Pharmaceutical Research

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

Leaching of Lopinavir Amorphous Solid Dispersions in Acidic Media

Research Paper

Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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

KEY WORDS

amorphous suspensions leaching solubilization surfactants 

ABBREVIATIONS

ASD

Amorphous solid dispersion

CAC

Critical aggregation concentration

CMC

Critical micelle concentration

HF

HPMCAS-HF

HPLC

High performance liquid chromatography

HPMCAS

Hydroxypropylmethylcellulose (hypromellose) acetate succinate

HPMCP

Hypromellose phthalate

LF

HPMCAS-LF

LOD

Limit of detection

LOQ

Limit of quantitation

LPV

Lopinavir

MF

HPMCAS-MF

P

HPMCP

PEG

Polyethylene glycol

PVP

Polyvinylpyrrolidone

PVPVA

Polyvinylpyrrolidone/vinyl acetate

SDS

Sodium dodecyl sulfate

STC

Sodium taurocholate.

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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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