Presented at the Advisory Committee for Pharmaceutical Science

meeting on March 12, 2003by

Lucinda Buhse, Ph.D.

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

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.

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

Appearance•Clear, translucent or opaque

•viscous

•Greasy vs. non-greasy•Cooling sensation

Feel

Physical Properties

Microscopy - 400x

No Peak

Soft Peak Stiff Peak

Creams and Lotions: Multivariate Analysis of Selected Physico-chemical Properties

Viscosity is potentially a significant variable.

Scores Loadings

Lotions Creams

Viscosity Measurements of Selected Topical Products

0

25,000

50,000

75,000

100,000

125,000

150,000

175,000

200,000

Selected Products

Vis

cosi

ty (

cp)

Lotions

Creams

30,000 cp

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

Viscosity of Selected Topical Products

0

200,000

400,000

600,000

800,000

1,000,000

1,200,000

1,400,000

1,600,000

1,800,000

2,000,000

Selected Products

Vis

cosi

ty (

cp)

CreamsOintments

Ointments <20% and Lotions >50%.

%Loss on Drying for Selected Topical Products

0

20

40

60

80

100

Selected Products

% L

oss

on

Dry

ing

LotionsCreamsOintments

Chemical Composition of Selected Topical Products

0

20

40

60

80

100

Selected Products

% h

ydro

carb

on a

nd

pol

yeth

ylen

e gl

ycol

Lotions

Creams

Ointments

Ointments have %hydrocarbon or Polyethylene Glycols >50%.

Chemical Composition (%) vs. Loss on Drying (%)

0

20

40

60

80

100

0 20 40 60 80 100

%LOD

% h

ydro

carb

on a

nd

pol

yeth

ylen

e gl

ycol

Lotions

Creams

Ointments

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

0.00 100.00 200.00 300.00 400.00 500.00Temp [C]

0.00

20.00

40.00

60.00

80.00

100.00

%TGA

cream

cream cream

cream

gel

gel

Thermal Analysis - TGA"Drug B"

Gel formulations have fewer transitions than the creams.

0.00 100.00 200.00 300.00 400.00 500.00Temp [C]

0.00

25.00

50.00

75.00

100.00

%TGA

lotion

cream

gel

Thermal Analysis - TGA"Drug C"

Thermogravimetric Analysis of Selected Products

Drug B Drug CCream

Cream

Cream

Cream

Gel

Gel

Lotion

Cream

Gel

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