1,498
Views
125
CrossRef citations to date
0
Altmetric
Reviews

Mesoporous silica formulation strategies for drug dissolution enhancement: a review

, , , &

Bibliography

Papers of special note have been highlighted as either of interest (*) or of considerable interest (**) to readers.

  • Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods. 2000;44(1):235–249.
  • van Hoogevest P, Liu X, Fahr A. Drug delivery strategies for poorly water-soluble drugs: the industrial perspective. Expert Opin Drug Deliv. 2011;8(11):1481–1500.
  • Monkhouse DC, Lach JL. Use of adsorbents in enhancement of drug dissolution. I. J Pharm Sci. 1972;61(9):1430–1435.
  • Unger K, Rupprecht H, Valentin B, et al. The use of porous and surface modified silicas as drug delivery and stabilizing agents. Drug Dev Ind Pharm. 1983;9(1–2):69–91.
  • Vallet-Regi M, Ramila A, Del Real R, et al. A new property of MCM-41: drug delivery system. Chem Mater. 2001;13(2):308–311.

**First report on the use of mesoporous silica for controlled drug delivery.

  • Van Speybroeck M, Barillaro V, Thi TD, et al. Ordered mesoporous silica material SBA‐15: a broad‐spectrum formulation platform for poorly soluble drugs. J Pharm Sci. 2009;98(8):2648–2658.
  • Mellaerts R, Aerts CA, Humbeeck JV, et al. Enhanced release of itraconazole from ordered mesoporous SBA-15 silica materials. Chem Commun. 2007;13:1375–1377.
  • Heikkilä T, Salonen J, Tuura J, et al. Mesoporous silica material TUD-1 as a drug delivery system. Int J Pharm. 2007;331(1):133–138.
  • Kresge C, Leonowicz M, Roth W, et al. Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature. 1992;359(6397):710–712.
  • Salonen J, Kaukonen AM, Hirvonen J, et al. Mesoporous silicon in drug delivery applications. J Pharm Sci. 2008;97(2):632–653.
  • Bley H, Fussnegger B, Bodmeier R. Characterization and stability of solid dispersions based on PEG/polymer blends. Int J Pharm. 2010;390(2):165–173.
  • U.S. Food and Drug Administration. Inactive Ingredient Search for Approved Drug Products; 2015 [cited 2015 Sep 14]. Available from: http://www.accessdata.fda.gov/scripts/cder/iig/getiigWEB.cfm.
  • Fu C, Liu T, Li L, et al. The absorption, distribution, excretion and toxicity of mesoporous silica nanoparticles in mice following different exposure routes. Biomaterials. 2013;34(10):2565–2575.
  • Hudson SP, Padera RF, Langer R, et al. The biocompatibility of mesoporous silicates. Biomaterials. 2008;29(30):4045–4055.
  • Manzano M, Colilla M, Vallet-Regí M. Drug delivery from ordered mesoporous matrices. Expert Opin Drug Deliv. 2009;6(12):1383–1400.
  • Jaganathan H, Godin B. Biocompatibility assessment of Si-based nano- and micro-particles. Adv Drug Deliv Rev. 2012;64(15):1800–1819.
  • Rowe RC, Sheskey PJ, Owen SC, et al. Handbook of pharmaceutical excipients. Vol. 6. London: Pharmaceutical press; 2006.
  • Kim J. Synthesis of MCM-48 single crystals. Chem Commun. 1998;2:259–260.
  • Izquierdo-Barba I, Martinez Á, Doadrio AL, et al. Release evaluation of drugs from ordered three-dimensional silica structures. Eur J Pharm Sci. 2005;26(5):365–373.
  • Zhao D, Feng J, Huo Q, et al. Triblock copolymer syntheses of mesoporous silica with periodic 50 to 300 angstrom pores. Science. 1998;279(5350):548–552.
  • Inagaki S, Koiwai A, Suzuki N, et al. Syntheses of highly ordered mesoporous materials, FSM-16, derived from Kanemite. Bull Chem Soc Jpn. 1996;69(5):1449–1457.
  • Jansen J, Shan Z, Marchese L, et al. A new templating method for three-dimensional mesopore networks. Chem Commun. 2001;8:713–714.
