Evaluating the solubility of compounds intended for intramammary infusion based upon tests conducted across a range of milk matrices.

Autor: Martinez MN; US FDA Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Rockville, MD, United States of America., Zhao F; Wegmans School of Pharmacy, St. John Fisher University, Rochester, NY, United States of America., Longstaff DG; US FDA Center for Veterinary Medicine, Office of New Animal Drug Evaluation, Rockville, MD, United States of America., Gabriel JJ; Wegmans School of Pharmacy, St. John Fisher University, Rochester, NY, United States of America., Coffey MJ; Research and Development, Bausch & Lomb, Rochester, NY, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2023 Jul 21; Vol. 18 (7), pp. e0288780. Date of Electronic Publication: 2023 Jul 21 (Print Publication: 2023).
DOI: 10.1371/journal.pone.0288780
Abstrakt: The ability to evaluate drug solubility in milk and milk-related products has relevance both to human and veterinary medicine. Model compounds explored in a previous investigation focused on drug solubility assessments when delivered in milk-associated vehicles for administration to human patients. In the current investigation, we focus on the solubility of drugs intended for delivery via intramammary infusion to cattle. Because there are logistic challenges typically associated with obtaining raw milk samples for these tests, there is a need to determine potential alternative media as a substitute for raw bovine milk. Given the complexity of the milk matrix, aqueous media do not reflect the range of factors that could impact these solubility assessments. This led to the current effort to explore the magnitude of differences that might occur when substituting raw bovine milk with off-the-shelf milk products such as whole milk, skim milk, or reconstituted whole milk powder. We considered conclusions based upon the solubility assessments derived from the use of the model compounds studied in our previous report and compared them to conclusions obtained when testing two drugs with differing physicochemical characteristics that are approved for administration via bovine intramammary infusion: cephapirin benzathine and cephapirin sodium. Based upon these results, we recommend that whole milk or reconstituted whole milk can substitute for bovine raw milk for the solubility assessment of compounds intended for administration via intramammary infusion. However, unlike the human drug situation, these tests should be conducted at 38°C.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
Databáze: MEDLINE
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