Formulation Development of Topical Products
Semi-solid and liquid drug products, including gels, creams, ointments, solutions, sprays and suspensions are developed at Dow Development Laboratories for use in the treatment of a wide variety of therapeutic indications including dermatologic, ophthalmic, women’s and men’s health, pain, wound healing, infection and others. Products are developed with the patient in mind.
For our clients who are new to topical product development, consulting services are provided to support decision making and inform regarding the differences between developing a topical drug product as opposed to an oral or a parenteral.
Target Product Profile
One of the initial activities is to develop a target product profile. A typical target product profile for a topical drug product often includes the following:
- Cosmetically elegant (appearance, smell, feel)
- Appropriately preserved
- Desired dosage form appropriate for the selected therapeutic indication
- Excipients appropriate for application to the skin of the patient with the specific disease
- Appropriate tissue penetration
- Chemical stability of the active pharmaceutical ingredient (API) in the product
- Physical stability of the product over the desired shelf life
- Excipients and their levels compliant from a regulatory perspective
- Scalable manufacturing process resulting in a robust product
- Solubility studies are conducted to determine the maximum saturated solubility of the API in solvents from the FDA’s Inactive Ingredient Database (IID) that are appropriate for topical application to a specific disease state.
- Excipient compatibility studies assess the stability of the API in the presence of selected excipients after heat stress to determine if any might negatively affect the stability of the API.
- Design and development of prototype formulations builds upon the data generated in the solubility and compatibility studies. Appropriate preservative systems are selected, and if appropriate, other excipients are evaluated including gelling agents, emulsification systems, anti-oxidants, skin penetration enhancers and emollients.
- Prototype screening includes an accelerated stability study (2 to 6 months) to compare the physical and chemical stability of the various prototypes at ambient and higher temperate conditions over time. Dependent on the therapeutic indication, an in vitro skin penetration study may also be conducted to compare the penetration of the API through the stratum corneum and into the viable epidermis and dermis from different prototypes. Prototype formulations may also be assessed in an R&D efficacy model if the client has access to one.
- Lead formulation selection occurs following screening and a lead formulation is selected to progress to IND-enabling Good Laboratory Practices (GLP) studies.