Improved oral absorption of dutasteride via Soluplus ® -based supersaturable self-emulsifying drug delivery system (S-SEDDS)

Lee, Dong Hoon; Yeom, Dong Woo; Song, Ye Seul; Cho, Ha Ra; Choi, Yong Seok; Kang, Myung Joo; Choi, Young Wook

doi:10.1016/j.ijpharm.2014.11.060

Cited by 58 publications

(39 citation statements)

References 21 publications

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“…Moreover, with repetitive dosing, severe GI irritation could be induced due to the high content of surfactant (~60%) in SMEDDS formulations. 12 The concept of supersaturation has been proposed to overcome these limitations of SMEDDS formulations. 12,13 If the volume of the solubilizing vehicle is reduced to a certain magnitude, drugs are prone to precipitate.…”

Section: Introductionmentioning

confidence: 99%

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

Yeom¹,

Chae²,

Son³

et al. 2017

IJN

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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.

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Section: Introductionmentioning

confidence: 99%

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

Yeom¹,

Chae²,

Son³

et al. 2017

IJN

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“…Soluplus has numerous advantages, such as amphiphilicity, minimum toxicity and low hygroscopicity, and has been used in a variety of pharmaceutical technologies, including the generation of micelles [24] , solid dispersions [25] , nanoparticles [26] and self-emulsifying drug delivery systems [27] . Soluplus has been proven to possess the potential to increase the solubility and bioavailability of a number of poorly water-soluble compounds, such as itraconazole [28] , osthole [29] , fenofibrate [30] and sorafenib [31] .…”

Section: Discussionmentioning

confidence: 99%

Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo

Zeng

Liu

et al. 2017

Acta Pharmacol Sin

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Scopoletin is an active coumarin possessing a variety of pharmacological activities, including anti-hyperuricemic effect, but with poor solubility. To improve its oral bioavailability, we attempted to encapsulate scopoletin into Soluplus micelles (Soluplus-based scopoletin micelles, Sco-Ms) and evaluated the hypouricemic action of Sco-Ms. Sco-Ms were prepared using a thin-film hydration method. Sco-Ms displayed near spherical shapes with an average size of 59.4±2.4 nm (PDI=0.08±0.02). The encapsulation efficiency of scopoletin was 87.3%±1.5% with a loading capacity of 5.5%±0.1%. Sco-Ms were further characterized using transmission electron microscopy, powder X-ray diffraction, Fourier transform infrared techniques and scanning electron microscopy. After oral administration in rats, Sco-Ms exhibited significantly improved absorption in each intestinal segment compared to free scopoletin, with the duodenum and jejunum being the main absorption regions. In rats administered Sco-Ms (at an equivalent dose of free scopoletin of 100 mg/kg, po), the AUC 0-∞ and C max of Sco-Ms were 4.38-and 8.43-fold, respectively, as large as those obtained following administration of free scopoletin. After oral administration in rats, Sco-Ms did not alter the tissue distributions of scopoletin, but significantly increased the scopoletin levels in the liver. In potassium oxonate-induced hyperuricemic mice, oral administration of Sco-Ms (at an equivalent dose of free scopoletin of 300 mg/kg) reduced the serum uric acid concentration to the normal level. The results suggest that Soluplus-based micelle system greatly improves the bioavailability of poorly water-soluble drugs, such as scopoletin, and represents a promising strategy for their oral delivery.

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“…With the marketed oral formulation (Avodart), dutasteride is dissolved in mono-di-glycerides of caprylic acid and capric acid, and then encapsulated in soft-gelatin capsule. However, the achieved bioavailability is still below satisfaction, with only between 40 to 60 per cent (Lee et al, 2015). To achieve optimal therapeutic effects of dutasteride with minimal side effect, dissolution and absorption of dutasteride must be improved.…”

Section: Introductionmentioning

confidence: 99%

“…SEDDS is a promising method as it is anhydrous isotropic mixture of oil, surfactant, co-surfactant, and drug, which spontaneously form oil-in-water emulsion following the dilution in aqueous medium upon agitation (Abdalla et al, 2008;Balakrishnan et al, 2009;Gursoy and Benita., 2004). Lee et al, (2015), designed supersaturable Self -microemulsifying drug delivery system (S-SMEDDS) of dutasteride for oral administration. Ali et al,( 2014) designed nanoemulsions of dutasteride as transdermal patch.…”

Section: Introductionmentioning

confidence: 99%

Self-Nanoemulsifying Drug Delivery Systems of Poorly Soluble Drug Dutasteride: Formulation and In-Vitro characterization

2017

J App Pharma Sci

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The present study aims to prepare and evaluate the self-nanoemulsifying drug delivery system (SNEDDS) to enhance the dissolution rate of a poorly soluble drug dutasteride. The formulation was prepared using capryol PGMC, Cremophor EL, and polyethylene glycol (PEG) 400 as oil, surfactant and co-surfactant, respectively. The pseudo-ternary phase diagrams with presence and absence of drug were plotted to find out the nanoemulsification range and also to evaluate the effect of dutasteride on the emulsification behavior of the phases. Prepared SNEDDS formulations were evaluated for its particle size distribution, nanoemulsifying properties, robustness to dilution, self-emulsification time, turbidity measurement, drug content and in-vitro dissolution. Furthermore, the optimized formulations were evaluated for heating cooling cycle, centrifugation studies, freeze thaw cycling, particle size distribution and zeta potential to confirm the stability of the formed SNEDDS formulations. The particle size, zeta potential and polydispersity index of the optimized formulation was found to be 35.45 nm, -15.45 and 0.19, respectively. The in vitro results revealed that the prepared formulation enhanced the dissolution rate of dutasteride significantly compared to pure drug. In 60 minutes, the formulation showed 83.15% and 82.04 % drug release for pH 6.8 and pH 1.2 respectively. Based on the results, it was concluded that the dutasteride-loaded SNEDDS revealed better dissolution compared to the raw drug suspension and commercial drug.

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Improved oral absorption of dutasteride via Soluplus ® -based supersaturable self-emulsifying drug delivery system (S-SEDDS)

Cited by 58 publications

References 21 publications

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

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

Soluplus micelles for improving the oral bioavailability of scopoletin and their hypouricemic effect in vivo

Self-Nanoemulsifying Drug Delivery Systems of Poorly Soluble Drug Dutasteride: Formulation and In-Vitro characterization

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