Improvement of Solubility Usnic Acid Loaded on Mesoporous Silica SBA-15 and Physicochemical Characterization

Lili Fitriani, Cindy Maynia Azzahra, Adhitya Jessica, Uswatul Hasanah, Erizal Zaini


Usnic acid, a secondary metabolite of lichen Usnea sp., has several pharmacological activities, but it is poorly soluble in water. This study aimed to improve the solubility and dissolution rate of usnic acid loaded in mesoporous silica SBA-15 at a mass ratio of 1:1. and evaluate its physical stability. Physicochemical characterization was carried out via the nitrogen adsorption desorption isotherm, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) spectroscopy, and powder X-ray diffraction (PXRD). Usnic acid-loaded SBA-15 was stored at 40 °C with various relative humidities (RH) and then analyzed by PXRD for the physical stability. Usnic acid adsorbed well in the pores of SBA-15, as shown by a decrease in the volume pore and surface area of SBA-15 according to the nitrogen adsorption. Moreover, usnic acid-SBA-15 showed a decrease in the degree of crystallinity according to PXRD analysis and no melting point based on DSC analysis. The FTIR spectrum of usnic acid–SBA-15 corresponds to the spectra of each raw material. The solubility of usnic acid increased 5.15 times after adsorbed on SBA-15. The dissolution rate also showed a significant increase (p < 0.05) from 19.51% to 84.27%. Usnic acid–SBA-15 was relatively stable at RH 75%. Thus, the adsorption of usnic acid on SBA-15 can increase its solubility, dissolution rate, and physical stability.


Adrover, M. E., M. Pedernera, M. Bonne, B. Lebeau, V. Bucalá, and L. Gallo (2020). Synthesis and Characterization of Mesoporous SBA-15 and SBA-16 As Carriers to Improve Albendazole Dissolution Rate. Saudi Pharmaceutical Journal, 28(1); 15–24

Ahern, R. J., J. P. Hanrahan, J. M. Tobin, K. B. Ryan, and A. M. Crean (2013). Comparison of Fenofibrate-Mesoporous Silica Drug-Loading Processes for Enhanced Drug Delivery. European Journal of Pharmaceutical Sciences, 50(3-4); 400–409

Behera, B., N. Verma, A. Sonone, and U. Makhija (2005). Antioxidant and Antibacterial Activities of Lichen Usnea Ghattensis in Vitro. Biotechnology letters, 27; 991–995

Brugnoli, B., G. Perna, S. Alfano, A. Piozzi, L. Galantini, E. Axioti, V. Taresco, A. Mariano, A. Scotto d’Abusco, and S. Vecchio Ciprioti (2024). Nanostructured Poly-l-lactide and Polyglycerol Adipate Carriers for the Encapsulation of Usnic Acid: A Promising Approach for Hepatoprotection. Polymers, 16(3); 427

Campanella, L., M. Delfini, P. Ercole, A. Iacoangeli, and G. Risuleo (2002). Molecular Characterization and Action of Usnic Acid: A Drug That Inhibits Proliferation of Mouse Polyomavirus in Vitro and Whose Main Target Is RNA Transcription. Biochimie, 84(4); 329–334

Chairunisa, U., D. K. Haryati, R. Wahyuni, I. Makmur, S. Effendy, R. D. Yetti, A. Eriadi, H. S. K. Uyun, D. D. A. Bakhtra, A. Halim, and M. Fadhilah (2022). Increasing the Dissolution Rate of USNAC PVP K-30 and PEG6000 Solid Dissolution Using Solution Method. International Journal of Research Publication and Reviews, 3(8); 458–463

Dadej, A., A. Woźniak Braszak, P. Bilski, H. Piotrowska Kempisty, M. Józkowiak, M. Geszke Moritz, M. Moritz, D. Dadej and A. Jelińska (2021). Modification of the Release of Poorly Soluble Sulindac with the APTES-Modified SBA-15 Mesoporous Silica. Pharmaceutics, 13(10); 1693

