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Drug Solubilization by Means of Partition/Association Equilibrium Using a Modified Nanosized Dendrimeric Biopolymer

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  • Theme: Paul Myrdal Memorial Issue - Pharmaceutical Formulation and Aerosol Sciences
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Abstract

The objective of this study is to elucidate the combined effects of a novel type of material being investigated as a new excipient, an octenylsuccinate-modified dendrimer-like biopolymer (OS-DLB) and poloxamer (PLX), on the solubility of poorly water-soluble compounds. Phenytoin (PHT), griseofulvin (GSF), ibuprofen (IBU), and loratadine (LOR) were used as model compounds. Phase solubility measurements were conducted to determine the relative proportions of API, OS-DLB, and PLX that result in the most stable dendrimeric complexes. The solubilizing power of OS-DLB increases with increasing hydrophobicity of the solute. In the presence of PLX, the solubilization effect of OS-DLB is modestly accentuated for the most hydrophobic drugs (IBU and LOR) but has no effect on the least hydrophobic one (PHT). The maximum potentiation effect of PLX on the solubilizing properties of OS-DLB was observed for GSF, the drug of intermediate hydrophobicity. Three different types of solubilization profiles were obtained in the study. All three different profiles can be appropriately described by a single solubilization model, depending on the specific parameter values. The defining parameters of the model reflect the hydrophobicity of the drug on the one hand and, on the other hand, the inherent tendency of the drug (crystal lattice energy) toward crystallization.

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Acknowledgments

We thank Prof. Yuan Yao’s laboratory for providing the DLB material used in the study.

Funding

Financial support from the Dane O. Kildsig Center for Pharmaceutical Processing Research (CPPR), Purdue Research Foundation, and the National Science Foundation (NSF DMR 1310475) is gratefully acknowledged.

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Authors and Affiliations

  1. Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Drive, West Lafayette, Indiana, 47907, USA

    Hwee Jing Ong & Rodolfo Pinal

Authors
  1. Hwee Jing Ong
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  2. Rodolfo Pinal
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Correspondence to Rodolfo Pinal.

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Guest Editors: Philip J. Kuehl and Stephen W. Stein

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Ong, H.J., Pinal, R. Drug Solubilization by Means of Partition/Association Equilibrium Using a Modified Nanosized Dendrimeric Biopolymer. AAPS PharmSciTech 20, 304 (2019). https://doi.org/10.1208/s12249-019-1490-0

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