Dosage forms to deliver pharmaceutical actives to the skin (definitions provided in Reference 5. Bolded entries are terms
being phased out of USP titles)
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If the dosage form is a liquid or semisolid, and not listed in Tables, then the next question in the decision tree is, Is
it a liquid or a semisolid? (4). To help answer this question, Buhse et al. and CDER Data Sandards Manual define liquid as being pourable; it flows and conforms to its container at room temperature, and displays Newtonian or pseudoplastic
flow behavior. A semisolid is defined as not being pourable; it does not flow or conform to its container at room temperature.
It does not flow at low-shear stress and generally exhibits plastic flow behavior (4, 6). Thus to distinguish between a liquid
and a semisolid, a rudimentary understanding of plastic and pseudoplastic flow behavior and Newtonian liquids is required.
Because these references do not define these terms, it appears in keeping with FDA's interpretation to use descriptive definitions.
Newtonian fluids such as water and solutions containing only low molecular-weight material are characterized by viscosity
that is independent of the rate of stirring. Thus, a plot of shear rate versus shear stress is linear and passes through the
origin. Pseudoplastic flow behavior is characterized by viscosity decreasing with the rate of shear (i.e., shear thinning).
Plastic flow behavior is characterized by a material behaving as a solid until a threshold stress is reached beyond which
the material flows. The slope of the rheogram can be extrapolated to determine the yield value. Because a threshold stress
is required before flow, the plot of shear rate versus shear stress can not pass through the origin for a material having plastic flow. Based on the data presented by Buhse et
al., the plot of shear rate versus shear stress for both pseudoplastic liquids and plastic semisolids are characterized by a yield value (D/cm2 ) and a curved response to changes in shear rate (4). In a presentation, Buhse suggested that semisolids have yield values
≥ 200 D/cm2 , and liquids capable of conforming to the container have yield values <200 D/cm2
(12).
Solutions, suspensions, and lotions
Once it is decided that a liquid is being applied to the skin surface, the next question in the decision tree is, Is the liquid
clear and homogeneous, a solid dispersed in a liquid, or an emulsion? (4). If the liquid is clear and homogeneous, then the
dosage form is classified as a solution. A solution is defined as "a clear, homogeneous liquid dosage form that contains one
or more chemical substances dissolved in a solvent or mixture of mutually miscible solvents." If the product is a solid dispersed
in a liquid, then the dosage form is classified as a suspension. Suspension is defined as "a liquid dosage form that contains
solid particles dispersed in a liquid vehicle." If the liquid is an emulsion, then the dosage form is classified as a lotion.
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