  • Takeuchi H, Nagira S, Yamamoto H, et al. Solid dispersion particles of amorphous indomethacin with fine porous silica particles by using spray-drying method. Int J Pharm. 2005;293(1–2):155–164.
  • Kinnari P, Mäkilä E, Heikkilä T, et al. Comparison of mesoporous silicon and non-ordered mesoporous silica materials as drug carriers for itraconazole. Int J Pharm. 2011;414(1–2):148–156.
  • Friedrich H, Fussnegger B, Kolter K, et al. Dissolution rate improvement of poorly water-soluble drugs obtained by adsorbing solutions of drugs in hydrophilic solvents onto high surface area carriers. Eur J Pharm Biopharm. 2006;62(2):171–177.
  • Bend Research. Spray-Dried NanoAdsorbate (SDNA) Technology; 2014 [cited 2015 Feb 4]. Available from: http://www.bendresearch.com/drug-delivery-technologies/spray-dried-composite-sdc-technology.
  • Tang F, Li L, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater. 2012;24(12):1504–1534.
  • Azaïs T, Tourné-Péteilh C, Aussenac F, et al. Solid-state NMR study of ibuprofen confined in MCM-41 material. Chem Mater. 2006;18(26):6382–6390.
  • Shen SC, Ng WK, Chia L, et al. Stabilized amorphous state of ibuprofen by co‐spray drying with mesoporous SBA‐15 to enhance dissolution properties. J Pharm Sci. 2010;99(4):1997–2007.
  • Charnay C, Bégu S, Tourné-Péteilh C, et al. Inclusion of ibuprofen in mesoporous templated silica: drug loading and release property. Eur J Pharm Biophar. 2004;57(3):533–540.
  • Hong S, Shen S, Tan DCT, 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. 2015;July 21:1–12.
  • Sliwinska-Bartkowiak M, Dudziak G, Gras R, et al. Freezing behavior in porous glasses and MCM-41. Colloids Surf A Physicochem Eng Asp. 2001;187:523–529.
  • Brás AR, Fonseca IM, Dionísio M, et al. Influence of nanoscale confinement on the molecular mobility of ibuprofen. J Phys Chem C. 2014;118(25):13857–13868.
  • Hancock BC, Parks M. What is the true solubility advantage for amorphous pharmaceuticals? Pharm Res. 2000;17(4):397–404.
  • FUJI SILYSIA CHEMICAL LTD. Sylysia; 2015 [cited 2015 Sep 14]. Available from: http://www.fujisilysia.com/products/sylysia/.
  • Grace WR, Conn C. Syloid silica excipients for pharmaceutical applications; 2014 [cited 2015 Apr 28]. Available from: https://grace.com/pharma-and-biotech/en-us/Documents/Syloid/B561b_SYLOID_8.5x11VERSION_9-18-14_FINAL.pdf.
  • Gumaste SG, Pawlak SA, Dalrymple DM, et al. Development of solid SEDDS, IV: effect of adsorbed lipid and surfactant on tableting properties and surface structures of different silicates. Pharm Res. 2013;30(12):3170–3185.
  • Galarneau A, Nader M, Guenneau F, et al. Understanding the stability in water of mesoporous SBA-15 and MCM-41. J Phys Chem C. 2007;111(23):8268–8277.
  • Merck Millipore. Merck Millipore Introduces Parteck® SLC, Silica-based Excipient for Enhanced Drug Solubility and Bioavailability. Darmstadt: Merck Millipore Corporation; 2013.
  • Andersson J, Rosenholm J, Areva S, et al. Influences of material characteristics on ibuprofen drug loading and release profiles from ordered micro-and mesoporous silica matrices. Chem Mater. 2004;16(21):4160–4167.
  • Singh A, Worku ZA, Van den Mooter G. Oral formulation strategies to improve solubility of poorly water-soluble drugs. Expert Opin Drug Deliv. 2011;8(10):1361–1378.
  • Prestidge CA, Barnes TJ, Lau C-H, et al. Mesoporous silicon: a platform for the delivery of therapeutics. Expert Opin Drug Deliv. 2007;4(2):101–110.
  • Ahern RJ, Hanrahan JP, Tobin JM, et al. Comparison of fenofibrate–mesoporous silica drug-loading processes for enhanced drug delivery. Eur J Pharm Sci. 2013;50(3–4):400–409.

