1. Presented at the Advisory Committee for Pharmaceutical Science meeting on March 12, 2003 by Lucinda Buhse, Ph.D.

2. Topical Drug Nomenclature Objective: To establish a scientific basis for a systematic and coherent classification of dosage forms for topical drugs. Working Group (ONDC/OGD/DPA): Cindy Buhse, Gil Jong Kang, Saleh Turujman, Mamta Gautam Basak, Chi Wan Chen DPA Laboratory Team: Dick Kolinski, Nick Westenberger, Anna Wokovich, Jack Spencer

3. Current FDA Definitions Cream: A semisolid dosage form containing one or more drug substances dissolved or dispersed in a suitable base. Gel: A semisolid system consisting of either suspensions made up of small inorganic particles or large organic molecules interpenetrated by a liquid. Lotion: "The term lotion" has been used to categorize many topical suspensions, solutions and emulsions intended for application to the skin. Ointment: A semisolid preparation intended for external application to the skin or mucous membranes.

4. What are the distinguishing properties? Physico-chemical Viscosity Loss on Drying (LOD) Specific Gravity Surface Tension Water Solubility Water Absorption Drying Properties Thermogravimetric Analysis (TGA) Chemical Base Composition Physical Properties Appearance Feel Microscopy

5. Appearance Clear, translucent or opaque viscous Greasy vs. non-greasy Cooling sensation Feel Physical Properties Microscopy - 400x No Peak Soft PeakStiff Peak

6. Creams and Lotions: Multivariate Analysis of Selected Physico-chemical Properties Viscosity is potentially a significant variable. ScoresLoadings LotionsCreams

7. Lotions are pourable (viscosity <30,000 cp at 5 rpm and 25ºC).

9. Ointments 50%.

10. Ointments have %hydrocarbon or Polyethylene Glycols >50%.

12. Common Characteristics of Most Marketed Gels Viscosity: low (10,000 - 70,000 cp) Loss on Drying : high (70-99%) Solubility : water soluble Water Absorption : no specific trend Drying Properties : no specific trend Thermogravimetric Analysis : fewer transitions Composition : contains gelling agents (carbomer) Appearance : clear Feel : non greasy, cooling Microscopy : no specific trend

13. Gel formulations have fewer transitions than the creams. Thermogravimetric Analysis of Selected Products Drug BDrug C Cream Gel Lotion Cream Gel

14. Classification of Topical Drugs Lotions: –pourable with viscosity <30,000 cp (at 5 rpm and 25ºC) –Loss on Drying > 50% Ointments: –Loss on Drying < 20% –hydrocarbon or polyethylene glycols content > 50% Gels: –contain sufficient gelling agent to form 3D matrix