Improving Flow Property of Nifedipine Loaded Solid-Lipid Nanoparticles by Means of Silica for Oral Solid Dosage Form


In this study, a new formulation of silica nanocomposite containing nifedipine (NI) loaded freeze-dried solid-lipid nanoparticles (NI-SLNs) and silica have been developed with improved flowability of powders, which can lead to the formulation of a widely acceptable oral dosage form. The stable NI-SLNs were prepared using two phospholipids, hydrogenated soybean phosphatidylcholine and dipalmitoylphosphatidylglycerol mixed with 2.5% w/v trehalose as a cryoprotectant followed by lyophilization. We employed various grades of two types of silica, such as fumed and precipitated. Silica improved the poor flow property of NI-SLNs to good category as per USP-29. In addition, most of the silica nanocomposites showed the satisfactory results in their physicochemical properties such as particle size, polydispersity index, zeta potential, and recovered potency by around 100 nm, 0.3, -50 mV, and 80%, respectively. Furthermore, it was found that NI-SLNs were easily released form nanocomposites within 30 min, therefore, suggesting an improvement of drug dissolutions. Among them, precipitated silica cooperated fairly in improving the powder characteristics as well as the physicochemical, morphological, and pharmaceutical properties.

Share and Cite:

Barman, R. , Iwao, Y. , Noguchi, S. , Wahed, M. and Itai, S. (2014) Improving Flow Property of Nifedipine Loaded Solid-Lipid Nanoparticles by Means of Silica for Oral Solid Dosage Form. Pharmacology & Pharmacy, 5, 1119-1129. doi: 10.4236/pp.2014.512122.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Lipinski, C.A., Lombardo, F., Dominy, B.W. and Feeney, P.J. (2001) Experimental and Computational Approaches to Estimate Solubility and Permeability in Drug Discovery and Development Settings. Advanced Drug Delivery Reviews, 46, 3-26.
[2] Fahr, A. and Liu, X. (2007) Drug Delivery Strategies for Poorly Water-Soluble Drugs. Expert Opinion on Drug Delivery, 4, 403-416.
[3] Dressman, J. and Christos, R. (2007) Drug Solubility: How to Measure It, How to Improve It. Advanced Drug Delivery Reviews, 59, 531-532.
[4] Merisko-Liversidge, E., Liversidge, G.G. and Cooper, E.R. (2003) Nanosizing: A Formulation Approach for Poorly Water-Soluble Compounds. European Journal of Pharmaceutical Sciences, 18, 113-120.
[5] Müller, R.H., Jacobs, C. and Kayser, O. (2001) Nanosuspensions as Particulate Drug Formulations in Therapy. Rationale for Development and What We Can Expect for the Future. Advanced Drug Delivery Reviews, 47, 3-19.
[6] Hauss, D.J. (2007) Oral Lipid-Based Formulations. Advanced Drug Delivery Reviews, 59, 667-676.
[7] Cole, E.T., Cade, D. and Benameur, H. (2008) Challenges and Opportunities in the Encapsulation of Liquid and Semi-Solid Formulations into Capsules for Oral Administration. Advanced Drug Delivery Reviews, 60, 747-756.
[8] Leuner, C. and Dressman, J. (2000) Improving Drug Solubility for Oral Delivery Using Solid Dispersions. European Journal of Pharmaceutics and Biopharmaceutics, 50, 47-60.
[9] Vasconcelos, T., Sarmento, B. and Costa, P. (2007) Solid Dispersions as Strategy to Improve Oral Bioavailability of Poor Water Soluble Drugs. Drug Discovery Today, 12, 1068-1075.
[10] Suri, S.S., Fenniri, H. and Singh, B. (2007) Nanotechnology-Based Drug Delivery Systems. Journal of Occupational Medicine and Toxicology, 2, 16.
[11] Bunjes, H., Westesen, K. and Koch M.H.J. (1996) Cystallization Tendency and Polymorphic Transitions in TriglyceRide Nanoparticles. International Journal of Pharmaceutics, 129, 159-173.
[12] Zimmermann, E., Müller, R.H. and Mader, K. (2000) Influence of Different Parameters on Reconstitution of Lyophilized SLN. International Journal of Pharmaceutics, 196, 211-213.
[13] Ohshima, H., Miyagishima, A., Kurita, T., Makino, Y., Iwao, Y., Sonobe, T. and Itai, S. (2009) Freeze-Dried Nifedipine-Lipid Nanoparticles with Long-Term Nano-Dispersion Stability after Reconstitution. International Journal of Pharmaceutics, 377, 180-184.