* Informative comparison of different drug loading methods

  • Mellaerts R, Jammaer JAG, Van Speybroeck M, et al. Physical state of poorly water soluble therapeutic molecules loaded into SBA-15 ordered mesoporous silica carriers: a case study with itraconazole and ibuprofen. Langmuir. 2008;24(16):8651–8659.

** Interesting article on drug distribution in pores

  • Waters LJ, Bedford S, Parkes GMB. Controlled microwave processing applied to the pharmaceutical formulation of ibuprofen. AAPS PharmSciTech. 2011;12(4):1038–1043.
  • Waters LJ, Hussain T, Parkes G, et al. Inclusion of fenofibrate in a series of mesoporous silicas using microwave irradiation. Eur J Pharm Biopharm. 2013;85(3):936–941.
  • Qu F, Zhu G, Lin H, et al. A controlled release of ibuprofen by systematically tailoring the morphology of mesoporous silica materials. J Solid State Chem. 2006;179(7):2027–2035.
  • Ambrogi V, Perioli L, Pagano C, et al. MCM-41 for furosemide dissolution improvement. Microporous Mesoporous Mater. 2012;147(1):343–349.
  • Qian KK, Bogner RH. Application of mesoporous silicon dioxide and silicate in oral amorphous drug delivery systems. J Pharm Sci. 2012;101(2): 444–463.
  • ICH. Impurities: guideline for residual solvents Q3C(R5) [Internet]. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use; 2011 Feb. [cited 2014 Oct 20]. Available from: http://www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q3C/Step4/Q3C_R5_Step4.pdf
  • Hata H, Saeki S, Kimura T, et al. Adsorption of taxol into ordered mesoporous silicas with various pore diameters. Chem Mater. 1999;11(4):1110–1119.
  • Heikkilä T, Salonen J, Tuura J, et al. Evaluation of mesoporous TCPSi, MCM-41, SBA-15, and TUD-1 materials as API carriers for oral drug delivery. Drug Deliv. 2007;14(6):337–347.
  • Lehto V, Riikonen J, Santos H. Drug loading and characterization of porous silicon materials. In: Santos HA, editor. Porous silicon for biomedical applications. Cambridge: Woodhead Publishing Limited; 2014. p. 337.
  • Mellaerts R, Houthoofd K, Elen K, et al. Aging behavior of pharmaceutical formulations of itraconazole on SBA-15 ordered mesoporous silica carrier material. Microporous Mesoporous Mater. 2010;130(1):154–161.

**Informative article on stability of mesoporous silica drug formulations

  • Van Speybroeck M, Mols R, Mellaerts R, et al. Combined use of ordered mesoporous silica and precipitation inhibitors for improved oral absorption of the poorly soluble weak base itraconazole. Eur J Pharm Biopharm. 2010;75(3):354–365.

* Interesting article on in vivo drug delivery from mesoporous silica formulations

  • Van Speybroeck M, Mellaerts R, Thi TD, et al. Preventing release in the acidic environment of the stomach via occlusion in ordered mesoporous silica enhances the absorption of poorly soluble weakly acidic drugs. J Pharm Sci. 2011;100(11):4864–4876.
  • Kruk M, Jaroniec M, Ko CH, et al. Characterization of the porous structure of SBA-15. Chem Mater. 2000;12(7):1961–1968.
  • Vetere A. A short-cut method to predict the solubilities of solids in supercritical carbon dioxide. Fluid Phase Equilib. 1998;148(1–2):83–93.
  • Gignone A, Manna L, Ronchetti S, et al. Incorporation of clotrimazole in ordered mesoporous silica by supercritical CO2. Microporous Mesoporous Mater. 2014;200:291–296.
  • Ahern RJ, Crean AM, Ryan KB. The influence of supercritical carbon dioxide (SC-CO2) processing conditions on drug loading and physicochemical properties. Int J Pharm. 2012;439(1):92–99.
  • Limnell T, Santos HA, Mäkilä E, et al. Drug delivery formulations of ordered and nonordered mesoporous silica: comparison of three drug loading methods. J Pharm Sci. 2011;100(8):3294–3306.

