Enhanced Piperine Solubility and Dissolution Rate in Piperine-Nicotinamide Multicomponent Crystal Adsorbed in Mesoporous Silica SBA-15
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Keywords:
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Piperine, Mesoporous SBA-15, Nicotinamide, Solubility, Dissolution Rate
Abstract
Piperine, classified as a Class II substance in the Biopharmaceutics Classification System (BCS), has poor solubility in water but high permeability. This research aims to improve the solubility and dissolution rate of piperine by adsorbing a multicomponent crystal (MCC) of piperine-nicotinamide onto mesoporous silica SBA-15. Tetraethyl orthosilicate (TEOS) was used as a silica precursor and Pluronic P123 as a pore-formation template to create SBA-15. Adsorption of the MCC was carried out by solvent evaporation with MCC:SBA-15 mass ratio (1:1). Solid state characterization was carried out by nitrogen adsorption-desorption isotherm, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, and scanning electron microscopy (SEM). Solubility tests were carried out for 24 hours and the dissolution rate profile was conducted for 60 minutes in distilled water. Dissolved piperine was determined using high performance liquid chromatography (HPLC) with methanol and distilled water as the mobile phase (75:25). The physical stability of MCC:SBA-15 was evaluated at various high relative humidities. The solid-state characterization results showed successful adsorption of the MCC in SBA-15 with a decrease in surface area, pore volume, and intensity of the X-ray diffraction peaks. The FT-IR spectrum of MCC:SBA-15 resembled that of SBA-15. The solubility test results showed 2.47-fold and 3.07-fold increases in solubility and dissolution rate compared to pure piperine, respectively. MCC:SBA-15 demonstrated high stability at 75% and 85% RH at 40◦C. In conclusion, adsorption of the MCC piperine-nicotinamide crystal in mesoporous silica SBA-15 can enhance the solubility and dissolution rate of piperine.
References
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Patel, R. D., M. K. Raval, T. M. Pethani, and N. R. Sheth (2020). Influence of Eutectic Mixture as a Multi-Component System in the Improvement of Physicomechanical and Pharmacokinetic Properties of Diacerein. Advanced Powder Technology, 31(4); 1441–1456
Patel, R. J., A. A. Patel, and H. P. Patel (2021). Stabilized Amorphous State of Riluzole by Immersion-Rotavapor Method With Synthesized Mesoporous SBA-15 Carrier to Augment In-Vitro Dissolution. Journal of Drug Delivery Science and Technology, 61; 102270
Quilaqueo, M., S. Millao, I. Luzardo-Ocampo, R. Campos-Vega, F. Acevedo, C. Shene, and M. Rubilar (2019). Inclusion of Piperine in β-Cyclodextrin Complexes Improves Their Bioaccessibility and In Vitro Antioxidant Capacity. Food Hydrocolloids, 91; 143–152
Sayyidina, F., A. Gumala, E. Zaini, D. Hanifa, and U. Hasanah (2025). Amine-Functionalized Mesoporous Silica SBA-15 for Enhanced Solubility and Release Rate of Gliclazide. Science and Technology Indonesia, 10(3); 963–971
Shen, S., W. A. I. K. Ng, L. Chia, Y. Dong, and R. B. H. 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
