Abstract

Low aqueous solubility of active pharmaceutical ingredients (APIs) is an enduring problem in pharmaceutical development, and it is becoming increasingly prevalent among new drug candidates. It is estimated that about 40% of drugs in the development pipeline and approximately 60% of the drugs coming directly from discovery suffer from poor aqueous solubility and slow dissolution, thereby reducing their bioavailability and efficacy and thus preventing their commercialization. It is well known that utilizing the amorphous form of a drug can be a useful approach to improve the dissolution rate and solubility of poorly water-soluble APIs. Amorphous compounds are thermodynamically unstable, but they can be stabilized by combining them with a carrier polymer (excipient) to form a solid dispersion. High-throughput Raman spectroscopy was used in this study to identify excipients that promote formation and stabilization of the amorphous drug form in solid dispersions. Four model APIs were used as poorly soluble drug candidates: ketoprofen, danazol, griseofulvin, and probucol. The Raman signals of excipients were generally negligible, and therefore Raman bands from the drugs were used with minimal spectral pre-processing. By comparing Raman spectra collected from the APIs in the crystalline and molten state, appropriate spectral features and regions were identified for the development of semi-quantitative methods to determine the amorphous content for each API. It is demonstrated that methods based on peak intensity ratio, peak width, peak distance, and classical least squares can all be effective methods for the screening of excipients. Interesting excipient-dependent phase transformation behavior was also observed for probucol.

Identification and investigation of the vibrational properties of crystalline and co-amorphous drugs with Raman and terahertz spectroscopy

Wei Liu, Yu Liu, Jiaoqi Huang, Zhongquan Lin, Xuancheng Pan, Xiaojun Zeng, Marc Lamy de la Chapelle, Yang Zhang, and Weiling Fu
Biomed. Opt. Express 10(8) 4290-4304 (2019)

Quantitative chemical sensing of drugs in scattering media with Bessel beam Raman spectroscopy

Nan Wang, Feng Ren, Li Li, Haoyu Wang, Lin Wang, Qi Zeng, Yali Song, Tingting Zeng, Shouping Zhu, and Xueli Chen
Biomed. Opt. Express 13(4) 2488-2502 (2022)

Label-free high-throughput cell screening in flow

Ata Mahjoubfar, Claire Chen, Kayvan R. Niazi, Shahrooz Rabizadeh, and Bahram Jalali
Biomed. Opt. Express 4(9) 1618-1625 (2013)

Demonstrating the application of Raman spectroscopy together with chemometric technique for screening of asthma disease

Rahat Ullah, Saranjam Khan, Fizah Farman, Muhammad Bilal, Christoph Krafft, and Shaheen Shahzad
Biomed. Opt. Express 10(2) 600-609 (2019)

ATR-FTIR and Raman spectroscopic investigation of the electroporation-mediated transdermal delivery of a nanocarrier system containing an antitumour drug

Boglárka Balázs, Péter Sipos, Corina Danciu, Stefana Avram, Codruta Soica, Cristina Dehelean, Gábor Varju, Gábor Erős, Mária Budai-Szűcs, Szilvia Berkó, and Erzsébet Csányi
Biomed. Opt. Express 7(1) 67-78 (2016)