Mesoporous Silica: for solubility enhancement of challenging compounds

Mesoporous Silica: An Emerging Solubility Enhancement Technology

Mesoporous silica refers to any number of a variety of materials synthesised to produce a SiO2 mesoporous structure1. Mesoporous silica can be ordered or non-ordered2, 3. The former include classic structures such as SBA-15 and MCM-414, whilst the latter include novel, proprietary excipients manufactured by drug delivery specialists, such as Parteck® SLC5,6. It has been widely reported that mesoporous silica can act as a solubility enhancer by adsorbing and stabilizing active pharmaceutical ingredients (APIs) in the amorphous form within the porous network5, 6, 7, 8, 9, 10.

Example of a commercially available unordered mesoporous silica, Parteck® SLC excipient, including key particle properties. (* bulk density of 30% w/w ibuprofen-loaded silica)
Example of a commercially available unordered mesoporous silica, Parteck® SLC excipient, including key particle properties. (* bulk density of 30% w/w ibuprofen-loaded silica)

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Loading APIs onto Mesoporous Silica

There are various methods of loading crystalline API onto mesoporous silica, which can be grouped into three broad categories: solvent-based5, mechanical activation11 and vapour-mediated (e.g. via sc-CO2)12. Although a wide variety of methods are present in the literature; generally speaking, the solvent-based approach is most commonly employed (Figure 2). These solvent approaches can be sub-grouped into two main categories: solvent impregnation and incipient wetness. During the solvent impregnation loading approach, API is dissolved in organic solvent (thus removing any crystal lattice) and added to mesoporous silica. Adsorption of API onto the silica is then initiated through mechanical agitation or sonication of the slurry. Finally, solvent is removed, which can be achieved using a number of methods including vacuum drying, spray drying, lyophilization or rotary evaporation5, 13, 14, 15. The second approach, incipient wetness, involves the steady addition of small volumes of concentrated API solution onto the heated silica. As a result, the full amount of solvent is adsorbed into the network and then rapidly evaporated, leaving the API within the pores6, 9. Both methods result in an API-loaded silica, in which the previously crystalline API is now amorphous or molecularly dispersed. Success can then be confirmed with analytical methods such as DSC or PXRD.

Solvent based loading of poorly soluble API onto mesoporous silica results in pore adsorption and nanoconfinement of the molecularly dispersed API, providing a stabilized amorphous solid form.
Solvent based loading of poorly soluble API onto mesoporous silica results in pore adsorption and nanoconfinement of the molecularly dispersed API, providing a stabilized amorphous solid form.

Recently, efforts by mesoporous silica manufacturer Merck KGaA, Darmstadt, Germany and contract development and manufacturing company Hovione FarmaCiencia SA, Lisboa, Portugal have described the commercial-scale loading of ibuprofen onto mesoporous silica. This was achieved in a 100 kg batch using standard manufacturing equipment and to a high degree of control.

Dissolution and Bioavailability Enhancement with Mesoporous Silica

Upon contact with aqueous medium, API loaded in mesoporous silica is released. As the drug is in the amorphous form, supersaturation can be generated, which can enhance oral bioavailability6. Due to the very high energy associated with the supersaturated state, mesoporous formulations are often coupled with precipitation inhibitors, (Figure 3). This is the basis of the spring and parachute model first proposed by Guzman, and is common when considering formulations that generate supersaturation16.

FaSSIF (pH 6.5) non-sink dissolution of glibenclamide (yellow), glibenclamide loaded silica (pink) and glibenclamide loaded silica + amino methacrylate copolymer (purple) showing the spring-parachute profile of API loaded silica and API loaded silica in combination with polymeric precipitation inhibitors. Data reproduced from Price et al. 2019. (Price, 2019).
FaSSIF (pH 6.5) non-sink dissolution of glibenclamide (yellow), glibenclamide loaded silica (pink) and glibenclamide loaded silica + amino methacrylate copolymer (purple) showing the spring-parachute profile of API loaded silica and API loaded silica in combination with polymeric precipitation inhibitors. Data reproduced from Price et al. 2019. (Price, 2019).

