Adsorption and in vitro release of vitamin B1 by synthetic nanoclays with montmorillonite structure

Applied Clay Science 112–113 (2015) 10–16

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Research paper

Adsorption and in vitro release of vitamin B1 by synthetic nanoclays with montmorillonite structure Olga Yu. Golubeva ⁎, Svetlana V. Pavlova, Alexander V. Yakovlev Institute of Silicate Chemistry, Russian Academy of Sciences, Adm. Makarova emb., 2, St. Petersburg, 199034 Russia

a r t i c l e

i n f o

Article history: Received 24 October 2014 Received in revised form 19 March 2015 Accepted 17 April 2015 Available online 25 May 2015 Keywords: Montmorillonite Synthetic clays Hydrothermal synthesis Vitamin B1 Adsorption In vitro release

a b s t r a c t Modelling experiments on vitamin B1 (thiamine hydrochloride) intercalation into synthetic montmorillonite (Mt) structures of the systematically varied compositions Na2x(Al2(1–x),Mg2x)Si4O10(OH)2 ∙ nH2O (where 0 b x b 1) were performed. Mt samples were prepared by hydrothermal synthesis during 72 h at the temperature 350 °C and a pressure of 70 MPa. In vitro release of vitamin B1 (VB1) in simulated gastric (SGF) and intestinal (SIF) fluids was performed. It was established that the intercalation of VB1 depends primarily on the composition and cation-exchange capacity of Mt and, to a lesser extent, on the pH of the solution. The adsorption data were fitted with several common isotherms, but the best regression parameters were obtained for the Langmuir model. Adsorption type was determined as the cation-exchange reaction according to the Dubinin–Radushkevich model. The release profile of VB1 from the VB1–Mt composite followed the Higuchi model. The maximum amount of released VB1 reached 54 wt.% and 19 wt.% in SGF and SIF, respectively, for synthetic Mt. For natural Mt K10, these values reached 37 wt.% and 11 wt.%, respectively. For the first time, the optimal Mt compositions for further drug delivery systems development were chosen. © 2015 Elsevier B.V. All rights reserved.

1. Introduction One of the most important problems in medicine today is the targeted delivery of drugs in an organism with subsequent controllable release. In recent years, a drug carrier of choice has been the family of layered silicates with Mt structure. For example, experiments have been performed on the delivery of the following substances: anticancer drugs (5-fluorouracil (Lin et al., 2002), paclitaxel (Dong and Feng, 2005), tamoxefin (Kevadiya et al., 2012), citostatic drugs (Iliescu et al., 2011)), nonsteroidal anti-inflammatory drugs (ibuprofen (Zheng et al., 2007) and phenyl salicylate (Hoyo et al., 1996)), antibiotics (metronidazole (Calabrese et al., 2013)), anaesthetic drugs (Kevadiya et al., 2011), antihistaminic drugs (promethazine (Seki and Kadir, 2006)), indispensable amino acids (histidine, methionine, lysine, tryptophan, and glycine) (Kollar et al., 2003), and antidepressants (amitriptyline (Chang et. al, 2014)). The use of Mt as a carrier is due to its structural properties, including the imperfection of its crystal lattice and its isomorphous substitution both in the octahedral and tetrahedral sheets. These substitutions produce a negative charge on the layers that results in the adsorption of cations in the interlayer space. Such imperfections are responsible for the possibility of exchange reactions with organic and biological molecules. Moreover, Mt has essential properties, such as ⁎ Corresponding author at: Institute of Silicate Chemistry of Russian Academy of Sciences, Adm. Makarova emb., 2, St. Petersburg, 199034 Russia. Tel./fax: +7 812 325 21 11. E-mail addresses: [email protected], [email protected] (O.Y. Golubeva).

http://dx.doi.org/10.1016/j.clay.2015.04.013 0169-1317/© 2015 Elsevier B.V. All rights reserved.

