Acid-base interactions in amorphous solid dispersions of lumefantrine prepared by spray-drying and hot-melt extrusion using X-ray photoelectron spectroscopy

Song, Yang; Zemlyanov, Dmitry; Chen, Xin; Su, Ziyang; Nie, Haichen; Lubach, Joseph W.; Smith, Daniel T.; Byrn, Stephen R.; Pinal, Rodolfo

doi:10.1016/j.ijpharm.2016.06.126

Cited by 40 publications

(55 citation statements)

References 23 publications

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“…In the presence of the acidic polymers, a second component of the N 1 s peak at 402 eV emerges. This peak has been previously assigned to a protonated nitrogen in lumefantrine ( Song et al, 2016 ), whereby the increase in binding energy is consistent with the increased energy required to remove the electrons in the presence of a positive charge. Thus, the basic lumefantrine undergoes partial salt formation with the acidic polymers.…”

Section: Resultssupporting

confidence: 71%

Physical stability and release properties of lumefantrine amorphous solid dispersion granules prepared by a simple solvent evaporation approach

Trasi

Bhujbal

Zemlyanov

et al. 2020

International Journal of Pharmaceutics: X

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Amorphous solid dispersions (ASDs) of lumefantrine, which has low aqueous solubility, have been shown to improve bioavailability relative to crystalline formulations. Herein, the crystallization tendency and release properties of a variety of lumefantrine ASD granules, formed on a blend of microcrystalline cellulose and anhydrous lactose, prepared using a simple solvent evaporation method, were evaluated. Several polymers, a majority of which contained acidic moieties, and different drug loadings were assessed. Crystallinity as a function of time following exposure to stress storage conditions of 40 °C and 75% relative humidity was monitored for the various dispersions. Release testing was performed and ASD characteristics were further evaluated using infrared and X-ray photoelectron spectroscopy (XPS). A large difference in stability to crystallization was observed between the various ASDs, most notably depending on polymer chemistry. This could be largely rationalized based on the extent of drug-polymer interactions, specifically the degree of lumefantrine-polymer salt formation, which could be readily assessed with XPS spectroscopy. Lumefantrine release from the ASDs also varied considerably, whereby the best polymer for promoting physical stability did not lead to the highest extent of drug release. Several formulations led to concentrations above the amorphous solubility of lumefantrine, with the formation of nano-sized drug-rich aggregates. A balance between the ability of a given polymer to promote physical stability and drug release may need to be sought.

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Section: Resultssupporting

confidence: 71%

Physical stability and release properties of lumefantrine amorphous solid dispersion granules prepared by a simple solvent evaporation approach

Trasi

Bhujbal

Zemlyanov

et al. 2020

International Journal of Pharmaceutics: X

View full text Add to dashboard Cite

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“…structures with high drug loadings and maintaining long-term stability of the amorphous form of the API [300]. To characterize the properties and evaluate stability and functional performance of electrospun ASDs, methods such as SEM, TEM, XRD, DSC, FTIR and Raman spectroscopy can be used with the well-known pharmacopoeia testing protocols, in addition to a number of novel approaches.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Electrospun amorphous solid dispersions of poorly water-soluble drugs: A review

Williams

et al. 2018

Journal of Controlled Release

250

156

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The development of oral dosage forms for poorly water-soluble active pharmaceutical ingredients (APIs) is a persistent challenge. A range of methods has been explored to address this issue, and amorphous solid dispersions (ASDs) have received increasing attention. ASDs are typically prepared by starting with a liquid precursor (a solution or melt) and applying energy for solidification. Many techniques can be used, with the emergence of electrospinning as a potent option in recent years. This method uses electrical energy to induce changes from liquid to solid. Through the direct applications of electrical energy, electrospinning can generate nanofiber-based ASDs from drug-loaded solutions, melts and melt-solutions. The technique can also be combined with other approaches using the application of mechanical, thermal or other energy sources. Electrospinning has numerous advantages over other approaches to produce ASDs. These advantages include extremely rapid drying speeds, ease of implentation, compatibility with a wide range of active ingredients (including those which are thermally labile), and the generation of products with large surface areas and high porosity. Furthermore, this technique exhibits the potential to create so-called 'fifth-generation' ASDs with nanostructured architectures, such as core/shell or Janus systems and their combinations. These advanced systems can improve dissolution behaviour and provide programmable drug release profiles. Additionally, the fiber components and their spatial distributions can be precisely controlled. Electrospun fiber-based ASDs can maintain an incorporated active ingredient in the amorphous physical form for prolonged periods of time because of their homogeneous drug distribution within the polymer matrix (typically they comprise solid solutions), and ability to inhibit molecular motion. These ASDs can be utilised to generate oral dosage forms for poorly water-soluble drugs, resulting in linear or multiple-phase release of one or more APIs. Electrospun ASDs can also be exploited as templates for manipulating molecular self-assembly, offering a bridge between ASDs and other types of dosage forms. This review addresses the development, advantages and pharmaceutical applications of electrospinning for producing polymeric ASDs. Material preparation and analysis procedures are considered. The mechanisms through which performance has been improved are also discussed.

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“…Therefore, miscibility and drug recrystallization must be considered in SD formulations with enteric coating agents [77]. The preparation method certainly affects the miscibility in SDs [78]. In an investigation of amorphous SDs of lumefantrine, Song et al showed that more favorable acid-base interactions were observed in SDs by spray-drying compared to hot-melt extrusion because of their exposure to the solution [78].…”

Section: Effects Of Enteric Coating Polymers and Preparation Methods mentioning

confidence: 99%

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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Acid-base interactions in amorphous solid dispersions of lumefantrine prepared by spray-drying and hot-melt extrusion using X-ray photoelectron spectroscopy

Cited by 40 publications

References 23 publications

Physical stability and release properties of lumefantrine amorphous solid dispersion granules prepared by a simple solvent evaporation approach

Physical stability and release properties of lumefantrine amorphous solid dispersion granules prepared by a simple solvent evaporation approach

Electrospun amorphous solid dispersions of poorly water-soluble drugs: A review

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

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