Amorphous binary dispersions of chloramphenicol in enantiomeric pure and racemic poly-lactic acid: Morphology, molecular relaxations, and controlled drug release

Valenti, Sofia; Díaz, Angélica; Romanini, Michela; Valle, Luís J. del; Puiggalı́, Jordi; Tamarit, J. Ll.

doi:10.1016/j.ijpharm.2019.118565

Cited by 14 publications

(28 citation statements)

References 57 publications

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“…5 b) implies that the internal rotation of BrBPh is a power-law function of the viscosity. Intramolecular relaxations are generally found to be independent of the structural mobility and of the viscosity 63 , 64 , especially when they correspond to a torsional degree of freedom involving only a small subunit of a larger molecule. In the case of BrBPh, however, the inter-enantiomeric conversion involves the relative reorientation of two moieties that constitute the whole of the molecule.…”

Section: Resultsmentioning

confidence: 99%

Inter-enantiomer conversion dynamics and Johari–Goldstein relaxation of benzophenones

Romanini

Macovez

Tamarit

2021

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We employ temperature- and pressure-dependent dielectric spectroscopy, as well as differential scanning calorimetry, to characterize benzophenone and the singly-substituted ortho-bromobenzophenone derivative in the liquid and glass states, and analyze the results in terms of the molecular conformations reported for these molecules. Despite the significantly higher mass of the brominated derivative, its dynamic and calorimetric glass transition temperatures are only ten degrees higher than those of benzophenone. The kinetic fragility index of the halogenated molecule is lower than that of the parent compound, and is found to decrease with increasing pressure. By a detailed analysis of the dielectric loss spectra, we provide evidence for the existence of a Johari–Goldstein (JG) relaxation in both compounds, thus settling the controversy concerning the possible lack of a JG process in benzophenone and confirming the universality of this dielectric loss feature in molecular glass-formers. Both compounds also display an intramolecular relaxation, whose characteristic timescale appears to be correlated with that of the cooperative structural relaxation associated with the glass transition. The limited molecular flexibility of ortho-bromobenzophenone allows identifying the intramolecular relaxation as the inter-enantiomeric conversion between two isoenergetic conformers of opposite chirality, which only differ in the sign of the angle between the brominated aryl ring and the coplanar phenyl-ketone subunit. The observation by dielectric spectroscopy of a similar relaxation also in liquid benzophenone indicates that the inter-enantiomer conversion between the two isoenergetic helicoidal ground-state conformers of opposite chirality occurs via a transition state characterized by a coplanar phenyl-ketone moiety.

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Section: Resultsmentioning

confidence: 99%

Inter-enantiomer conversion dynamics and Johari–Goldstein relaxation of benzophenones

Romanini

Macovez

Tamarit

2021

Sci Rep

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“…Surface of fibers for all samples is mainly smooth with no electrospun-related defects, such as breakages, globules, or diameter fluctuation, even though drug loading is considerably high compared to previous studies [ 15 , 16 ]. The drug crystals were also not observed on the surface of fibers, which is a positive result, since it is known that the formation of an amorphous drug is favored [ 9 ].…”

Section: Resultsmentioning

confidence: 76%

“…New polymer-based carriers, such as liposomes [ 15 ], were proposed to eliminate those negative effects. Several studies where the drug was incorporated into the structure of electrospun scaffolds have been published [ 16 , 17 , 18 ]. The materials were studied as potential candidates for wound dressings, and their antibacterial properties were demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Reactive Magnetron Plasma Modification of Electrospun PLLA Scaffolds with Incorporated Chloramphenicol for Controlled Drug Release

