Effect of Drug Loading in Mesoporous Silica on Amorphous Stability and Performance
Abstract
1. Introduction
2. Materials and Methods
2.1. Nitrogen Adsorption
2.2. Determination of the Monomolecular Loading Capacity and Pore Filling Capacity
2.3. X-ray Powder Diffraction (XRPD)
2.4. Non-Sink Dissolution Experiment
2.5. Stability and Storage Conditions
3. Results
3.1. Loading Capacity/Drug Loading
3.2. Storage Stability/Physical Stability
3.3. Drug Release
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sastry, S.V.; Nyshadham, J.R.; Fix, J.A. Recent technological advances in oral drug delivery—A review. Pharm. Sci. Technol. Today 2000, 3, 138–145. [Google Scholar] [CrossRef] [PubMed]
- Stegemann, S.; Leveiller, F.; Franchi, D.; De Jong, H.; Lindén, H. When poor solubility becomes an issue: From early stage to proof of concept. Eur. J. Pharm. Sci. 2007, 31, 249–261. [Google Scholar] [CrossRef]
- Artursson, P.; Karlsson, J. Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells. Biochem. Biophys. Res. Commun. 1991, 175, 880–885. [Google Scholar] [CrossRef] [PubMed]
- Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. 1997, 23, 3–25. [Google Scholar] [CrossRef]
- Engers, D.; Teng, J.; Jimenez-Novoa, J.; Gent, P.; Hossack, S.; Campbell, C.; Thomson, J.; Ivanisevic, I.; Templeton, A.; Byrn, S. A Solid-State Approach to Enable Early Development Compounds: Selection and Animsal Bioavailability Studies of an Itraconazole Amorphous Solid Dispersion. J. Pharm. Sci. 2010, 99, 3901–3922. [Google Scholar] [CrossRef] [PubMed]
- Bukara, K.; Schueller, L.; Rosier, J.; Martens, M.A.; Daems, T.; Verheyden, L.; Eelen, S.; Van Speybroeck, M.; Libanati, C.; Martens, J.A. Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man. Eur. J. Pharm. Biopharm. 2016, 108, 220–225. [Google Scholar] [CrossRef]
- Newa, M.; Bhandari, K.H.; Oh, D.H.; Kim, Y.R.; Sung, J.H.; Kim, J.O.; Woo, J.S.; Choi, H.G.; Yong, C.S. Enhanced dissolution of ibuprofen using solid dispersion with poloxamer 407. Arch. Pharmacal Res. 2008, 31, 1497–1507. [Google Scholar] [CrossRef]
- Hong, S.; Shen, S.; Tan, D.C.T.; Ng, W.K.; Liu, X.; Chia, L.S.O.; Irwan, A.W.; Tan, R.; Nowak, S.A.; Marsh, K.; et al. High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: A comparison of spray drying versus solvent impregnation methods. Drug Deliv. 2016, 23, 316–327. [Google Scholar] [CrossRef]
- Mellaerts, R.; Mols, R.; Jammaer, J.A.; Aerts, C.A.; Annaert, P.; Van Humbeeck, J.; Van den Mooter, G.; Augustijns, P.; Martens, J.A. Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica. Eur. J. Pharm. Biopharm. 2008, 69, 223–230. [Google Scholar] [CrossRef]
- U.S. Food and Drug Adminstration. GRAS Substances (SCOGS) Database. 2015. Available online: https://www.fda.gov/food/generally-recognized-safe-gras/gras-substances-scogs-database (accessed on 17 January 2024).
