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Surface Enrichment and Depletion of the Active Ingredient in Spray Dried Amorphous Solid Dispersions

  • Research Paper
  • Theme: Formulation and Manufacturing of Solid Dosage Forms
  • Published:
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Abstract

Purpose

To study the effects of physicochemical properties of drug and polymer, as well as the drug-polymer interactions, on the surface composition of SDDs.

Methods

Ethanol solutions containing a model drug (IMC, NMP or FCZ) and a model polymer (PVPK12, PVPK30 or PVP-VA) were spray dried, and the surface composition of SDDs was analyzed by XPS. The surface tensions of pure components and their solutions were measured using Wilhelmy plate and/or calculated using ACD/Labs. NMR and DLS were used to obtain the diffusion coefficients of IMC, NMP, PVPK12 and PVPK30 in solvents. Flory-Huggins interaction parameters for selected drug-polymer pairs were obtained using a melting point depression method.

Results

Significant surface enrichment or depletion of the drug was observed in SDDs depending on the particular drug-polymer combination. With PVP as the dispersion polymer, IMC and NMP were surface enriched; whereas FCZ, a hydrophilic drug, was surface depleted. With increasing PVP molecular weight, the surface drug concentration increased, and the effect was greater in the NMP/PVP and FCZ/PVP systems than in the IMC/PVP system where strong drug-polymer interaction existed. Changing the polymer from PVP to PVP-VA reduced the surface concentration of the drug.

Conclusions

The surface concentration of a SDD can be significantly different from the bulk concentration. The main results of this work are consistent with the notion that the relative surface tensions control surface enrichment or depletion. Besides, the relative diffusion rates of the components and the strength of their interactions may also affect the surface composition of the SDDs.

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Abbreviations

DLS:

Dynamic light scattering

DOSY:

Diffusion-ordered spectroscopy

DSC:

Differential scanning calorimetry

FCZ:

Fluconazole

HPLC:

High performance liquid chromatography

IMC:

Indomethacin

NMP:

Nimodipine

NMR:

Nuclear magnetic resonance

PVP:

Poly(vinyl pyrrolidone)

PVP-VA:

Poly(vinyl pyrrolidone − vinyl acetate) copolymer

SDD:

Spray dried dispersion

SEM:

Scanning electron microscopy

VP dimer:

Dimer of vinyl pyrrolidone

XPS:

X-ray photoelectron spectroscopy

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Acknowledgments and Disclosures

This research is supported by China National Nature Science Foundation (Project Number 81573355), and Janssen Pharmaceuticals, Inc., a pharmaceutical company of Johnson & Johnson. FQ also acknowledges the funds provided by the Center for Life Sciences at Tsinghua and Peking Universities (Beijing, China) and by the China Recruitment Program of Global Experts. LY acknowledges partial support by the Bill and Melinda Gates Foundation.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Tsinghua University, Beijing, 100084, People’s Republic of China

    Zhen Chen, Kuan Yang & Feng Qian

  2. School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, 53705, USA

    Chengbin Huang & Lian Yu

  3. Pharmaceutical Development & Manufacturing Sciences China R&D and Medical Affairs, Janssen Research & Development, Shanghai, 200233, People’s Republic of China

    Alan Zhu

  4. Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53705, USA

    Lian Yu

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  1. Zhen Chen
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  2. Kuan Yang
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Correspondence to Lian Yu or Feng Qian.

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Guest Editors: Tony Zhou and Tonglei Li

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Chen, Z., Yang, K., Huang, C. et al. Surface Enrichment and Depletion of the Active Ingredient in Spray Dried Amorphous Solid Dispersions. Pharm Res 35, 38 (2018). https://doi.org/10.1007/s11095-018-2345-1

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