Hydrogel-Based Ultra-moisturizing Cream Formulation for Skin Hydration and Enhanced Dermal Drug Delivery

• Published in: Biological & pharmaceutical bulletin Vol. 37; no. 10; pp. 1674 - 1682
• Main Authors: Lee, Sang Gon, Kim, Sung Rae, Cho, Hye In, Kang, Mean Hyung, Yeom, Dong Woo, Lee, Seo Hyun, Lee, Sangkil, Choi, Young Wook
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01-10-2014; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Administration, Cutaneous; Animals; Drug Delivery Systems - methods; Emollients - administration & dosage; Emollients - metabolism; Hydrogel, Polyethylene Glycol Dimethacrylate - administration & dosage; Hydrogel, Polyethylene Glycol Dimethacrylate - metabolism; hydrogel-based cream; Hypodermoclysis - methods; Male; Mice; Mice, Hairless; moisturizer; Organ Culture Techniques; Skin Absorption - drug effects; Skin Absorption - physiology; Skin Cream - administration & dosage; Skin Cream - metabolism; skin distribution; skin hydration; skin permeation; topical delivery
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.b14-00458

To develop an external vehicle for skin hydration and enhanced dermal drug delivery, a hydrogel-based ultra-moisturizing cream (HUMC) was successfully formulated with carbopol 934P, urea, Tinocare GL, grape seed oil, and other excipients. The HUMC showed plastic flow behavior due to a gel structure with a cream base. Different types of drug-free vehicles such as a hydrogel, conventional cream (CC), and three HUMCs were prepared and subjected to an in vivo skin hydration test on a hairless mouse using a corneometer. Hydration effect (∆AU) was in the order of HUMC2>HUMC1 ≥ CC>HUMC3>hydrogel. Using nile red (NR) and 5-carboxyfluorescein (5-CF) as lipophilic and hydrophilic fluorescent probes, respectively, in vitro skin permeation and accumulation studies were conducted using Franz diffusion cells. The values of steady-state flux (Jss, ng/h/cm2) were obtained: 74.8 (CC), 145.6 (HUMC1), and 161.9 (HUMC2) for NR delivery; 6.8 (CC), 8.3 (HUMC1), and 10.9 (HUMC2) for 5-CF delivery. The amounts retained in the skin at 12 h (Qr, ng/cm2) were determined: 86.4 (CC) and 102.0 (HUMC2) for NR; and 70.1 (CC) and 195.6 (HUMC2) for 5-CF. Confocal microscopy was used to visualize the distribution of the fluorescent probes. NR tended to be localized into the deeper part of the skin with adipose tissue whereas 5-CF localized in the upper layer of the skin. Thus we propose that HUMC2 is an efficacious vehicle for skin hydration and enhances dermal delivery of lipophilic and hydrophilic drugs.