- Christoforidou, T.; Giasafaki, D.; Andriotis, E.G.; Bouropoulos, N.; Theodoroula, N.F.; Vizirianakis, I.S.; Steriotis, T.; Charalambopoulou, G.; Fatouros, D.G. Oral drug delivery systems based on ordered mesoporous silica nanoparticles for modulating the release of aprepitant. Int. J. Mol. Sci. 2021, 22, 1896. [Google Scholar] [CrossRef]
- Rengarajan, G.T.; Enke, D.; Steinhart, M.; Beiner, M. Stabilization of the amorphous state of pharmaceuticals in nanopores. J. Mater. Chem. 2008, 18, 2537–2539. [Google Scholar] [CrossRef]
- Physical Chemistry Division Commission on Colloid; McCusker, L.; Liebau, F.; Engelhardt, G. Nomenclature of structural and compositional characteristics of ordered microporous and mesoporous materials with inorganic hosts:(IUPAC recommendations 2001). Microporous Mesoporous Mater. 2003, 58, 3–13. [Google Scholar]
- Antonino, R.S.; Ruggiero, M.; Song, Z.; Nascimento, T.L.; Lima, E.M.; Bohr, A.; Knopp, M.M.; Löbmann, K. Impact of drug loading in mesoporous silica-amorphous formulations on the physical stability of drugs with high recrystallization tendency. Int. J. Pharm. X 2019, 1, 100026. [Google Scholar] [CrossRef] [PubMed]
- Kramarczyk, D.; Knapik-Kowalczuk, J.; Smolka, W.; Monteiro, M.F.; Tajber, L.; Paluch, M. Inhibition of celecoxib crystallization by mesoporous silica–Molecular dynamics studies leading to the discovery of the stabilization origin. Eur. J. Pharm. Sci. 2022, 171, 106132. [Google Scholar] [CrossRef] [PubMed]
- Qian, K.K.; Bogner, R.H. Spontaneous crystalline-to-amorphous phase transformation of organic or medicinal compounds in the presence of porous media, part 1: Thermodynamics of spontaneous amorphization. J. Pharm. Sci. 2011, 100, 2801–2815. [Google Scholar] [CrossRef]
- Limnell, T.; Santos, H.A.; Mäkilä, E.; Heikkilä, T.; Salonen, J.; Murzin, D.Y.; Kumar, N.; Laaksonen, T.; Peltonen, L.; Hirvonen, J. Drug delivery formulations of ordered and nonordered mesoporous silica: Comparison of three drug loading methods. J. Pharm. Sci. 2011, 100, 3294–3306. [Google Scholar] [CrossRef] [PubMed]
- Ahern, R.J.; Hanrahan, J.P.; Tobin, J.M.; Ryan, K.B.; Crean, A.M. Comparison of fenofibrate–mesoporous silica drug-loading processes for enhanced drug delivery. Eur. J. Pharm. Sci. 2013, 50, 400–409. [Google Scholar] [CrossRef]
- Mellaerts, R.; Aerts, C.A.; Humbeeck, J.V.; Augustijns, P.; Den Mooter, G.V.; Martens, J.A. Enhanced release of itraconazole from ordered mesoporous SBA-15 silica materials. Chem. Commun. 2007, 1375–1377. [Google Scholar] [CrossRef]
- Hempel, N.-J.; Brede, K.; Olesen, N.E.; Genina, N.; Knopp, M.M.; Lobmann, K. A fast and reliable DSC-based method to determine the monomolecular loading capacity of drugs with good glass-forming ability in mesoporous silica.(Report). Int. J. Pharm. 2018, 544, 153. [Google Scholar] [CrossRef]
