2 3 1 +C × 100 C A= C (4) Ng C = Amount of niacinamide in original PLO gel , 1 Ng 2 = Amount of niacinamide in receptor , C Ng = Amount of niacinamide in membrane . C3 Th e sk in permeat ion effi ciency of the formulated PLO gel was calculated by substituting C1, C2, and C3 values obtained by HPLC analysis into the aforementioned equation. As a result, skin permeation effi ciency was 22.62±3.59% in the formulation #2–1, and this outcome reconfi rmed the applicability of the formulated PLO gel as a TDDS. CONCLUSION This study was performed to investigate the applicability of (PLO gel) in cosmetics as a topical drug delivery system. To achieve this objective, the formulation and assessment of PLO gel were conducted using RSM by mixing three major compositions, including lecithin, PEG-400, and poloxamer 407 prepared at different ratios. To evaluate the stability of PLO gel formulations, the elapsed time change was observed by storing these formulations at low temperature (4°C), room temperature (25°C), and constant temperature (45°C). The all-formulated organogels were stable at room and constant temperatures, but formulations #2–6 and #2–11 were unstable by exhibiting phase separation. To examine the pro perties of the formulated PLO gel, the relatively smooth and spread- able formulation #2–3 was measured using SEM, and this PLO gel exhibited a bicon- tinuous microemulsion structure. To determine gelation temperature exhibiting phase separation at low temperatures, DSC measurement was performed. To evaluate the char- acteristics of the gel formulations, elasticity and viscosity were also measured. RSM was used in an alyzing the measurements of elasticity, viscosity, and DSC varying depending on the content ratios of hydrogenated lecithin, PEG-400, and poloxamer 407 that have a signifi cant impact on the properties of the formulated PLO gel, and assessing the degree of infl uence of each composition. In the degree of infl uence on elasticity, the content of PEG-400 was most infl uential, followed by hydrogenated lecithin and polox- amer 407. In the degree of impact on viscosity, the amount of PEG-400 was most infl u- ential, followed by hydrogenated lecithin. The content of poloxamer 407 alone in the formulated gels appeared to have almost no effect, but had an infl uence to some extent in association with the other two compositions. In DSC analysis, the concentration of polox- amer 407 was most infl uential, followed by hydrogenated lecithin. The content of PEG- 400 seemed to have almost no effect. As previously intr oduced, PLO gel has shown problems by displaying fl owability at low temperatures issues have been raised concerning the safety of PLO gel in cosmetic formu- lations. This research has verifi ed the possibility of PLO gel as a safe formulation without fl owability at cold temperatures. In addition, skin permeation effi ciency was measured using the transdermal Franz diffusion cell system, and the measured value was 22.62±3.59%. This outcome demonstrated that PLO gel is suitable as a TDDS. JOURNAL OF COSMETIC SCIENCE 344

In conclusion, the stability of PLO gel has to be maintained without phase separation at low temperature, room temperature, and constant temperature to evaluate the suitability of PLO gel as a cosmetic ingredient. In particular, stability has to be maintained without fl owability at cold temperatures. Moreover, because excessively high viscoelasticity may infl uence the texture and application of the formulation when spreading it on the skin, the formulation with adequate viscoelasticity seems to be most appropriate. Based on the previous fi ndings, the formulation #2–3 is suggested as the most suitable PLO gel in cosmetic formulations. ACKNOWLEDGMENTS Th is research was supported by the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region (P0002162). REFERENCES (1) H. E. Jin, J. H . Kim, and I. Y. Paik, Transdermal drug delivery system, J. Korean Ind. Eng. Chem., 16(1), 15–20 (2005). (2) B. W. Barry, D r ug delivery routes in skin: a novel approach. Adv. Drug Deliv. Rev., 54, 31–40 (2002). (3) S. Saha, R. Sh i varajakumar, and V. Karri, Pluronic lecithin organogels: an effective topical and transder- mal, ISJPRS, 9(11), 4540–4550 (2018). (4) J. Hadgraft an d M. E. Lane, Skin permeation: the years of enlightenment. Int. J. Pharm., 305(1–2), 2–11 (2005). (5) M. Foldvari, N o n-invasive administration of drugs through the skin: challenges in delivery system de- sign. PSST, 3(12) 417–425 (2000). (6) H. C. Ansel, P h armaceutical Dosage Forms and Drug Delivery Systems, N. G. Popovich and L. V. Al- len, Eds. (Lea & Febiger, Philadelphia, PA, 1995), 357. (7) J. Franckum, D . Ramsay, N. G. Das, and S. K. Das, Pluronic lecithin organogel for local delivery of anti-infl ammatory drugs, Int. J. Pharm. Comp., 8(2), 101–105 (2004). (8) R. Kumar and O . P. Katare, Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review, AAPS PharmSciTech, 6(2), 299–310 (2005). (9) M. Pandey, V. B elgamwar, S. Ganttani, S. Surana, and A. Tekade, Pluronic lecithin organogel as a topi- cal drug delivery, Drug Deliv., 17(1), 38–47 (2010). (10) V. S. Belgamw a r, M. S. Pdney, D. S. Chauk, and S. J. Surana, Pluronic lecithin organogel, Asian J. Pharm., 2(3), 134–138 (2008). (11) S. Murdan, A r eview of pluronic lecithin organogel as a topical and transdermal drug delivery system, Hosp. Pharm., 12, 267–270 (2005). (12) P. Terech and R. G. Weiss, Low molecular mass gelators of organic liquids and the properties of their gels, Chem. Rev., 97(8), 3133–3159 (1997). (13) K. E. Hill, P . C. Mills, B. R. Jones, C. F. Bolwell, D. Aberdein, and J. P. Chambers, Percutaneous ab- sorption of methimazole: an in vitro study of the absorption pharmacokinetics for two different vehicles, J. Vet. Pharmacol. Ther., 38(6), 616–618 (2015). (14) A. S. Hickey and N. A. Peppas, Mesh size and diffusive characteristics of semicrystalline poly (vinyl alcohol) membranes prepared by freezing/thawing techniques, J. Membr. Sci., 107, 229–237 (1995). (15) M. M. Adbel-Mottaleb, N. D. Mortada, A. A. Elshamy, and G. A. Awad, Preparation and evaluation of fl uconazole gels, Egypt. J. Biomed. Sci., 23(1), 266–286 (2007). (16) H. Almeida, M. H. Amaral, P. Lobão, and J. M. S. Lobo, Pluronic F-127 and pluronic lecithin organogel (PLO gel): main features and their applications in topical and transdermal administration of drugs, J. Pharm. Pharm. Sci., 15(4), 592–605 (2012). ( 17) C. L. Esposito, P. Kirilov, and V. G. Roullin, Organogels, promising drug delivery systems: an update of state-of-the-art and recent applications, J. Control. Release, 271, 1–20 (2018). PREPARATION AND EVALUATION OF PLURONIC LECITHIN ORGANOGELS 345