* Informative report on loading methods for scale-up processes

  • Bahl D, Hudak J, Bogner RH. Comparison of the ability of various pharmaceutical silicates to amorphize and enhance dissolution of indomethacin upon co-grinding. Pharm Dev Technol. 2008;13(3):255–269.
  • Aerts CA, Verraedt E, Mellaerts R, et al. Tunability of pore diameter and particle size of amorphous microporous silica for diffusive controlled release of drug compounds. J Phys Chem C. 2007;111(36):13404–13409.
  • Horcajada P, Ramila A, Perez-Pariente J, et al. Influence of pore size of MCM-41 matrices on drug delivery rate. Microporous Mesoporous Mater. 2004;68(1):105–109.
  • Tozuka Y, Wongmekiat A, Kimura K, et al. Effect of pore size of FSM-16 on the entrapment of flurbiprofen in mesoporous structures. Chem Pharm Bull. 2005;53(8):974–977.
  • Ukmar T, Maver U, Planinšek O, et al. Understanding controlled drug release from mesoporous silicates: theory and experiment. J Control Release. 2011;155(3):409–417.
  • Gao L, Sun J, Zhang L, et al. Influence of different structured channels of mesoporous silicate on the controlled ibuprofen delivery. Mater Chem Phys. 2012;135(2–3):786–797.
  • Zhu Y-F, Shi J-L, Li Y-S, et al. Hollow mesoporous spheres with cubic pore network as a potential carrier for drug storage and its in vitro release kinetics. J Mater Res. 2005;20(1):54–61.
  • Zhang Y, Zhi Z, Jiang T, et al. Spherical mesoporous silica nanoparticles for loading and release of the poorly water-soluble drug telmisartan. J Control Release. 2010;145(3):257–263.
  • Rengarajan G, Enke D, Steinhart M, et al. Stabilization of the amorphous state of pharmaceuticals in nanopores. J Mater Chem. 2008;18(22):2537–2539.
  • Jia LJ, Shen JY, Li ZY, et al. Successfully tailoring the pore size of mesoporous silica nanoparticles: exploitation of delivery systems for poorly water-soluble drugs. Int J Pharm. 2012;439(1–2):81–91.
  • Shen S-C, Ng WK, Chia L, et al. Physical state and dissolution of ibuprofen formulated by co-spray drying with mesoporous silica: effect of pore and particle size. Int J Pharm. 2011;410(1–2):188–195.
  • Hu Y, Wang J, Zhi Z, et al. Facile synthesis of 3D cubic mesoporous silica microspheres with a controllable pore size and their application for improved delivery of a water-insoluble drug. J Colloid Interface Sci. 2011;363(1): 410–417.
  • Xu W, Riikonen J, Lehto V-P. Mesoporous systems for poorly soluble drugs. Int J Pharm. 2013;453(1):181–197.

** Comprehensive review of the utilization of inorganic mesoporous materials in formulations of poorly water-soluble drugs to enhance their dissolution

