Category: Formulation and Quality
Purpose: The aim of this work was to identify stable topical platform cream formulations (placebo creams without active drug substance) using the quality attributes of cream consistency (spreadability, appearance, and feel), droplet size distribution (< 1 um), and separation or instability index of < 0.1 to accelerate the development of topical cream drug product.
Methods: A total of hundred and eight platform cream formulations (oil in water) were developed with total solvent combination amount kept constant at 40%, total emulsifier combination kept constant at 5%, Oil was used at 5% and viscosity building agent was used at 3% w/w. The formulations were developed with six emulsifier systems that were screened in three different solvent systems across a range of emulsifier ratios. Each formulation was characterized by microscopy (particle size), phase separation/physical stability (separation index) and consistency (spreadability (rheology), appearance and hand-feel).
Results: The data concluded that there are three emulsifier combination (PEG 40 Stearate: Glyceryl monostearate, Steareth 21:Steareth 2, and PEG 40 Stearate:Span 60) that works well with the solvent systems. Nine platform cream formulations were found to meet the all three attributes for a long-term stable platform cream formulation. Microscopic images were used to measure the droplet sizes and their uniformity, see Figures 1. Separation index measurements of formulations were analysed by statistical model. see example in Figure 2. The maximum separation index standard deviation observed was 0.02. Shear viscosity measurements were performed and used to categorize the formulations flow behavior as liquid/lotion, creams, and paste, see Figure 3.
Conclusion: Formulation development for topical administered drug product can be very time consuming, expensive, and resourceful in identifying a chemically and physically stable product. In early development, where it can take 1 to 2 years traditionally to develop a first time in human (FTIH) formulation for a new chemical entity it is paramount to expedite development for patients benefit. The use of the platform base cream formulations will expedite the early development timeline for new chemical entity by 3 - 6 months by eliminating the pre-formulation compatibility studies with solvent system, excipients and drug substance.