- Bavnhøj, C.G.; Knopp, M.M.; Madsen, C.M.; Löbmann, K. The role interplay between mesoporous silica pore volume and surface area and their effect on drug loading capacity. Int. J. Pharm. X 2019, 1, 100008. [Google Scholar] [CrossRef]
- Brás, A.R.; Merino, E.G.; Neves, P.D.; Fonseca, I.M.; Dionísio, M.; Schönhals, A.; Correia, N.T. Amorphous ibuprofen confined in nanostructured silica materials: A dynamical approach. J. Phys. Chem. C 2011, 115, 4616–4623. [Google Scholar] [CrossRef]
- Le, T.-T.; Elzhry Elyafi, A.K.; Mohammed, A.R.; Al-Khattawi, A. Delivery of poorly soluble drugs via mesoporous silica: Impact of drug overloading on release and thermal profiles. Pharmaceutics 2019, 11, 269. [Google Scholar] [CrossRef]
- Noyes, A.A.; Whitney, W.R. The Rate of Solution of Solid Substances in Their Own Solutions. J. Am. Chem. Soc. 1897, 19, 930–934. [Google Scholar] [CrossRef]
- Riikonen, J.; Correia, A.; Kovalainen, M.; Näkki, S.; Lehtonen, M.; Leppänen, J.; Rantanen, J.; Xu, W.; Araújo, F.; Hirvonen, J. Systematic in vitro and in vivo study on porous silicon to improve the oral bioavailability of celecoxib. Biomaterials 2015, 52, 44–55. [Google Scholar] [CrossRef] [PubMed]
- Dedroog, S.; Pas, T.; Vergauwen, B.; Huygens, C.; Van den Mooter, G. Solid-state analysis of amorphous solid dispersions: Why DSC and XRPD may not be regarded as stand-alone techniques. J. Pharm. Biomed. Anal. 2020, 178, 112937. [Google Scholar] [CrossRef] [PubMed]
- Andronis, V.; Yoshioka, M.; Zografi, G. Effects of Sorbed Water on the Crystallization of Indomethacin from the Amorphous State. J. Pharm. Sci. 1997, 86, 346–351. [Google Scholar] [CrossRef]
- Shamblin, S.L.; Zografi, G. The effects of absorbed water on the properties of amorphous mixtures containing sucrose. Pharm. Res. 1999, 16, 1119–1124. [Google Scholar] [CrossRef]
- Zhuravlev, L. Concentration of hydroxyl groups on the surface of amorphous silicas. Langmuir 1987, 3, 316–318. [Google Scholar] [CrossRef]
- Zharavlev, L. The surface chemistry of amorphous silica. Zhuravlev Model Colloids Surf. A 2000, 173, 1–38. [Google Scholar] [CrossRef]
- Palmelund, H.; Madsen, C.M.; Plum, J.; Mullertz, A.; Rades, T. Studying the Propensity of Compounds to Supersaturate: A Practical and Broadly Applicable Approach. J Pharm Sci 2016, 105, 3021–3029. [Google Scholar] [CrossRef]
- Zhu, W.; Zhao, Q.; Sun, C.; Zhang, Z.; Jiang, T.; Sun, J.; Li, Y.; Wang, S. Mesoporous carbon with spherical pores as a carrier for celecoxib with needle-like crystallinity: Improve dissolution rate and bioavailability. Mater. Sci. Eng. C 2014, 39, 13–20. [Google Scholar] [CrossRef] [PubMed]
- Hancock, B.C.; Zografi, G. The Relationship Between the Glass Transition Temperature and the Water Content of Amorphous Pharmaceutical Solids. Pharm. Res. 1994, 11, 471–477. [Google Scholar] [CrossRef] [PubMed]