[14] Barman, R.K., Iwao, Y., Funakoshi, Y., Ranneh, A.H., Noguchi, S., Wahed, M.I.I. and Itai, S. (2014) Development of Highly Stable Nifedipine Solid-Lipid Nanoparticles. Chemical and Pharmaceutical Bulletin, 62, 399-406.
[15] Barman, R.K., Iwao, Y., Islam, M.R., Funakoshi, Y., Noguchi, S., Wahed, M.I.I. and Itai, S. (2014) In Vivo Pharmacokinetic and Hemocompatible Evaluation of Lyophilization Induced Nifedipine Solid-Lipid Nanoparticle. Journal of Pharmacy and Pharmacology, 5, 455-461.
[16] Funakoshi, Y., Iwao, Y., Noguchi, S. and Itai, S. (2013) Lipid Nanoparticles with No Surfactant Improve Oral Absorption Rate of Poorly Water-Soluble Drug. International Journal of Pharmaceutics, 451, 92-94.
[17] Vallet-Regi, M., Ramila, A., Del Real, R. and Perez-Pariente J. (2001) A New Property of MCM-41: Drug Delivery System. Chemistry of Materials, 13, 308-311.
[18] Fu, T., Lu, J., Guo, L., Zhang, L., Cai, X. and Zhu, H. (2012) Improving Bioavailability of Silybin by Inclusion into SBA-15 Mesoporous Silica Materials. Journal of Nanoscience and Nanotechnology, 12, 3997-4006.
[19] Li, L., Huang, X., Liu, T., Liu, H., Hao, N., Chen, D., Zhang, Y. and Tang, F. (2012) Overcoming Multidrug Resistance with Mesoporous Silica Nanorods as Nanocarrier of Doxorubicin. Journal of Nanoscience and Nanotechnology, 12, 4458-4466.
[20] Moon, D.S. and Lee, J.K. (2012) Tunable Synthesis of Hierarchical Mesoporous Silica Nanoparticles with Radial Wrinkle Structure. Langmuir, 28, 12341-12347.
[21] Song, B., Wu, C. and Chang, J. (2012) Controllable Delivery of Hydrophilic and Hydrophobic Drugs from Electrospun Poly(Lactic-Co-Glycolic Acid)/Mesoporous Silica Nanoparticles Composite Mats. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 100, 2178-2186.
[22] Shen, S., Chow, P.S., Kim, S., Zhu, K. and Tan, R.B.H. (2008) Synthesis of Carboxyl-Modified Rod-Like SBA-15 by Rapid Co-Condensation. Journal of Colloid and Interface Science, 321, 365-372.
[23] Zhang, Y., Zhi, Z., Jiang, T., Zhang, J., Wang, Z. and Wang, S. (2010) Spherical Mesoporous Silica Nanoparticles for Loading and Release of the Poorly Water-Soluble Drug Telmisartan. Journal of Controlled Release, 145, 257-263.
[24] Yasmin, R., Tan, A., Bremmell, K.E. and Prestidge, C.A. (2014) Lyophilized Silica-Lipid Hybrid Carriers for Poorly Water-Soluble Drugs: Physicochemical and in Vitro Pharmaceutical Investigations. Journal of Pharmaceutical Sciences, 103, 2950-2959.
[25] Simovic, S., Heard, P., Hui, H., Song, Y., Peddie, F., Davey, A.K., Lewis, A., Rades, T. and Prestidge, C.A. (2009) Dry Hybrid Lipid-Silica Microcapsules Engineered from Submicron Lipid Droplets and Nanoparticles as a Novel Delivery System for Poorly Soluble Drugs. Molecular Pharmaceutics, 6, 861-872.
[26] Tan, A., Simovic, S., Davey, A.K., Rades, T. and Prestidge, C.A. (2009) Silica-Lipid Hybrid (SLH) Microcapsules: A Novel Oral Delivery System for Poorly Soluble Drugs. Journal of Controlled Release, 134, 62-70.
[27] Perge, L., Robitzer, M., Guillemot, C., Devoisselle, J.M., Quignard, F. and Legrand P. (2012) New Solid Lipid Microparticles for Controlled Ibuprofen Release: Formulation and Characterization Study. International Journal of Pharmaceutics, 422, 59-67.
[28] Kamiya, S., Yamada, M., Kurita, T., Miyagishima, A., Arakawa, M. and Sonobe, T. (2008) Preparation and Stabilization of Nifedipine Lipid Nanoparticles. International Journal of Pharmaceutics, 354, 242-247.
[29] Carr, R.L. (1965) Evaluating Flow Properties of Solids. Chemical Engineering Journal, 72, 163-168.
[30] United States of Pharmacopeia (USP)-29 and National Formulary (NF)-24: 1174.
[31] Schwarz, C., Mehnert, W., Lucks, J.S. and Muller, R.H. (1994) Solid Lipid Nanoparticles (SLN) for Controlled Drug Delivery. I. Production, Characterization and Sterilization. Journal of Controlled Release, 30, 83-96.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.