  • Miura H, Kanebako M, Shirai H, et al. Stability of amorphous drug, 2-benzyl-5-(4-chlorophenyl)-6-[4-(methylthio)phenyl]-2H-pyridazin-3-one, in silica mesopores and measurement of its molecular mobility by solid-state 13C NMR spectroscopy. Int J Pharm. 2011;410(1–2):61–67.
  • Van Speybroeck M, Mellaerts R, Mols R, et al. Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica. Eur J Pharm Sci. 2010;41(5): 623–630.
  • Qi L, Ma J, Cheng H, et al. Micrometer-sized mesoporous silica spheres grown under static conditions. Chem Mater. 1998;10(6):1623–1626.
  • Slowing II, Vivero-Escoto JL, Wu C-W, et al. Mesoporous silica nanoparticles as controlled release drug delivery and gene transfection carriers. Adv Drug Deliv Rev. 2008;60(11):1278–1288.
  • Qu F, Zhu G, Huang S, et al. Controlled release of captopril by regulating the pore size and morphology of ordered mesoporous silica. Microporous Mesoporous Mater. 2006;92(1–3):1–9.
  • Manzano M, Aina V, Areán CO, et al. Studies on MCM-41 mesoporous silica for drug delivery: effect of particle morphology and amine functionalization. Chem Eng J. 2008;137(1):30–37.
  • Hu J, Rogers TL, Brown J, et al. Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology. Pharm Res. 2002;19(9):1278–1284.
  • Kumar D, Sailaja Chirravuri SV, Shastri NR. 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(1–2):459–468.
  • Song SW, Hidajat K, Kawi S. Functionalized SBA-15 materials as carriers for controlled drug delivery: influence of surface properties on matrix−drug interactions. Langmuir. 2005;21(21):9568–9575.
  • Balas F, Manzano M, Horcajada P, et al. Confinement and controlled release of bisphosphonates on ordered mesoporous silica-based materials. J Am Chem Soc. 2006;128(25):8116–8117.
  • Doadrio JC, Sousa EM, Izquierdo-Barba I, et al. Functionalization of mesoporous materials with long alkyl chains as a strategy for controlling drug delivery pattern. J Mater Chem. 2006;16(5):462–466.
  • Qu F, Zhu G, Huang S, et al. Effective controlled release of captopril by silylation of mesoporous MCM-41. Chem Phys Chem. 2006;7(2):400–406.
  • Tang Q, Yao X, Dong W, et al. Studies on a new carrier of trimethylsilyl-modified mesoporous material for controlled drug delivery. J Control Release. 2006;114(1):41–46.
  • Moritz M, Łaniecki M. SBA-15 mesoporous material modified with APTES as the carrier for 2-(3-benzoylphenyl) propionic acid. Appl Surf Sci. 2012;258(19):7523–7529.
  • Guo Z, Liu X-M, Ma L, et al. Effects of particle morphology, pore size and surface coating of mesoporous silica on naproxen dissolution rate enhancement. Colloids Surf B Biointerfaces. 2013;101:228–235.
  • Nastase S, Bajenaru L, Matei C, et al. Ordered mesoporous silica and aluminosilicate-type matrix for amikacin delivery systems. Microporous Mesoporous Mater. 2013;182:32–39.
  • Carmona D, Balas F, Santamaria J. Pore ordering and surface properties of FDU-12 and SBA-15 mesoporous materials and their relation to drug loading and release in aqueous environments. Mater Res Bull. 2014;59:311–322.
  • Jambhrunkar S, Qu Z, Popat A, et al. Modulating in vitro release and solubility of griseofulvin using functionalized mesoporous silica nanoparticles. J Colloid Interface Sci. 2014;434:218–225.
  • Yoncheva K, Popova M, Szegedi A, et al. Functionalized mesoporous silica nanoparticles for oral delivery of budesonide. J Solid State Chem. 2014;211:154–161.
  • Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci. 1997;86(1):1–12.
  • Morris KR, Griesser UJ, Eckhardt CJ, et al. Theoretical approaches to physical transformations of active pharmaceutical ingredients during manufacturing processes. Adv Drug Deliv Rev. 2001;48(1):91–114.
  • Limnell T, Riikonen J, Salonen J, et al. Surface chemistry and pore size affect carrier properties of mesoporous silicon microparticles. Int J Pharm. 2007;343(1–2):141–147.
  • Limnell T, Heikkilä T, Santos HA, et al. Physicochemical stability of high indomethacin payload ordered mesoporous silica MCM-41 and SBA-15 microparticles. Int J Pharm. 2011;416(1):242–251.
