Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products

Pandi, Palpandi; Bulusu, Raviteja; Kommineni, Nagavendra; Khan, Wahid; Singh, Mandip

doi:10.1016/j.ijpharm.2020.119560

Cited by 240 publications

(162 citation statements)

References 109 publications

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“…Among these formulation approaches, amorphous solid dispersions (ASDs) were successfully applied. ASDs were shown to be able to enhance the oral bioavailability and there are several approved ASD formulations on the marked (6)(7)(8). An ASD consists of a drug, which is incorporated into a polymeric matrix, preferably in a molecularly dispersed state (single phase ASDs or solid solution) (9,10).…”

Section: Introductionmentioning

confidence: 99%

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

2021

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Among 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%.

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Section: Introductionmentioning

confidence: 99%

“…The most common preparation techniques for ASDs are hot-melt extrusion (melt based) and spray-drying (solvent based) (7). For a hot-melt extrusion process, the material needs to be thermally stable and its melt viscosity should be in an acceptable range, additionally drug and polymer should be miscible in the ratio which is used (27,28).…”

Section: Introductionmentioning

confidence: 99%

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

2021

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“…First, the level of drug crystallinity in SDs can be evaluated via techniques such as powder X-ray diffraction and different scanning calorimetry [57]. Second, the molecular interactions can be characterized by infrared spectroscopy, Raman spectroscopy, nuclear magnetic resonance spectroscopy, X-ray photoelectron spectroscopy, molecular modeling, quantum chemical calculation, and water vapor sorption [58,59]. Third, scanning electron microscopy, atomic force microscopy, and transmission electron microscopy are usually utilized to observe the morphologies of SDs and nano-sized particles [26,58].…”

Section: Fundamental Properties and Physicochemical Characterization mentioning

confidence: 99%

“…Second, the molecular interactions can be characterized by infrared spectroscopy, Raman spectroscopy, nuclear magnetic resonance spectroscopy, X-ray photoelectron spectroscopy, molecular modeling, quantum chemical calculation, and water vapor sorption [58,59]. Third, scanning electron microscopy, atomic force microscopy, and transmission electron microscopy are usually utilized to observe the morphologies of SDs and nano-sized particles [26,58]. The details of those methods can be found in prominent reviews [57][58][59].…”

Section: Fundamental Properties and Physicochemical Characterization mentioning

confidence: 99%

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Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

Tran

2020

Polymers

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In recent decades, solid dispersions have been demonstrated as an effective approach for improving the bioavailability of poorly water-soluble drugs, as have solid dispersion techniques that include the application of nanotechnology. Many studies have reported on the ability to change drug crystallinity and molecular interactions to enhance the dissolution rate of solid dispersions using hydrophilic carriers. However, numerous studies have indicated that insoluble carriers are also promising excipients in solid dispersions. In this report, an overview of solid dispersion strategies involving insoluble carriers has been provided. In addition to the role of solubility and dissolution enhancement, the perspectives of the use of these polymers in controlled release solid dispersions have been classified and discussed. Moreover, the compatibility between methods and carriers and between drug and carrier is mentioned. In general, this report on solid dispersions using insoluble carriers could provide a specific approach and/or a selection of these polymers for further formulation development and clinical applications.

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High‐Pressure Synthesis of Amorphous Si₃N₄ and SiBN‐Based Monoliths without Sintering Additives

Li,

Ma,

Cui

et al. 2024

Adv Eng Mater

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Amorphous Si3N4 and SiBN monoliths without sintering additives were successfully prepared by high‐pressure‐low‐temperature (HPLT) sintering using the single‐source‐precursor derived amorphous Si3N4 and SiBN powders as raw materials. The microstructural evolution and crystallization behavior of the as‐prepared samples were investigated using scanning electron and transmission electron microscopy and X‐ray powder diffraction, respectively. The results showed that the incorporation of boron in the Si–N network enhanced the crystallization temperature up to 1200 °C. The Vickers’ hardness of the HPLT‐sintered Si3N4 sample amounts ∽ 11.6 GPa whether prepared at 1000 °C or 1200 °C, while the maximum hardness of the SiBN sample is up to 16.3 GPa. The fracture toughness of amorphous Si3N4 and SiBN5 samples are almost identical (around 2.5 MPa·m1/2) whether prepared at 1000 oC or 1200 oC, and SiBN2 and SiBN5 samples show an improved fracture toughness. In addition, the oxidation resistance of the as‐prepared samples was investigated at temperatures up to 1000 oC. A comparison between amorphous Si3N4 and SiBN monoliths demonstrated a positive effect of the presence of boron on their oxidation resistance.This article is protected by copyright. All rights reserved.

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Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products

Cited by 240 publications

References 109 publications

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

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

Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

High‐Pressure Synthesis of Amorphous Si₃N₄ and SiBN‐Based Monoliths without Sintering Additives

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Amorphous solid dispersions: An update for preparation, characterization, mechanism on bioavailability, stability, regulatory considerations and marketed products

Cited by 240 publications

References 109 publications

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

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

Insoluble Polymers in Solid Dispersions for Improving Bioavailability of Poorly Water-Soluble Drugs

High‐Pressure Synthesis of Amorphous Si3N4 and SiBN‐Based Monoliths without Sintering Additives

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High‐Pressure Synthesis of Amorphous Si₃N₄ and SiBN‐Based Monoliths without Sintering Additives