Song, Y., Y. Cong, B. Wang, and N. Zhang (2020). Applications of Fourier Transform Infrared Spectroscopy to Pharmaceutical Preparations. Expert Opinion on Drug Delivery, 17(4); 551–571
Springuel-Huet, M.-A., J.-L. Bonardet, A. Gédéon, Y. Yue, V. N. Romannikov, and J. Fraissard (2001). Mechanical Properties of Mesoporous Silicas and Alumina–Silicas MCM-41 and SBA-15 Studied by N2 Adsorption and 129Xe NMR. Microporous and Mesoporous Materials, 44–45; 775–784
Strydom, S., W. Liebenberg, L. Yu, and M. de Villiers (2009). The Effect of Temperature and Moisture on the Amorphous-to-Crystalline Transformation of Stavudine. International Journal of Pharmaceutics, 379(1–2); 72–81
Supraba, W., J. Yuliantoni, and A. Dwi (2021). The Effect of Stirring Speeds to the Entrapment Efficiency in a Nanoparticles Formulation of Java Plum’s Seed Ethanol Extract (Syzygium Cumini). Acta Chim. Asiana, 4(1); 197–202
Thahir, R., A. W. Wahab, N. L. Nafie, and I. Raya (2019). Synthesis of High Surface Area Mesoporous Silica SBA-15 by Adjusting Hydrothermal Treatment Time and the Amount of Polyvinyl Alcohol. Open Chemistry, 17(1); 963–971
Thommes, M. and K. A. Cychosz (2014). Physical Adsorption Characterization of Nanoporous Materials: Progress and Challenges. Adsorption, 20(2); 233–250
Van Der Meer, J., I. Bardez-Giboire, C. Mercier, B. Revel, A. Davidson, and R. Denoyel (2010). Mechanism of Metal Oxide Nanoparticle Loading in SBA-15 by the Double Solvent Technique. Journal of Physical Chemistry C, 114(8); 3507–3515
Wdowiak, K., R. Pietrzak, E. Tykarska, and J. Cielecka-Piontek (2023). Hot-Melt Extrusion as an Effective Technique for Obtaining an Amorphous System of Curcumin and Piperine with Improved Properties Essential for Their Better Biological Activities. Molecules, 28(9); 3848
Yadav, D., J. Savjani, K. Savjani, A. Kumar, and S. Patel (2022). Pharmaceutical Co-Crystal of Antiviral Agent Efavirenz with Nicotinamide for the Enhancement of Solubility, Physicochemical Stability, and Oral Bioavailability. AAPS PharmSciTech, 24(1); 7
Zafar, A., S. S. Imam, N. K. Alruwaili, O. A. Alsaidan, M. H. Elkomy, M. M. Ghoneim, S. Alshehri, A. M. A. Ali, K. S. Alharbi, and M. Yasir (2021). Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation. Nanomaterials, 11(11); 2920
Zafar, F., N. Jahan, Khalil-Ur-Rahman, and H. N. Bhatti (2019). Increased Oral Bioavailability of Piperine from an Optimized Piper Nigrum Nanosuspension. Planta Medica, 85(3); 249–257
Zaini, E., A. Afriyani, L. Fitriani, F. Ismed, A. Horikawa, and H. Uekusa (2020a). Improved Solubility and Dissolution Rates in Novel Multicomponent Crystals of Piperine with Succinic Acid. Scientia Pharmaceutica, 88(2); 21
Zaini, E., L. Fitriani, R. Y. Sari, H. Rosaini, A. Horikawa, and H. Uekusa (2019). Multicomponent Crystal of Mefenamic Acid and N-Methyl-D-Glucamine: Crystal Structures and Dissolution Study. Journal of Pharmaceutical Sciences, 108(7); 2341–2348
Zaini, E., R. P. Marhammah, L. Fitriani, U. Hasanah, and S. Umar (2021). The Preparation and Characterization of the Solid Dispersion of Piperine with Hydroxypropyl Methylcellulose (HPMC) 2910 Using Spray Drying. Tropical Journal of Natural Product Research (TJNPR), 5(12); 2103–2107
