A high-throughput spectrophotometric approach for evaluation of precipitation resistance

J Pharm Biomed Anal. 2011 Dec 5;56(4):698-704. doi: 10.1016/j.jpba.2011.07.009. Epub 2011 Jul 19.

Abstract

Many drugs that come out of discovery today are extremely challenging to formulate because of their high hydrophobicity and low water solubility. A kinetic, spectrophotometric approach for the rapid evaluation of precipitation resistance of multiple solubilized formulations that can be run on a very small scale is proposed. Using this high-throughput approach, multiple formulations are screened for inhibition of precipitation upon dilution into an aqueous environment. Data generated using the in vitro spectrophotometric approach is comparable to the traditional chromatographic approaches. Similar approaches have been previously attempted, but in this study, the focus is on pharmaceutical development of solubilized formulations by evaluation of the events post precipitation as opposed to determining the moment at which precipitation is observed, which is usually the case in kinetic solubility measurements. The information garnered thus offers insights not just into amount of precipitation, but also to the size and nature of the precipitate. Overall, this technique offers the potential to change the approach to the development of toxicology vehicles and solubilized clinical formulations for oral administration.

MeSH terms

  • Anti-Infective Agents, Local / analysis*
  • Anti-Infective Agents, Local / chemistry
  • Anti-Infective Agents, Local / metabolism
  • Anti-Inflammatory Agents, Non-Steroidal / analysis*
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Camphor / analysis*
  • Camphor / chemistry
  • Camphor / metabolism
  • Chemical Precipitation
  • Drug Compounding
  • Drug Discovery
  • Estradiol / analysis*
  • Estradiol / metabolism
  • Estrogens / analysis*
  • Estrogens / chemistry
  • Estrogens / metabolism
  • Excipients
  • High-Throughput Screening Assays / methods*
  • Humans
  • Naproxen / analysis*
  • Naproxen / chemistry
  • Naproxen / metabolism
  • Particle Size
  • Solubility
  • Spectrophotometry

Substances

  • Anti-Infective Agents, Local
  • Anti-Inflammatory Agents, Non-Steroidal
  • Estrogens
  • Excipients
  • Estradiol
  • Naproxen
  • Camphor