Model-based optimization of the primary drying phase of oral lyophilizates

• Main Authors: Brecht Vanbillemont, Thomas De Beer
• Format: Article
• Language: English
• Published: Elsevier 2020-12-01
• Series: International Journal of Pharmaceutics: X
• Subjects: Orodispersable tablets; Process optimization; Dynamic processing; Cold-form blisters; Freeze-drying
• Online Access: http://www.sciencedirect.com/science/article/pii/S2590156720300190

Oral lyophilizates also called orally disintegrating tablets (ODTs) are a patient friendly and convenient dosage form. They are manufactured by dosing a suspension in blister cups and subsequently freeze-drying these blisters to achieve porous tablets that disintegrate quickly (< 10 s) when placed upon the tongue. This paper proposes a mechanistic model of the primary drying phase of these oral lyophilizates processed in cold-form blisters. A heat transfer coefficient (Kv) and dried layer resistance (Rp) are regressed and applied in a dynamic optimization of the primary drying phase. The optimization exercise showed the possibility of ultra-short sublimation times for polyvinyl acetate (PVA) based formulations with a primary drying time of 3.68 h for a 500 mg acetaminophen tablet.