Zaini, E., D. Riska, M. D. Oktavia, F. Ismed, and L. Fitriani (2020b). Improving Dissolution Rate of Piperine by Multicomponent Crystal Formation with Saccharin. Research Journal of Pharmacy and Technology, 13(4); 1928–1932
Buya, A. B., A. Beloqui, P. B. Memvanga, and V. Préat (2020). Self-Nano-Emulsifying Drug-Delivery Systems: From the Development to the Current Applications and Challenges in Oral Drug Delivery. Pharmaceutics, 12(12); 1194
Chakravorty, R. (2022). Nanosuspension as an Emerging Nanotechnology and Techniques for Its Development. Research Journal of Pharmacy and Technology, 15(1); 489–493
Charalabidis, A., M. Sfouni, C. Bergström, and P. Macheras (2019). The Biopharmaceutics Classification System (BCS) and the Biopharmaceutics Drug Disposition Classification System (BDDCS): Beyond Guidelines. International Journal of Pharmaceutics, 566; 264–281
Chaudhary, V. and S. Sharma (2017). An Overview of Ordered Mesoporous Material SBA-15: Synthesis, Functionalization and Application in Oxidation Reactions. Journal of Porous Materials, 24(3); 741–749
Dadej, A., A. Woźniak-Braszak, P. Bilski, H. Piotrowska-Kempisty, M. Jóźkowiak, A. Pawełczyk, D. Dadej, D. Łażewska, and A. Jelińska (2022). Improved Solubility of Lornoxicam by Inclusion into SBA-15: Comparison of Loading Methods. European Journal of Pharmaceutical Sciences, 171; 106133
Fitriani, L., H. Azizah, U. Hasanah, and E. Zaini (2022). Enhancement of Curcumin Solubility and Dissolution by Adsorption in Mesoporous SBA-15. International Journal of Applied Pharmaceutics, 15(1); 61–67
Fitriani, L., C. M. Azzahra, A. Jessica, U. Hasanah, and E. Zaini (2024a). Improvement of Solubility Usnic Acid Loaded on Mesoporous Silica SBA-15 and Physicochemical Characterization. Science and Technology Indonesia, 9(2); 251–259
Fitriani, L., S. Tirtania, S. Umar, and E. Zaini (2024b). Enhancing the Solubility and Dissolution Rate of Piperine via Preparation of Piperine–Hydroxypropyl Methylcellulose 2910 Solid Dispersion System Using Freeze-Drying Method. Journal of Pharmacy & Pharmacognosy Research, 12(1); 175–183
Guo, Z., X. M. Liu, L. Ma, J. Li, H. Zhang, Y. P. Gao, and Y. Yuan (2013). Effects of Particle Morphology, Pore Size and Surface Coating of Mesoporous Silica on Naproxen Dissolution Rate Enhancement. Colloids and Surfaces B: Biointerfaces, 101; 228–235
Haq, I., M. Imran, M. Nadeem, T. Tufail, T. A. Gondal, and M. S. Mubarak (2021). Piperine: A Review of Its Biological Effects. Phytotherapy Research, 35(2); 680–700
Hasanah, U., F. Rizky, M. C. I. Mohd Amin, and E. Zaini (2025). Ticagrelor Solubility and Dissolution Rate Enhancement Using Mesoporous Silica SBA-15. Science and Technology Indonesia, 10(2); 598–604
Jangra, S., P. Girotra, V. Chhokar, and V. K. Tomer (2016). In-Vitro Drug Release Kinetics Studies of Mesoporous SBA-15–Azathioprine Composite. Journal of Porous Materials, 23; 679–688
Jaramillo, L. Y., W. Henao, and M. Romero-Sáez (2020). Synthesis and Characterization of MCM-41–SBA-15 Mixed-Phase Silica with Trimodal Mesoporous System and Thick Pore Wall. Journal of Porous Materials, 27(6); 1669–1676
