The Composition of NF-Defined Emulsifiers: Sorbitan Monolaurate, Monopalmitate, Monostearate, Monooleate, Polysorbate 20, Polysorbate 40, Polysorbate 60, and Polysorbate 80

Abstract

Using the analytical constants for sorbitan monolaurate, monopalmitate, monostearate, and monooleate given in the National Formulary (NF), calculations were carried out that indicated that these emulsifiers are esters of sorbitol mono- and dianhydrides. Contrary to the NF description, no significant amount of sorbitol ester was calculated to be present, in agreement with recent experimental findings. Further calculations were made using the NF-defined analytical constants of polysorbate 20, polysorbate 40, polysorbate 60, and polysorbate 80, which indicate that these emulsifiers are esters primarily of polyoxyethylated sorbitol monoanhydride (i.e., sorbitan), with lesser quantities of polyoxyethylated esters of sorbitol dianhydride. Since all hydroxyl groups of the polysorbates are primary, random distribution of acyl groups on the available hydroxyls can be assumed, and the likely composition of these emulsifiers can be calculated. The most abundant compounds appear to be polyoxyethylated sorbitan mono-, di-, and triesters. Although the polysorbates are stated to contain 20 moles of ethylene oxide per mole of ester, the oxyethylene contents stated in the Food Chemicals Codex reveal that somewhat more than 20 moles of ethylene oxide are combined.

A Quantitative Kinetic Study of Polysorbate Autoxidation: The Role of Unsaturated Fatty Acid Ester Substituents

“…With this information in hand, it is worth making a brief comment about the autoxidation of PS-20. As stated earlier, PS-20 and PS-80 are generally sold as mixtures, varying in their fatty acid ester substituents (7)(8)(9). The PS-20 sample has an iodine value of 0.9, giving an average of 0.04 unsaturated fatty acid groups per polysorbate, indicating a 28-fold lower double bond concentration than the PS-80 sample (41).…”

“…The laurate moiety of PS-20 is a saturated straight chain hydrocarbon, and the oleate moiety of PS-80 is unsaturated, containing a double-bond, resulting in a kink in the hydrocarbon chain. Commercially available polysorbates are generally chemically diverse mixtures of different fatty acid esters (7)(8)(9). While the European Pharmacopoeia specifies the composition of the fatty acid ester substituents for PS-20 and PS-80, as summarized in Table I (10), the United States Pharmacopoeia does not define the percentage of fatty acid esters in polysorbates (10,11).…”

Polysorbates 20 and 80 Used in the Formulation of Protein Biotherapeutics: Structure and Degradation Pathways

“…The structures shown here are those of the chemically homogenous polysorbates. Solutions of polysorbate sold by manufacturers and labeled as polysorbate 20 or 80 are chemically diverse mixtures of different fatty acid esters23–25 and will be discussed later. Both types of polysorbates have a common backbone and only differ between the structures of the fatty acid side chains.…”

The Degradation of Polysorbates 20 and 80 and its Potential Impact on the Stability of Biotherapeutics

“…Commercially available polysorbates (PS) 20 and 80 are chemically diverse mixtures containing mainly sorbitan POE fatty acid esters. Additionally, substantial amounts of POE, sorbitan POE and isosorbide POE fatty acid esters are present (12)(13)(14). This leads to a significant degree of lot-to-lot variability requiring a close scrutiny of each lot in order to ensure uniform behavior (15).…”