Development of Self-Microemulsifying Drug Delivery Systems of Poorly Water-Soluble Pazopanib for Improvement of Oral Absorption

2020 ◽  
Vol 12 (1) ◽  
pp. 152-160
Author(s):  
Sung-Up Choi ◽  
Mi Jeong Kim ◽  
Sung Tae Kim ◽  
Hee-Cheol Kim ◽  
Kwan Hyung Cho ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Delivery Systems ◽  
Water Soluble ◽  
Pharmacokinetic Parameters ◽  
Poorly Water Soluble

Self-microemulsifying drug delivery systems represent a stable formulation for enhancing the solubility and absorption efficacy of poorly soluble drugs. In this study, a self-microemulsifying drug delivery system (SMEDDS) was designed and applied for oral administration of poorly water-soluble pazopanib, a Biopharmaceutical Classification Class II anticancer drug. The solubility of pazopanib was first evaluated using various oils, surfactants, and co-surfactants. Pseudoternary phase diagrams were plotted to identify the selfemulsifying region and the phase behavior of optimized vehicle selected after screening of oils, surfactants, and co-surfactants. The SMEDDS comprising Capmul MCM NF, Tween 80, and PEG 400 was fabricated for incorporating pazopanib. It exhibited spherical droplets with size of 86.9 ± 0.8 nm and zeta potential value of –14.7 ± 0.1 mV. In vitro dissolution profiles of the SMEDDS were 2.40-fold (pH 4.0) and 6.45-fold (pH 6.8) higher than that of pazopanib powder. In particular, pazopanib-SMEDDS showed pH-independent dissolution profiles. In vivo pharmacokinetic parameters of the SMEDDS revealed enhanced bioavailability of pazopanib, which was 3.32-fold higher than that of pazopanib powder when administered orally. Taken together, the SMEDDS is effective as an oral delivery vehicle for pazopanib. In addition, our findings demonstrate that self-microemulsifying drug delivery systems could be a potential tool for improving bioavailability of other poorly water-soluble drugs.

Lipid Nanocarriers for Oral Delivery of Serenoa repens CO2 Extract: A Study of Microemulsion and Self-Microemulsifying Drug Delivery Systems

Planta Medica ◽  
2018 ◽  
Vol 84 (09/10) ◽  
pp. 736-742 ◽  
Author(s):  
Clizia Guccione ◽  
Maria Bergonzi ◽  
Khaled Awada ◽  
Vieri Piazzini ◽  
Anna Bilia
Keyword(s):  
Drug Delivery ◽  
Oral Delivery ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Delivery Systems ◽  
Array Detector ◽  
Serenoa Repens ◽  
Lipid Nanocarriers

AbstractThe aim of this study was the development and characterization of lipid nanocarriers using food grade components for oral delivery of Serenoa repens CO2 extract, namely microemulsions (MEs) and self-microemulsifying drug delivery systems (SMEDDSs) to improve the oral absorption. A commercial blend (CB) containing 320 of S. repens CO2 extract plus the aqueous soluble extracts of nettle root and pineapple stem was formulated in two MEs and two SMEDDSs. The optimized ME loaded with the CB (CBM2) had a very low content of water (only 17.3%). The drug delivery systems were characterized by dynamic light scattering, transmission electron microscopy, and high-performance liquid chromatography (HPLC) with a diode-array detector analyses in order to evaluate the size, the homogeneity, the morphology, and the encapsulation efficiency. β-carotene was selected as marker for the quantitative HPLC analysis. Additionally, physical and chemical stabilities were acceptable during 3 wk at 4 °C. Stability of these nanocarriers in simulated stomach and intestinal conditions was proved. Finally, the improvement of oral absorption of S. repens was studied in vitro using parallel artificial membrane permeability assay. An enhancement of oral permeation was found in both CBM2 and CBS2 nanoformulations comparing with the CB and S. repens CO2 extract. The best performance was obtained by the CBM2 nanoformulation (~ 17%) predicting a 30 – 70% passive oral human absorption in vivo.

