Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire® 44/14

Shin, Dong Jun; Chae, Bo Ram; Goo, Yoon Tae; Yoon, Ho Yub; Kim, Chang‐Hyun; Sohn, Se I.; Oh, Dong-Ho; Lee, Ahram; Song, Seh Hyon; Choi, Young Wook

doi:10.3390/pharmaceutics11020058

Cited by 25 publications

(9 citation statements)

References 38 publications

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“… 8 The solid carriers produced characteristic intrinsic peaks: 29º for FLO and 21º for VP105. 51 PM yielded similar major peaks of RVP, demonstrating that RVP maintained its crystallinity in PM. In contrast, no intrinsic peaks were found for SSuM.…”

Section: Resultsmentioning

confidence: 69%

Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design

Goo¹,

Sa²,

Choi³

et al. 2021

IJN

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Purpose To enhance the oral bioavailability of revaprazan (RVP), a novel solid, supersaturable micelle (SSuM) was developed. Methods Surfactants and solid carriers were screened based on a solubility and a flowability test, respectively. Supersaturating agents, including Poloxamer 407 (P407), were screened. The SSuM was optimized using a Box-Behnken design with three independent variables, including Gelucire 44/14:Brij L4 (G44/BL4; X 1 ) and the amounts of Florite PS-10 (FLO; X 2 ) and Vivapur 105 (VP105; X 3 ), and three response variables, ie, dissolution efficiency at 30 min (Y 1 ), dissolution enhancing capacity (Y 2 ), and Carr’s index (Y 3 ). The solid state property was evaluated, and a dissolution test was conducted. RVP, Revanex ® , solid micelle (P407-free from the composition of SSuM), and SSuM were orally administrated to rats (RVP 20 mg equivalent/kg) for in vivo pharmacokinetic study. Results G44 and BL4 showed great solubility, with a critical micelle concentration range of 119.2–333.0 μg/mL. P407 had an excellent supersaturating effect. FLO and VP105 were selected as solid carriers, with a critical solidifying ratio (g/mL) of 0.30 and 0.91, respectively. With optimized values of X 1 (–0.41), X 2 (0.31), and X 3 (–0.78), RVP (200 mg)-containing SSuM consisting of G44 (253.8 mg), BL4 (106.2 mg), FLO (99.3 mg), VP105 (199.8 mg), and P407 (40 mg) was developed, resulting in Y 1 (40.3%), Y 2 (0.008), and Y 3 (12.3%). RVP existed in an amorphous state in the optimized SSuM, and the SSuM formed a nanosized dispersion in the aqueous phase, with approximately 71.7% dissolution at 2 h. The optimized SSuM improved the relative bioavailability of RVP in rats by approximately 478%, 276%, and 161% compared to raw RVP, Revanex ® , and solid micelle, respectively. Conclusion The optimized SSuM has great potential for the development of solidified formulations of poorly water-soluble drugs with improved oral absorption.

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Section: Resultsmentioning

confidence: 69%

Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design

Goo¹,

Sa²,

Choi³

et al. 2021

IJN

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“…By pre-dissolving the API in lipid excipients together with surfactants and co-solvents, the apparent solubility within the GI tract is less affected by the timing of administration. LBF has also been shown to increase the bioavailability of BCS (biopharmaceutics classification system) class II and IV drugs (5)(6)(7)(8), possibly by circumventing the dissolution step in the intestine. However, several studies have shown that an API does not necessarily have to be fully dissolved within an LBF, but that co-administration with crystalline material can be sufficient to increase the amount of solubilized drug and bioavailability (9,10), in a phenomenon sometimes described as the "chasing principle" (11).…”

Section: Introductionmentioning

confidence: 99%

Suitability of Artificial Membranes in Lipolysis-Permeation Assays of Oral Lipid-Based Formulations