et al. 2022

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Surface modification with the plasma of the direct current reactive magnetron sputtering has demonstrated its efficacy as a tool for enhancing the biocompatibility of polymeric electrospun scaffolds. Improvement of the surface wettability of materials with water, as well as the formation of active chemical bonds in the near-surface layers, are the main reasons for the described effect. These surface effects are also known to increase the release rate of drugs incorporated in fibers. Herein, we investigated the effect of plasma modification on the chloramphenicol release from electrospun poly (lactic acid) fibrous scaffolds. Scaffolds with high—50 wt./wt. %—drug content were obtained. It was shown that plasma modification leads to an increase in the drug release rate and drug diffusion coefficient, while not deteriorating surface morphology and mechanical properties of scaffolds. The materials’ antibacterial activity was observed to increase in the first day of the experiment, while remaining on the same level as the unmodified group during the next six days. The proposed technique for modifying the surface of scaffolds will be useful for obtaining drug delivery systems with controlled accelerated release, which can expand the possibilities of local applications of antibiotics and other drugs.

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“…The low T g of biodegradable polymers means that binary samples can be easily obtained where the small-molecule drugs with higher T g . Because the T g of a binary mixture is generally intermediate between those of the two components [ 2 , 3 , 4 , 5 ], the drug could then act as a “genuine” antiplasticizing agent [ 6 ] for the macromolecule (as opposed to a purely mechanical antiplasticizer [ 7 , 8 ]), resulting in a higher T g of the dispersion compared to the pure polymer. While understanding the fundamental properties of dispersions of poorly-water soluble drugs in biopolymers is a crucial prerequisite for their implementation as viable medications, to the best of our knowledge no systematic study has appeared on the glass transition temperature and molecular mobility of biodegradable polymer dispersions of drugs with slightly higher T g than the macromolecular matrix.…”

Section: Introductionmentioning

confidence: 99%

Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations

Valenti

Valle

Romanini

et al. 2022

IJMS

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Amorphous molecule-macromolecule mixtures are ubiquitous in polymer technology and are one of the most studied routes for the development of amorphous drug formulations. For these applications it is crucial to understand how the preparation method affects the properties of the mixtures. Here, we employ differential scanning calorimetry and broadband dielectric spectroscopy to investigate dispersions of a small-molecule drug (the Nordazepam anxiolytic) in biodegradable polylactide, both in the form of solvent-cast films and electrospun microfibres. We show that the dispersion of the same small-molecule compound can have opposite (plasticizing or antiplasticizing) effects on the segmental mobility of a biopolymer depending on preparation method, temperature, and polymer enantiomerism. We compare two different chiral forms of the polymer, namely, the enantiomeric pure, semicrystalline L-polymer (PLLA), and a random, fully amorphous copolymer containing both L and D monomers (PDLLA), both of which have lower glass transition temperature (Tg) than the drug. While the drug has a weak antiplasticizing effect on the films, consistent with its higher Tg, we find that it actually acts as a plasticizer for the PLLA microfibres, reducing their Tg by as much as 14 K at 30%-weight drug loading, namely, to a value that is lower than the Tg of fully amorphous films. The structural relaxation time of the samples similarly depends on chemical composition and morphology. Most mixtures displayed a single structural relaxation, as expected for homogeneous samples. In the PLLA microfibres, the presence of crystalline domains increases the structural relaxation time of the amorphous fraction, while the presence of the drug lowers the structural relaxation time of the (partially stretched) chains in the microfibres, increasing chain mobility well above that of the fully amorphous polymer matrix. Even fully amorphous homogeneous mixtures exhibit two distinct Johari–Goldstein relaxation processes, one for each chemical component. Our findings have important implications for the interpretation of the Johari–Goldstein process as well as for the physical stability and mechanical properties of microfibres with small-molecule additives.

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Amorphous binary dispersions of chloramphenicol in enantiomeric pure and racemic poly-lactic acid: Morphology, molecular relaxations, and controlled drug release

Cited by 14 publications

References 57 publications

Inter-enantiomer conversion dynamics and Johari–Goldstein relaxation of benzophenones

Inter-enantiomer conversion dynamics and Johari–Goldstein relaxation of benzophenones

Reactive Magnetron Plasma Modification of Electrospun PLLA Scaffolds with Incorporated Chloramphenicol for Controlled Drug Release

Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations

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