In Vitro Drug Permeation Studies

Unique models resulting in the most reliable and reproducible in vitro skin penetration data available.

Value of In Vitro Testing for Release and Delivery of API

Before you select a topical formulation to progress in development, you should ensure that your API is released from the formulation and penetrates the skin as required for your clinical indication. This prevents false negatives in your early proof-of-concept and efficacy studies.

At Dow we conduct unique in vitro studies to screen multiple prototype formulations. With topical dermatological products, it is imperative that the formulation used in early non-clinical and clinical studies be very close to the final commercial formulation. If you make formulation changes later in development, you will most likely be required to repeat the expensive and time consuming non-clinical studies.

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Unique In Vitro Studies Conducted at Dow

Using Dow’s unique in vitro test models, we conduct studies to measure the rate and extent of API transport across the skin as well as retention on and in the skin. Formulations are applied to excised human or animal skin or tissue mounted in Franz static or Bronaugh flow-through diffusion chambers. Assessment of API penetration and skin retention is made by counting radioactivity from radiolabeled applied drugs, or by HPLC analysis. These studies provide information for selecting the dosage form(s) most suited for optimal delivery for topical or transdermal therapeutic products.

For dermatological formulations we use freshly excised human skin from elective surgery. For ophthalmic formulations we use newborn bovine corneal/scleral tissue. For vaginal formulations we use sheep tissue and for buccal formulations we use porcine tissue. A synthetic membrane is used to evaluate release rate of API from semi-solid formulations (SUPAC).

Skin Source and Preparation

The outcome of an in vitro skin penetration study is only as good as the quality of the skin used. At Dow, we use human skin obtained from healthy individuals following elective abdominal surgery. Staff who conduct our in vitro studies also are responsible for preparing the skin, ensuring that only high quality tissue is used. If striations or abrasions that may alter the barrier function are identified, the tissue is rejected immediately. Adipose tissue is removed and the skin is dermatomed to the level of the capillary plexus in the dermis. The result is skin uniformity, preservation of normal skin barrier function, consistent permeability, and reproducibility of skin penetration results - verified by the studies we complete weekly for our clients. Dermatomed skin from a single donor is used for each study, resulting in less variation, reduced standard deviation, and results far superior to those from cadaver skin studies.

In Vitro Cell Systems and State-of-the-art Equipment

Depending on your need and the study protocol, we use our Franz static or Bronaugh flow-through diffusion cell systems, The Franz system has 30 cells and up to 5-6 formulations can be tested per study. The Bronaugh system has 54 cells and 9-10 prototypes can be tested. We target 80-120% recovery of test material dosed, and we usually achieve 90-110%. Our Mettler-Toledo Semi-Micro Analytical Balance 205XP contributes to the accuracy of our calculations. Our Perkin Elmer liquid scintillation analyzer (LSA) provides data electronically which allows us to analyze results quickly while avoiding transcription errors.

The Dow Difference - Beyond Instrumentation

Dow’s in vitro laboratory staff is as important as our equipment, SOP’s, GXP compliance, and tissue sources. They conduct each study and troubleshoot as a team. Not all studies are straightforward, but our team can address all issues in a timely manner. With 25+ years of experience interpreting in vitro data - what it means and how to improve products - they provide crucial information for development and selection of promising formulations. While a variety of study designs are conducted routinely, the protocol, calculations and report for each study are tailored to the specific need of the Client, and are finalized for IND filings.

To Learn More

Please contact Karen Hanley, Associate Director of Business Development, Tel 707.665.4665 for additional information.