TY - JOUR

T1 - In situ co-amorphisation in coated tablets – The combination of carvedilol with aspartic acid during immersion in an acidic medium

AU - Petry, Ina

AU - Löbmann, Korbinian

AU - Grohganz, Holger

AU - Rades, Thomas

AU - Leopold, Claudia S.

PY - 2019/3/10

Y1 - 2019/3/10

N2 - In the present study the feasibility of an in situ co-amorphisation of the basic drug carvedilol with the acidic co-former aspartic acid was investigated by immersion of film-coated tablets consisting of the two compounds in 0.1 M HCl. Tablets containing either crystalline carvedilol with aspartic acid or only crystalline carvedilol were prepared and coated with a gastro-resistant but water-permeable coating of a methacrylic acid – ethyl acrylate copolymer (Eudragit® L 55). The film-coated tablets were immersed in 0.1 M HCl for 0, 45, and 120 min and their solid-state properties were analysed by X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and Fourier transformed infrared spectroscopy (FTIR). The drug release behaviour from these tablets was investigated at pH 6.8. It was shown that the formulation containing carvedilol with aspartic acid formed a co-amorphous system during immersion, while the formulation containing only carvedilol remained crystalline. FTIR spectroscopy indicated molecular interactions in the co-amorphous carvedilol-aspartic acid system, which explained the single T g found using DMA (106 ± 4 °C). However, because of a lack of sufficient disintegration, drug release of the immersed co-amorphous formulation was lower than from the untreated tablets (immersed for 0 min) containing only carvedilol or the crystalline physical mixture of carvedilol and aspartic acid. After overcoming the disadvantage of the insufficient disintegration, it may be concluded that in situ co-amorphisation in a film-coated tablet by immersion in 0.1 M HCl appears to be a feasible formulation approach for poorly water-soluble basic drugs.

AB - In the present study the feasibility of an in situ co-amorphisation of the basic drug carvedilol with the acidic co-former aspartic acid was investigated by immersion of film-coated tablets consisting of the two compounds in 0.1 M HCl. Tablets containing either crystalline carvedilol with aspartic acid or only crystalline carvedilol were prepared and coated with a gastro-resistant but water-permeable coating of a methacrylic acid – ethyl acrylate copolymer (Eudragit® L 55). The film-coated tablets were immersed in 0.1 M HCl for 0, 45, and 120 min and their solid-state properties were analysed by X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and Fourier transformed infrared spectroscopy (FTIR). The drug release behaviour from these tablets was investigated at pH 6.8. It was shown that the formulation containing carvedilol with aspartic acid formed a co-amorphous system during immersion, while the formulation containing only carvedilol remained crystalline. FTIR spectroscopy indicated molecular interactions in the co-amorphous carvedilol-aspartic acid system, which explained the single T g found using DMA (106 ± 4 °C). However, because of a lack of sufficient disintegration, drug release of the immersed co-amorphous formulation was lower than from the untreated tablets (immersed for 0 min) containing only carvedilol or the crystalline physical mixture of carvedilol and aspartic acid. After overcoming the disadvantage of the insufficient disintegration, it may be concluded that in situ co-amorphisation in a film-coated tablet by immersion in 0.1 M HCl appears to be a feasible formulation approach for poorly water-soluble basic drugs.

KW - Aspartic acid

KW - Carvedilol

KW - Co-amorphous system

KW - Eudragit® L 55

KW - In situ amorphisation

U2 - 10.1016/j.ijpharm.2018.12.091

DO - 10.1016/j.ijpharm.2018.12.091

M3 - Journal article

C2 - 30641182

AN - SCOPUS:85060335160

VL - 558

SP - 357

EP - 366

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

ER -