Rattavut Teerakapibal1, Yue Gui1, Lian Yu2,3. 1. School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, 53705, USA. 2. School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, 53705, USA. lian.yu@wisc.edu. 3. Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53705, USA. lian.yu@wisc.edu.
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.
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.
Authors: Frank Theil; Sankaran Anantharaman; Samuel O Kyeremateng; Holger van Lishaut; Sebastian H Dreis-Kühne; Jörg Rosenberg; Markus Mägerlein; Gerd H Woehrle Journal: Mol Pharm Date: 2016-11-30 Impact factor: 4.939
Authors: Sonal V Bhujbal; Dmitry Y Zemlyanov; Alex Cavallaro; Sharad Mangal; Lynne S Taylor; Qi Tony Zhou Journal: Mol Pharm Date: 2018-04-17 Impact factor: 4.939