was set up to 75 min after incubation by referring to these previous studies.…”

<p>Strategic approach to developing a self-microemulsifying drug delivery system to enhance antiplatelet activity and bioavailability of ticagrelor</p>

“…[10][11][12] They have been applied to BCS class II or IV drugs such as atorvastatin, valsartan, lopinavir, nelfinavir, and tamoxifen citrate. [12][13][14][15][16] A SMEDDS formulation is a stable, single-phase, and isotropic mixture of oil, surfactant, and cosurfactant without an aqueous phase. It forms an oil-inwater (o/w) microemulsion with a globule size in the range of 20-200 nm when dispersed in the gastrointestinal tract via gentle gastric motility or in an aqueous phase after oral administration.…”

<p>Novel Drug Delivery Systems for Loading of Natural Plant Extracts and Their Biomedical Applications</p>

“…The role of surfactant in SMEDDS is to improve intestinal permeability by lowering surface tension and hence facilitating touch with gastrointestinal mucosa and additionally inhibiting drug efflux by P-glycoprotein. 186,187 Among the most preferred property of SMEDDS is bioavailability improvement due to its small particles and wide surface area, which ameliorate absorption, solubilization, and releasing capacity. Additionally, SMEDDS decreases the first-pass metabolism by facilitating drug absorption via the lymphatic system of the intestine, and thus it provides a promising way to raise bioavailability for poorly hydrophilic products.…”