chemical inertness, low toxicity and allergenicity (Lee et al., 2005), that offer great promise for the solution of a variety of medical problems. In the studies mentioned above, natural Mt were used. However, natural clays differ in their chemical and mineralogical compositions, depending on their source mines, in ways that affect their characteristics, such as surface charge, surface area, cation-exchange capacity (CEC), and structural and microstructural parameters. This limits the usage of natural Mt in a number of areas that require precise control of these characteristics, for example, in catalysis and medicine, because it is impossible to perform precise comparative analyses and to trace the dependence of the described Mt properties on the composition. In the present study, Mt were produced by hydrothermal synthesis, which makes it possible to obtain compounds with given compositions, particle sizes, and composition-dependent characteristics, such as the morphology of the particles, interlayer distance, specific surface area (SSA) and porosity (Golubeva et al., 2013). The possibility of obtaining synthetic Mt with various CEC, which can be achieved through controlled isomorphous substitution of cations into the octahedral and/or tetrahedral positions, is of practical interest. The aim of this study was to verify the possibility of using synthetic Mt as drug carriers, determine the optimal synthetic Mt compositions and compare these compositions with natural analogues. This paper addresses this task by modelling VB1 (Fig. 1) intercalation into synthetic Mt with various degrees of substitution of magnesium atoms into the octahedral positions of the aluminium atoms, as well as using experiments on in vitro release in simulated organismal media.

O.Y. Golubeva et al. / Applied Clay Science 112–113 (2015) 10–16

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2.3. Intercalation of VB1 VB1 intercalation was performed by the following method. First, 100 mg of Mt was dispersed in 20 ml of deionised water containing 100 mg of VB1. To study the influence of the pH on the character of VB1 adsorption, the pH values were varied from 2.0 to 8.0 using HCl and NaOH solutions. The pH values were measured by a pH meter (HANNA Instruments, USA). The experiments were performed under stirring at 50 °C for 1 h. Next, the dispersions were filtered, and the VB1 concentrations were determined by the same method as for the adsorption isotherm construction.

Fig. 1. VB1 structure.

2.4. Sample characterisation VB1 was selected as a water-soluble vitamin that has a direct impact on the energy metabolism of cells because it plays an important role in the metabolism of carbohydrates and lipids. The investigation of the sorption ability of synthetic Mt with various compositions makes it possible to select the optimal composition of the carrier and to define reaction conditions to permit effective intercalation of the drug into the interlayer space of Mt and its subsequent release.

2. Materials and methods 2.1. Materials Mt samples with the calculated composition Na2x(Al2(1–x),Mg2x)Si4O10 (OH)2∙nH2O (where 0 b x b 1) were prepared by hydrothermal synthesis during 72 h at a temperature of 350 °C and a pressure of 70 MPa (Golubeva et al., 2013). The initial gels for synthesis were prepared with the use of tetraethoxysilane TEOS ((C2H5O)4Si, special purity grade), Mg(NO3)2 · 6H2O (reagent grade), Al(NO3)3 · 9H2O (reagent grade), HNO3 (reagent grade, 65 wt.%), NH4OH (special purity grade), and ethanol. VB1 C12H17ClN4OS·HCl was purchased from Hubei Maxpharm Industries Co., Ltd., China. HCl, KCl, NaCl, NaOH, KH2PO4 and hexammine cobalt (III) chloride were purchased from NevaReaktiv, Russia. Mt K10 was purchased from Sigma-Aldrich, USA.

Chemical analysis of the initial Mt samples was performed gravimetrically for determination of the Si, Mg and Al content using an oxyquinoline silicomolybdic complex and the complexometric titration method. The sodium content in the samples was determined by flame photometry with an atomic absorption spectrometer iCE3000 (Thermo Electron Manufacturing Ltd., Cambridge, USA). Powder X-ray diffraction (PXRD) characterisation of all samples was performed on Bruker D8-Advance diffractometer (Bruker, Germany) with Cu Kα radiation in the 2θ range 4–65°. The average particle size was determined according to the Scherrer equation by the reflection band of 2θ = 19° (d110) that characterises the particles size in the plane perpendicular to the c axis. CEC was measured by the ion-exchange reaction with hexammine cobalt (III) ions [Co(NH3)6]3 + (Thomas et al., 1999). First, 500 mg of Mt samples was dispersed in 30 ml of a 0.05 M hexammine cobalt (III) chloride solution. The dispersion was stirred for 2 h and centrifuged twice. The equilibrium concentrations of hexammine cobalt (III) ions were determined by the UV–visible absorbance of the supernatant solutions at the wavelength 473 nm (LEKI SS2109UV spectrophotometer, LEKI Instruments, Russia). CEC values were taken as the average of three measurements. SSA of the samples was determined by the BET method by N2 adsorption using a NOVA 1200e Surface Area Analyzer (Quantachrome Instruments, USA). 2.5. In vitro release of VB1

