scholarly journals The Development and Optimization of Hot-Melt Extruded Amorphous Solid Dispersions Containing Rivaroxaban in Combination with Polymers

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 344
Author(s):  
Jong-Hwa Lee ◽  
Hyeong Sik Jeong ◽  
Jong-Woo Jeong ◽  
Tae-Sung Koo ◽  
Do-Kyun Kim ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Dissolution Rate ◽  
Solid Dispersion ◽  
Oral Drug Delivery ◽  
Amorphous Solid ◽  
Drug Dissolution ◽  
Oral Drug ◽  
Amorphous Solid Dispersion ◽  
Screw Speed ◽  
Hot Melt

Rivaroxaban (RXB), a novel oral anticoagulant that directly inhibits factor Xa, is a poorly soluble drug belonging to Biopharmaceutics Classification System (BCS) class II. In this study, a hot-melt extruded amorphous solid dispersion (HME-ASD) containing RXB is prepared by changing the drug:polymer ratio (Polyvinylpyrrolidione-vinyl acetate 64, 1:1–1:4) and barrel temperature (200–240 °C), fixed at 20% of Cremophor® RH 40 and 15 rpm of the screw speed, using the hot-melt extruding technique. This study evaluates the solubility, dissolution behavior, and bioavailability for application to oral drug delivery and optimizes the formulation of rivaroxaban amorphous solid dispersion (RXB-ASD). Based on a central composite design, optimized RXB-ASD (PVP VA 64 ratio 1:4.1, barrel temperature 216.1 °C, Cremophor® RH 40 20%, screw speed 15 rpm) showed satisfactory results for dependent variables. An in vitro drug dissolution study exhibited relatively high dissolution in four media and achieved around an 80% cumulative drug release in 120 min. Optimized RXB-ASD was stable under the accelerated condition for three months without a change in crystallinity and the dissolution rate. A pharmacokinetic study of RXB-ASD in rats showed that the absorption was markedly increased in terms of rate and amount, i.e., the systemic exposure values, compared to raw RXB powder. These results showed the application of quality by design (QbD) in the formulation development of hot-melt extruded RXB-ASD, which can be used as an oral drug delivery system by increasing the dissolution rate and bioavailability.

scholarly journals Drug-Rich Phases Induced by Amorphous Solid Dispersion: Arbitrary or Intentional Goal in Oral Drug Delivery?

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 889
Author(s):  
Kaijie Qian ◽  
Lorenzo Stella ◽  
David S. Jones ◽  
Gavin P. Andrews ◽  
Huachuan Du ◽  
...  
Keyword(s):  
Solid Dispersion ◽  
Oral Drug Delivery ◽  
Drug Product ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Nucleation Theory ◽  
Product Development Process ◽  
Classical Nucleation Theory ◽  
Oral Drug ◽  
Amorphous Solid Dispersion

Among many methods to mitigate the solubility limitations of drug compounds, amorphous solid dispersion (ASD) is considered to be one of the most promising strategies to enhance the dissolution and bioavailability of poorly water-soluble drugs. The enhancement of ASD in the oral absorption of drugs has been mainly attributed to the high apparent drug solubility during the dissolution. In the last decade, with the implementations of new knowledge and advanced analytical techniques, a drug-rich transient metastable phase was frequently highlighted within the supersaturation stage of the ASD dissolution. The extended drug absorption and bioavailability enhancement may be attributed to the metastability of such drug-rich phases. In this paper, we have reviewed (i) the possible theory behind the formation and stabilization of such metastable drug-rich phases, with a focus on non-classical nucleation; (ii) the additional benefits of the ASD-induced drug-rich phases for bioavailability enhancements. It is envisaged that a greater understanding of the non-classical nucleation theory and its application on the ASD design might accelerate the drug product development process in the future.

scholarly journals Influence of Drug Load on the Printability and Solid-State Properties of 3D-Printed Naproxen-Based Amorphous Solid Dispersion

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4492
Author(s):  
Eric Ofosu Kissi ◽  
Robin Nilsson ◽  
Liebert Parreiras Nogueira ◽  
Anette Larsson ◽  
Ingunn Tho
Keyword(s):  
Solid State ◽  
3D Printing ◽  
Solid Dispersion ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Drug Load ◽  
X Ray ◽  
3D Printed ◽  
Hot Melt

