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. 2023 Jul 13;15(14):3034.
doi: 10.3390/polym15143034.

Effect of Drug-Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin

Arif Budiman  1 , Neng Vera Nurani  1 , Eli Laelasari  1 , Muchtaridi Muchtaridi  2 , Sriwidodo Sriwidodo  1 , Diah Lia Aulifa  2
Affiliations

Effect of Drug-Polymer Interaction in Amorphous Solid Dispersion on the Physical Stability and Dissolution of Drugs: The Case of Alpha-Mangostin

Arif Budiman et al. Polymers (Basel). .

Abstract

Improving drug solubility is necessary for formulations of poorly water-soluble drugs, especially for oral administration. Amorphous solid dispersions (ASDs) are widely used in the pharmaceutical industry to improve the physical stability and solubility of drugs. Therefore, this study aims to characterize interaction between a drug and polymer in ASD, as well as evaluate the impact on the physical stability and dissolution of alpha-mangostin (AM). AM was used as a model of a poorly water-soluble drug, while polyvinylpyrrolidone (PVP) and eudragit were used as polymers. The amorphization of AM-eudragit and AM-PVP was confirmed as having a halo pattern with powder X-ray diffraction measurements and the absence of an AM melting peak in the differential scanning calorimetry (DSC) curve. The solubility of amorphous AM increased in the presence of either eudragit or PVP due to amorphization and interactions of AM-polymer. Furthermore, FT-IR spectroscopy and in silico studies revealed hydrogen bond interactions between the carbonyl group of AM and the proton of eudragit as well as PVP. AM-eudragit with a ratio of 1:1 recrystallized after 7 days of storage at 25 °C and 90% RH, while the AM-PVP 1:4 and 1:10 samples retained the X-ray halo patterns, even under humid conditions. In a dissolution test, the presence of polymer in ASD significantly improved the dissolution profile due to the intermolecular interaction of AM-polymer. AM-eudragit 1:4 maintained AM supersaturation for a longer time compared to the 1:1 sample. However, a high supersaturation was not achieved in AM-PVP 1:10 due to the formation of large agglomerations, leading to a slow dissolution rate. Based on the results, interaction of AM-polymer in ASD can significantly improve the pharmaceutical properties of AM including the physical stability and dissolution.

Keywords: alpha-mangostin; amorphous solid dispersion; dissolution; hydrogen bond; physical stability.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical structures of (a) AM, (b) PVP, and (c) eudragit.
Figure 2
Figure 2
PXRD patterns of AM, AM SE, AM-eudragit, and AM-PVP with various weight ratios.
Figure 3
Figure 3
DSC curves of AM, AM SE, AM-eudragit, and AM-PVP with various weight ratios.
Figure 4
Figure 4
The entrapment efficiency of AM-eudragit, and AM-PVP with various weight ratios.
Figure 5
Figure 5
FT−IR spectra of AM−eudragit with various weight ratios. ꟷ AM, ꟷ Eudragit, ꟷ AM-Eud 1:1, ꟷAM-Eud 1:4, ꟷAM-Eud 1:6, ꟷAM-Eud 1:8, ꟷAM-Eud 1:10.
Figure 6
Figure 6
FT−IR spectra of AM−PVP with various weight ratios. ꟷ AM, ꟷ PVP, ꟷ AM-PVP 1:1, ꟷAM-PVP 1:4, ꟷAM-PVP 1:6, ꟷAM-PVP 1:8, ꟷAM-PVP 1:10.
Figure 7
Figure 7
Two-dimensional visualization of AM with PVP and eudragit in ASD. Adapted from data presented originally in [33]. (- - -) hydrogen bond interaction. Reproduced with permission from Arif et al, (2022).
Figure 8
Figure 8
PXRD patterns of AM crystal, AM SE, AM-eudragit 1:1, and AM-eudragit 1:4 after storage at 25 °C 0% RH (left) and 40 °C, 90% RH (right). (*) Characteristic peaks of AM.
Figure 9
Figure 9
Dissolution profiles of each sample in 50 mM phosphate buffer (pH 7.4) at 37 °C (n = 3, mean ± SD).
Figure 10
Figure 10
Schematic illustration of AM dissolution from AM-eudragit 1:1, AM-eudragit 1:4, and AM-PVP 1:10. (-) and (→ ←) is the hydrogen bond interaction.
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