2.2. Adsorption isotherms Adsorption isotherms were constructed at various initial concentrations of VB1 at a constant time and pH. First, 100 mg of Mt were dispersed in 20 ml of deionised water containing various amounts of VB1. The dispersions were mixed for 1 h (until equilibrium was established) at pH 6.4. The reaction mixtures were filtered, and the VB1 concentrations were determined in the filtrate by UV–visible spectroscopy at the wavelength 242 nm (Joshi et al., 2009). Each concentration was taken as the average of three measurements.

Gastric fluid was simulated by a buffer solution with pH = 1.2, prepared by mixing 250 ml of 0.2 M HCl and 147 ml of 0.2 M KCl. Intestinal fluid was simulated by a buffer solution with pH = 7.4, prepared by mixing 250 ml of 0.1 M KH2PO4 and 195.5 ml of 0.1 M NaOH. VB1 release was performed by the dissolution of 100 mg of the Mt– VB1 samples containing 30 ± 2 wt.% of VB1 and placing them in dialysis bags (3.5 kDa) (Orange Scientific, Belgium) in 300 ml of each medium in beakers under a rotation speed of 100 rpm. The temperature 37 ± 0.5 °С was maintained by a thermostatically controlled water bath. VB1 release

Table 1 Chemical compositions and characteristics of the synthetic Mt samples. Sample symbol

Composition by synthesis (omitting water)

Al 0 Al 0.2 Al 0.5 Al 0.7 Al 1.0 Al 1.6 Al 1.8

Mg3Si4O10(OH)2 Na1.8Al0.2Mg1.8Si4O10(OH)2 Na1.5Al0.5Mg1.5Si4O10(OH)2 Na1.3Al0.7Mg1.3Si4O10(OH)2 NaAlMgSi4O10(OH)2 Na0.4Al1.6Mg0.4Si4O10(OH)2 Na0.2Al1.8Mg0.2Si4O10(OH)2

a b

CEC – cation-exchange capacity. SSA – specific surface area.

Surface charge,

Oxide content by chemical analysis, %

x

SiO2

Al2O3

MgO

Na2O

0 0.9 0.75 0.65 0.5 0.2 0.1

54.11 58.10 56.01 53.89 53.00 47.53 56.96

0 5.32 12.08 14.12 22.82 32.17 24.81

32.52 18.31 13.73 12.51 8.04 2.50 2.10

0.11 3.52 3.47 3.16 2.69 3.20 2.99

CECa, meq 100 g−1

SSAb, m2 g−1

0 20 30 55 110 40 35

160 280 240 180 190 120 120

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Fig. 2. XRD patterns of the Mt samples: a – Al 0, b – Al 0.2, c – Al 0.5, d – Al 0.7, e – Al 1.0, f – Al 1.6, g – Al 1.8, h – K 10, ● – Mt, * – quartz, and ■ – muscovite.

from the Mt–VB1 composites was measured every 30 min by sampling 2 ml of the solution, followed by its renewal in the beaker to the original value. Each concentration was taken as the average of three measurements. The experiments were performed for 7 h, simulating the duration of the digestion. 2.6. Calculations 2.6.1. Adsorption isotherms The interaction between the adsorbate and adsorbent was determined by the equilibrium adsorption isotherms that were measured for all synthetic Mt as well as for the natural K10. The adsorption data were described by the Freundlich (1) and Langmuir (2) isotherms (Freundlich, 1906; Langmuir, 1916): C s ¼ K F C en ;

