258 JOURNAL OF COSMETIC SCIENCE 70% (2,3). Clinical studies have shown that topical treatment with AHAs, especially lactic and glycolic acids, can moisturize dry skin (4), relieve hyperkeratotic conditions such as moderate xerosis (5), and alleviate signs of photoaging (6). In recent years, this has led to the introduction of large numbers of AHA-containing cosmetic products in the marketplace with great consumer acceptance. The efficacy of AHA-containing products is linked to their ability to deliver these actives to specific skin strata. Depending on the type and formulation, the AHAs can act either at the stratum corneum or at the deeper, viable tissue level. AHAs enhance the extensibility and the water-binding capability of stratum corneum (7). They may modu- late stratum corneum (SC) formation through diminished cellular cohesion between corneocytes at the lowest levels of the SC (4,8). The benefits of smaller water-soluble AHA homologues such as (L+) lactic or glycolic acid is believed to be related to their ability to enhance epidermal cell turnover (9) and collagen and mucopolysaccharide synthesis in the dermis (10). It is well known that percutaneous absorption depends not only on the nature of the active but also on the vehicle composition. AHAs are currently formulated in a wide variety of cosmetic creams and lotions with differing pH, compositions, or product structure. Although all these products claim efficacy, very little is known about skin absorption of AHAs from complex emulsion systems. Only a few reports (11-13) of systematic study on uptake of AHAs to various skin strata from topical application have been published. Moreover, results of some of these studies appear to be in conflict. For example, in one study (11), decreasing the pH of the aqueous delivery vehicle from 7.4 to 3.8 did not affect skin penetration of glycolic acid (pKa = 3.8), whereas in another (13), changing the pH of an oil-in water emulsion vehicle from 7.0 to 3.0 led to a significantly greater glycolic acid delivery. The objective of this study was to gain insights into how absorption of small water- soluble AHAs into various skin strata could be modulated by compositional and struc- tural changes in the delivery vehicle. Percutaneous absorption of (L+) lactic acid (pKa = 3.8) through dermatomed porcine skin was measured in an in vitro flow-through Bro- naugh diffusion cell (14) using well characterized emulsions as test vehicles. The effects of vehicle pH and propylene glycol (as a penetration enhancer) on skin permeation of lactic acid were studied using an oil-in-water (o/w) emulsion. The o/w emulsion was applied either as a 2-pl topical film or as a 75-pl "infinite"-dose (i.e., in large excess) occluded patch on a 0.64-cm 2 skin disc. Comparison of the results provided insights into penetration pathways of lactic acid in stratum corneum. The effect of vehicle structure on delivery was studied by comparing distributions of lactic acid to different skin strata from topical application of oil-in-water (o/w), water- in-oil (w/o), and multiple (water-in-oil-in water [w/o/w]) emulsions. The composition of the emulsions was kept constant to minimize the effect of formulation variation on AHA delivery. The role of emulsion structure on dermal delivery of a water-soluble active, glucose, in an infinite-dose situation has been studied (15). No similar study for AHAs, either in an infinite-dose or in consumer-relevant finite-dose application, has been reported in the literature.

PERCUTANEOUS ABSORPTION OF LACTIC ACID 259 EXPERIMENTAL MATERIALS L+[•4C(u)] lactic acid, specific activity 150 mCi/mmol, was obtained from American Radiolabelled Chemicals Inc. The following chemicals were used in formulation of the emulsions: a hydrophilic surfactant (Synperonic PE/F127, a block copolymer of ethylene oxide and propylene oxide ICI Surfactants, Wilmington, DE) a lipophilic surfactant (Hypermer A60, a modified polyester ICI Surfactants) lactic acid (USP grade Purac) paraffin oil (Penreco) and propylene glycol (Fischer Chemical). The scintillation cock- tails used were Ecolume TM (ICN), Scintiverse7 ScintanalyzerTM (Fischer Chemicals), and NCS-II-Tissue solubilizer (Amersham Canada Limited). PREPARATION OF EMULSIONS All emulsions were prepared from the same formula: paraffin oil 35% w/w, Hypermer A60 2.8% w/w, Synperonic 1.2% w/w, lactic acid 8% w/w, pH adjuster KOH, and balance water. The hydrophilic lipophilic balance (HLB) (16) for Synperonic, was ap- proximately 20, and that of Hypermer was between 2 and 4. The calculated HLB of the surfactant mixture was 9.0. The radiochemical concentration of lactic acid in all the emulsions was 30 pCi/g. The emulsions were stored at 4øC overnight before use in the experiments. The simple emulsions (o/w or w/o) were prepared by adding the aqueous phase, con- taining unlabeled lactic acid and the L-[14C(u)] lactic acid, to the oil phase at 65ø-70øC. For the o/w emulsion, the hydrophilic surfactant was in the aqueous phase and the lipophilic surfactant was incorporated in the oil phase, whereas for the w/o emulsion both the surfactants were in the oil phase. A coarse emulsion was first formed by mixing the two phases at 65ø-70øC in a Tekmar RW 20 DZM mixer for fifteen minutes at 1500 rpm. The emulsion was then homogenized for five minutes with the Silverson L4R homogenizer. Although the bulk compositions were the same, the interfacial compositions varied depending on the formulation procedure. The adsorption of surfactant monomers at the oil-water interface involves dissociation of the surfactant aggregates in the bulk phase to monomers followed by diffusion of the monomers to the interface. The more soluble the surfactant is in the bulk phase, the faster are the aggregate-monomer breakdown kinet- ics. When the hydrophilic and hydrophobic surfactants are in the water and oil phases, respectively, the aggregate-monomer breakdown kinetics is high for both of them. As a result, both the hydrophilic and hydrophobic monomers adsorb at the oil-water interface during the emulsification process. The HLB of the surfactant mixture at the interface in that situation is quite similar to the HLB of the total system. For the surfactant system (HLB of 9) chosen in this study, such an interface stabilizes an o/w emulsion. However, when the hydrophilic surfactant is dispersed in the oil phase, the aggregate-monomer dissociation kinetics are slow, and consequently only a small amount of the monomer reaches the oil-water interface during the emulsification process. The interface in this situation predominantly contains the low-HLB hydrophobic surfactant that stabilizes a w/o emulsion.