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Gelatin Nano-coating for Inhibiting Surface Crystallization of Amorphous Drugs

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  • Theme: Formulation and Manufacturing of Solid Dosage Forms
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Abstract

Purpose

Inhibit the fast surface crystallization of amorphous drugs with gelatin nano-coatings.

Methods

The free surface of amorphous films of indomethacin or nifedipine was coated by a gelatin solution (type A or B) and dried. The coating’s effect on surface crystallization was evaluated. Coating thickness was estimated from mass change after coating.

Results

For indomethacin (weak acid, pKa = 4.5), a gelatin coating of either type deposited at pH 5 and 10 inhibited its fast surface crystal growth. The coating thickness was 20 ± 10 nm. A gelatin coating deposited at pH 3, however, provided no protective effect. These results suggest that an effective gelatin coating does not require that the drug and the polymer have opposite charges. The ineffective pH 3 coating might reflect the poor wetting of indomethacin’s neutral, hydrophobic surface by the coating solution. For nifedipine (weak base, pKa = 2.6), a gelatin coating of either type deposited at pH 5 inhibited its fast surface crystal growth.

Conclusions

Gelatin nano-coatings can be conveniently applied to amorphous drugs from solution to inhibit fast surface crystallization. Unlike strong polyelectrolyte coatings, a protective gelatin coating does not require strict pairing of opposite charges. This could make gelatin coating a versatile, pharmaceutically acceptable coating for stabilizing amorphous drugs.

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Abbreviations

IMC:

Indomethacin

NIF:

Nifedipine

PDDA:

Poly(dimethyldiallyl ammonium chloride)

PSS:

Sodium poly(styrenesulfonate)

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ACKNOWLEDGMENTS

We thank the Bill and Melinda Gates Foundation for financial support and Melgardt de Villiers, Ed Elders, Mark Sacchetti, Niya Bowers, Phil Goliber, and Ellen Harrington for helpful discussions.

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Authors and Affiliations

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

    Rattavut Teerakapibal, Yue Gui & Lian Yu

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

    Lian Yu

Authors
  1. Rattavut Teerakapibal
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  2. Yue Gui
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  3. Lian Yu
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Correspondence to Lian Yu.

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Guest Editors: Tony Zhou and Tonglei Li

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Teerakapibal, R., Gui, Y. & Yu, L. Gelatin Nano-coating for Inhibiting Surface Crystallization of Amorphous Drugs. Pharm Res 35, 23 (2018). https://doi.org/10.1007/s11095-017-2315-z

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  • DOI: https://doi.org/10.1007/s11095-017-2315-z

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