학술논문
Factors Influencing the Selection of Medium for Evaluating Drug Solubility and Dissolution in Bovine Milk
Document Type
Academic Journal
Source
Dissolution Technologies. August, 2023, Vol. 30 Issue 3, p134, 9 p.
Subject
Language
English
ISSN
1521-298X
Abstract
INTRODUCTION The United States Pharmacopeia (USP) general chapter Solubility Measurements describes the measurement of drug solubility across a range of biorelevant media relevant both to human and veterinary medicine. (1). […]
Milk or milk-containing beverages can be used as vehicles for drug product administration and as a component of human fed-state simulated gastric fluids. Unprocessed bovine milk is also the matrix within which drugs must be solubilized or released when formulations are administered into the bovine mammary gland. Therefore, an appreciation of factors impacting the effect of milk on drug solubility and product dissolution is necessary. Although an off-the-shelf container of cow milk may be adequate for evaluating drug solubility, the composition of milk varies as a function of fat content (e.g., differences in fat content). Differences can occur between bovine breeds, diet, environment, and suppliers. Importantly, it is unclear how to quantify differences in drug solubility across types of milk products versus when the drug is infused directly into the bovine udder. To address these concerns, a two-tiered approach was employed. The first tier involved comparing drug solubility across a range of milk products, including raw (unprocessed) bovine milk obtained from healthy cattle and an aqueous buffer. The second tier, which is the subject of this review, explores publicly available information on the composition of bovine milk and the potential variability of its constituents. The goal of this work is to provide the basis for inclusion of milk as one of the biologically relevant media described in the United States Pharmacopeia general chapter on solubility testing. KEYWORDS: Solubility, complex matrices, bovine milk, bioavailability, dissolution
Milk or milk-containing beverages can be used as vehicles for drug product administration and as a component of human fed-state simulated gastric fluids. Unprocessed bovine milk is also the matrix within which drugs must be solubilized or released when formulations are administered into the bovine mammary gland. Therefore, an appreciation of factors impacting the effect of milk on drug solubility and product dissolution is necessary. Although an off-the-shelf container of cow milk may be adequate for evaluating drug solubility, the composition of milk varies as a function of fat content (e.g., differences in fat content). Differences can occur between bovine breeds, diet, environment, and suppliers. Importantly, it is unclear how to quantify differences in drug solubility across types of milk products versus when the drug is infused directly into the bovine udder. To address these concerns, a two-tiered approach was employed. The first tier involved comparing drug solubility across a range of milk products, including raw (unprocessed) bovine milk obtained from healthy cattle and an aqueous buffer. The second tier, which is the subject of this review, explores publicly available information on the composition of bovine milk and the potential variability of its constituents. The goal of this work is to provide the basis for inclusion of milk as one of the biologically relevant media described in the United States Pharmacopeia general chapter on solubility testing. KEYWORDS: Solubility, complex matrices, bovine milk, bioavailability, dissolution