In this, the mode of action of mesoporous silica is analogous to spray dried dispersions (SDDs) and hot melt extrusion (HME).  However, the entire loading process can be achieved with common-place laboratory equipment and does not require expensive spray driers or extruders, this makes for a very attractive formulation option from an industrial perspective5. Furthermore, scaling of this technology is feasible and offered by commercial-scale CDMO companies.

Unparalleled Amorphous Stability

One of the potential benefits of mesoporous silica relative to alternative amorphous formulations, is the high stabilities that are achievable. This is due to the energetic favorability of the loaded system; the very small environment of the mesoporous network (so-called ‘nano-confinement’)17 and complimentary interactions (yet to be fully resolved) with the silica surfaces, which lower the free energy of the system further18. API-loaded silica can often be stored in open containers and at elevated temperatures and pressures, though this too can be API-dependent. Muller and co-workers demonstrated stability of the amorphous form at ambient and accelerated conditions for 30 different formulations of API-loaded silica, exceeding the requirements for regulatory stability studies19. This could be particularly used for compounds that have high tendency to re-crystallise (poor glass-formers)19.1, where stability problems may arise with alternative formulations such as SDDs4, 20, 21.

This is underlined in the physical chemistry of drug adsorption of APIs to mesoporous silica. Crucially, it has been shown in various scientific papers that this process reduced the types of molecular mobility associated with re-crystallization. For example, it was demonstrated how menthol could be successfully loaded onto mesoporous silica in the amorphous form due to a reduction in beta relaxation. Menthol is especially unstable in the amorphous form, with a glass transition temperature of -54.3°C, an extremely poor glass former22. This was also observed with the small molecule, ibuprofen, where nanoconfinement in mesoporous silica substantially reduced all types of molecular mobility even in the presence of elevated temperatures and moisture.

Nanoconfinement and reduction of molecular mobility make mesoporous silica the prime candidate to stabilize extremely unstable compounds, poor glass formers, in the amorphous form. Recent work by Ditzinger and Price demonstrated this application of mesoporous silica experimentally. In their study, the two poor glass formers haloperidol and carbamazepine were formulated with both mesoporous silica and polymeric amorphous solid dispersion. These formulations were then stored under accelerated stability conditions, where it was observed that both APIs remained amorphous when formulated with mesoporous silica. For HME, on the other hand, re-crystallization was observed after only one month22.1.


In conclusion, mesoporous silica is an exciting prospect to add to the formulator’s toolbox when considering poorly soluble APIs. Mesoporous silica has particular advantages in pre-clinical development due to the low capital investment requirements and relatively accessible loading method. The loading of mesoporous silica can be achieved using simple laboratory equipment and scaled to commercial batches using regular manufacturing equipment. Finally, recent developments have established mesoporous silica as a best-in-class excipient for stabilization of poor glass forming APIs. This has solidified mesoporous silica’s future as an excipient to formulate poorly soluble molecules that are challenging to stabilize with standard amorphous technologies.

Illustrative Blog Post for – Prepared by Merck KGaA, Darmstadt, Germany by Daniel Joseph Price. The life science business of Merck KGaA, Darmstadt, Germany operates as MilliporeSigma in the U.S. and Canada. — All Rights Reserved

Daniel Joseph Price is technical product manager for Merck Life Science’s SAFC(R) portfolio of solubility enhancement and sustained release excipients with profound expertise in mesoporous silica and thermodynamics of amorphous systems.

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1 – Ambrogi, V. et al. Use of SBA-15 for furosemide oral delivery enhancement. European Jourlan of Pharmaceutical Science. 2012; 46(1-2): 43-48

2 – Barbe, C. et al. Silica particles: A Novel Drug Delivery System. Advanced Materials. 2004; 16:1959-1966.

