Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jun 9;15(6):730.
doi: 10.3390/ph15060730.

A Comparative Study of the Pharmaceutical Properties between Amorphous Drugs Loaded-Mesoporous Silica and Pure Amorphous Drugs Prepared by Solvent Evaporation

Arif Budiman  1 , Diah Lia Aulifa  2
Affiliations

A Comparative Study of the Pharmaceutical Properties between Amorphous Drugs Loaded-Mesoporous Silica and Pure Amorphous Drugs Prepared by Solvent Evaporation

Arif Budiman et al. Pharmaceuticals (Basel). .

Abstract

The formulation of poorly water-soluble drugs is one of the main challenges in the pharmaceutical industry, especially in the development of oral dosage forms. Meanwhile, there is an increase in the number of poorly soluble drugs that have been discovered as new chemical entities. It was also reported that the physical transformation of a drug from a crystalline form into an amorphous state could be used to increase its solubility. Therefore, this study aims to evaluate the pharmaceutical properties of amorphous drug loaded-mesoporous silica (MPS) and pure amorphous drugs. Ritonavir (RTV) was used as a model of a poorly water-soluble drug due to its low recrystallization tendency. RTV loaded-MPS (RTV/MPS) and RTV amorphous were prepared using the solvent evaporation method. Based on observation, a halo pattern in the powder X-ray diffraction pattern and a single glass transition (Tg) in the modulated differential scanning calorimetry (MDSC) curve was discovered in RTV amorphous, indicating its amorphization. The Tg was not detected in RTV/MPS, which showed that the loading RTV was completed. The solid-state NMR and FT-IR spectroscopy also showed the interaction between RTV and the surface of MPS in the mesopores. The high supersaturation of RTV was not achieved for both RTV/MPS and the amorphous state due to its strong interaction with the surface of MPS and was not properly dispersed in the medium, respectively. In the dissolution test, the molecular dispersion of RTV within MPS caused rapid dissolution at the beginning, while the amorphous showed a low rate due to its agglomeration. The stability examination showed that the loading process significantly improved the physical and chemical stability of RTV amorphous. These results indicated that the pharmaceutical properties of amorphous drugs could be improved by loaded-MPS.

Keywords: amorphous; mesoporous silica; pharmaceutical properties; ritonavir.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The PXRD patterns of (a) RTV crystal, (b) RTV amorphous, RTV/MPS = (c) 8:2, and (d) 3:7.
Figure 2
Figure 2
The MDSC curve of (a) RTV crystal, (b) RTV amorphous, RTV/MPS = (c) 8:2, and (d) 3:7.
Figure 3
Figure 3
13C NMR spectra (υ = 5 kHz) of (a) RTV crystal, (b) RTV amorphous, and (c) RTV/MPS = 3:7.
Figure 4
Figure 4
FT−IR spectrum of (a) RTV crystal, (b) RTV amorphous, and (c) RTV/MPS = 3:7, in the OH stretch region.
Figure 5
Figure 5
The solubility of each sample at three different times (n = 3, mean ± S.D).
Figure 6
Figure 6
The saturation solubility of RTV amorphous is determined by the centrifugation method (n = 3, mean ± S.D).
Figure 7
Figure 7
The PXRD pattern of the precipitate following the solubility of each sample in 50 mM phosphate buffer pH 6.8.
Figure 8
Figure 8
Dissolution profiles of RTV crystal, RTV amorphous, and RTV/MPS = 3:7 in 50 mM phosphate buffer pH 6.8 at 37 °C. (n = 3, mean ± S.D).
Figure 9
Figure 9
The PXRD patterns of (a) RTV amorphous, (b) RTV crystal (I), (c) RTV amorphous after 7 day storage at 40 °C, 96% RH, (d) RTV crystal (II), and (e) RTV/MPS = 3:7 after 7 day storage at 40 °C, 96% RH.
Figure 10
Figure 10
The concentration of RTV from RTV/MPS = 3:7 after 2 day storage at 80 °C, 0% RH (n = 3, mean ± S.D).
Figure 11
Figure 11
Schematic illustration of RTV amorphous and RTV/MPS in the 50 mM phosphate buffer pH 6.8.
Figure 12
Figure 12
Schematic illustration of RTV amorphous and RTV/MPS after storage in humidified conditions.
Figure 13
Figure 13
Chemical structures of RTV.
See this image and copyright information in PMC

References

    1. Skorupska E., Jeziorna A., Potrzebowski M.J. Thermal solvent-free method of loading of pharmaceutical cocrystals into the pores of silica particles: A Case of naproxen/picolinamide cocrystal. J. Phys. Chem. C. 2016;120:13169–13180. doi: 10.1021/acs.jpcc.6b05302. - DOI
    1. Wu W., Löbmann K., Schnitzkewitz J., Knuhtsen A., Pedersen D.S., Grohganz H., Rades T. Aspartame as a co-former in co-amorphous systems. Int. J. Pharm. 2018;549:380–387. doi: 10.1016/j.ijpharm.2018.07.063. - DOI - PubMed
    1. Zhao Z., Katai H., Higashi K., Ueda K., Kawakami K., Moribe K. Cryo-TEM and AFM Observation of the Time-Dependent Evolution of Amorphous Probucol Nanoparticles Formed by the Aqueous Dispersion of Ternary Solid Dispersions. Mol. Pharm. 2019;16:2184–2198. doi: 10.1021/acs.molpharmaceut.9b00158. - DOI - PubMed
    1. Skorupska E., Paluch P., Jeziorna A., Potrzebowski M.J. NMR study of BA/FBA cocrystal confined within mesoporous silica nanoparticles employing thermal solid phase transformation. J. Phys. Chem. C. 2015;119:8652–8661. doi: 10.1021/jp5123008. - DOI
    1. Budiman A., Aulifa D.L. Characterization of Drugs with Good Glass Formers in Loaded-Mesoporous Silica and Its Theoretical Value Relevance with Mesopores Surface and Pore-Filling Capacity. Pharmaceuticals. 2022;15:93. doi: 10.3390/ph15010093. - DOI - PMC - PubMed

LinkOut - more resources