- McCarthy, C.A.; Ahern, R.J.; Dontireddy, R.; Ryan, K.B.; Crean, A.M. Mesoporous silica formulation strategies for drug dissolution enhancement: A review. Expert Opin. Drug Deliv. 2016, 13, 93–108. [Google Scholar] [CrossRef] [PubMed]
- Kumar, D.; Chirravuri, S.S.; Shastri, N.R. Impact of surface area of silica particles on dissolution rate and oral bioavailability of poorly water soluble drugs: A case study with aceclofenac. Int. J. Pharm. 2014, 461, 459–468. [Google Scholar] [CrossRef]
CCX | Tg, ∆Cp | 59.0 °C, 0.41 J∙g−1∙°C−1 |
Tm, ∆Hm | 162.4 °C, 95.9 J∙g−1 | |
Solubility | 1.1 ± 0.1 µg∙mL−1 | |
Mw | 381.4 g∙mol−1 | |
ρamorphous | 1.35 a g∙cm−3 | |
Min. proj. area | 0.57 b nm2 | |
Max. proj. area | 0.99 b nm2 | |
tMLC, min/max | 22.2/33.1 wt.% | |
tPFC | 48.4 wt.% | |
xMLC | 33.5 (31.7–35.1) wt.% | |
SLC | Surface area c | 443.68 m2∙g−1 |
Particle size d | Approx. 10 µm | |
Pore volume d | 0.73 cm3∙g−1 |
Loading Degree (wt.%) | Day “0” | 18 Months, 40 °C, 0% RH | 18 Months, 40 °C, 75% RH | |||
---|---|---|---|---|---|---|
Tg | Tm | Tg | Tm | Tg | Tm | |
PFC | + | ÷ | + | + | ÷ | + |
MLC-PFC | + | ÷ | + | ÷ | ÷ | + |
MLC | ÷ | ÷ | ÷ | ÷ | ÷ | + |
<MLC | ÷ | ÷ | ÷ | ÷ | ÷ | + |
CCX Loading | Cmax (µg/mL) | Tmax (min) | Diss. Rate (µg/mL/min) |
---|---|---|---|
PFC (day 0) | 6.0 ± 0.5 | 7.2 ± 0.3 | 1.9 ± 0.2 |
40 °C/0% RH 18 mo. | 2.3 ± 0.4 | 32.7 ± 10.2 | 0.5 ± 0.1 |
40 °C/75% RH, 18 mo. | 1.0 ± 0.2 | 58.7 ± 2.4 | Not detectable |
MLC-PFC (day 0) | 15.4 ± 0.7 | 5.9 ± 0.5 | 5.0 ± 0.1 |
40 °C/0% RH 18 mo. | 13.8 ± 1.6 | 5.8 ± 0.6 | 4.7 ± 0.6 |
40 °C/75% RH, 18 mo. | 2.6 ± 0.2 | 4.8 ± 0.5 | 1.3 ± 0.0 |
MLC (day 0) | 16.1 ± 0.7 | 4.9 ± 0.3 | 6.8 ± 0.4 |
40 °C/0%RH 18 mo. | 17.3 ± 1.9 | 5.3 ± 1.3 | 7.1 ± 1.1 |
40 °C/75% RH, 18 mo. | 4.9 ± 0.7 | 3.7 ± 0.3 | 2.6 ± 0.4 |
<MLC (day 0) | 17.3 ± 0.6 | 4.4 ± 0.5 | 8.7 ± 0.2 |
40 °C/0% RH 18 mo. | 17.6 ± 0.6 | 4.1 ± 0.6 | 9.1 ± 1.1 |
40 °C/75% RH, 18 mo. | 11.1 ± 0.9 | 3.4 ± 0.3 | 6.0 ± 0.8 |
Amorphous CCX (day 0) | 3.6 ± 0.5 | 20.2 ± 2.0 | 0.8 ± 0.0 |
Crystalline CCX | 1.1 ± 0.1 | Not determined | Not determined |
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Bavnhøj, C.G.; Knopp, M.M.; Löbmann, K. Effect of Drug Loading in Mesoporous Silica on Amorphous Stability and Performance. Pharmaceutics 2024, 16, 163. https://doi.org/10.3390/pharmaceutics16020163
Bavnhøj CG, Knopp MM, Löbmann K. Effect of Drug Loading in Mesoporous Silica on Amorphous Stability and Performance. Pharmaceutics. 2024; 16(2):163. https://doi.org/10.3390/pharmaceutics16020163
Chicago/Turabian StyleBavnhøj, Christoffer G., Matthias M. Knopp, and Korbinian Löbmann. 2024. "Effect of Drug Loading in Mesoporous Silica on Amorphous Stability and Performance" Pharmaceutics 16, no. 2: 163. https://doi.org/10.3390/pharmaceutics16020163
APA StyleBavnhøj, C. G., Knopp, M. M., & Löbmann, K. (2024). Effect of Drug Loading in Mesoporous Silica on Amorphous Stability and Performance. Pharmaceutics, 16(2), 163. https://doi.org/10.3390/pharmaceutics16020163