3 – Kresse, C.T. et al. Ordered Mesoporous Molecular Sieves Synthesized by a Liquid-crystal Template Mechanism. Nature. 1992; 359: 710-712.

4 – Mellaerts, R. et al. Aging Behaviour of Pharmaceutical Formulations of Itraconazole on SBA-15 Ordered Mesoporous Silica Carrier Material. Microporous and Mesoporous Materials. 2010; 180(1-3):154-161.

5 – Laine, A.L. et al. Enhanced oral delivery of celecoxib via the development of a supersaturable amorphous formulation utilising mesoporous silica and co-loaded HPMCAS. International Journal of Pharmaceutical Sciences. 2016; (1):118-25

6 – O’Shea, J.P et al. Mesoporous silica-based dosage forms improve bioavailability of poorly soluble drugs in pigs: case example fenofibrate. Journal of Pharmacy and Pharmacology. 2017 (epub ahead of print)

7 – drfebroeck, M. et al. Enhanced absorption of the poorly soluble drug fenofibrate by tuning its release rate from ordered mesoporous silica. European Journal of Pharmaceutical Sciences. 2010; 41(5): 623-630

8 – M. Vialpando, J.A.  et al.  Use of ordered mesoporous silica for oral delivery of poorly soluble drugs. Therapeutic Delivery. 2011; 2(8): 1079-1091

9 – Dressman, B. et al. Mesoporous silica-based dosage forms improve release characteristics of poorly soluble drugs: case example fenofibrate. Journal of Pharmacy and Pharmacology. 2015; 68(5): 634-645

10 – Xu, W. et al. Mesoporous systems for poorly soluble drugs. International Journal of Pharmaceutics. 2013; 453(1): 181-197

11 – Qian KK, and Bogner RH. Spontaneous crystalline-to-amorphous phase transformation of organic or medicinal compounds in the presence of porous media, part 1: Thermodynamics of spontaneous amorphization. Journal of Pharmaceutical Science. 2011; 100(7): 2801-2815.

12 – Zhang, Z. et al. Loading amorphous Asarone in mesoporous silica SBA-15 through supercritical carbon dioxide technology to enhance dissolution and bioavailability. European Journal of Pharmaceutics and Biopharmaceutics. 2015; 92: 28-31

13 – Wei, Q. et al. Oral hesperidin-Amorphization and improved dissolution properties by controlled loading onto porous silica. International Journal of Pharmacy. 2017; 518(1-2): 253-263

14 – Limnell, T. et al. Drug Delivery Formulations of Ordered and Nonordered Mesoporous Silica: Comparisons of Three Drug Loading Methods. Journal of Pharmaceutical Sciences. 2011; 100(8): 3294-3306.

15 – Meer, T. et al. Solubility modulation of bicalutamide using porous silica. Journal of Pharmaceutical Investigation. 2013; 43: 7

16 – Guzman, H.R. et al. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. Journal of Pharmaceutical Sciences. 2007; 96(10): 2686-2702

17 – Sliwinska-Bartkowiak, et al. Freezing behavior in porous glasses and MCM-41. Colloids and Surfaces A: Phsyiochemical Engineering Aspects. 2001; 187: 523-529

18 – Azais, et al. Solid-State NMR Study of Ibuprofen Confined in MCM-41 Material. Chemistry of Materials. 2006; 18(26): 6382-6390

19 – Muller et al. CapsMorph: >4 Years Long-Term Stability of Industrially Feasible Amorphous Drug Formulations. Controlled Release Society, Honolulu, Hawaii, USA. 2013

19.1 – Baird, JA. et al. Classification System to Assess the Crystallization Tendency of Organic Molecules from Undercooled Melts. Journal of Pharmaceutical Sciences. 2010; 99: 3787–3806

20 – Salonen, J. et al. Mesoporous silicon in drug delivery applications. Journal of Pharmaceutical Sciences. 2008; 97(2)

21 – Williams, H.D. et al. Strategies to Address Low Drug Solubility in Discovery and Development. Pharmacological Reviews. 2013; 65: 315-499

22 – Cordeiro, T., Castiñeira, C., Mendes, D., Danède, F., Sotomayor, J., Fonseca, I.M., Gomes da Silva, M., Paiva, A., Barreiros, S., Cardoso, M.M., Viciosa, M.T., Correia, N.T., Dionisio, M., 2017. Stabilizing Unstable Amorphous Menthol through Inclusion in Mesoporous Silica Hosts. Mol. Pharm. 14, 3164–3177.

