The classification of topical dosage forms has recently been updated and codified. While some terms commonly used to describe specific vehicles are actually developed for marketing purposes, FDA recognizes eight topical dosage forms: Solution, Suspension, Lotion, Paste, Gel, Ointment, Cream, or “Other,” which includes foams, aerosols, powders, patches, etc.22 (See Table 1.)
The clinical significance of these classifications varies; however there are many situations where the vehicle matters. Clinicians may favor certain dosage forms for specific uses, and they often ascertain the benefits of various forms from clinical study data, practical experience, product package inserts, manufacturer's materials, and peer educators. For conditions such as atopic dermatitis, psoriasis, and contact dermatitis with unique skin reactivity, the improper choice of vehicle can impact therapeutic outcomes leading to signs and symptoms of cutaneous irritation, poor patient compliance, and production of allergic contact dermatitis due to a preservative.
An occasional mismatch between the official designation of a product and its practical appearance may have a significant impact on patient care. Despite its dosage form designation, Diprolene Lotion 0.05% (betamethasone dipropionate, Shering Corp.) would be categorized as a solution under today's FDA naming system, as the vehicle is in fact a clear hydroalcoholic solution intended for scalp treatment, and not a fluid emulsion of oil and water (i.e. lotion).
These dosage form classifications are particularly relevant to the development of generic challengers of innovator formulations. To apply for marketing approval from the FDA, a generic formulation must challenge a specific existing product (active drug, concentration, and dosage form). For example, if the FDA had only approved a New Drug Application (NDA) for triamcinolone acetonide 0.1% cream, and no other dosage form were yet available; a generic manufacturer could only challenge the branded product with a 0.1% cream dosage form via the inexpensive generic approval route with an Abreviated New Drug Application (ANDA). Triamcinolone 0.1% in any other dosage form (lotion or gel) would need to go through the full NDA and review process in this hypothetical case. For this reason, and because choice of vehicle matters to dermatologists for unique and clinically important reasons specific to the individual patient, non-dermatologists, pharmacists, and insurance providers should not substitute different dosage forms or vehicles than the one prescribed by the dermatologist.
Gels and foams, both of which will be further addressed in the second installment of this series, are the dosage forms that have probably witnessed the greatest advancement in recent years. Alcohol-based gels, once considered appropriate only for oily skin, have largely been replaced by hydrogels and nonaqueous gels, changing the way that clinicians view gels and broadening their use.
The term “hydrogel” is a descriptive marketing term. Although it is not an official designation recognized by the FDA, it does have a technical meaning in the industry. A hydrogel has low residue, is nonsticky when applied, has a high cosmetic acceptability, is free of acetone, alcohol and significant levels of harsh solvents, and has a very high water content. In this sense, the term describes the consistency and appearance of the hydrogel, as well as potential benefits to the patient. These formulations do not sting or burn and are associated with a lower incidence of adverse events compared to alcohol- based gels. Typically, a humectant ingredient is incorporated to provide what is called a “pillow effect.” Whereas traditional gels dry down very quickly and make the skin feel tight, the water-retention properties of the humectant in a hydrogel impart a softness to the skin.
Many of the gel formulations marketed today are hydrogels, with a few exceptions. Generic tretinoin gel 0.025% is an alcohol gel, and Xolagel (Ketoconazole 2%, Stiefel) is an anhydrous gel, different from a hydrogel.