Investigations on Alkanediols as Alternative Preservatives in a Nonionic Hydrophilic Cream

Abstract

Alkanediols are often used as alternative antimicrobial preservatives for dermal formulations, e.g., hydrophilic creams. These substances show an antimicrobial effect due to their amphiphilic structure. At the same time, their amphiphilic behavior enables various interactions with the cream base itself. Therefore, the effect of four different alkanediols, namely 1,2-pentanediol, 2-methyl-2,4-pentanediol (hexylene glycol), 1,2-hexanediol, and 1,2-octanediol on the physical stability of a nonionic hydrophilic cream was investigated. Further, the incorporation of the alkanediols into lamellar structures of the cream was evaluated using differential scanning calorimetry (DSC) and small-angle X-ray scattering (SAXS) measurements. The interaction with the mixed crystals of the cream was found to increase with raising alkyl chain length of the added alkanediol. As a result, consistency and stability of the cream are slightly impaired. A test for efficacy of antimicrobial preservation according to the European Pharmacopoeia (Ph.Eur.) revealed that the antimicrobial activity is directly linked to the length of the alkyl chain of the alkanediols. 2-Methyl-2,4-pentanediol differs from both findings. This compound has non-vicinal hydroxy groups which result in a reduced amphiphilicity compared to the others. Consequently, it has a smaller impact on the colloidal structure of the cream and shows a comparatively low antimicrobial activity.

Impact of Alkanediols on Stratum Corneum Lipids and Triamcinolone Acetonide Skin Penetration

“…The amphiphilic nature of alkanediols enables them to interact with the microbial cell membranes [ 51 ] as well as with the surfactant and co-surfactant system of the cream bases used [ 4 ]. Thus, it appeared very likely that they also interact with SC lipids.…”

“…Since the extent of antimicrobial activity of the alkanediols depends on their amphiphilicity, which favors their incorporation into the lipophilic bilayer of the bacterial cell wall, 2-methyl-2,4-pentanediol was found to be less effective in antimicrobial performance than the other alkanediols. In addition, due to the reduced amphiphilicity, the interaction with surfactants and co-surfactants present in the formulation is likewise diminished [ 4 ]. In our study, the reduced amphiphilicity leads, on the one hand, to a lower TAA solubility of this compound compared to the other alkanediols [ 18 ].…”

“…This could have been expected as it is not a 1,2-alkanediol. Hence, it has a lower amphiphilicity and its interaction with the SC lipids as well as cell membranes [ 4 ] is comparatively lower than those of the other alkanediols.…”

“…The most commonly used alkanediols are 1,2-pentanediol, 2-methyl-2,4-pentanediol (hexylene glycol), 1,2-hexanediol and 1,2-octanediol. Their preservative effect has already been demonstrated [ 4 , 5 ] and can primarily be attributed to their amphiphilic properties. With their hydrophilic head group on the one hand and their lipophilic alkyl chain on the other hand, they are enabled to interact and disorder the cell membranes of microorganisms [ 5 ].…”

“…Due to their amphiphilic nature, they can also interact with the surfactant and co-surfactant system of an emulsion or cream. This interaction becomes more intense with rising alkyl chain length [ 4 , 6 ]. In addition, the alkanediols used for alternative preservation must be safe and non-hazardous to health.…”