22.1 – Ditzinger, F. and Price, DJ. et al. Opportunities for Successful Stabilization of Poor Glass-Forming Drugs: A Stability-Based Comparison of Mesoporous Silica Versus Hot Melt Extrusion Technologies. Pharmaceutics. 2019; 11(577)

23 – Abd-Elrahman, A.A. et al. Ketoprofen mesoporous silica nanoparticles SBA-15 hard gelatin capsules: preparation and in vitro/in vivo characterization. Drug Delivery. 2016; 23(9): 3387-3398

24 – Aftab Alam, M. et al. Commercially bioavailable proprietary technologies and their marketed products. Drug Discovery Today. 2013; 18(19-20): 936-949

25 – Alhalaweh, A. et al. Physical stability of drugs after storage above and below the glass transition temperature: Relationship to glass-forming ability. International Journal of Pharmacy. 2015; 495(1): 312-317

26 – Ambrogi, V.M. et al. Improvement of dissolution rate of piroxicam by inclusion into MCM-41 mesoporous silicate. European Journal of Pharmaceutical Sciences. 2007; 32(3): 216-222

27- Andersson, J. et al. Influences of material characteristics on ibuprofen drug loading and release profiles from ordered micro- and mesoporous silica matrices. Chemistry of Materials. 2004; 16: 4160-4167

28 – Atkin, R. et al. Mechanism of cationic surfactant adsorption at the solid–aqueous interface. Advanced Colloid and Interface Sciences. 2003; 103(3): 219-304

29 – Bartsch, S. et al. Physicochemical properties of the binary system glibenclamide and polyethylene glycol 4000. Journal of Thermal Analysis and Calorimetry. 2005; 77(2)

30 – Bathfield, M. et al. Thermosensitive and Drug-Loaded Ordered Mesoporous Silica: A Direct and Effective Synthesis Using PEO-b-PNIPAM Block Copolymers. Chemistry of Materials. 2016; 28(10): 3374-3384

31 – Bhatnagar, A and Sillanpaa, M. Utilization of Agro-industrial and Municipal Waste Materials as Potential Adsorbents for Water Treatment- a Review. Chemical Engineering Journal. 2010; 157: 277-296.

32 – Biswas, N. Modified mesoporous silica nanoparticles for enhancing oral bioavailability and antihypertensive activity of poorly water soluble valsartan. European Journal of Pharmaceutical Science. 2017; 99: 152-160

33 – Bouchoucha, M. et al. Size-Controlled Functionalized Mesoporous Silica Nanoparticles for Tunable Drug Release and Enhanced Anti-Tumoral Activity. Chemistry of Materials. 2016; 28(12): 4243-4258

34 – Brás, A.R., Fonseca, I.M., Dionísio, M., Schönhals, A., Affouard, F., Correia, N.T., 2014. Influence of Nanoscale Confinement on the Molecular Mobility of Ibuprofen. J. Phys. Chem. C 118, 13857–13868

35 – Bukara, K. et al. Ordered mesoporous silica to enhance the bioavailability of poorly water-soluble drugs: Proof of concept in man. European Journal of Pharmaceutics and Biopharmaceutics. 2016; 108: 220-225

36 – Elder, J.P. A new accelerated oxidative stability test for glass-forming organic compounds. Thermochimica Acta. 1990; 166: 199-206

