1. Topical Dermatologic Dosage Forms and Vehicle Properties: Issues and Opportunities Jonathan Wilkin, M.D. Director, Division of Dermatologic and Dental Drug Products, FDA

2. 2 Background I If it’s dry, wet it. If it’s wet, dry it. Paleodermatologic aphorism.

3. 3 Background II Originally, no “active” ingredient. Therapeutic choice based on physical and sensory properties.

4. 4 Background III In the 1800s l “Active” ingredients began to be added l Topical dosage formulations grouped under commonly used terms.

5. 5 Background IV Powder (crystals) for bath solution Colloid baths Bath oils (including bath tars) Solutions or suspensions for wet dressings and soaks Shake lotions - “shake” to disperse powders Creamy-type lotions - (w/o and o/w) Creams Ointments

6. 6 Background IV (cont’d) Pastes Solutions Tinctures Suspensions (shake lotions) Varnishes Powders

7. 7 Background V Later additions: Gels Foams Emollient creams

8. 8 Problems FDA and USP dosage forms insufficiently defined Manufacturers produce dosage form intergrades, e.g., between creams and lotions that resist classification

9. 9 Opportunities Creation of mutually exclusive definitions for dosage forms and consistent terminology Summary of relevant vehicle properties in the Description section of product labeling Provide clinically important information to health care providers choosing among topical dermatologic products

10. 10 Relevant Vehicle Properties l Dosage form - a rough guide l Description section - specific information

11. 11 Examples of Potential, Relevant Vehicle Properties Viscosity - could be an ordinal classification and nonlinear Spreadability - spread value in mm 2 in 10 minutes Wash and rub resistance Skin smoothness - time curve Usual appearance of product, incl. color Odor of product

12. 12 Examples of Potential, Relevant Vehicle Properties (cont’d) Permanence on skin surface - residue at 10 minutes Moisturization - TEWL time curve Volatilization - time curve

13. 13

14. 14

15. 15

16. 16 Salka, Barry A. Choosing emollients. Cosmetics & Toiletries 112:101-106, 1997

17. 17 Vehicle Choice l Important factor in patient compliance l Prescribing physician needs relevant information: well-defined dosage forms description of relevant vehicle properties

18. 18 Impact on Stakeholders Innovators - more specific description of product may reduce generic competition Generics - better defined target leads to greater sameness of generic product Health care providers - better choice among products Patients - product acceptability improves compliance leading to better outcomes

19. 19 Looking Ahead 1. Definitions and Classification of Topical Dermatologic Dosage Forms Need industry, academia, professional scientific societies, USP and FDA consensus

20. 20 2. Development of Consistent Methodology and Terminology to Describe Relevant Vehicle Properties (for Description Section of Labeling) Industry may already have the methods and terminology. Industry must decide if this is desirable. If so, they must be leaders in this effort.