Fused deposition modelling-based 3D printing of pharmaceutical products is facing challenges like brittleness and printability of the drug-loaded hot-melt extruded filament feedstock and stabilization of the solid-state form of the drug in the final product. The aim of this study was to investigate the influence of the drug load on printability and physical stability. The poor glass former naproxen (NAP) was hot-melt extruded with Kollidon® VA 64 at 10–30% w/w drug load. The extrudates (filaments) were characterised using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). It was confirmed that an amorphous solid dispersion was formed. A temperature profile was developed based on the results from TGA, DSC, and DMA and temperatures used for 3D printing were selected from the profile. The 3D-printed tablets were characterised using DSC, X-ray computer microtomography (XµCT), and X-ray powder diffraction (XRPD). From the DSC and XRPD analysis, it was found that the drug in the 3D-printed tablets (20 and 30% NAP) was amorphous and remained amorphous after 23 weeks of storage (room temperature (RT), 37% relative humidity (RH)). This shows that adjusting the drug ratio can modulate the brittleness and improve printability without compromising the physical stability of the amorphous solid dispersion.

scholarly journals Evaluation of Drug Load and Polymer by Using a 96-Well Plate Vacuum Dry System for Amorphous Solid Dispersion Drug Delivery

2012 ◽  
Vol 13 (2) ◽  
pp. 713-722 ◽  
Author(s):  
Po-Chang Chiang ◽  
Yingqing Ran ◽  
Kang-Jye Chou ◽  
Yong Cui ◽  
Amy Sambrone ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Solid Dispersion ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Drug Load

In Situ Salification in Polar Solvents: a Paradigm for Enabling Drug Delivery of Weakly Ionic Drugs as Amorphous Solid Dispersion

2017 ◽  
Vol 19 (1) ◽  
pp. 326-337
Author(s):  
Rashmi Nair ◽  
Ioorika Lamare ◽  
Nirbhay Kumar Tiwari ◽  
Punna Rao Ravi ◽  
Raviraj Pillai
Keyword(s):  
Drug Delivery ◽  
Solid Dispersion ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersion ◽  
Polar Solvents

scholarly journals Optimization of amorphous solid dispersion techniques to enhance solubility of febuxostat

Folia Medica ◽  
2021 ◽  
Vol 63 (4) ◽  
pp. 557-568
Author(s):  
Vaishali P. Patel ◽  
Anita P. Patel ◽  
Ashish Shah
Keyword(s):  
Dissolution Rate ◽  
Solid Dispersion ◽  
Amorphous Solid ◽  
Amorphous Powder ◽  
Amorphous Solid Dispersion ◽  
Scanning Calorimetry ◽  
Residual Solvent ◽  
Percentage Yield ◽  
Poorly Soluble ◽  
Powder Characteristics

Febuxostat is a selective inhibitor of xanthine oxidase and belongs to BCS class II drugs having low solubility and high permeability. Solubility is the most important parameter which directly affects dissolution, absorption and bioavailability of the drugs. There are different techniques by which we can improve solubility and dissolution rate of poorly soluble drug. Amorphous solid dispersion is one of the methods which can improve solubility as well as powder characteristics. The aim of the present study was to formulate and optimize various methods of formulating solid dispersion by using various drug-to-polymer ratios and identifying the batch which gives higher solubility as well as amorphous powder of the drug febuxostat. Different techniques like hot melt method, solvent evaporation method and spray drying techniques were selected for optimization. Attempts were made to improve solubility of febuxostat by employing Kolliphor P 188, Kolliphor P 237, Eudragit RLPO in different drug-to-polymer ratios (1:1, 1:1.5, 1:2) as carrier. The prepared solid dispersion was characterized for the saturation solubility, percentage yield, using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), powdered X-ray diffraction studies (PXRD), and residual solvent determination. Solid state characterization indicated that febuxostat was present in the amorphous form after mixing with polymeric carrier. In contrast to the pure form of drug, solid dispersion of the drug showed better solubility and amorphous characteristics which can be attributed to decreased crystallinity due to hydrotrophy. Thus, amorphous solid dispersion approach can be used successfully to enhance solubility, dissolution rate and bioavailability of febuxostat.

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