Development of an in vivo -relevant drug product performance method for an amorphous solid dispersion

Among many methods to mitigate the solubility limitations of drug compounds, amorphous solid dispersion (ASD) is considered to be one of the most promising strategies to enhance the dissolution and bioavailability of poorly water-soluble drugs. The enhancement of ASD in the oral absorption of drugs has been mainly attributed to the high apparent drug solubility during the dissolution. In the last decade, with the implementations of new knowledge and advanced analytical techniques, a drug-rich transient metastable phase was frequently highlighted within the supersaturation stage of the ASD dissolution. The extended drug absorption and bioavailability enhancement may be attributed to the metastability of such drug-rich phases. In this paper, we have reviewed (i) the possible theory behind the formation and stabilization of such metastable drug-rich phases, with a focus on non-classical nucleation; (ii) the additional benefits of the ASD-induced drug-rich phases for bioavailability enhancements. It is envisaged that a greater understanding of the non-classical nucleation theory and its application on the ASD design might accelerate the drug product development process in the future.

Download Full-text

Relationship between amorphous solid dispersion in vivo absorption and in vitro dissolution: phase behavior during dissolution, speciation, and membrane mass transport

Journal of Controlled Release ◽

10.1016/j.jconrel.2018.11.003 ◽

2018 ◽

Vol 292 ◽

pp. 172-182 ◽

Cited By ~ 46

Author(s):

Venecia Wilson ◽

Xiaochun Lou ◽

Donald J. Osterling ◽

Deanne F. Stolarik ◽

Gary Jenkins ◽

...

Keyword(s):

Mass Transport ◽

Phase Behavior ◽

Solid Dispersion ◽

Amorphous Solid ◽

In Vitro Dissolution ◽

Amorphous Solid Dispersion ◽

In Vivo Absorption

Download Full-text

Systemic in vitro and in vivo evaluation for determining the feasibility of making an amorphous solid dispersion of a B-Raf (rapidly accelerated fibrosarcoma) inhibitor

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2013.06.064 ◽

2013 ◽

Vol 454 (1) ◽

pp. 241-248 ◽

Cited By ~ 8

Author(s):

Yong Cui ◽

Po-Chang Chiang ◽

Edna F. Choo ◽

Jason Boggs ◽

Joachim Rudolph ◽

...

Keyword(s):

Solid Dispersion ◽

Amorphous Solid ◽

Amorphous Solid Dispersion ◽

In Vivo Evaluation

Download Full-text

Preparation, characterization and in vivo studies of amorphous solid dispersion of berberine with hydrogenated phosphatidylcholine

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2015.04.001 ◽

2015 ◽

Vol 74 ◽

pp. 11-17 ◽

Cited By ~ 13

Author(s):

Chunyang Shi ◽

Qing Tong ◽

Jianguo Fang ◽

Chenguang Wang ◽

Jizhou Wu ◽

...

Keyword(s):

Solid Dispersion ◽

Amorphous Solid ◽

In Vivo Studies ◽

Amorphous Solid Dispersion

Download Full-text

Preparation and Characterization of Spherical Amorphous Solid Dispersion with Amphotericin B

Pharmaceutics ◽

10.3390/pharmaceutics10040235 ◽

2018 ◽

Vol 10 (4) ◽

pp. 235 ◽

Cited By ~ 10

Author(s):

Lyes Mehenni ◽

Malika Lahiani-Skiba ◽

Guy Ladam ◽

François Hallouard ◽

Mohamed Skiba

Keyword(s):

Amphotericin B ◽

Solid Dispersion ◽

In Vitro Release ◽

Amorphous Solid ◽

Amorphous Solid Dispersion ◽

Scanning Calorimetry ◽

New Generation ◽

Powder Aerosols

In the present study, new polymer microspheres of amphotericin B (AmB) were prepared by a spray drying technique using cyclodextrin polymers (Poly-CD) to improve the solubility and dissolution of AmB, to prevent in vivo toxic AmB aggregations. Formulations were characterized through scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermal analysis, Raman spectroscopy, particle size, drug purity test and in vitro release studies. The analysis indicated that the chemical structure of AmB remained unchanged in the amorphous solid dispersion, but the structure was changed from crystalline to amorphous. AmB was completely release from such optimized formulations in dissolution media in 40 min. This work may contribute to a new generation of spherical amorphous solid dispersion using a cyclodextrin polymer, which has implications for the possibility of drug development for oral utilization or as powder aerosols for pulmonary administration.

Download Full-text