37 – Friesen, D.T. et al. Hydroxypropyl Methylcellulose Acetate Succinate-Based

38 – Fu, T. et al. Improving bioavailability of silybin by inclusion into SBA-15 mesoporous silica materials. Journal of Nanoscience and Nanotechnology. 2012; 12(5): 3997-4006

39 – Guzman, H.R. et al. Combined use of crystalline salt forms and precipitation inhibitors to improve oral absorption of celecoxib from solid oral formulations. Journal of Pharmaceutical Sciences. 2007; 96(10): 2686-2702

40 – Hacene. Y.C. et al. Drug loaded and ethylcellulose coated mesoporous silica for controlled drug release prepared using a pilot scale fluid bed system. International Journal of Pharmacy. 2016; 506: 132-147

41 – Hartono, S.B. et al.  Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement. Nanotechnology. 2016; 27(50):

42 – Heikkila, T. et al. Evaluation of mesoporous TCPSi, MCM-41, SBA-15, and TUD-1 materials as API carriers for oral drug delivery. Drug Delivery. 2007; 14(6): 337-347

43 – Higuchi, T. Rate of Release of Medicaments from Ointment Bases Containing Drugs in Suspension. Journal of Pharmaceutical Sciences. 1961; 50(10): 874-875

44 – Hillerstrom, A, et al. Solvent strategies for loading and release in mesoporous silica. Colloid and Interface Science Communications. 2014; 3: 5-8

45 – Horcajada, P. et al. Influence of pore size of MCM-41 matrices on drug delivery rate. Microporous and Mesoporous Materials. 2004; 68: 105-109

46 – Hu, L. et al. Multilayer encapsulated mesoporous silica nanospheres as an oral sustained drug delivery system for the poorly water-soluble drug felodipine. Materials Science and Engineering: C. 2015; 47: 313-324

47 – Hu. Y. et al. 3D cubic mesoporous silica microsphere as a carrier for poorly soluble drug carvedilol. Microporous and Mesoporous Materials. 2012; 147(1): 94-101

48 – Khanfar, M. and Al-Nimry, S. Stabilization and Amorphization of Lovastatin Using Different Types of Silica. AAPS PharmSciTech. 2017 (epub ahead of print)

49 – Kiekens, F. et al. Use of ordered mesoporous silica to enhance the oral bioavailability of ezetimibe in dogs. Journal of Pharmaceutical Science. 2012; 101: 1136-1144

50 – Kinnari, P. et al. Comparison of mesoporous silicon and non-ordered mesoporous silica materials as drug carriers for itraconazole. International Journal of Pharmaceutics. 2011; 414: 148-156

51 – Knapik, J. et al. Physical stability of the amorphous anticholesterol agent (ezetimibe): the role of molecular mobility. Molecular Pharmaceutics. 2014; 11(11): 4280-4290

52 – Kumar, D. et al.  Impact of surface area of silica particles on dissolution rate and oral bioavailability of poorly water soluble drugs: a case study with aceclofenac. International Journal of Pharmacy. 2014; 461(1-2): 459-468

53 – Lepek, P. et al. Effect of amorphization method on telmisartan solubility and the tableting process. European Journal of Pharmaceutics and Biopharmaceutics. 2013; 83(1): 113-121

54 – Letchmanan, K. et al. Dissolution and physicochemical stability enhancement of artemisinin and mefloquine co-formulation via nano-confinement with mesoporous SBA-15. Colloids and Surfaces B: Biointerfaces. 2017; 155: 560-568

55 – Li, Y. et al. In situ dehydration of carbamazepine dihydrate: a novel technique to prepare amorphous anhydrous carbamazepine. Pharmaceutical Development Technology. 2000; 5(2): 257-266

56 – Loodha, A. et al.  Synthesis of mesoporous silica nanoparticles and drug loading of poorly water soluble drug cyclosporin A. Journal of Pharmacy and Bioallied Sciences. 2012; 1: 92-94

57 – Lungare, al. Phytochemical-loaded mesoporous silica nanoparticles for nose-to-brain olfactory drug delivery. International Journal of Pharmacy. 2016; 513(1-2): 280-293

58 – Majors, R.E. High Performance Liquid Chromatography on Small Particle Silica Gel. Analytical Chemistry. 1972; 44: 1722-1726.

