Effect of Pore Size of FSM-16 on the Entrapment of Flurbiprofen in Mesoporous Structures

Abstract

The improvement of bioavailability of poorly water-soluble drugs is important for oral administration. Amorphization is one of the techniques that has been commonly used for solubility enhancement.1,2) Amorphous material of drug can be obtained by several methods, e.g., spray-drying, 3) solid dispersion, 4) co-grinding with cyclodextrins 5) or crystalline cellulose, 6) and mixing with porous materials. 7,8) Porous materials have a unique capacity to adsorb organic compounds due to their large specific surface area and porous structure. Activated carbon, porous crystalline cellulose, and zeolites are examples of porous materials that have been used widely for pharmaceuticals. [9][10][11] Folded sheets mesoporous material (FSM-16) has been synthesized by an intercalation of quaternary ammonium surfactant as a template in a layered polysilicate kanemite, followed by calcination.12-16) FSM-16 is composed of hexagonal channels and has extremely large specific surface area and large pore volume. Due to its highly uniform porous structure with hexagonal arrays, FSM-16 is widely used as a reactor for catalytic reaction, as an adsorbent and as a host for the inclusion of large molecules. 17,18) Itoh et al. 19) studied the photostability of chlorophyll a after adsorption into FSM-16. The enhancement of the photostability was attributable to the interactions between chlorophyll and FSM-16 to form chlorophyll-FSM conjugate, and also between two chlorophyll molecules to form a chlorophyll dimer within the pores of FSM-16.In the previous paper, we investigated the use of FSM-16 for pharmaceutical applications. We reported the change in molecular state of salicylamide from crystal to amorphous by adsorption into the FSM-16 channels during sealed-heating process. The amorphization of the drug accordingly resulted in enhanced dissolution of sealed-heated sample. 20) In the present study, three kinds of FSM-16 with different pore diameters [FSM-16(Oc), FSM-16(Do) and FSM-16(Doc)] were employed to investigate the molecular state of the drug and its interaction with FSM-16. Flurbiprofen (FBP), a poorly water-soluble non-steroidal anti-inflammatory drug, was used as a model compound. Changes in the molecular state of FBP were investigated using powder X-ray diffractometry, thermal analysis and FT-IR spectroscopy. The changes in pore diameter and specific surface area of samples prepared by various methods were investigated using small angle X-ray scattering and nitrogen gas adsorption BET method for understanding the effect of adsorption of FBP molecules on pore structure of FSM-16. ExperimentalMaterials Flurbiporfen (FBP) of reagent grade was kindly supplied by Kaken Pharmaceutical, Co. Ltd., Japan, and was used without further purification. Three kinds of mesoporous silica FSM-16, i.e., FSM-16(Oc), FSM-16(Do) and FSM-16(Doc), were kindly supplied by Toyota Central R&D Labs., Inc., Japan. Mean pore width and specific surface area of FSM-16(Oc), FSM-16(Do), FSM-16(Doc) were 16.0, 21.6, 45.0 Å and 700, 1250, 1040 m 2 /g, respectively...

Submicron Particles of SBA-15 Modified with MgO as Carriers for Controlled Drug Delivery

“…[8][9][10] The large pore volume allows high drug loading into the ordered matrix. The large surface area of the internal surface can be modified according to specific purposes for different drugs association on the surface of matrix.…”

Release profile of insulin entrapped on mesoporous materials by freeze–thaw method

“…The decrease in the mean pore width was considered to be a result of the shrinkage of FSM mesopores due to the formation of hydrogen bonds between flurbiprofen and FSM in the solid dispersions. The existence of adsorbed flurbiprofen layers was proposed from the decrease in the specific surface area and pore volume of mesoporous silica (Tozuka et al, 2005). Our findings from nitrogen sorption isotherms suggested that insulin molecules were entrapped in the mesopores of FSMs after the samples were freeze-thawed 10 times.…”

Dendritic cell internalization of foam-structured fluorescent mesoporous silica nanoparticles

“…Recently, other MSN porous structures, including the spherical structures, the hierarchically porous structures, and single-crystal structures, were produced by different methods, e.g. sol-gel [9,10], microemulsion [11,12], and template [13,14]. The porous nature of the MSNs allows them to be loaded with different types of molecules.…”