Effect of surfactant on the in vitro dissolution and the oral bioavailability of a weakly basic drug from an amorphous solid dispersion

2021 ◽  
pp. 105836
Author(s):  
Nguyen-Thach Tung ◽  
Cao-Son Tran ◽  
Tran-Linh Nguyen ◽  
Thi-Minh-Hue Pham ◽  
Sang-Cheol Chi ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Amorphous Solid ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Basic Drug

Importance of in vitro dissolution conditions for the in vivo predictability of an amorphous solid dispersion containing a pH-sensitive carrier

2017 ◽  
Vol 531 (1) ◽  
pp. 324-331 ◽  
Author(s):  
Johan Wendelboe ◽  
Matthias Manne Knopp ◽  
Fauzan Khan ◽  
Nabil Chourak ◽  
Thomas Rades ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Ph Sensitive ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion

Fenofibrate Solid Dispersion Processed by Hot-Melt Extrusion: Elevated Bioavailability and Its Cell Transport Mechanism

2019 ◽  
Vol 16 (6) ◽  
pp. 538-547 ◽  
Author(s):  
Ting Wen ◽  
Boyi Niu ◽  
Qiaoli Wu ◽  
Yixian Zhou ◽  
Xin Pan ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Dissolution Test ◽  
Melt Extrusion ◽  
Cell Transport ◽  
Hot Melt

Background: Fenofibrate (FNB) is an effective drug for the treatment of hypertriglyceridemia, hypercholesterolemia as well as mixed hyperlipidemia. However, due to its poor aqueous solubility, FNB has the problem of poor oral absorption followed by low bioavailability. Objective: The aim of this research was to construct FNB amorphous solid dispersion employing PVP VA64 as the carrier by hot-melt extrusion method, in order to improve the oral bioavailability. Additionally, the cell transport experiment was conducted to further investigate the mechanism of promoted osmotic absorption. Methods: The physical state of the obtained solid dispersion was characterized using SEM, DSC and XRD. Besides, in vitro Caco-2 cells were used to evaluate the cytotoxicity of the carrier and mimic gastrointestinal drug permeation. At last, in vitro dissolution test and in vivo bioavailability study were also carried out. Results: The prepared FNB solid dispersion was found to be an amorphous state after hot-melt extrusion process. In vitro cytotoxicity test on Caco-2 cells confirmed the excellent biocompatibility of the carrier PVP VA64. Besides, transwell cell transport assay and in vitro dissolution test revealed that FNB released from amorphous solid dispersion was equipped with an improved transmembrane transport and dissolution rate. Moreover, pharmacokinetic study in beagle dogs showed that comparing with commercial micronized product Lipanthyl®, the oral bioavailability of FNB solid dispersion was significantly enhanced (2.45 fold). Conclusion: In conclusion, PVP VA64 can be regarded as a promising polymer to enhance the bioavailability of poorly water-soluble drugs such as FNB processed by hot-melt extrusion. Besides, investigations on the mechanism of the enhanced penetration are expected to lay a foundation on the subsequent development of effective and practical solid dispersion.

scholarly journals Developing pH-Modulated Spray Dried Amorphous Solid Dispersion of Candesartan Cilexetil with Enhanced In Vitro and In Vivo Performance

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 497
Author(s):  
Surendra Poudel ◽  
Dong Wuk Kim
Keyword(s):  
Solid Dispersion ◽  
Oral Absorption ◽  
Candesartan Cilexetil ◽  
Amorphous State ◽  
Amorphous Solid ◽  
In Vitro Dissolution ◽  
Amorphous Solid Dispersion ◽  
Pharmacokinetic Parameters ◽  
Highly Effective

Candesartan cilexetil (CC), a prodrug and highly effective antihypertensive agent, is a poorly soluble (BCS Class II) drug with limited bioavailability. Here, we attempted to improve CC’s bioavailability by formulating several CC-loaded amorphous solid dispersions with a hydrophilic carrier (PVPK30) and pH modifier (sodium carbonate) using the spray drying technique. Solubility, in vitro dissolution, and moisture content tests were used for screening the optimized formulation. We identified an optimized formulation of CC/PVPK30/SC, which at the ratio of 1:0.5:1 (w/w/w) exhibited a 30,000-fold increase in solubility and a more than 9-fold enhancement in dissolution compared to pure CC. Solid-state characterization revealed that in pH-modulated CC amorphous solid dispersion (CCSDpM), CC’s crystallinity was altered to an amorphous state with the absence of undesirable interactions. Stability studies also showed that the optimized formulation was stable with good drug content and drug release under accelerated conditions of up to 4 weeks and real-time stability conditions of up to 12 weeks. Furthermore, pharmacokinetic parameters, such as AUC and Cmax of candesartan, had a 4.45-fold and 7.42-fold improvement, respectively, in CCSDpM-treated rats compared to those in the CC-treated rats. Thus, these results suggest that CCSDpM is highly effective for increasing oral absorption. The application of these techniques can be a viable strategy to improve a drug’s bioavailability.

scholarly journals Enhanced Oral Bioavailability of Resveratrol by Using Neutralized Eudragit E Solid Dispersion Prepared via Spray Drying

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 90
Author(s):  
Eun-Sol Ha ◽  
Du Hyung Choi ◽  
In-hwan Baek ◽  
Heejun Park ◽  
Min-Soo Kim
Keyword(s):  
Spray Drying ◽  
Solid Dispersion ◽  
Oral Bioavailability ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Pharmaceutical Products ◽  
In Vitro Dissolution ◽  
Dependent Manner ◽  
Amorphous Solid Dispersions ◽  
Eudragit E

In this study, we designed amorphous solid dispersions based on Eudragit E/HCl (neutralized Eudragit E using hydrochloric acid) to maximize the dissolution of trans-resveratrol. Solid-state characterization of amorphous solid dispersions of trans-resveratrol was performed using powder X-ray diffraction, scanning electron microscopy, and particle size measurements. In addition, an in vitro dissolution study and an in vivo pharmacokinetic study in rats were carried out. Among the tested polymers, Eudragit E/HCl was the most effective solid dispersion for the solubilization of trans-resveratrol. Eudragit E/HCl significantly inhibited the precipitation of trans-resveratrol in a pH 1.2 dissolution medium in a dose-dependent manner. The amorphous Eudragit E/HCl solid dispersion at a trans-resveratrol/polymer ratio of 10/90 exhibited a high degree of supersaturation without trans-resveratrol precipitation for at least 48 h by the formation of Eudragit E/HCl micelles. In rats, the absolute oral bioavailability (F%) of trans-resveratrol from Eudragit E/HCl solid dispersion (10/90) was estimated to be 40%. Therefore, trans-resveratrol-loaded Eudragit E/HCl solid dispersions prepared by spray drying offer a promising formulation strategy with high oral bioavailability for developing high-quality health supplements, nutraceutical, and pharmaceutical products.

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