Formulation and Quality – Chemical
2019 PharmSci 360
Dexamethasone (DEX) ointments are semi-solid formulations containing DEX as particles dispersed in a petrolatum matrix. Crystallinity and polymorphism play a role in DEX release from ointments, thus, understanding their impact on DEX release from ointments is important for formulation development, quality control and regulatory assessment purposes. It is also important to understand the impact of amorphous DEX on DEX stability and release if present in the formulation. The amorphous DEX was prepared by spray-drying and ball-milling, followed by ointment preparation using levigation or high-shear mixing. Petrolatum bases obtained from three sources were assessed due to their distinct hydrocarbon compositions, viscosity and hydrophobicity. Thermal and X-ray diffraction analyses demonstrated amorphous DEX is unstable upon ointment preparation, recrystallizing into DEX Form B. Furthermore, ointments containing crystalline DEX Form A showed phase transition to Form B. The implications of findings on DEX dissolution profiles and assessment of generic ophthalmic ointments will be discussed.