Polymeric Emulsion Technology Applied to Tretinoin

April 2019 | Volume 18 | Issue 4 | Supplement Individual Articles | 148 | Copyright © April 2019

Leon H. Kircik MD,a Zoe D. Draelos MD,b Diane S. Berson MDc

School of Medicine at Mount Sinai, New York, NY; Indiana School of Medicine, Indianapolis, IN; Physicians Skin Care, PLLC, Louisville, KY; DermResearch, PLLC, Louisville, KY; Skin Sciences, PLLC, Louisville, KY BDermatology Consulting Services, PLLC, High Point, NC cDepartment of Dermatology, Weill Medical College of Cornell University, New York-Presbyterian Hospital, New York, NY

Figure 1more lipophilic the vehicle used to suspend the tretinoin is, the greater the concentration of tretinoin at the surface of the skin and higher the risk of potential irritation. A novel formulation of micronized tretinoin 0.05% gel has been developed that potentially enables more efficient penetration into the crevasses and follicular openings of the skin because of its optimal particle size.The development of this novel aqueous gel formulation that incorporates micronized active drug, suspended in a moisturizing hydrogel vehicle provides a number of advantages; limiting the concentration of tretinoin in solution and by limited solubility-controlled release at the surface of the skin and improving delivery to the pilosebaceous units. In such a hydrogel, hydrophobic drugs like tretinoin are not in solution but a solid state, dispersed and suspended by a polymeric gelling agent. The gel is alcohol-free, contains humectants and moisturizers (soluble collagen, sodium hyaluronate, and glycerin), and produces very little or no additional skin barrier disruption. The sustained delivery of tretinoin, which can eliminate the burst-release characteristics of some tretinoin formulations, and the humectants/moisturizers used in the formulation allow for controlled release over time and should help minimize tretinoin-associated irritation, dryness, scaling, and redness.Tretinoin particles normally range in size from 200 to 300μm in more traditional formulations. In this formulation of tretinoin 0.05% aqueous gel, at least 85% of the micronized particles are smaller than 10μm. Having such a small particle size could allow for easier penetration into the follicular openings, which are typically 11 to 77μm, with resultant direct uptake into the sebum.10,11 A more efficient penetration of micronized tretinoin particles into the epidermis/dermis has been reported when compared to tretinoin microsphere 0.1% gel. Micronized tretinoin in this aqueous gel had a three-fold greater efficiency for epidermal and dermal deposition of tretinoin (21% and 3% of the applied dose, respectively, with tretinoin 0.05% aqueous gel, compared with 7% and 1% with tretinoin microsphere 0.1% gel).12 The total amount of tretinoin delivered is depending upon the concentration of tretinoin as well as the efficiency of its delivery. In this in vitro 24-hour percutaneous absorption study, the epidermal deposition with micronized tretinoin 0.05% aqueous gel was 0.526 μg/cm2 compared with 0.336 μg/cm2 with tretinoin microsphere 0.1% gel.12 In addition, photodegradation of micronized tretinoin 0.05% aqueous gel is reduced, and the lowest seen with tretinoin formulations so far, and there is no apparent degradation when used with BP. Photodegradation of tretinoin appears to correlate with specific light conditions and formulations used. This phenomenon may also be clinically relevant.13-15 Photodegradation of micronized tretinoin 0.05% aqueous gel was minimal after eight hours exposure to UVA light, the major contributor to tretinoin photodegradation. The 9% degradation observed (compared with 72% degradation of tretinoin 0.025% gel) was lower than that seen in other studies with tretinoin 0.1% microsphere gel exposed to a stimulated solar UV light source for a shorter period of time.16

Polymeric Matrix to Deliver Micronized Tretinoin

A number of different strategies have been proposed to achieve efficient drug delivery systems. Hydrogels are the latest advance; they are three-dimensional, cross-linked networks of water-soluble polymers commonly used in cosmetic formulations for skin care. Different polymers can be selected to formulate these hydrogels; some of the most commonly used gelling agents are carbomers, high molecular weight polymer of acrylic acid. In formulating these hydrogels product spreadability for correct dosage transfer to the target site, ease of application, extrudability from the proposed packaging, and most importantly consumer preference, must be considered.17