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University of Wisconsin-Madison

Pharm Sci Seminar–Geoff Zhang, PhD

November

30,

2017

Geoff Zhang, PhD
Vowiler Senior Research Fellow
AbbVie
Host: Lian Yu

Dissolution of Amorphous Solid Dispersions: Congruency; Nanoparticle Formation and Its Mechanism

Amorphous solid dispersions (ASDs) have been widely used for delivering poorly water soluble pharmaceuticals in recent years. Dissolution of ritonavir, a poorly soluble HIV protease inhibitor, from its ASDs with PVPVA, a water soluble polymeric carrier, was studied as a function of drug loading (DL). At lower DLs, the ASDs dissolve/erode rapidly and congruently with the polymer controlling the dissolution process.

As DL increases, dissolution becomes incongruent. Eventually ASD dissolution transitions to a drug controlled process, which is significantly slower. This behavior is consistent with decades of observations made with PVPVA-based ASDs. It is suggested that a parallel amorphous-amorphous phase separation (AAPS) is responsible for this abrupt change in dissolution behavior. When ASDs release the drug fast (i.e. at lower DLs), they generate colloidal amorphous ritonavir droplets. These nanoparticles serve as a drug reservoir, effectively feeding the aqueous compartment (in the gastrointestinal track), sustaining the continued absorption over time. This reservoir effect was fully demonstrated, in vitro, using clotrimazole as a model system. The mechanism of nanoparticle formation during ASD dissolution was proven, for nifedipine ASDs, to be dissolution/precipitation (in bulk or in the diffusion layer) using an isotope scrambling technique.

Date
Thursday, November 30, 2017
Time
4:00 PM – 5:00 PM

This event is brought to you by: Pharmaceutical Sciences Division