59 – Maleki, A. et al. 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 Drug Delivery. 2016; 13(2): 171-181

60 – McCarthy, C.A. et al. Mesoporous silica formulation strategies for drug dissolution enhancement: a review. Expert Opinion on Drug Delivery. 2015; 13

61 – Mellaerts, R. et al. In situ FT-IR investigation of etravirine speciation in pores of SBA-15 ordered mesoporous silica material upon contact with water. Molecular Pharmaceutics. 2013; 10(2): 567-573

62 – Nielsen, L.H. et al. Stabilisation of amorphous furosemide increases the oral drug bioavailability in rats. International Journal of Pharmacy. 2015; 490(1-2): 334-340

63 – Pawar, Y. B. et al. Phase behavior and oral bioavailability of amorphous Curcumin. European Journal of Pharmaceutics and Biopharmaceutics. 2012; 47(1): 56-64

64 – Price, D.J., Nair, A., Kuentz, M., Dressman, J., Saal, C., 2019b. Calculation of drug-polymer mixing enthalpy as a new screening method of precipitation inhibitors for supersaturating pharmaceutical formulations. Eur. J. Pharm. Sci. 132, 142–156.

65 – Saad, A. Triazole/Triazine-Functionalized Mesoporous Silica As a Hybrid Material Support for Palladium Nanocatalyst. Langmuir. 2017 (epub ahead of print)

66 – Salonen, J. et al. Mesoporous silicon microparticles for oral drug delivery: loading and release of five model drugs. Journal of Controlled Release. 2005; 108: 362-374

67 – Shete, G. et al. Solid State Characterization of Commercial Crystalline and Amorphous Atorvastatin Calcium Samples. AAPS PharmSciTech. 2010; 11(2): 598-609

68 – Shete, G. Molecular Relaxation Behavior and Isothermal Crystallization above Glass Transition Temperature of Amorphous Hesperetin. Journal of Pharmaceutical Sciences.  2014; 103(1): 167-178

69 – Siepmann, J. et al. Higuchi equation: Derivation, applications, use and misuse. International Journal of Pharmaceutics. 2011; 418(1): 6-12

70 – Skotnicki, M. et al. Thermal behavior and phase identification of Valsartan by standard and temperature-modulated differential scanning calorimetry. Drug Development and Industrial Pharmacy. 2013; 39(10): 1508-1514

71 – Spray-Dried Dispersions: An Overview. Molecular Pharmaceutics. 2008; 5(6): 1003-1019

72 – Summerlin, N. et al. Colloidal mesoporous silica nanoparticles enhance the biological activity of resveratrol. Colloids and Surfaces B: Biointerfaces. 2016; 144: 1-7

73 – Thomas, M.J.K. et al. Inclusion of poorly soluble drugs in highly ordered mesoporous silica nanoparticles. International Journal of Pharmaceutics. 2010; 387(1-2): 272-277

74 – Tozuka, Y. et al. Effect of pore size of FSM-16 on the entrapment of flurbiprofen in mesoporous structures. Chemical and Pharmaceutical Bulletin. 2005; 53: 974-977

75 – Trasi, N. S. et al. Mechanically Induced Amorphization of Drugs: A Study of the Thermal Behavior of Cryomilled Compounds. AAPS PharmSciTech. 2012; 13(3): 772-784

76 – Turku, et al. Thermodynamics of tetracycline adsorption on silica. Environmental Chemistry Letters. 2007; 5(4): 225-228

77 – Vadia, N. et al. Study on formulation variables of methotrexate loaded mesoporous MCM-41 nanoparticles for dissolution enhancement. European Journal of Pharmaceutics and Biopharmaceutics. 2012; 45(1-2): 8-18

78 – Vallet-Regi M. Ordered Mesoporous Materials in the Context of Drug Delivery and Tissue Engineering. Chemistry: A European Journal. 2010; 27:5593-5604.

