Purdue University Graduate School
SS thesis Apr 26,20.pdf (35.74 MB)

Mechanistic Understanding of Dissolution of Amorphous Solid Dispersions

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posted on 2020-04-27, 03:18 authored by Sugandha SabooSugandha Saboo

As amorphous solid dispersions (ASDs) are more widely employed as a formulation strategy for poorly water-soluble drugs, there is a pressing need to increase the drug loading in these formulations. The drug loading is typically kept low to obtain the desired drug release rate, but often results in large or even multiple dosage units, which is undesirable from a patient compliance perspective. We have identified the cause of this conundrum to be the drug loading dependent dissolution mechanism of ASDs. At low drug loadings, the dissolution rate of ASDs is polymer-controlled, while at high drug loadings, the dissolution rate is drug-controlled and considerably slower. This phenomenon is most pronounced for ASDs with hydrophilic polymers, such as poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA) and the change in dissolution mechanism from being polymer-controlled to drug-controlled has been attributed to water-induced amorphous-amorphous phase separation (AAPS) in higher drug loading ASD matrices of hydrophilic polymers. The drug loading limit for this switch has been found to be dependent on drug properties as well as drug-polymer interactions. Interestingly, drug-polymer hydrogen bonding interaction has been found to be detrimental and decrease the drug loading limit for polymer-controlled release while drug log P did not have any impact on this limit. Variable dissolution temperature studies indicated a detrimental impact on the polymer-controlled drug loading limit when the drug-rich phase (of phase separated ASD matrix) exists in a glassy state. ASDs with relatively hydrophobic polymers, such as hypromellose acetate succinate (HPMCAS), have been found to be polymer-controlled up to higher drug loadings. The mechanistic understanding obtained in this body of work can thus be adopted to develop strategies enabling ASD formulations with optimized performance and improved drug loading.


Bristol-Myers Squibb

McKeehan Fellowship


Degree Type

  • Doctor of Philosophy


  • Industrial and Physical Pharmacy

Campus location

  • West Lafayette

Advisor/Supervisor/Committee Chair

Dr. Lynne S. Taylor

Additional Committee Member 2

Dr. Stephen R. Byrn

Additional Committee Member 3

Dr. Qi (Tony) Zhou

Additional Committee Member 4

Dr. Stephen P. Beaudoin

Additional Committee Member 5

Dr. Umesh S. Kestur

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