Proposed Definitions and Decision Tree for Topical Dosage Forms

1. Proposed Definitions and Decision Tree for Topical Dosage Forms Advisory Committee for Pharmaceutical Science March 12, 2003 Chi-wan Chen, Ph.D. Director, DNDCIII/ONDC/OPS CDER/FDA

2. Scope • Dermatological application only • Five topical dosage forms, i.e., lotion, gel, cream, ointment, paste, because the existing definitions are less than adequate and because they cannot readily distinguish between • lotion vs cream • Gel vs cream/lotion • Ointment vs cream • Paste vs ointment

3. Gel • A semisolid emulsion or suspension • Contains a gelling agent in sufficient quantities to impart a 3-dimensional, cross-linked matrix • Provides a cooling sensation when applied to the skin • Usually translucent and non-greasy

4. Paste • A semisolid suspension • Contains a large proportion (i.e., 20-50%) of solids finely dispersed in an aqueous or fatty vehicle • Opaque, viscous, greasy to mildly greasy • Adheres well to the skin, forming a protective layer

5. Lotion • A liquid emulsion • Generally contains a water-based vehicle with > 50% of volatiles • Has sufficiently low viscosity that it may be poured • Opaque and non-greasy • Tends to evaporate rapidly with a cooling sensation when applied to the skin

6. Ointment • A semisolid emulsion or suspension • Generally contains > 50% of hydrocarbons or PEGs as the vehicle and < 20% of volatiles • Opaque or translucent, viscous, greasy • Tends not to evaporate or be absorbed when applied to the skin

7. Cream • A semisolid emulsion or suspension • Generally contains < 50% of hydrocarbons or PEGs as the vehicle and/or > 20% of volatiles • Opaque, viscous, non-greasy to mildly greasy • Tends to mostly evaporate or be absorbed when applied to the skin • Can be hydrophilic or lipophilic

8. Decision Tree • Intended to be a tool to help determine the correct topical dosage form • Includes several key tests based on NDA/ANDA data and FDA lab results

9. Decision Tree Topical d.f. A topical dosage form for dermatological application What kind is it?

10. Test 1 Topical d.f. Is it a liquid emulsion or a semisolid emulsion or suspension? Solution aerosol powder suspension N 1 Y 2 3 5b 4 • If no, it is a solution, aerosol, powder, or suspension • If yes, go to Test 2 5a

11. Test 2 Topical d.f. Does it contain sufficient quantities of a gelling agent to form a 3D matrix? Solution aerosol powder suspension 1 Y N 2 3 Gel 5b 4 • If yes, it is a gel • If no, go to Test 3 5a

12. Test 3 Topical d.f. Does it contain a large proportion (20-50%) of dispersed solids? Solution aerosol powder suspension 1 Y 2 3 Gel Paste N 5b 4 • If yes, it is a paste • If no, go to Test 4 5a

13. Test 4 Topical d.f. Does it contain > 50% of volatiles (as measured by LOD)? Solution aerosol powder suspension 1 2 3 Gel Paste N 5b 4 • If yes, go to Test 5a • If no, go to Test 5b Y 5a

14. Test 5a Topical d.f. Is it a pourable liquid with a viscosity of < 30,000 cps)? Solution aerosol powder suspension 1 2 3 Gel Paste 5b 4 • If yes, it is a lotion • If no, it is a cream Y 5a Lotion N Cream

15. Test 5b Topical d.f. Does it contain (1) > 50% of hydrocarbons or PEG as the vehicle and (2) < 20% of volatiles? Solution aerosol powder suspension 1 2 3 Gel Paste Y 5b 4 Ointment • If yes to both, it is an ointment • If no to either or both, it is a cream N 5a Lotion Cream