Júnior, J. V. C., J. A. B. Dos Santos, T. B. Lins, R. S. de Araújo Batista, S. A. de Lima Neto, A. de Santana Oliveira, F. H. A. Nogueira, A. P. B. Gomes, D. P. de Sousa, and F. S. de Souza (2020). A New Ferulic Acid–Nicotinamide Cocrystal with Improved Solubility and Dissolution Performance. Journal of Pharmaceutical Sciences, 109(3); 1330–1337
Kusumorini, N., A. K. Nugroho, S. Pramono, and R. Martien (2022). Spray-Dried Self-Nanoemulsifying Drug Delivery Systems as Carriers for the Oral Delivery of Piperine: Characterization and In Vitro Evaluation. Journal of Applied Pharmaceutical Science, 12(9); 43–57
Lutfiyah, D. S., L. Fitriani, M. Taher, and E. Zaini (2022). Crystal Engineering Approach in Physicochemical Properties Modifications of Phytochemical. Science and Technology Indonesia, 7(3); 353–371
Nair, A. R., Y. D. Lakshman, V. S. K. Anand, K. S. N. Sree, K. Bhat, and S. J. Dengale (2020). Overview of Extensively Employed Polymeric Carriers in Solid Dispersion Technology. AAPS PharmSciTech, 21; 1–20
Octavia, M. D., H. Hasmiwati, G. Revilla, and E. Zaini (2023). Multicomponent Crystals of Piperine-Nicotinic Acid: The Physicochemical and Dissolution Rate Properties. Tropical Journal of Natural Product Research, 7(8); 3701–3705
Pardhi, V., R. B. Chavan, R. Thipparaboina, S. Thatikonda, V. G. M. Naidu, and N. R. Shastri (2017). Preparation, Characterization, and Cytotoxicity Studies of Niclosamide Loaded Mesoporous Drug Delivery Systems. International Journal of Pharmaceutics, 528(1–2); 202–214
Patel, R. D., M. K. Raval, T. M. Pethani, and N. R. Sheth (2020). Influence of Eutectic Mixture as a Multi-Component System in the Improvement of Physicomechanical and Pharmacokinetic Properties of Diacerein. Advanced Powder Technology, 31(4); 1441–1456
Patel, R. J., A. A. Patel, and H. P. Patel (2021). Stabilized Amorphous State of Riluzole by Immersion-Rotavapor Method With Synthesized Mesoporous SBA-15 Carrier to Augment In-Vitro Dissolution. Journal of Drug Delivery Science and Technology, 61; 102270
Quilaqueo, M., S. Millao, I. Luzardo-Ocampo, R. Campos-Vega, F. Acevedo, C. Shene, and M. Rubilar (2019). Inclusion of Piperine in β-Cyclodextrin Complexes Improves Their Bioaccessibility and In Vitro Antioxidant Capacity. Food Hydrocolloids, 91; 143–152
Sayyidina, F., A. Gumala, E. Zaini, D. Hanifa, and U. Hasanah (2025). Amine-Functionalized Mesoporous Silica SBA-15 for Enhanced Solubility and Release Rate of Gliclazide. Science and Technology Indonesia, 10(3); 963–971
Shen, S., W. A. I. K. Ng, L. Chia, Y. Dong, and R. B. H. 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
Song, Y., Y. Cong, B. Wang, and N. Zhang (2020). Applications of Fourier Transform Infrared Spectroscopy to Pharmaceutical Preparations. Expert Opinion on Drug Delivery, 17(4); 551–571
Springuel-Huet, M.-A., J.-L. Bonardet, A. Gédéon, Y. Yue, V. N. Romannikov, and J. Fraissard (2001). Mechanical Properties of Mesoporous Silicas and Alumina–Silicas MCM-41 and SBA-15 Studied by N2 Adsorption and 129Xe NMR. Microporous and Mesoporous Materials, 44–45; 775–784
Strydom, S., W. Liebenberg, L. Yu, and M. de Villiers (2009). The Effect of Temperature and Moisture on the Amorphous-to-Crystalline Transformation of Stavudine. International Journal of Pharmaceutics, 379(1–2); 72–81
