Dissolution behavior of co-amorphous amino acid-indomethacin mixtures: The ability of amino acids to stabilize the supersaturated state of indomethacin

Ojarinta, Rami; Heikkinen, Aki T.; Sievänen, Elina; Laitinen, Riikka

doi:10.1016/j.ejpb.2016.11.023

Cited by 56 publications

(32 citation statements)

References 43 publications

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“…In the coamorphous system, drug-drug or drug-excipient interacts with each other and inhibits crystallization at the amorphous state. 9,10) Several researchers have shown that a co-amorphous system improved stability of the amorphous state compared with that of single compound. 11,12) Hence SCL based on the co-amorphous approach, which stabilizes the thermodynamically unstable state by intermolecular interactions, should also improve the stability of the SCL state.…”

Section: Introductionmentioning

confidence: 99%

A Novel Binary Supercooled Liquid Formulation for Transdermal Drug Delivery

Hirakawa

Ueda

Wakabayashi

et al. 2020

Biological & Pharmaceutical Bulletin

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The aim of this study was to prepare binary supercooled liquid (SCL) by intermolecular interaction and apply this formulation to transdermal drug delivery. Ketoprofen (KET) and ethenzamide (ETH) were selected as binary SCL component. Thermal analysis of physical mixtures of KET and ETH showed decreases in melting points and glass transition below room temperature, thereby indicating formation of KET-ETH SCL. Intermolecular interactions between KET and ETH in the SCL were evaluated from Fourier transform (FT)-IR spectra. KET-ETH SCL maintained SCL state at 25°C with silica gel over 31 d and at 40°C/89% relative humidity (RH) over 7 d. KET SCL and KET-ETH SCL showed similar permeability of KET for hairless mice skin, which was twofold higher than that of KET aqueous suspension. Our findings suggest that the SCL state could enhance the skin permeation of drugs and the binary SCL formed by intermolecular interaction could also improve the stability of the SCL. The binary SCL system could become a new drug form for transdermal drug delivery.

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Section: Introductionmentioning

confidence: 99%

A Novel Binary Supercooled Liquid Formulation for Transdermal Drug Delivery

Hirakawa

Ueda

Wakabayashi

et al. 2020

Biological & Pharmaceutical Bulletin

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“…This is supported by the studies where supersaturation has been most efficiently stabilized when strong intermolecular interactions have been detected between the components, i.e. amorphous salt formation (Ojarinta et al, 2017;Paluch et al, 2010) or hydrogen bonding (Wang et al, 2017). It is also possible that adsorption on the "surfaces" of nuclei and, in some cases solubilization, may inhibit drug recrystallization.…”

Section: Future Prospects: Novel Preparation Methods For Co-amorphousmentioning

confidence: 92%

“…From the above discussion it can be concluded that co-amorphous salt formation has been proven effective in stabilizing supersaturation. Amorphous salt formation may thus have the best potential for precipitation inhibition of the co-amorphous formulations, as, for example, arginine showed a significant inhibitory effect for indomethacin precipitation in FaSSIF (Ojarinta et al, 2017). However in future, further in vitro evaluation under biorelevant conditions would be necessary to extrapolate in vitro supersaturation assessment to the in vivo situation.…”

Section: Future Prospects: Novel Preparation Methods For Co-amorphousmentioning

confidence: 99%

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Supersaturating drug delivery systems: The potential of co-amorphous drug formulations

Laitinen

Löbmann

Priemel

et al. 2017

International Journal of Pharmaceutics

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101

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Amorphous solid dispersions (ASDs) are probably the most common and important supersaturating drug delivery systems for the formulation of poorly water-soluble compounds. These delivery systems are able to achieve and maintain a sustained drug supersaturation which enables improvement of the bioavailability of poorly water-soluble drugs by increasing the driving force for drug absorption. However, ASDs often require a high weight percentage of carrier (usually a hydrophilic polymer) to ensure molecular mixing of the drug in the carrier and stabilization of the supersaturated state, often leading to high dosage volumes and thereby challenges in the formulation of the final dosage form. As a response to the shortcomings of the ASDs, the so-called co-amorphous formulations, which are amorphous combinations of two or more low molecular weight components, have emerged as an alternative formulation strategy for poorly-soluble drugs. While the current research on co-amorphous formulations is focused on preparation and characterization of these systems, more detailed research on their supersaturation and precipitation behavior and the effect of co-formers on nucleation and crystal growth inhibition is needed. The current status of this research is reviewed in this paper. Furthermore, the potential of novel preparation methods for co-amorphous systems with respect to the current preparation methods are discussed.

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“…However, thermodynamic instability due to the recrystallization tendency during processing, storage and in contact with the biological fluids, limits the potential application of amorphous systems [ 5 ]. Therefore, new formulation strategies based on solid molecular dispersions are being exploited and co-amorphous dispersions is one of them with very promising results [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

2018

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The amorphous solid state offers an improved apparent solubility and dissolution rate. However, due to thermodynamic instability and recrystallization tendencies during processing, storage and dissolution, their potential application is limited. For this reason, the production of amorphous drugs with adequate stability remains a major challenge and formulation strategies based on solid molecular dispersions are being exploited. Co-amorphous systems are a new formulation approach where the amorphous drug is stabilized through strong intermolecular interactions by a low molecular co-former. This review covers several topics applicable to co-amorphous drug delivery systems. In particular, it describes recent advances in the co-amorphous composition, preparation and solid-state characterization, as well as improvements of dissolution performance and absorption are detailed. Examples of drug-drug, drug-carboxylic acid and drug-amino acid co-amorphous dispersions interacting via hydrogen bonding, π−π interactions and ionic forces, are presented together with corresponding final dosage forms.

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Dissolution behavior of co-amorphous amino acid-indomethacin mixtures: The ability of amino acids to stabilize the supersaturated state of indomethacin

Cited by 56 publications

References 43 publications

A Novel Binary Supercooled Liquid Formulation for Transdermal Drug Delivery

A Novel Binary Supercooled Liquid Formulation for Transdermal Drug Delivery

Supersaturating drug delivery systems: The potential of co-amorphous drug formulations

Co-Amorphous Solid Dispersions for Solubility and Absorption Improvement of Drugs: Composition, Preparation, Characterization and Formulations for Oral Delivery

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