scholarly journals Direct Visualization of Drug–Polymer Phase Separation in Ritonavir–Copovidone Amorphous Solid Dispersions Using in situ Synchrotron X-ray Fluorescence Imaging of Thin Films

2019 ◽  
Vol 16 (11) ◽  
pp. 4751-4754
Author(s):  
Chenyang Shi ◽  
Luxi Li ◽  
Geoff G. Z. Zhang ◽  
Thomas B. Borchardt
Keyword(s):  
Thin Films ◽  
Phase Separation ◽  
Fluorescence Imaging ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Direct Visualization ◽  
Polymer Phase ◽  
Amorphous Solid Dispersions ◽  
X Ray

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 Modelling phase separation in amorphous solid dispersions

2019 ◽  
Vol 94 ◽  
pp. 410-424 ◽  
Author(s):  
Martin Meere ◽  
Giuseppe Pontrelli ◽  
Sean McGinty
Keyword(s):  
Phase Separation ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

scholarly journals Compression-Induced Phase Transitions of Bicalutamide

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 438 ◽  
Author(s):  
Joanna Szafraniec-Szczęsny ◽  
Agata Antosik-Rogóż ◽  
Justyna Knapik-Kowalczuk ◽  
Mateusz Kurek ◽  
Ewa Szefer ◽  
...  
Keyword(s):  
Solid Dispersions ◽  
Amorphous Solid ◽  
Active Pharmaceutical Ingredient ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
X Ray ◽  
High Propensity ◽  
Poorly Soluble ◽  
Amorphous Drug

The formation of solid dispersions with the amorphous drug dispersed in the polymeric matrix improves the dissolution characteristics of poorly soluble drugs. Although they provide an improved absorption after oral administration, the recrystallization, which can occur upon absorption of moisture or during solidification and other formulation stages, serves as a major challenge. This work aims at understanding the amorphization-recrystallization changes of bicalutamide. Amorphous solid dispersions with poly(vinylpyrrolidone-co-vinyl acetate) (PVP/VA) were obtained by either ball milling or spray drying. The applied processes led to drug amorphization as confirmed using X-ray diffraction and differential scanning calorimetry. Due to a high propensity towards mechanical activation, the changes of the crystal structure of physical blends of active pharmaceutical ingredient (API) and polymer upon pressure were also examined. The compression led to drug amorphization or transition from form I to form II polymorph, depending on the composition and applied force. The formation of hydrogen bonds confirmed using infrared spectroscopy and high miscibility of drug and polymer determined using non-isothermal dielectric measurements contributed to the high stability of amorphous solid dispersions. They exhibited improved wettability and dissolution enhanced by 2.5- to 11-fold in comparison with the crystalline drug. The drug remained amorphous upon compression when the content of PVP/VA in solid dispersions exceeded 20% or 33%, in the case of spray-dried and milled systems, respectively.

scholarly journals Understanding the Tendency of Amorphous Solid Dispersions to Undergo Amorphous–Amorphous Phase Separation in the Presence of Absorbed Moisture

2011 ◽  
Vol 12 (4) ◽  
pp. 1209-1219 ◽  
Author(s):  
Alfred C. F. Rumondor ◽  
Håkan Wikström ◽  
Bernard Van Eerdenbrugh ◽  
Lynne S. Taylor
Keyword(s):  
Phase Separation ◽  
Amorphous Phase ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

scholarly journals Fluoroquinolone Amorphous Polymeric Salts and Dispersions for Veterinary Uses

Pharmaceutics ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 268 ◽  
Author(s):  
Hanah Mesallati ◽  
Anita Umerska ◽  
Lidia Tajber
Keyword(s):  
Solid Dispersions ◽  
Hydroxypropyl Methylcellulose ◽  
Amorphous Solid ◽  
Ionic Bond ◽  
Amorphous Solid Dispersions ◽  
X Ray ◽  
Poorly Soluble ◽  
Pure Drug ◽  
Poorly Soluble Drug ◽  
Pharmaceutical Properties

Enrofloxacin (ENRO) is a poorly soluble drug used in veterinary medicine. It differs from the more widely used fluoroquinolone ciprofloxacin (CIP) by the presence of an ethyl substituent on its piperazine amino group. While a number of recent studies have examined amorphous composite formulations of CIP, little research has been conducted with ENRO in this area. Therefore, the main purpose of this work was to produce amorphous solid dispersions (ASDs) of ENRO. The solid-state properties of these samples were investigated and compared to those of the equivalent CIP ASDs, and their water uptake behavior, solubility, dissolution, and antibacterial activity were assessed. Like CIP, X-ray amorphous solid dispersions were obtained when ENRO was ball milled with acidic polymers, whereas the use of neutral polymers resulted in semi-crystalline products. Proton transfer from the carboxylic acids of the polymers to the tertiary amine of ENRO’s piperazine group appears to occur in the ASDs, resulting in an ionic bond between the two components. Therefore, these ASDs can be referred to as amorphous polymeric salts (APSs). The glass transition temperatures of the APSs were significantly higher than that of ENRO, and they were also resistant to crystallization when exposed to high humidity levels. Greater concentrations were achieved with the APSs than the pure drug during solubility and dissolution studies, and this enhancement was sustained for the duration of the experiments. In addition, the antimicrobial activity of ENRO was not affected by APS formation, while the minimum inhibitory concentrations and minimum bactericidal concentrations obtained with the APS containing hydroxypropyl methylcellulose acetate succinate grade MG (HPMCAS-MG) were significantly lower than those of the pure drug. Therefore, APS formation is one method of improving the pharmaceutical properties of this drug.

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