Supraba, W., J. Yuliantoni, and A. Dwi (2021). The Effect of Stirring Speeds to the Entrapment Efficiency in a Nanoparticles Formulation of Java Plum’s Seed Ethanol Extract (Syzygium Cumini). Acta Chim. Asiana, 4(1); 197–202
Thahir, R., A. W. Wahab, N. L. Nafie, and I. Raya (2019). Synthesis of High Surface Area Mesoporous Silica SBA-15 by Adjusting Hydrothermal Treatment Time and the Amount of Polyvinyl Alcohol. Open Chemistry, 17(1); 963–971
Thommes, M. and K. A. Cychosz (2014). Physical Adsorption Characterization of Nanoporous Materials: Progress and Challenges. Adsorption, 20(2); 233–250
Van Der Meer, J., I. Bardez-Giboire, C. Mercier, B. Revel, A. Davidson, and R. Denoyel (2010). Mechanism of Metal Oxide Nanoparticle Loading in SBA-15 by the Double Solvent Technique. Journal of Physical Chemistry C, 114(8); 3507–3515
Wdowiak, K., R. Pietrzak, E. Tykarska, and J. Cielecka-Piontek (2023). Hot-Melt Extrusion as an Effective Technique for Obtaining an Amorphous System of Curcumin and Piperine with Improved Properties Essential for Their Better Biological Activities. Molecules, 28(9); 3848
Yadav, D., J. Savjani, K. Savjani, A. Kumar, and S. Patel (2022). Pharmaceutical Co-Crystal of Antiviral Agent Efavirenz with Nicotinamide for the Enhancement of Solubility, Physicochemical Stability, and Oral Bioavailability. AAPS PharmSciTech, 24(1); 7
Zafar, A., S. S. Imam, N. K. Alruwaili, O. A. Alsaidan, M. H. Elkomy, M. M. Ghoneim, S. Alshehri, A. M. A. Ali, K. S. Alharbi, and M. Yasir (2021). Development of Piperine-Loaded Solid Self-Nanoemulsifying Drug Delivery System: Optimization, In-Vitro, Ex-Vivo, and In-Vivo Evaluation. Nanomaterials, 11(11); 2920
Zafar, F., N. Jahan, Khalil-Ur-Rahman, and H. N. Bhatti (2019). Increased Oral Bioavailability of Piperine from an Optimized Piper Nigrum Nanosuspension. Planta Medica, 85(3); 249–257
Zaini, E., A. Afriyani, L. Fitriani, F. Ismed, A. Horikawa, and H. Uekusa (2020a). Improved Solubility and Dissolution Rates in Novel Multicomponent Crystals of Piperine with Succinic Acid. Scientia Pharmaceutica, 88(2); 21
Zaini, E., L. Fitriani, R. Y. Sari, H. Rosaini, A. Horikawa, and H. Uekusa (2019). Multicomponent Crystal of Mefenamic Acid and N-Methyl-D-Glucamine: Crystal Structures and Dissolution Study. Journal of Pharmaceutical Sciences, 108(7); 2341–2348
Zaini, E., R. P. Marhammah, L. Fitriani, U. Hasanah, and S. Umar (2021). The Preparation and Characterization of the Solid Dispersion of Piperine with Hydroxypropyl Methylcellulose (HPMC) 2910 Using Spray Drying. Tropical Journal of Natural Product Research (TJNPR), 5(12); 2103–2107
Zaini, E., D. Riska, M. D. Oktavia, F. Ismed, and L. Fitriani (2020b). Improving Dissolution Rate of Piperine by Multicomponent Crystal Formation with Saccharin. Research Journal of Pharmacy and Technology, 13(4); 1928–1932
Authors
Fitriani, L., Fauziah, G., Hasanah, U., Agustin, R., & Zaini, E. (2026). Enhanced Piperine Solubility and Dissolution Rate in Piperine-Nicotinamide Multicomponent Crystal Adsorbed in Mesoporous Silica SBA-15. Science and Technology Indonesia, 11(1), 109–120. https://doi.org/10.26554/sti.2026.11.1.109-120
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