Topical drug classification

Abstract

Current definitions of lotions, gels, creams and ointments vary depending on literature source, market history or traditional use. This often leads to confusion when deciding which dosage form to prescribe and/or purchase. The existing classification of topical dosage forms needs to be re-examined to ensure that definitions for different dosage forms are based on consistent scientific principles and that dosage forms can be distinguished from one another. The purpose of this study is to obtain a scientifically based, systematic classification of dosage forms for topical drugs.

A variety of prescription and over-the-counter topical products currently marketed as lotions, gels, creams, and ointments are evaluated using different techniques including rheology (viscosity and shear rate versus shear stress), loss on drying (LOD), specific gravity, surface tension, thermogravimetric analysis (TGA), water absorption, dilution properties, microscopic evaluation, transmittance of visible light, appearance and composition. Rheology is the most discriminating property separating creams and lotions. Water plus volatiles (as measured by LOD) and composition separate ointments and creams. Composition and thermal behavior separate gels from the other dosage forms. Based on these findings, new definitions and a decision tree are presented to assist in the determination of the appropriate nomenclature for a topical dosage form.

Introduction

The classification of topical dosage forms has not been based on any scientific definition. Current definitions of lotions, gels, creams and ointments vary depending on literature source, market history or traditional use. Some of these dosage form terms are ill defined and not very concise. The current Food and Drug Administration (FDA), Center for Drug Evaluation and Research (CDER) Data Standards Manual defines ointment as “a semisolid preparation intended for external application to the skin or mucous membranes”, cream as “a semisolid dosage form containing one or more drug substances dissolved or dispersed in a suitable base…” and lotion as “…topical suspensions, solutions and emulsions intended for application to the skin.” (See CDER Data Standards Manual at http://www.fda.gov/cder/dsm/DRG/drg00201.htm (January 2005), CDER approval date 14 April 1992) These definitions do not differentiate between the three dosage forms (i.e., ointment, cream and lotion). The United States Pharmacopeia (USP) definitions for ointments and creams are essentially the same as the definitions the FDA uses. The USP does not define lotions; instead, one is referred to solutions or suspensions (See USP 28 〈1151〉 Pharmaceutical Dosage Forms; USP 28, The United States Pharmacopeial Convention: Rockville, MD, 2005. 2701–2712). The British Pharmacopoeia (BP) defines lotions as liquids, but does not clearly differentiate between lotions and other liquids such as suspensions and solutions (See BP 2004, “Liquids for Cutaneous Application of the British Pharmacopoeia”). The Japanese Pharmacopoeia (JP) includes creams with the ointment definition, and the European Pharmacopoeia defines ointments as single-phase and creams as multiphase systems (See JP, December 2001, “General Rules for Preparations” and EP 01/2005:0132, “ Semi-solid Preparations for Cutaneous Application”.)

These ambiguities can cause confusion for drug developers and regulators when deciding on the nomenclature for topical dosage forms as well as determining market exclusivity. Can one formulation be marketed as both a cream and a lotion? Can a light scattering material be added to a gel to create a formulation that can now be marketed as a cream or lotion? Physicians have certain expectations when prescribing a certain dosage form. Lotions and creams are expected to be easy to apply and remove (water washable) and can leave a cooling sensation on the skin. Ointments are usually more difficult to apply or remove, but are expected to act as a barrier and increase the hydration of the skin.

The purpose of this study is to establish a scientific basis for a systematic, coherent and meaningful classification of dosage forms for topical drugs. Such a classification will allow physicians to use the dosage form as a guide to the desired properties that may be critical in prescribing topical drugs for a patient. Subjective tests like feel and appearance are often used to describe topical dosage forms. This study strives to replace these observations with more precise analytical measurements that can be used as a basis to define these dosage forms. Definitions will be consistent with the subjective expectations of patients and physicians when prescribing a topical product (e.g. ease of application and removal, feel of the product on the skin, barrier properties, etc.)

In this study, topical drugs refer to those drugs administered to a spot on the outer surface of the body (dermatological applications). Drugs meant for other topical application (e.g. oral, nasal, aural, vaginal, and rectal areas) are not included in this study. However, the proposed definitions may be utilized in the future for these alternative applications. Dosage forms tested are limited to solutions, lotions, gels, creams and ointments. Revised definitions are proposed for topical solution, topical suspension, lotion, gel, cream, ointment and paste.

The vehicle plays a key role in the appearance, feel, and successful application of a topical drug (Barry, 1983). Therefore, the composition of a topical drug vehicle should be considered in its nomenclature. However, composition alone cannot be used to define a dosage form since one ingredient can have multiple functions (e.g. poloxamer functions as a suspending agent, gelling agent, thickening agent, emulsifier and/or wetting agent), and the manufacturing process can change product properties. In determining what additional properties should be used to define a dosage form, the following physical properties were studied in 58 topical products: rheology (viscosity and shear rate versus shear stress), loss on drying (LOD, a measure of water and volatiles), specific gravity, surface tension, thermogravimetric analysis (TGA), water absorption, dilution properties, microscopic evaluation and transmittance of visible light. The more subjective properties (e.g. appearance and feel) were used to evaluate products that had properties bordering between two dosage forms.