scholarly journals Effect of Storage Humidity on Physical Stability of Spray-Dried Naproxen Amorphous Solid Dispersions with Polyvinylpyrrolidone: Two Fluid Nozzle vs. Three Fluid Nozzle

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1074
Author(s):  
Sonal V. Bhujbal ◽  
Yongchao Su ◽  
Vaibhav Pathak ◽  
Dmitry Y. Zemlyanov ◽  
Alex-Anthony Cavallaro ◽  
...  
Keyword(s):  
Spray Drying ◽  
Single Channel ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Volume Ratio ◽  
Amorphous Solid ◽  
Drug Dissolution ◽  
Amorphous Solid Dispersions ◽  
Two Fluid ◽  
Spray Dried

In a spray drying operation, a two-fluid nozzle (2FN) with a single channel is commonly used for atomizing the feed solution. However, the less commonly used three-fluid nozzle (3FN) has two separate channels, which allow spray drying of materials in two incompatible solution systems. Although amorphous solid dispersions (ASDs) prepared using a 3FN have been reported to deliver comparable drug dissolution performance relative to those prepared using a 2FN, few studies have systematically examined the effect of 3FN on the physical stability. Therefore, the goal of this work is to systematically study the physical stability of ASDs that are spray-dried using a 3FN compared to those prepared using the traditional 2FN. For the 2FN, a single solution of naproxen and polyvinylpyrrolidone (PVP) was prepared in a mixture of acetone and water at a 1:1 volume ratio because 2FN allows for only one solution inlet. For the 3FN, naproxen and PVP were dissolved individually in acetone and water, respectively, because 3FN allows simultaneous entry of two solutions. Upon storage of the formulated ASDs at different humidity levels (25%, 55% and 75% RH), naproxen crystallized more quickly from the 3FN ASDs as compared with the 2FN ASDs. 3FN ASDs crystallized after 5 days of storage at all conditions, whereas 2FN ASDs did not crystallize even at 55% RH for two months. This relatively higher crystallization tendency of 3FN ASDs was attributed to the inhomogeneity of drug and polymers as identified by the solid-state Nuclear Magnetic Resonance findings, specifically due to poor mixing of water- and acetone-based solutions at the 3FN nozzle. When only acetone was used as a solvent to prepare drug-polymer solutions for 3FN, the formulated ASD was found to be stable for >3 months of storage (at 75% RH), which suggests that instability of the 3FN ASD was due to the insufficient mixing of water and acetone solutions. This study provides insights into the effects of solvent and nozzle choices on the physical stability of spray-dried ASDs.

scholarly journals Polyelectrolyte Matrices in the Modulation of Intermolecular Electrostatic Interactions for Amorphous Solid Dispersions: A Comprehensive Review

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1467
Author(s):  
Anastasia Tsiaxerli ◽  
Anna Karagianni ◽  
Andreas Ouranidis ◽  
Kyriakos Kachrimanis
Keyword(s):  
Electrostatic Interactions ◽  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Drug Dissolution ◽  
Amorphous Solid Dispersions ◽  
Continuous Processes ◽  
Interpolyelectrolyte Complexes ◽  
Nonionic Polymers ◽  
Hot Melt

Polyelectrolyte polymers have been widely used in the pharmaceutical field as excipients to facilitate various drug delivery systems. Polyelectrolytes have been used to modulate the electrostatic environment and enhance favorable interactions between the drug and the polymer in amorphous solid dispersions (ASDs) prepared mainly by hot-melt extrusion. Polyelectrolytes have been used alone, or in combination with nonionic polymers as interpolyelectrolyte complexes, or after the addition of small molecular additives. They were found to enhance physical stability by favoring stabilizing intermolecular interactions, as well as to exert an antiplasticizing effect. Moreover, they not only enhance drug dissolution, but they have also been used for maintaining supersaturation, especially in the case of weakly basic drugs that tend to precipitate in the intestine. Additional uses include controlled and/or targeted drug release with enhanced physical stability and ease of preparation via novel continuous processes. Polyelectrolyte matrices, used along with scalable manufacturing methods in accordance with green chemistry principles, emerge as an attractive viable alternative for the preparation of ASDs with improved physical stability and biopharmaceutic performance.