Using in vitro lipolysis and SPECT/CT in vivo imaging to understand oral absorption of fenofibrate from lipid-based drug delivery systems

2020 ◽  
Vol 317 ◽  
pp. 375-384 ◽  
Author(s):  
Thuy Tran ◽  
Peter Bønløkke ◽  
Cristina Rodríguez-Rodríguez ◽  
Zeynab Nosrati ◽  
Pedro Luis Esquinas ◽  
...  
Keyword(s):  
Drug Delivery ◽  
In Vivo Imaging ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Delivery Systems ◽  
In Vitro Lipolysis

scholarly journals Effects of Hydrophilic Carriers on Structural Transitions and In Vitro Properties of Solid Self-Microemulsifying Drug Delivery Systems

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 267 ◽  
Author(s):  
Tao Yi ◽  
Jifen Zhang
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Water Soluble ◽  
Drug Dissolution ◽  
Commercial Application ◽  
Simulated Gastric Fluid ◽  
Structural Transitions

Self-microemulsifying drug delivery systems (SMEDDS) offer potential for improving the oral bioavailability of poorly water-soluble drugs. However, their susceptibilities during long term storage and in vivo precipitation issues limit their successful commercial application. To overcome these limitations, SMEDDS can be solidified with solid carriers, thus producing solid self-microemulsifying drug delivery systems (S-SMEDDS). In this study, effects of various hydrophilic carriers on structural transitions and in vitro properties of S-SMEDDS were investigated in order to set up in vitro methods for screening out appropriate carriers for S-SMEDDS. Liquid SMEDDS was prepared and characterized using nimodipine as a model drug. The effects of various hydrophilic carriers on internal microstructure and solubilization of SMEDDS were investigated by conductivity measurement and in vitro dispersion test. The results showed that hydrophilic carriers including dextran 40, maltodextrin and PVP K30 seemed to delay the percolation transition of SMEDDS, allowing it to maintain a microstructure that was more conducive to drug dissolution, thus significantly increasing the solubilization of nimodipine in the self-microemulsifying system and decreasing drug precipitation when dispersed in simulated gastric fluid. S-SMEDDS of nimodipine were prepared by using spray drying with hydrophilic carriers. The effects of various hydrophilic carriers on in vitro properties of S-SMEDDS were investigated by using SEM, DSC, PXRD and in vitro dissolution. The results showed that properties of hydrophilic carriers, especially relative molecular mass of carriers, had obvious influences on surface morphologies of S-SMEDDS, reconstitution of microemulsion and physical state of nimodipine in S-SMEDDS. Considering that in vitro properties of S-SMEDDS are closely related to their pharmacokinetic properties in vivo, the simple and economical in vitro evaluation methods established in this paper can be used to screen solid carriers of S-SMEDDS well.

scholarly journals Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 365 ◽  
Author(s):  
Heejun Park ◽  
Eun-Sol Ha ◽  
Min-Soo Kim
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Drug Application ◽  
In Vitro Digestion ◽  
Delivery Systems ◽  
Water Soluble ◽  
Current Status ◽  
In Vitro Tests

Self-emulsifying drug delivery systems (SEDDSs) are a vital strategy to enhance the bioavailability (BA) of formulations of poorly water-soluble compounds. However, these formulations have certain limitations, including in vivo drug precipitation, poor in vitro in vivo correlation due to a lack of predictive in vitro tests, issues in handling of liquid formulation, and physico-chemical instability of drug and/or vehicle components. To overcome these limitations, which restrict the potential usage of such systems, the supersaturable SEDDSs (su-SEDDSs) have gained attention based on the fact that the inclusion of precipitation inhibitors (PIs) within SEDDSs helps maintain drug supersaturation after dispersion and digestion in the gastrointestinal tract. This improves the BA of drugs and reduces the variability of exposure. In addition, the formulation of solid su-SEDDSs has helped to overcome disadvantages of liquid or capsule dosage form. This review article discusses, in detail, the current status of su-SEDDSs that overcome the limitations of conventional SEDDSs. It discusses the definition and range of su-SEDDSs, the principle mechanisms underlying precipitation inhibition and enhanced in vivo absorption, drug application cases, biorelevance in vitro digestion models, and the development of liquid su-SEDDSs to solid dosage forms. This review also describes the effects of various physiological factors and the potential interactions between PIs and lipid, lipase or lipid digested products on the in vivo performance of su-SEDDSs. In particular, several considerations relating to the properties of PIs are discussed from various perspectives.