Douglas A. Araújo, H., J. G. Silva Júnior, J. R. Saturnino Oliveira, M. Helena ML Ribeiro, M. C. Barroso Martins, M. A. Cavalcanti Bezerra, A. Lima Aires, M. CP Azevedo Albuquerque, M. R. Melo Júnior, and N. T. Pontes Filho (2019). Usnic Acid Potassium Salt: Evaluation of the Acute Toxicity and Antinociceptive Effect in Murine Model. Molecules, 24(11); 2042

Fitriani, L., I. Afriyanti, F. Ismed, and E. Zaini (2018a). Solid Dispersion of Usnic acid-HPMC 2910 Prepared by Spray drying and Freeze drying Techniques. Oriental Journal of Chemistry, 34(4)

Fitriani, L., H. Azizah, U. Hasanah, and E. Zaini (2022). Enhancement of Curcumin Solubility and Dissolution by Adsorption in Mesoporous SBA-15. In International Conference on Contemporary Science and Clinical Pharmacy. page 61

Fitriani, L., E. Rismawati, S. Umar, and E. Zaini (2018b). Solid Dispersion of Usnic Acid-PVP K30 and Evaluation of Antioxidant Activity. Rasayan Journal of Chemistry, 11; 1643–1648

Galarneau, A., M. Nader, F. Guenneau, F. Di Renzo, and A. Gedeon (2007). Understanding the Stability in Water of Mesoporous SBA-15 and MCM-41. The Journal of Physical Chemistry C, 111(23); 8268–8277

Gao, Y., B. Glennon, Y. He, and P. Donnellan (2021). Dissolution Kinetics of a BCS Class II Active Pharmaceutical Ingredient: Diffusion-Based Model Validation and Prediction. ACS Omega, 6(12); 8056–8067

Heikkilä, T., J. Salonen, J. Tuura, N. Kumar, T. Salmi, D. Y. Murzin, M. Hamdy, G. Mul, L. Laitinen, and A. M. Kaukonen (2007). Evaluation of Mesoporous TCPSi, MCM-41, SBA-15, and TUD-1 Materials as API Carriers for Oral Drug Delivery. Drug Delivery, 14(6); 337–347

Holford, N. H. and L. B. Sheiner (1981). Understanding the Dose-Effect Relationship: Clinical Application of Pharmacokinetic-Pharmacodynamic Models. Clinical Pharmacokinetics, 6(6); 429-453

Letchmanan, K., S.-C. Shen, W. K. Ng, and R. B. Tan (2017). Dissolution and Physicochemical Stability Enhancement of Artemisinin and Mefloquine Co-Formulation Via Nano Confinement with Mesoporous SBA-15. Colloids and Surfaces B: Biointerfaces, 155; 560–568

Lira, M. C., M. S. Ferraz, D. G. da Silva, M. E. Cortes, K. I. Teixeira, N. P. Caetano, R. D. Sinisterra, G. Ponchel, and N. S. Santos-Magalhaes (2009). Inclusion Complex of Usnic Acid with ???? -Cyclodextrin: Characterization and Nanoencapsulation into Liposomes. Journal of Inclusion Phenomena and Macrocyclic Chemistry, 64; 215–224

Liu, X., N. Liu, X. Li, X. Li, B. Hu, and S. He (2023). Surface Properties and Microstructures of Al SBA-15 under Different Temperature Calcinations in Relation to Adsorption Performance. The Journal of Physical Chemistry C, 127(13); 6446-6455

Maleki, A. and M. Hamidi (2015). Dissolution Enhancement of a Model Poorly Water-Soluble Drug, Atorvastatin, with Ordered Mesoporous Silica: Comparison of Msf with SBA-15 As Drug Carriers. Expert Opinion on Drug Delivery, 13(2); 171–181

Maleki, A., H. Kettiger, A. Schoubben, J. M. Rosenholm, V. Ambrogi, and M. Hamidi (2017). Mesoporous Silica Materials: From Physico-Chemical Properties to Enhanced Dissolution of Poorly Water-Soluble Drugs. Journal of Controlled Release, 262; 329–347

Mayer, M., M. A. O’Neill, K. E. Murray, N. S. Santos-Magalhães, A. M. A. Carneiro-Leão, A. M. Thompson, and V. C. Appleyard (2005). Usnic Acid: A Non-Genotoxic Compound with Anti-Cancer Properties. Anti-Cancer Drugs, 16(8); 805–809

