Amorphous Drug-Polymer Salts

Amorphous formulations provide a general approach to improving the solubility and bioavailability of drugs. Amorphous medicines for global health should resist crystallization under the stressful tropical conditions (high temperature and humidity) and often require high drug loading. We discuss the recent progress in employing drug–polymer salts to meet these goals. Through local salt formation, an ultra-thin polyelectrolyte coating can form on the surface of amorphous drugs, immobilizing interfacial molecules and inhibiting fast crystal growth at the surface. The coated particles show improved wetting and dissolution. By forming an amorphous drug–polymer salt throughout the bulk, stability can be vastly enhanced against crystallization under tropical conditions without sacrificing the dissolution rate. Examples of these approaches are given, along with suggestions for future work.

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Improved Release of Celecoxib from High Drug Loading Amorphous Solid Dispersions Formulated with Polyacrylic Acid and Cellulose Derivatives

10.26226/morressier.57d6b2bbd462b8028d88d1d4 ◽

2016 ◽

Author(s):

Tian Xie

Keyword(s):

Polyacrylic Acid ◽

Drug Loading ◽

Solid Dispersions ◽

Amorphous Solid ◽

Cellulose Derivatives ◽

Amorphous Solid Dispersions ◽

High Drug ◽

High Drug Loading

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Investigating the influence of aromatic moieties on the formulation of hydrophobic natural products and drugs in poly(2-oxazoline) based amphiphiles

10.26434/chemrxiv.5787711.v1 ◽

2018 ◽

Author(s):

Robert Luxenhofer ◽

Michael M Lübtow ◽

Lukas Hahn ◽

Thomas Lorson ◽

Rainer Schobert

Keyword(s):

Natural Products ◽

Small Molecules ◽

Water Solubility ◽

Drug Loading ◽

High Drug ◽

Long Term Stability ◽

Aromatic Content ◽

Important Interaction ◽

Amorphous Structures ◽

High Drug Loading

Many natural compounds with interesting biomedical properties share one physicochemical property, namely a low water solubility. Polymer micelles are, among others, a popular means to solubilize hydrophobic compounds. The specific molecular interactions between the polymers and the hydrophobic drugs are diverse and recently it has been discussed that macromolecular engineering can be used to optimize drug loaded micelles. Specifically, π-π stacking between small molecules and polymers has been discussed as an important interaction that can be employed to increase drug loading and formulation stability. Here, we test this hypothesis using four different polymer amphiphiles with varying aromatic content and various natural products that also contain different relative amounts of aromatic moieties. While in the case of paclitaxel, having the lowest relative content of aromatic moieties, the drug loading decreases with increasing relative aromatic amount in the polymer, the drug loading of curcumin, having a much higher relative aromatic content, is increased. Interestingly, the loading using schizandrin A, a dibenzo[a,c]cyclooctadiene lignan with intermediate relative aromatic content is not influenced significantly by the aromatic content of the polymers employed. The very high drug loading, long term stability, the ability to form stable highly loaded binary coformulations in different drug combinations, small sized formulations and amorphous structures in all cases, corroborate earlier reports that poly(2-oxazoline) based micelles exhibit an extraordinarily high drug loading and are promising candidates for further biomedical applications. The presented results underline that the interaction between the polymers and the incorporated small molecules are complex and must be investigated in every specific case.<br>

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