Pharmaceutical Research

, Volume 33, Issue 7, pp 1723–1735 | Cite as

Leaching of Lopinavir Amorphous Solid Dispersions in Acidic Media

  • Na Li
  • James D. Ormes
  • Lynne S. TaylorEmail author
Research Paper



Amorphous solid dispersions (ASDs) formulated with acid-insoluble (enteric) polymers form suspensions in acidic media where the polymer is largely insoluble. However, a small amount of drug can dissolve and a supersaturated solution may be generated. The goal of this study was to gain insight into the leaching mechanisms of both drug and polymer from the suspended particles, studying the impact of solution additives such as surfactants.


ASDs were prepared by spray drying lopinavir (LPV) with an enteric polymer, either hydroxypropylmethylcellulose acetate succinate (HPMCAS) or hydroxypropylmethylcellulose phthalate (HPMCP). Four surfactants and a suspending agent were added to the liquid media to evaluate the effect of these excipients on leaching. pH 3 and pH 5 buffers were used to investigate the effect of pH.


The extent of drug leaching from the amorphous formulation was proportional to the crystalline solubility of the drug in the same medium. All surfactants promoted solubilization of LPV with the exception of poloxamer and sodium dodecyl sulfate-HPMCP combinations. A small amount of polymer ionization significantly enhanced LPV leaching in solutions containing an ionic surfactant.


The mechanism of enhanced leaching appeared to be solubilization, with the apparent supersaturation remaining the same for systems containing the same polymer.


amorphous suspensions leaching solubilization surfactants 



Amorphous solid dispersion


Critical aggregation concentration


Critical micelle concentration




High performance liquid chromatography


Hydroxypropylmethylcellulose (hypromellose) acetate succinate


Hypromellose phthalate




Limit of detection


Limit of quantitation








Polyethylene glycol




Polyvinylpyrrolidone/vinyl acetate


Sodium dodecyl sulfate


Sodium taurocholate.



The authors gratefully thank Merck & Co. for providing financial support for this study. We would like to acknowledge John Higgins, Mike Lowinger, Annette Bak, Nicole Buist and Pete Wuelfing for scientific support and guidance.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Department of Industrial and Physical PharmacyPurdue UniversityWest LafayetteUSA
  2. 2.Discovery Pharmaceutical Sciences, Merck Research LaboratoriesMerck & Co., Inc.RahwayUSA

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