scholarly journals Spray-Dried Paracetamol/Polyvinylpyrrolidone Amorphous Solid Dispersions: Part I—Stability of Powders and Tablets

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1938
Author(s):  
Lena Ritters ◽  
Yuanyuan Tian ◽  
Stephan Reichl
Keyword(s):  
Solid Dispersions ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Polymorphic Form ◽  
Scanning Calorimetry ◽  
Amorphous Solid Dispersions ◽  
Pharmaceutical Ingredients ◽  
Poorly Soluble ◽  
The Stability ◽  
Spray Dried

The formulation of active pharmaceutical ingredients (APIs) in amorphous solid dispersions (ASDs) is a promising approach to improve the bioavailability of poorly soluble compounds. However, problems often arise in the production of tablets from ASDs regarding the compressibility and recrystallization of the API. In the present study, the preparation of spray-dried ASDs of paracetamol (PCM) and four different types of polyvinylpyrrolidone (PVP) and their further processing into tablets were investigated. The influence of PVP type on the glass transition temperature (Tg) and the physical stability of ASD powders were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). ASD powders with 10 to 30% PCM were stable for at least 48 weeks. PCM contents of 40 to 50% led to recrystallization of the amorphous PCM within a few days or weeks. ASD with PVP/vinyl acetate (VA) copolymer (PVP/VA) was the most unstable and tended to recrystallize in PCM polymorphic form II. This formulation was therefore used for tablet studies. The influence of compression force on recrystallization, crushing strength, and drug release was investigated. Even high compression forces did not affect the stability of the ASD. However, the ASD tablets led to slow release of the API.

scholarly journals Hierarchical Particle Approach for Co-Precipitated Amorphous Solid Dispersions for Use in Preclinical In Vivo Studies

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1034
Author(s):  
Luke Schenck ◽  
Christopher Boyce ◽  
Derek Frank ◽  
Sampada Koranne ◽  
Heidi Ferguson ◽  
...  
Keyword(s):  
Spray Drying ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Water Soluble ◽  
Amorphous Solid Dispersions ◽  
Amorphous Dispersions ◽  
Co Precipitation ◽  
Particle Approach ◽  
Spray Dried

Amorphous solid dispersions (ASD) have become a well-established strategy to improve exposure for compounds with insufficient aqueous solubility. Of methods to generate ASDs, spray drying is a leading route due to its relative simplicity, availability of equipment, and commercial scale capacity. However, the broader industry adoption of spray drying has revealed potential limitations, including the inability to process compounds with low solubility in volatile solvents, inconsistent molecular uniformity of spray dried amorphous dispersions, variable physical properties across batches and scales, and challenges containing potent compounds. In contrast, generating ASDs via co-precipitation to yield co-precipitated amorphous dispersions (cPAD) offers solutions to many of those challenges and has been shown to achieve ASDs comparable to those manufactured via spray drying. This manuscript applies co-precipitation for early safety studies, developing a streamlined process to achieve material suitable for dosing as a suspension in conventional toxicity studies. Development targets involved achieving a rapid, safely contained process for generating ASDs with high recovery yields. Furthermore, a hierarchical particle approach was used to generate composite particles where the cPAD material is incorporated in a matrix of water-soluble excipients to allow for rapid re-dispersibility in the safety study vehicle to achieve a uniform suspension for consistent dosing. Adopting such an approach yielded a co-precipitated amorphous dispersion with comparable stability, thermal properties, and in vivo pharmacokinetics to spray dried amorphous materials of the same composition.

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.

scholarly journals Spray-Dried Amorphous Solid Dispersions of Griseofulvin in HPC/Soluplus/SDS: Elucidating the Multifaceted Impact of SDS as a Minor Component

Pharmaceutics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 197 ◽  
Author(s):  
Mahbubur Rahman ◽  
Stephanie Ahmad ◽  
James Tarabokija ◽  
Nathaniel Parker ◽  
Ecevit Bilgili
Keyword(s):  
Solid Dispersions ◽  
Sodium Dodecyl ◽  
Minor Component ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions ◽  
Acetone Water ◽  
Poorly Soluble ◽  
A Minor ◽  
The Impact ◽  
Spray Dried