  • Qian K, Wurster D, Bogner R. Spontaneous crystalline-to-amorphous phase transformation of organic or medicinal compounds in the presence of porous media, part 3: effect of moisture. Pharm Res. 2012;29(10):2698–2709.
  • Hailu SA, Bogner RH. Complex effects of drug/silicate ratio, solid-state equivalent pH, and moisture on chemical stability of amorphous quinapril hydrochloride coground with silicates. J Pharm Sci. 2011;100(4):1503–1515.
  • Pan X, Julian T, Augsburger L. Increasing the dissolution rate of a low-solubility drug through a crystalline-amorphous transition: a case study with indomethicin. Drug Dev Ind Pharm. 2008;34(2):221–231.
  • Bahl D, Bogner R. Amorphization of indomethacin by co-grinding with Neusilin US2: amorphization kinetics, physical stability and mechanism. Pharm Res. 2006;23(10):2317–2325.
  • Mellaerts R, Roeffaers MBJ, Houthoofd K, et al. Molecular organization of hydrophobic molecules and co-adsorbed water in SBA-15 ordered mesoporous silica material. Phys Chem Chem Phys. 2011;13(7): 2706–2713.
  • Shalaev EY, Zografi G. How does residual water affect the solid‐state degradation of drugs in the amorphous state? J Pharm Sci. 1996;85(11):1137–1141.
  • Byrn SR, Xu W, Newman AW. Chemical reactivity in solid-state pharmaceuticals: formulation implications. Adv Drug Deliv Rev. 2001;48(1):115–136.
  • Siepmann J, Siepmann F. Mathematical modeling of drug dissolution. Int J Pharm. 2013;453(1):12–24.
  • Vialpando M, Martens JA, Van den Mooter G. Potential of ordered mesoporous silica for oral delivery of poorly soluble drugs. Ther Deliv. 2011;2(8):1079–1091.
  • Wang S. Ordered mesoporous materials for drug delivery. Microporous Mesoporous Mater. 2009;117(1):1–9.
  • Xue JM, Shi M. PLGA/mesoporous silica hybrid structure for controlled drug release. J Control Release. 2004;98(2):209–217.
  • Bui TX, Choi H. Adsorptive removal of selected pharmaceuticals by mesoporous silica SBA-15. J Hazard Mater. 2009;168(2):602–608.
  • Turku I, Sainio T, Paatero E. Thermodynamics of tetracycline adsorption on silica. Environ Chem Lett. 2007;5(4):225–228.
  • Ahern RJ. Application of mesoporous silica for the oral delivery of poorly water soluble drugs, in school of pharmacy. Ireland: University College Cork; 2013.
  • Atkin R, Craig VSJ, Wanless EJ, et al. Mechanism of cationic surfactant adsorption at the solid–aqueous interface. Adv Colloid Interface Sci. 2003;103(3):219–304.
  • Guzman HR, Tawa M, Zhang Z, et al. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. J Pharm Sci. 2007;96(10):2686–2702.
  • Vandecruys R, Peeters J, Verreck G, et al. Use of a screening method to determine excipients which optimize the extent and stability of supersaturated drug solutions and application of this system to solid formulation design. Int J Pharm. 2007;342(1):168–175.
  • Mellaerts R, Mols R, Kayaert P, et al. Ordered mesoporous silica induces pH-independent supersaturation of the basic low solubility compound itraconazole resulting in enhanced transepithelial transport. Int J Pharm. 2008;357(1–2):169–179.
  • Mellaerts R, Mols R, Jammaer JAG, et al. Increasing the oral bioavailability of the poorly water soluble drug itraconazole with ordered mesoporous silica. Eur J Pharm Biopharm. 2008;69(1):223–230.
  • Vialpando M, Aerts A, Persoons J, et al. Evaluation of ordered mesoporous silica as a carrier for poorly soluble drugs: influence of pressure on the structure and drug release. J Pharm Sci. 2011;100(8):3411–3420.
  • Kiekens F, Eelen S, Verheyden L, et al. Use of ordered mesoporous silica to enhance the oral bioavailability of ezetimibe in dogs. J Pharm Sci. 2012;101(3):1136–1144.
  • Peng T, Zhu C, Huang Y, et al. Improvement of the stability of doxycycline hydrochloride pellet-containing tablets through a novel granulation technique and proper excipients. Powder Technol. 2015;270, (Part A): 221–229.
  • Vialpando M, Backhuijs F, Martens JA, et al. Risk assessment of premature drug release during wet granulation of ordered mesoporous silica loaded with poorly soluble compounds itraconazole, fenofibrate, naproxen, and ibuprofen. Eur J Pharm Biopharm. 2012;81(1): 190–198.

* Informative report on manufacturing challenges

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.