Gelatin Nano-coating for Inhibiting Surface Crystallization of Amorphous Drugs
- 474 Downloads
Inhibit the fast surface crystallization of amorphous drugs with gelatin nano-coatings.
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.
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.
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.
KEY WORDSamorphous crystallization gelatin indomethacin nano-coating nifedipine surface
Poly(dimethyldiallyl ammonium chloride)
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.
- 3.Wu T, Yu L. Surface crystallization of indomethacin below T g. Pharm Res. 2006;23:2350–5.Google Scholar
- 9.Baghel S, Cathcart H, O’Reilly NJ. Polymeric amorphous solid dispersions: a review of amorphization crystallization, stabilization, solid-state characterization, and aqueous solubilization of biopharmaceutical classification system class II drugs. J Pharm Sci. 2016;105:2527–44.CrossRefPubMedGoogle Scholar
- 12.Roew RC, Sheskey PJ, Owem SC. Handbook of pharmaceutical excipients, fifth edition. Great Britain: Pharmaceutical Press; 2006. PrintGoogle Scholar
- 16.Holmes-Farley SR, Bain CD, Whitesides GM. Wetting of functionalized polyethylene film having ionizable organic acids and bases at the polymer-water interface: relations between functional group polarity, extent of ionization, and contact angle with water. Langmuir. 1988;4:921–37.CrossRefGoogle Scholar
- 18.Whitesides GM, Biebuyck HA, Folkers JP, Prime KL. Acid-base interactions in wetting. J Adhes Sci Technol. 1991;5:57–69.Google Scholar