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. 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. 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. 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. 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. 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. 7 Cream A semisolid emulsion or suspension Generally contains 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. 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. 9 Decision Tree A topical dosage form for dermatological application What kind is it? Topical d.f.

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

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

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

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

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

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