Hedge

Bergström

2020

Pharm Res

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Purpose To evaluate the performance of artificial membranes in in vitro lipolysis-permeation assays useful for absorption studies of drugs loaded in lipid-based formulations (LBFs). Methods Polycarbonate as well as PVDF filters were treated with hexadecane, or lecithin in n-dodecane solution (LiDo) to form artificial membranes. They were thereafter used as absorption membranes separating two compartments mimicking the luminal and serosal side of the intestine in vitro. Membranes were subjected to dispersions of an LBF that had been digested by porcine pancreatin and spiked with the membrane integrity marker Lucifer Yellow (LY). Three fenofibrate-loaded LBFs were used to explore the in vivo relevance of the assay. Results Of the explored artificial membranes, only LiDo applied to PVDF was compatible with lipolysis by porcine pancreatin. Formulation ranking based on mass transfer in the LiDo model exposed was the same as drug release in singlecompartment lipolysis. Ranking based on observed apparent permeability coefficients of fenofibrate with different LBFs were the same as those obtained in a cell-based model. Conclusions The LiDo membrane was able to withstand lipolysis for a sufficient assay period. However, the assay with porcine pancreatin as digestive agent did not predict the in vivo ranking of the assayed formulations better than existing methods. Comparison with a Caco-2 based assay method nonetheless indicates that the in vitro in vivo relationship of this cell-free model could be improved with alternative digestive agents.

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“…Additionally, the coexistence of hydrophilic carriers like Gelurice ® 48/16 may decrease the hydrophobicity of the drug particle surfaces, which will subsequently increase interaction with the aqueous medium and boost the rate of CXB’s dissolution [ 7 ]. Several previous studies showed the enhanced release performance exhibited after the addition of Gelurice ® 48/16 [ 27 , 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Fabrication of Celecoxib PVP Microparticles Stabilized by Gelucire 48/16 via Electrospraying for Enhanced Anti-Inflammatory Action

et al. 2023

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Electrospraying (ES) technology is considered an efficient micro/nanoparticle fabrication technique with controlled dimensions and diverse morphology. Gelurice® 48/16 (GLR) has been employed to stabilize the aqueous dispersion of Celecoxib (CXB) for enhancing its solubility and oral bioavailability. Our formula is composed of CXB loaded in polyvinylpyllodine (PVP) stabilized with GLR to formulate microparticles (MPs) (CXB-GLR-PVP MPs). CXB-GLR-PVP MPs display excellent in vitro properties regarding particle size (548 ± 10.23 nm), zeta potential (−20.21 ± 2.45 mV), and drug loading (DL, 1.98 ± 0.059 mg per 10 mg MPs). CXB-GLR-PVP MPs showed a significant (p < 0.05) higher % cumulative release after ten minutes (50.31 ± 4.36) compared to free CXB (10.63 ± 2.89). CXB exhibited good dispersibility, proved by X-ray diffractometry (XRD), adequate compatibility of all components, confirmed by Fourier-Transform Infrared Spectroscopy (FTIR), and spherical geometry as revealed in scanning electron microscopy (SEM). Concerning our anti-inflammatory study, there was a significant decrease in the scores of the inflammatory markers’ immunostaining in the CXB-GLR-PVP MPs treated group. Also, the amounts of the oxidative stress biomarkers, as well as mRNA expression of interleukins (IL-1β and IL-6), considerably declined (p < 0.05) in CXB-GLR-PVP MPs treated group alongside an enhancement in the histological features was revealed. CXB-GLR-PVP MPs is an up-and-coming delivery system that could be elucidated in future clinical investigations.

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Improved Dissolution and Oral Bioavailability of Valsartan Using a Solidified Supersaturable Self-Microemulsifying Drug Delivery System Containing Gelucire® 44/14

Cited by 25 publications

References 38 publications

Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design

Development of a Solid Supersaturable Micelle of Revaprazan for Improved Dissolution and Oral Bioavailability Using Box-Behnken Design

Suitability of Artificial Membranes in Lipolysis-Permeation Assays of Oral Lipid-Based Formulations

Fabrication of Celecoxib PVP Microparticles Stabilized by Gelucire 48/16 via Electrospraying for Enhanced Anti-Inflammatory Action

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