The influence of polymeric excipients on desupersaturation profiles of active pharmaceutical ingredients. 1: Polyethylene glycol

[Display omitted] Polymeric excipients have proven to be beneficial in stabilizing supersaturated solutions of poorly soluble active pharmaceutical ingredients (APIs). They are therefore considered an important tool in improving oral bioavailability of such APIs. To better understand this effect, de...

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Published inInternational journal of pharmaceutics Vol. 582; p. 119317
Main Authors Schneider, Raj, Taspinar, Lütfi, Ji, Yuanhui, Sadowski, Gabriele
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier B.V 30.05.2020
Subjects
Active pharmaceutical ingredients
Crystal-growth kinetics
Crystallization
Desupersaturation kinetics
Drug Compounding
Excipients - chemistry
Indomethacin
Indomethacin - chemistry
Kinetics
Models, Chemical
Naproxen
Naproxen - chemistry
Polyethylene glycol
Polyethylene Glycols - chemistry
Proof of Concept Study
Solubility
Desupersaturation kinetics
Indomethacin
Polyethylene glycol
Active pharmaceutical ingredients
Crystal-growth kinetics
Naproxen
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Summary:[Display omitted] Polymeric excipients have proven to be beneficial in stabilizing supersaturated solutions of poorly soluble active pharmaceutical ingredients (APIs). They are therefore considered an important tool in improving oral bioavailability of such APIs. To better understand this effect, desupersaturation of two model APIs – naproxen and indomethacin– were investigated with up to 1 wt% of polyethylene glycol (PEG) in aqueous solution. A crystal-growth model is proposed that allows simultaneous differentiation between thermodynamic and kinetic effects. It could be revealed that PEG, independent of molecular weight and concentration, acts as a solubilizer, thus increasing the equilibrium solubility of the API and thereby reducing the thermodynamic driving force for crystal growth from supersaturated solutions. In contrast, PEG does not change the kinetic crystal-growth parameters. This theoretical approach allowed predicting the API crystal-growth-dominated desupersaturation profiles in the presence of PEG at different concentrations only using the kinetic crystal-growth parameters determined for polymer-free systems and API solubilities measured in the presence of PEG.
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ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2020.119317