A High Throughput Approach of Selecting Excipients for Solubility Enhancement of BCS Class II Active Pharmaceutical Ingredients for Oral Dosage Forms

Scientists have been faced with the challenge of selecting the right solubilizing excipients for solubility enhancement of poorly water-soluble active pharmaceutical ingredients for decades. In this investigation, the purpose was to ease some of those challenges by developing a first-intent matrix for selecting solubilizing excipients that may potentially be used in an oral solid dosage formulation. This was accomplished by generating 2,304 data points using high throughput experimentation to assess the impact of eleven commonly used formulation excipients, at varying levels, on the solubility enhancement of a weak acid (Ibuprofen), weak base (Cinnarizine), and non-ionizable (Griseofulvin) drug substance over a time span from 1 hour to equilibrium in simulated gastrointestinal fluids (SGF, FaSSIF, FeSSIF) and water. The results indicate that the enhancement of drug concentrations by use of solubilizing excipients (surfactants and stabilizers) in oral solid dosage forms depends on the type, the amount of excipient, and the pH of the media.

The importance of this work is that formulation scientists now have a new addition to the formulation development toolkit for selecting the right solubilizing excipients and amounts suitable for solubility enhancement based on the class of active pharmaceutical ingredients. This first-intent solubilizer selection approach for the different drug classes simplifies the early development process to enable acceleration to candidate selection, formulation design, and product development for first-time-in-human studies.

Matthew N. Bahr, Sharon V. Matamoros, Gossett A. Campbell, A High Throughput Approach of Selecting Excipients for Solubility Enhancement of BCS Class II Active Pharmaceutical Ingredients for Oral Dosage Forms, Chemical Engineering Research and Design, 2023, ISSN 0263-8762, https://doi.org/10.1016/j.cherd.2023.04.011.

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