Typical Approaches For the Development of Topical Formulations
When developing topical products, there are three development phases that must be undertaken to ensure that the finished product will perform optimally when applied to the skin.
Phase 1: Ingredient Characterization
As discussed elsewhere, the first step in any product development is to identify safe and effective ingredients that can be well characterized in terms of their effects on skin cells. Skin care products contain numerous ingredients including moisturizers, emulsifiers, humectants, antioxidants, exfoliants, and with all of these ingredients it is important to know what their effects on skin cells are. Through the use of screening programs discussed elsewhere it is possible to identify both the positive and negative effects (if any) of any ingredient on cultured skin cells. That type of screeing allows one to determine:
- The skin cell types affected by the ingredient.
- The specific molecular and cellular processes in each cell type that are regulated by a particular ingredient.
- The optimal amount of each ingredient to use in the product.
Phase 2: Development of Topical Formulations to Optimize Skin Delivery
Even though an ingredient may be found to have beneficial effects in cell culture models, that ingredient will only be beneficial when applied topically if it is delivered across the dead skin cells comprising the stratum corneum efficiently.The delivery of any ingredient across the skin's surface can be verified by laboratory tests that use actual human skin.
The test is called Skin Percutaneous Absorption Analysis.
Regardless of how promising a botanically derived compound may seem to be from screening studies using cell culture models, there is no guarantee that this compound will be beneficial when applied topically. Such potential problems as compatibility with formulation ingredients, inability to penetrate through the stratum corneum, inherent instability, etc. can prevent a potential candidate from ever being developed into a product. One of the first tests that is conducted on any potential "candidate" is to incorporate it into a topical formulation and test its ability to move into the stratum corneum. To conduct this test, Percutaneous Absorption Analysis (commonly called Franz Cell Testing) is used.
What is Franz Cell Analysis?
A Franz cell is a specially designed apparatus that allows for the determination of the precise amount of any compound that can penetrate through either human skin (the preferred method), or through a synthetic membrane. To obtain the most useful and predictive data, human skin is used . A diagram of a Franz cell unit is shown here.
As shown in the diagram, a section of human skin is sandwiched between an upper donor chamber and a lower receptor chamber. The lower receptor chamber is filled with fluid and is equilibrated to a temperature of 37 C (normal body temperature) by the circulating water jacket. The test formulation is applied to surface of the skin through the upper chamber and samples of fluid in the lower receptor chamber are taken at specific time intervals (ex. 4, 8, 12 and 24 hours). The samples from the receptor chamber are then analyzed by HPLC to quantify the amount of any ingredient (bioactive) that has penetrated through the skin and entered the receptor chamber.
Phase 3: Clinical Studies to Determine Product Efficacy
For any product to meet customer expectations for improving skin appearance, it must first be tested clinically using an independent testing site to evaluate the product's effectiveness. There are typically two types of clinical studies run on skin care products. The simplest study is to simply give the product to patients (an "open label study") and have the clinical investigator assess the effect of the product in improving such parameters as skin redness, smoothness, or lines and wrinkles after one to two months. If a product contains a proprietary ingredient that the company feels is superior in improving skin appearance, then a blinded, placebo controlled clinical study is run in which two patient groups are enrolled. One group is given the test formulation that contains the proprietary ingredient while the other group receives exactly the same formulation that does not contain the proprietary ingredient. Obviously the second type of study is the only study that should be run to evaluate the efficacy of a proprietary ingredient.