This study aimed to elucidate the impact of a common anionic surfactant, sodium dodecyl sulfate (SDS), along with hydroxypropyl cellulose (HPC) and Soluplus (Sol) on the release of griseofulvin (GF), a poorly soluble drug, from amorphous solid dispersions (ASDs). Solutions of 2.5% GF and 2.5%–12.5% HPC/Sol with 0.125% SDS/without SDS were prepared in acetone–water and spray-dried. The solid-state characterization of the ASDs suggests that GF–Sol had better miscibility and stronger interactions than GF–HPC and formed XRPD-amorphous GF, whereas HPC-based ASDs, especially the ones with a lower HPC loading, had crystalline GF. The dissolution tests show that without SDS, ASDs provided limited GF supersaturation (max. 250%) due to poor wettability of Sol-based ASDs and extensive GF recrystallization in HPC-based ASDs (max. 50%). Sol-based ASDs with SDS exhibited a dramatic increase in supersaturation (max. 570%), especially at a higher Sol loading, whereas HPC-based ASDs with SDS did not. SDS did not interfere with Sol’s ability to inhibit GF recrystallization, as confirmed by the precipitation from the supersaturated state and PLM imaging. The favorable use of SDS in a ternary ASD was attributed to both the wettability enhancement and its inability to promote GF recrystallization when used as a minor component along with Sol.

scholarly journals Development of a small-scale spray-drying approach for amorphous solid dispersions (ASDs) screening in early drug development

2018 ◽  
Vol 24 (5) ◽  
pp. 560-574 ◽  
Author(s):  
Aymeric Ousset ◽  
Céline Bassand ◽  
Pierre-François Chavez ◽  
Joke Meeus ◽  
Florent Robin ◽  
...  
Keyword(s):  
Drug Development ◽  
Spray Drying ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Small Scale ◽  
Amorphous Solid Dispersions ◽  
Early Drug

scholarly journals Rapid Assessment of the Physical Stability of Amorphous Solid Dispersions

2017 ◽  
Vol 17 (5) ◽  
pp. 2478-2485 ◽  
Author(s):  
Pinal Mistry ◽  
Kweku K. Amponsah-Efah ◽  
Raj Suryanarayanan
Keyword(s):  
Solid Dispersions ◽  
Rapid Assessment ◽  
Physical Stability ◽  
Amorphous Solid ◽  
Amorphous Solid Dispersions

scholarly journals Development of a Surface Coating Technique with Predictive Value for Bead Coating in the Manufacturing of Amorphous Solid Dispersions

Pharmaceutics ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 878
Author(s):  
Eline Boel ◽  
Piyush Panini ◽  
Guy Van den Mooter
Keyword(s):  
Phase Behavior ◽  
Spray Drying ◽  
Surface Coating ◽  
Drug Loading ◽  
Solid Dispersions ◽  
Amorphous Solid ◽  
Film Casting ◽  
Amorphous Solid Dispersions ◽  
Coating Technique ◽  
Amorphous System

The aim of this paper was to investigate whether a surface coating technique could be developed that can predict the phase behavior of amorphous solid dispersions (ASDs) coated on beads. ASDs of miconazole (MIC) and poly(vinylpyrrolidone-co-vinyl acetate) (PVP-VA) in methanol (MeOH) were studied as a model system. First, the low crystallization tendency of the model drug in MeOH was evaluated and confirmed. In a next step, a drug loading screening was performed on casted films and coated beads in order to define the highest possible MIC loading that still results in a one-phase amorphous system. These results indicate that film casting is not suitable for phase behavior predictions of ASDs coated on beads. Therefore, a setup for coating a solid surface was established inside the drying chamber of a spray dryer and it was found that this surface coating technique could predict the phase behavior of MIC-PVP-VA systems coated on beads, in case an intermittent spraying procedure is applied. Finally, spray drying was also evaluated for its ability to manufacture high drug-loaded ASDs. The highest possible drug loadings that still result in a one-phase amorphous system were obtained for bead coating and its predictive intermittent surface coating technique, followed by spray drying and finally by film casting and the continuous surface coating technique, thereby underlining the importance for further research into the underexplored bead coating process.

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