Formulating CARBOWAX™ SENTRY™ PEGs in ointment applications

Topical drugs are often preferred due to their ease of application and affordability, which make them ideal for at home consumer use and high patient compliance. The market for these drugs is expected to grow at an average of six percent over the next several years, driven by high rates of both skin diseases and burn injuries, as well as an increasing incidence of diabetes and eye diseases.

Topical drugs come in many forms, the most common of which are creams, ointments and gels. Ointments usually contain greater than 50% hydrocarbons, waxes or polyols and less than 20% water and other volatiles. They are typically divided into four classes according to the type of base: hydrocarbon, absorption, water removable, and water-soluble. Polyethylene glycols (PEGs) are commonly used as water-soluble bases in ointments because they spread evenly over application areas and can be easily removed with water. The following study will focus on ointment formulations and the role of PEG excipients, such as CARBOWAX™ SENTRY™ on desired finished drug properties including formulation stability, melting point and mechanical and rheological properties.

Choosing the proper molecular weight (MW) and and ratio of solid and liquid PEGs for an ointment formulation can be challenging due to tradeoffs in performance among the required properties of the finished product. Therefore, formulating is often a matter of optimizing performance across a range of desired attributes, as shown in the figure below. Each of these elements is explored in more detail on the following pages.

Definitions

The ratio and molecular weight (MW) of PEGs used in the ointment formulation impact the physical properties of the finished formula. For simplicity, a low MW PEG can be considered a PEG that is liquid at room temperature, such as CARBOWAX™ SENTRY™ PEG 300 and CARBOWAX™ SENTRY™ PEG 400. Conversely, a high MW PEG can be considered a PEG that is solid at room temperature, such as CARBOWAX™ SENTRY™ PEG 1450 and higher. Throughout the study below the blend ratio is often referenced. The blend ratio (BR) is defined as:

Our testing capabilities and R&D expertise can help you pinpoint the best blend ratios for your formulation

Yield stress

The first step to applying an ointment is to exert a force to squeeze the ointment out of tube. Yield stress can be used to characterize this process. A higher yield stress means greater force is required to squeeze the product out of the tube and onto the skin. The yield stress can be increased by increasing the MW of the solid PEG or increasing its use level (thereby decreasing the BR), as shown in Figure 1 below.

Shear stress

After applying an ointment, a shear stress is applied to spread the ointment onto the skin. The shear rates used to apply topical ointments are typically in the range of upper hundreds to lower thousands of reciprocal seconds. Figure 2 below shows flow curves measured for different formulations. At higher shear rates, the formulation using high MW PEGs is higher in viscosity, indicating a higher resistance to application. The shear stress can be optimized by adjusting the blend ratio.

Melting point

Ointments should have the ability to soften into a semi-solid during the application process so that they can be spread evenly over an application area. Softening can be adjusted by changing the PEG MW and BR between liquid and solid MW to tailor the melting point of the ointment. Solid PEG with MW above 1450 g/mol allows the melting point of the ointment to be above human body temperature about 37°C. This is critical to maintaining a semi-solid form so that the ointment remains localized at the application area.