As part of an ongoing effort to create the highest quality products, PCCA has aggressively studied the ability of Lipoderm® and PLO to deliver ketoprofen across human skin. PCCA teamed up with the highly regarded dermatologic laboratory PRACS Institute – Cetero Researchto conduct this study. Using PCCA’s Special Micronized Ketoprofen USP, PCCA Lipoderm performed better than PLO.
Evaluation of the Percutaneous Absorption of Ketoprofen, In Vitro, Using the Human Cadaver (Ex Vivo) Skin Model
The study was designed to evaluate the percutaneous absorption pharmacokinetics of PCCA’s Special Micronized Ketoprofen. Absorption was measured in human cadaver skin, in vitro, using the finite dose technique and Franz Diffusion Cells.
The products were tested on replicate sections from three different cadaver skin donors, for the percutaneous absorption of PCCA’s Special Micronized Ketoprofen over a 48-hour dose period. At pre-selected times after dose application, the dermal receptor solution was removed in its entirety, replaced with fresh receptor solution, and an aliquot saved for subsequent analysis. In addition, the epidermis and dermis were recovered and evaluated for drug content. The samples were analyzed for ketoprofen content by High Performance Liquid Chromatography (HPLC).
Methods and Procedures
Percutaneous absorption was measured using thein vitrocadaver skin finite dose technique. Human cadaver trunk skin without obvious signs of skin disease, obtained within ~24-48 hours of death, was used in this study.
Skin from a single donor was cut into multiple smaller sections large enough to fit on static 1.0 cm2 Franz diffusion cells. To assure the integrity of each skin section, its permeability to tritiated water was determined before application of the test products. All formula- tions were then applied to the skin sections using a positive dis- placement pipette set to deliver 5 μL formulation/cm2. The dose was spread across the surface with the Teflon® tip of the pipette. At pre-selected times after dosing (4, 8, 12, 24, 32, and 48 hours), the reservoir solution was removed in its entirety, replaced with fresh reservoir solution, and an aliquot saved for subsequent analysis.
The data indicate that PCCA’s Special Micronized Ketoprofen did penetrate into and through human cadaver skin, in vitro, from the test formulations provided.
The absorption profiles indicate a rapid penetration to a peak flux occurring at approximately 7-8 hours after dose application fol- lowed by a steady decline thereafter. PCCA Lipoderm performed significantly better than PLO at delivering PCCA’s Special Micronized Ketoprofen through human skin (see Figure 1). This formulation also delivered PCCA’s Special Micronized Ketoprofen