Okuyama, E., K. Umeyama, M. Yamazaki, Y. Kinoshita, and Y. Yamamoto (1995). Usnic Acid and Diffractaic Acid As Analgesic and Antipyretic Components of Usnea Diffracta. Planta Medica, 61(02); 113–115

Palapa, N. R., N. Ahmad, A. Wijaya, and Z. A. Zahara (2023). Facile Fabrication of Layered Double Hydroxide-Lignin for Efficient Adsorption of Malachite Green. Science and Technology Indonesia, 8(2); 305–311

Shen, S. C., W. K. Ng, L. Chia, Y. C. Dong, and R. B. Tan (2010). Stabilized Amorphous State of Ibuprofen by Co-Spray Drying with Mesoporous SBA-15 to Enhance Dissolution Properties. Journal of Pharmaceutical Sciences, 99(4); 1997–2007

Sokolov, D. N., V. V. Zarubaev, A. A. Shtro, M. P. Polovinka, O. A. Luzina, N. I. Komarova, N. F. Salakhutdinov, and O. I. Kiselev (2012). Anti-Viral Activity of (-)-and (+)- Usnic Acids and Their Derivatives against Influenza Virus A (H1N1) 2009. Bioorganic & Medicinal Chemistry Letters, 22(23); 7060–7064

Supraba, W., Y. Juliantoni, and A. D. Ananto (2021). The Effect of Stirring Speeds to the Entrapment Efficiency in a Nanoparticles Formulation of Java Plum’s seed Ethanol Extract (Syzygium cumini). Acta Chimica Asiana, 4(1); 197–103

Thahir, R., A. W. Wahid, N. La Nafie, and I. Raya (2019). Synthesis of Mesoporous Silica SBA-15 through Surfactant Set-Up and Hydrothermal Process. Rasayan Journal of Chemistry, 12(3); 1117–1126

Tng, D. J. H. and J. G. H. Low (2023). Current Status of Silica-Based Nanoparticles As Therapeutics and Its Potential As Therapies against Viruses. Antiviral Research, 210; 105488

Van Speybroeck, M., V. Barillaro, T. Do Thi, R. Mellaerts, J. Martens, J. Van Humbeeck, J. Vermant, P. Annaert, G. Van Den Mooter, and P. Augustijns (2009). Ordered Mesoporous Silica Material SBA-15: A Broad-Spectrum Formulation Platform for Poorly Soluble Drugs. Journal of Pharmaceutical Sciences, 98(8); 2648–2658

Vijayakumar, C., S. Viswanathan, M. K. Reddy, S. Parvathavarthini, A. B. Kundu, and E. Sukumar (2000). Anti-Inflammatory Activity of (+)-Usnic Acid. Fitoterapia, 71(5); 564–566

Vinu, A., T. Mori, and K. Ariga (2006). New Families of Mesoporous Materials. Science and Technology of Advanced Materials, 7(8); 753–771

Wang, Z., B. Chen, G. Quan, F. Li, Q. Wu, L. Dian, Y. Dong, G. Li, and C. Wu (2012). Increasing the Oral Bioavailability of Poorly Water-Soluble Carbamazepine Using Immediate-Release Pellets Supported on SBA-15 Mesoporous Silica. International Journal of Nanomedicine, 7; 5807–5818

Yu, C., B. Tian, J. Fan, G. D. Stucky, and D. Zhao (2001). Salt Effect in the Synthesis of Mesoporous Silica Templated by Non-Ionic Block Copolymers. Chemical Communications, (24); 2726–2727

Zaini, E., D. Azhari, and L. Fitriani (2016). Identification and Characterization of Solid Binary System of Quercetin-Nicotinamide. Oriental Journal of Chemistry, 32(3); 1545–1550


Lili Fitriani
Cindy Maynia Azzahra
Adhitya Jessica
Uswatul Hasanah
Erizal Zaini (Primary Contact)
Fitriani, L., Azzahra, C. M., Jessica, A. ., Hasanah, U., & Zaini, E. (2024). Improvement of Solubility Usnic Acid Loaded on Mesoporous Silica SBA-15 and Physicochemical Characterization. Science and Technology Indonesia, 9(2), 251–259.

Article Details