pH-Dependent supersaturation from amorphous solid dispersions of weakly basic drugs

2021 ◽  
Author(s):  
Bo Wang ◽  
Matthew J. Nethercott ◽  
Akshay Narula ◽  
Michael Hanrahan ◽  
Shanming Kuang ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Basic Drugs ◽  
Amorphous Solid Dispersions ◽  
Ph Dependent

scholarly journals Influence of Particle Size and Drug Load on Amorphous Solid Dispersions Containing pH-Dependent Soluble Polymers and the Weak Base Ketoconazole

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Marius Monschke ◽  
Kevin Kayser ◽  
Karl G. Wagner
Keyword(s):  
Particle Size ◽  
Phase Separation ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions ◽  
Drug Load ◽  
Soluble Polymers ◽  
Eudragit L100 ◽  
Ph Dependent ◽  
Hot Melt

AbstractAmong the great number of poorly soluble drugs in pharmaceutical development, most of them are weak bases. Typically, they readily dissolve in an acidic environment but are prone to precipitation at elevated pH. This was aimed to be counteracted by the preparation of amorphous solid dispersions (ASDs) using the pH-dependent soluble polymers methacrylic acid ethylacrylate copolymer (Eudragit L100–55) and hydroxypropylmethylcellulose acetate succinate (HPMCAS) via hot-melt extrusion. The hot-melt extruded ASDs were of amorphous nature and single phased with the presence of specific interactions between drug and polymer as revealed by X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier-transform infrared spectroscopy (FT-IR). The ASDs were milled and classified into six particle size fractions. We investigated the influence of particle size, drug load, and polymer type on the dissolution performance. The best dissolution performance was achieved for the ASD made from Eudragit L100–55 at a drug load of 10%, whereby the dissolution rate was inversely proportional to the particle size. Within a pH-shift dissolution experiment (from pH 1 to pH 6.8), amorphous-amorphous phase separation occurred as a result of exposure to acidic medium which caused markedly reduced dissolution rates at subsequent higher pH values. Phase separation could be prevented by using enteric capsules (Vcaps Enteric®), which provided optimal dissolution profiles for the Eudragit L100–55 ASD at a drug load of 10%.

scholarly journals Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion—Preparation of Amorphous Solid Dispersions

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 337 ◽  
Author(s):  
Marius Monschke ◽  
Kevin Kayser ◽  
Karl G. Wagner
Keyword(s):  
Polyvinyl Acetate ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Hot Melt Extrusion ◽  
Extrusion Process ◽  
Dissolution Time ◽  
Melt Extrusion ◽  
Amorphous Solid Dispersions ◽  
Ph Dependent ◽  
Hot Melt

The preparation of amorphous solid dispersions (ASDs) is a suitable approach to overcome solubility-limited absorption of poorly soluble drugs. In particular, pH-dependent soluble polymers have proven to be an excellently suitable carrier material for ASDs. Polyvinyl acetate phthalate (PVAP) is a polymer with a pH-dependent solubility, which is as yet not thoroughly characterized regarding its suitability for a hot-melt extrusion process. The objective of this study was to assess the processability of PVAP within a hot-melt extrusion process with the aim of preparing an ASD. Therefore, the influence of different process parameters (temperature, feed-rate) on the degree of degradation, solid-state and dissolution time of the neat polymer was studied. Subsequently, drug-containing ASDs with indomethacin (IND) and dipyridamole (DPD) were prepared, respectively, and analyzed regarding drug content, solid-state, non-sink dissolution performance and storage stability. PVAP was extrudable in combination with 10% (w/w) PEG 3000 as plasticizer. The dissolution time of PVAP was only slightly influenced by different process parameters. For IND no degradation occurred in combination with PVAP and single phased ASDs could be generated. The dissolution performance of the IND-PVAP ASD at pH 5.5 was superior and at pH 6.8 equivalent compared to commonly used polymers hydroxypropylmethylcellulose acetate succinate (HPMCAS) and Eudragit L100-55.

Development of novel darunavir amorphous solid dispersions with mesoporous carriers

2021 ◽  
Vol 159 ◽  
pp. 105700
Author(s):  
Sergey A. Zolotov ◽  
Natalia B. Demina ◽  
Anna S. Zolotova ◽  
Natalia V. Shevlyagina ◽  
Grigorii A. Buzanov ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

Effect of Carrier Type and Tween® 80 Concentration on the Release of Silymarin from Amorphous Solid Dispersions

2021 ◽  
pp. 102416
Author(s):  
Valentyn Mohylyuk ◽  
Thomas Pauly ◽  
Oleksandr Dobrovolnyi ◽  
Nathan Scott ◽  
David S. Jones ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

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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