POLYGL¾CEROL ESTERS IN PHARMACEUTICAL PREPARATIONS 475 TABLE I--SOME PHYSICAt, AND CHEMICAL CHAR.ACTEKISTICS OF POLYGLYCEKOLS Molecular Number of Calculated Found Specific Compound Weight OH Groups OH Value OH Value Gravity Glycerol 92 3 1830 1828 1.24 Di-glycerol 166 4 1352 1320 Tri-glycerol 240 5 l 169 1166 l'. • Tetra-glycerol 314 6 1071 1082 ... Penta-glycerol 388 7 1012 1028 Hexa-glycerol 462 8 970 1010 1"2'4 Hepta-glycerol 536 9 941 972 ... Octa-glycerol 610 10 920 951 ... Nona-glycerol 684 11 903 903 Deca-glycerol 758 12 880 888 l' • Polyglycerols are prepared by the polymerization of glycerine under alkaline conditions. The process has been recently developed, and a patent is pending with the U.S. Patent OfFice. The controlled polym- erization of glycerol to yield a specific molecular weight polymer produces water white to pale yellow products with pleasant odor and flavor. The polyglycerols thus prepared are then esterified with specific fatty acids or subjected to alcoholysis or ester exchange to prepare a mixed fatty acid ester. Thus, a hexaglycerol monostearate may best be made by reacting hexaglycerol with stearic acid, while a hexaglycerol coconut oil ester may best be prepared by the alcoholysis of coconut oil with hexaglycerol. Investigations thus far indicate that the polymerization of glycerol is progressing in a straight line manner without cyclization or ring formation. Although Markley (11) indicates cyclic structure formation, we have not been able to identify the presence of any ring structures in our product. Work is continuing to shed light on the mechanism of this reaction, but it appears, at present, that the polymerization gives rise to the type of chain growth which is shown below: OH OH H H OH H H OH OH HC C--C-4)--C--C--C---O--C--C C--H H H H H H H H H H The polymerization can continue in this manner, with the terminal hy- droxyl groups forming ether linkages by elimination of water. CHEMICAL AND PHYSICAL PROPERTIES The polyglycerols have the characteristics normally associated with polyols. They are water-soluble in all proportions and have excellent emollient and humectant properties. They differ from glycerol mainly in that the viscosity increases as the chain length does. Table I shows some

476 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS of the chemical properties of polyglycerols, starting with the single glycerol molecule and going up to the decaglycerol molecule which contains 10 moles of glycerol. It should be noted that there will always be two more hydroxyl groups than there are moles of glycerol. These figures show the numerical increase in the hydroxyl groups in each polyglycerol as the poly- mer is increased in size and molecular weight. Also, the calculated hy- droxyl values and the actual hydroxyl values obtained by analysis are given to demonstrate the correlation between hydroxyl value and molec- ular weight. It has been possible to prepare polymers from diglycerol (2 moles of glycerol) to tricontaglycerol (30 moles of glycerol) in the initial stages of polymerization. The polyglycerols are high-molecular weight, water- soluble fluids which may be used as thickening agents, humectants, chemi- cal intermediates and for other purposes. One or more of the hydroxyl groups present in a polyglycerol molecule may be esterified thus, since decaglycerol contains 12 hydroxyl groups, any ester from mono to dodeca may be prepared. Since any number of fatty acids may be used in the esterification, the number of possible poly- glycerol esters becomes virtually unlimited. These polyglycerol esters may be liquid to waxy saturated or unsaturated low to high molecular weight and hydrophilic or lipophilic, depending on the number of hy- droxyl groups that are reacted with the fatty acids and/or oils in question. Polyglycerol esters ranging from complete oil solubility to complete water solubility may be prepared, with the possibility of many intermediate properties between these two extremes. Therefore, it becomes possible to synthesize an entire class of emulsifiers, tailor-made to perform any specific function. Table II illustrates some of the chemical and physical proper- ties of a selected list of the polyglycerol esters, and Table III shows their solubilities in various solvents. Regardless of the molecular weight of the polyglycerol and regardless of the type of fatty acid or amount of such fatty acid present in the poly- glycerol ester, feeding studies (12) have indicated that such esters are completely nontoxic and are degraded fully by the body to yield glycerol and the fatty acid. Why a three-carbon ether linkage should be utilized by the body while a two-carbon ether linkage of the polyoxyethylene prod- ucts should not be utilized is not clearly understood. The repeated re- sults of testing, however, leave no question that this is true. Based on these feeding studies, which were conducted with saturated and unsatu- rated esters of polyglycerol ranging from two to thirty moles of glycerine, the F.D.A. not only gave approval on the use of these polyglycerol esters in food but also placed no limits on the amounts that could be used (13). This F.D.A. approval currently covers esters up to and including the decaglycerol esters of the fatty acids derived from corn, cottonseed, lard,