Coamorphous Loratadine-Citric Acid System with Enhanced Physical Stability and Bioavailability

Wang, Jin; Chang, Ruimiao; Zhao, Yongju; Zhang, Jiye; Zhang, Ting; Fu, Qiang; Chang, Chun Ming; Zeng, Aiguo

doi:10.1208/s12249-017-0734-0

Cited by 52 publications

(28 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It is known that temperature and moisture affect nucleation and crystal growth. 18) These results suggest that the binary SCL system could enhance stability compared with the SCL of single compound similar to glassy co-amorphous systems. 11,12,19) Therefore KET-ETH (2 : 1) SCL was selected and evaluated as a suitable formulation from the viewpoint of physical stability.…”

Section: Crystal Form Of Scls After Recrystallization Induced By Stimmentioning

confidence: 86%

“…It is known that external stimulus and higher temperature induce nucleation and crystal growth of undercooled compounds. 17,18) Figure 4 shows the XRPD patterns of the recrystallized samples by physical stimulation and storage. Samples except for KET-ETH (1 : 2) before grinding were viscous liquid and confirmed the SCL state.…”

Section: Crystal Form Of Scls After Recrystallization Induced By Stimmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Binary Supercooled Liquid Formulation for Transdermal Drug Delivery

Hirakawa

Ueda

Wakabayashi

et al. 2020

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

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.

show abstract

Section: Crystal Form Of Scls After Recrystallization Induced By Stimmentioning

confidence: 86%

Section: Crystal Form Of Scls After Recrystallization Induced By Stimmentioning

confidence: 99%

A Novel Binary Supercooled Liquid Formulation for Transdermal Drug Delivery

Hirakawa

Ueda

Wakabayashi

et al. 2020

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…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: 91%

“…This was also reflected in the pharmacokinetic study in rats, as co-amorphous loratadine-citric acid 1:1 significantly improved absorption and bioavailability of loratadine over that of the crystalline form. Wang et al, 2017 NA=not assessed…”

Section: Na Löbmann Et Al 2011bmentioning

confidence: 99%

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

Laitinen

Löbmann

Priemel

et al. 2017

International Journal of Pharmaceutics

101

View full text Add to dashboard Cite

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.

show abstract

“…Similar results reported that formation of salt from sulfamethizole and oxalic acid had a higher melting point than that of each constituent component ( 29 ). The phenomenon of DES-SA was a coamorphous formation that was observed in atorvastatin calcium with nicotinamide ( 30 ), and loratadine with citric acid ( 31 ). Therefore, no peak was observed in the DSC results and PXRD confirming their crystallinity.…”

Section: Discussionmentioning

confidence: 99%

Synthesis, characterization, and stability study of desloratadine multicomponent crystal formation

Ainurofiq¹,

Mauludin²,

Mudhakir³

et al. 2018

Res Pharma Sci

View full text Add to dashboard Cite

This study describes the formation of multicomponent crystal (MCC) of desloratadine (DES). The objective of this study was to discover the new pharmaceutical MCC of DES using several coformers. The MCC synthesis was performed between DES and 26 coformers using an equimolar ratio with a solvent evaporation technique. The selection of the appropriate solvent was carried out using 12 solvents. The preview of the MCC of DES was performed using polarized light microscopy (PLM). The formation of MCC was confirmed using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The accelerated stability of MCC at 40 °C and relative humidity of 75% was investigated using PXRD and FTIR. Depending on the prior evaluation, DES and benzoic acid (BA) formed the MCC. PLM and SEM results showed that crystal habit of combination between DES and BA differed from the constituent components. Moreover, the diffractogram pattern of DES-BA was distinct from the constituent components. The DSC thermogram showed a new peak which was distinct from both constituent components. The FTIR study proved a new spectrum. All characterizations indicated that a new solid crystal was formed, ensuring the MCC formation. In addition, DES-BA MCC had both chemical and physical stabilities for a period of 4 months.

show abstract

Coamorphous Loratadine-Citric Acid System with Enhanced Physical Stability and Bioavailability

Cited by 52 publications

References 31 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

Synthesis, characterization, and stability study of desloratadine multicomponent crystal formation

Contact Info

Product

Resources

About