79 – Vallet-Regi, M. et al. Drug Confinement and Delivery in Ceramic Implants. Drug Metabolism Letters. 2007; 1: 37-40

80 – Van Speybroeck, M. et al. Ordered mesoporous silica material SBA-15: a broad-spectrum formulation platform for poorly soluble drugs. Journal of Pharmaceutical Science. 2009; 98: 2648-2658

81 – Van Speybroeck, M. 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. Journal of Pharmaceutical Sciences. 2011; 100(11): 4864-4876

82 – Van Speybroeck, M. et al., Combined use of ordered mesoporous silica and precipitation inhibitors for improved oral absorption of the poorly soluble weak base itraconazole. European Journal of Pharmaceutics and Biopharmaceutics. 2010; 75(3): 354-365

83 – Wang, F. et al. Oxidized mesoporous silicon microparticles for improved oral delivery of poorly soluble drugs. Molecular Pharmaceutics. 2010; 7: 227-236

84 – Wang, F. et al. Oxidized mesoporous silicon microparticles for improved oral delivery of poorly soluble drugs. Molecular Pharmaceutics. 2010; 226: 81-91

85 – Wang, S. Ordered Mesoporous Materials for Drug Delivery. Microporous Materials, 2009; 117: 1-9.

86 – Wang, Z. et al. Increasing the oral bioavailability of poorly water-soluble carbamazepine using immediate-release pellets supported on SBA-15 mesoporous silica. International Journal of Nanomedicine. 2012; 7: 5807-5818

87 – Wang. Y. et al. The investigation of MCM-48-type and MCM-41-type mesoporous silica as oral solid dispersion carriers for water insoluble cilostazol. Drug Development and Industrial Pharmacy. 2014; 40(6): 819-828

88 – Watanabe T, et al. Solid state radical recombination and charge transfer across the boundary between indomethacin and silica under mechanical stress. Journal of Solid State Chemistry. 2000; 164(1): 27-33.

89 – Weuts, I. et al. Physicochemical Properties of the Amorphous Drug, Cast Films, and Spray Dried Powders to Predict Formulation Probability of Success for Solid Dispersions: Etravirine. Pharmaceutical Technology. 2010; 100(1)

90 – Wu, Z. et al. Effects of surface coating on the controlled release of vitamin B1 from mesoporous silica tablets. Journal of Controlled Release. 2007; 119(2): 215-221

91 – Wyttenbach, N. et al. Theoretical Considerations of the Prigogine−Defay Ratio with Regard to the Glass-Forming Ability of Drugs from Undercooled Melts. Molecular Pharmaceutics. 2016; 13: 241-250

92 – Xia, X. et al. Encapsulation of Anti-Tuberculosis Drugs within Mesoporous Silica and Intracellular Antibacterial Activities. Nanomaterials. 2014; 4(3): 813-826

93 – Xia, X. et al. In vivo enhancement in bioavailability of atazanavir in the presence of proton-pump inhibitors using mesoporous materials. ChemMedChem. 2012; 7: 43-48

94 – Zhang, H. et al. Synthesis of novel mesoporous silica nanoparticles for loading and release of ibuprofen. Journal of Controlled Release. 2011; 30

95 – Zhao, et al. Uniform mesoporous carbon as a carrier for poorly water soluble drug and its cytotoxicity study. European Journal of Pharmaceutics and Biopharmaceutics. 2012; 80: 535-543

96 – Zhao, W. et al. Uniform rattle-type hollow magnetic mesoporous spheres as drug delivery carriers and their sustained-release property. Advanced Functional Materials. 2008; 18: 2780-2788

97 – Zhu, L. et al. Fast surface crystallization of amorphous griseofulvin below Tg. Pharmaceutical Research. 2010; 27(8): 1558-1567