Self-Nanoemulsifying Drug Delivery Systems (SNEDDS) Containing Rice Bran Oil for Enhanced Fenofibrate Oral Delivery: In Vitro Digestion, Ex Vivo Permeability, and In Vivo Bioavailability Studies

2020 ◽  
Vol 21 (6) ◽  
Author(s):  
Christina Karavasili ◽  
Ioannis I. Andreadis ◽  
Maria P. Tsantarliotou ◽  
Ioannis A. Taitzoglou ◽  
Paschalina Chatzopoulou ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Rice Bran ◽  
Oral Delivery ◽  
Drug Delivery Systems ◽  
Rice Bran Oil ◽  
Ex Vivo ◽  
In Vitro Digestion ◽  
Delivery Systems

scholarly journals Ex Vivo and In Vivo Characterization of Interpolymeric Blend/Nanoenabled Gastroretentive Levodopa Delivery Systems

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Ndidi C. Ngwuluka ◽  
Yahya E. Choonara ◽  
Girish Modi ◽  
Lisa C. du Toit ◽  
Pradeep Kumar ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Ex Vivo ◽  
Delivery Systems ◽  
Pharmacokinetic Parameters ◽  
Gastric Residence Time ◽  
Systemic Bioavailability ◽  
Absorption Window

One approach for delivery of narrow absorption window drugs is to formulate gastroretentive drug delivery systems. This study was undertaken to provide insight into in vivo performances of two gastroretentive systems (PXLNETand IPB matrices) in comparison to Madopar® HBS capsules. The pig model was used to assess gastric residence time and pharmacokinetic parameters using blood, cerebrospinal fluid (CSF), and urine samples. Histopathology and cytotoxicity testing were also undertaken. The pharmacokinetic parameters indicated that levodopa was liberated from the drug delivery systems, absorbed, widely distributed, metabolized, and excreted.Cmaxwere 372.37, 257.02, and 461.28 ng/mL and MRT were 15.36, 14.98, and 13.30 for Madopar HBS capsules,PXLNET, and IPB, respectively. In addition, X-ray imaging indicated that the gastroretentive systems have the potential to reside in the stomach for 7 hours. There was strong in vitro-in vivo correlation for all formulations withr2values of 0.906, 0.935, and 0.945 for Madopar HBS capsules,PXLNET, and IPB, respectively. Consequently,PXLNETand IPB matrices have pertinent potential as gastroretentive systems for narrow absorption window drugs (e.g., L-dopa) and, in this application specifically, enhanced the central nervous system and/or systemic bioavailability of such drugs.

scholarly journals Estimating the Oral Absorption from Self-Nanoemulsifying Drug Delivery Systems Using an In Vitro Lipolysis-Permeation Method

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 489
Author(s):  
Mette Klitgaard ◽  
Anette Müllertz ◽  
Ragna Berthelsen
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Oral Absorption ◽  
Aqueous Suspension ◽  
Delivery Systems ◽  
Time Curve ◽  
Drug Permeation ◽  
In Vitro Lipolysis

The aim of this study was to design an in vitro lipolysis-permeation method to estimate drug absorption following the oral administration of self-nanoemulsifying drug delivery systems (SNEDDSs). The method was evaluated by testing five oral formulations containing cinnarizine (four SNEDDSs and one aqueous suspension) from a previously published pharmacokinetic study in rats. In that study, the pharmacokinetic profiles of the five formulations did not correlate with the drug solubilization profiles obtained during in vitro intestinal lipolysis. Using the designed lipolysis-permeation method, in vitro lipolysis of the five formulations was followed by in vitro drug permeation in Franz diffusion cells equipped with PermeaPad® barriers. A linear in vivo–in vitro correlation was obtained when comparing the area under the in vitro drug permeation–time curve (AUC0–3h), to the AUC0–3h of the plasma concentration–time profile obtained from the in vivo study. Based on these results, the evaluated lipolysis-permeation method was found to be a promising tool for estimating the in vivo performance of SNEDDSs, but more studies are needed to evaluate the method further.

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