Surface Enrichment and Depletion of the Active Ingredient in Spray Dried Amorphous Solid Dispersions

Chen, Zhe; Yang, Kuan; Huang, Chengbin; Zhu, Alan Donghua; Yu, Lian; Qian, Feng

doi:10.1007/s11095-018-2345-1

Cited by 30 publications

(47 citation statements)

References 44 publications

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“… 25 , 29 , 30 X-ray photoelectron spectroscopy (XPS) has also been used in the surface characterization of spray-dried ASD particles because of its short penetration depth. 9 , 31 , 32 …”

Section: Introductionmentioning

confidence: 99%

Water-Induced Phase Separation of Spray-Dried Amorphous Solid Dispersions

Cape

Mankani

et al. 2020

Mol. Pharmaceutics

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Spray drying is widely used in the manufacturing of amorphous solid dispersion (ASD) systems due to its fast drying rate, enabling kinetic trapping of the drug in amorphous form. Spray-drying conditions, such as solvent composition, can have a profound impact on the properties of spray-dried dispersions. In this study, the phase behavior of spray-dried dispersions from methanol and methanol–water mixtures was assessed using ritonavir and copovidone [poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA)] as dispersion components. The resultant ASDs were characterized using differential scanning calorimetry (DSC), fluorescence spectroscopy, X-ray photoelectron spectroscopy (XPS), as well as surface-normalized dissolution rate (SNDR) measurements. Quaternary phase diagrams were calculated using a four-component Flory–Huggins model. It was found that the addition of water to the solvent system can lead to phase separation during the spray-drying process. A 10:90 H 2 O/MeOH solvent system caused a minor extent of phase separation. Phase heterogeneity in the 50 and 75% drug loading ASDs prepared from this spray solvent can be detected using DSC but not with other techniques used. The 25% drug loading system did not show phase heterogeneity in solid-state characterization but exhibited a compromised dissolution rate compared to that of the miscible ASD prepared from H 2 O-free solvent. This is possibly due to the formation of slow-releasing drug-rich phases upon phase separation. ASDs prepared with a 60:40 H 2 O/MeOH solvent mixture showed phase heterogeneity with all analytical methods used. The surface composition of dispersion particles as measured by fluorescence spectroscopy and XPS showed good agreement, suggesting surface drug enrichment of the spray-dried ASD particles prepared from this solvent system. Calculated phase diagrams and drying trajectories were consistent with experimental observations, suggesting that small variations in solvent composition may cause significant changes in ASD phase behavior during drying. These findings should aid in spray-drying process development for ASD manufacturing and can be applied broadly to assess the risk of phase separation for spray-drying systems using mixed organic solvents or other solvent-based processes.

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“… 25 , 29 , 30 X-ray photoelectron spectroscopy (XPS) has also been used in the surface characterization of spray-dried ASD particles because of its short penetration depth. 9 , 31 , 32 …”

Section: Introductionmentioning

confidence: 99%

Water-Induced Phase Separation of Spray-Dried Amorphous Solid Dispersions

Cape

Mankani

et al. 2020

Mol. Pharmaceutics

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“…Chen et al showed surface tension may also impact surface composition of spray dried ASD particles because solutes with lower surface tension may concentrate on the air–liquid interface when droplets are formed so as to assemble a surface with low free energy. 48 Thus, it is important to note that the process of spray drying is complex with several material properties and processing conditions affecting the particle surface composition. Hence, further systematic studies are warranted to unveil the true mechanisms of such heterogeneity surfaces of spray dried ASD particles.…”

Section: Resultsmentioning

confidence: 99%

Qualitative and Quantitative Characterization of Composition Heterogeneity on the Surface of Spray Dried Amorphous Solid Dispersion Particles by an Advanced Surface Analysis Platform with High Surface Sensitivity and Superior Spatial Resolution

et al. 2018

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Surface composition critically impacts stability (e.g., crystallization) and performance (e.g., dissolution) of spray dried amorphous solid dispersion (ASD) formulations; however, traditional characterization techniques such as Raman and infrared spectroscopies may not provide useful information on surface composition on the spray dried ASD particles due to low spatial resolution, high probing depth, and lack of quantitative information. This study presents an advanced surface characterization platform consisting of two complementary techniques: X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS). Such a platform enables qualitative and quantitative measurements of surface composition for the fine spray dried ASD particles with ultrasurface-sensitivity (less than 10 nm from the surface) and superior spatial resolution (approximately 250 nm for ToF-SIMS). Both XPS and ToF-SIMS demonstrated that the polymer (PVPVA) was dominantly enriched on the surface of our spray dried naproxen-PVPVA ASD particles. Of a particular note was that XPS could differentiate two batches of spray dried ASD particles with a subtle difference in surface composition produced by varying feed solution solvents. This advanced surface characterization platform will provide essential surface information to understand the mechanisms underlying the impact of surface composition on stability (e.g., crystallization) and functionality (e.g., dissolution) in future studies.

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“…Through spray drying, aspects of particle morphology, such as shape, size and surface properties, can be highly controlled, which deems the technique appropriate for formulating inhalation powders. Many papers have controlled particle morphology through variations to the inlet temperature, the spray nozzle diameter and properties of the feed solution, such as concentration and viscosity [ 136 ]. The inlet temperature (also known as the drying temperature) and the feed rate are parameters of high importance as they control the rate of evaporation and drying load, which determine particle properties and product yield [ 137 ].…”

Section: The Design Of Carrier Free Formulations Using Coamorphous Solid Dispersions (Cacds)mentioning

confidence: 99%

Pulmonary Drug Delivery of Antimicrobials and Anticancer Drugs Using Solid Dispersions

et al. 2021

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It is well established that currently available inhaled drug formulations are associated with extremely low lung deposition. Currently available technologies alleviate this low deposition problem via mixing the drug with inert larger particles, such as lactose monohydrate. Those inert particles are retained in the inhalation device or impacted in the throat and swallowed, allowing the smaller drug particles to continue their journey towards the lungs. While this seems like a practical approach, in some formulations, the ratio between the carrier to drug particles can be as much as 30 to 1. This limitation becomes more critical when treating lung conditions that inherently require large doses of the drug, such as antibiotics and antivirals that treat lung infections and anticancer drugs. The focus of this review article is to review the recent advancements in carrier free technologies that are based on coamorphous solid dispersions and cocrystals that can improve flow properties, and help with delivering larger doses of the drug to the lungs.

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Surface Enrichment and Depletion of the Active Ingredient in Spray Dried Amorphous Solid Dispersions

Cited by 30 publications

References 44 publications

Water-Induced Phase Separation of Spray-Dried Amorphous Solid Dispersions

Water-Induced Phase Separation of Spray-Dried Amorphous Solid Dispersions

Qualitative and Quantitative Characterization of Composition Heterogeneity on the Surface of Spray Dried Amorphous Solid Dispersion Particles by an Advanced Surface Analysis Platform with High Surface Sensitivity and Superior Spatial Resolution

Pulmonary Drug Delivery of Antimicrobials and Anticancer Drugs Using Solid Dispersions

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