Fig. 4. Effect of pH on the intercalation of VB1 into Mt with the following compositions: ♦ Al 0, ◊ Al 0.2, □ Al 0.5, ■ Al 0.7, ○ Al 1.0, ▲ Al1.6, Δ Al 1.8 and ● K 10.

where Cm (mg g−1) and KL (L mg−1) are Langmuir constants related to the adsorption capacity and adsorption energy, which are calculated from the linear regression of Ce/Cs versus Ce. Another constant, the factor RL, which is considered as a more reliable indicator of adsorption (Annadurai et al., 2008), was calculated from: RL ¼ 1=ð1 þ K L C 0 Þ;

ð3Þ

where C0 (mg l−1) is the initial concentration in the liquid phase. Favourable adsorption is indicated by 0 b RL b 1. Next, in order to understand the nature of adsorption type, the Dubinin–Radushkevich equation was used (Dubinin and Radushkevich, 1947):

ð1Þ ln C s ¼ ln X m −kε2 ;

−1

where Cs (mg g ) is the amount of VB1 adsorbed onto the unit mass of Mt, Ce (mg l−1) is the equilibrium concentration of VB1 in solution, and n and KF (mg g−1) are the Freundlich's constants. C e =Cs ¼ ð1=C m K L Þ þ ð1=C m ÞC e ;

ð2Þ

where ε = RT ln(1 + 1 / Ce) is the Polanyi adsorption potential, R (kJ mol−1 K−1) is the gas constant, T (K) is temperature, Xm is the adsorption capacity and k is a constant related to adsorption energy through the following equation (Malik et al., 2005): − 0 :5

E ¼ −ð2kÞ

Fig. 3. XRD patterns of Mt Al 1.8 in the absence and in the presence of various VB1 concentrations.

ð4Þ

ð5Þ

Fig. 5. Comparison of CEC (♦) and the adsorbed amount of VB1 (■) for various Mt compositions with the general formula Na2x(Al2(1–x),Mg2x)Si4O10(OH)2∙ nH2O.

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Table 2 Adsorption isotherm parameters for VB1 adsorption on the Mt samples. Mt sample

Freundlich constants n

KF, mg g−1

R2

KL, L mg−1

Langmuir constants Cm, mg g−1

RL

R2

Al 0 Al 0.2 Al 0.5 Al 0.7 Al 1.0 Al 1.6 Al 1.8 K 10

0.031 0.025 0.022 0.021 0.027 0.016 0.011 0.030

88 112 165 185 191 145 172 30

0.9945 0.9862 0.9983 0.9732 0.9425 0.9734 0.9802 0.9596

0.41 0.28 0.60 0.11 0.02 0.71 3.19 0.31

2.7 3.7 4.5 5.9 8.2 4.1 4.3 0.8

0.0060 0.0060 0.0042 0.0020 0.0026 0.0023 0.0005 0.0080

0.9906 0.9912 0.9941 0.9860 0.9939 0.9986 0.9994 0.9803

The values of Xm, k and E are determined from the linear plot of ln Cs versus ε2. The value of E is useful for estimating the type of adsorption (Malik et al., 2005): when E is in the range 8–16 kJ mol−1, it can be assumed that the drug is adsorbed through the cation-exchange process. 2.6.2. Drug-release kinetics To analyse the in vitro release data, various kinetic models were used to describe the release kinetics. The zero-order rate model (Eq. (4)) describes systems in which the drug release rate is independent of its concentration (Dash et al., 2010). The first-order rate model (Eq. (5)) describes the release from systems in which the release rate is concentration dependent (Dash et al., 2010). The Higuchi model (Higuchi, 1963) describes the release of drugs from an insoluble matrix as the square root of time based on Fickian diffusion (Eq. (6)): C ¼ k0 t;

ð4Þ

where k0 is zero-order rate constant, and t is the time. LogC ¼ LogC 0 −k1 t=2:303;

ð5Þ

where C0 is the initial concentration of the drug, and k1 is the first-order rate constant. Q ¼ kH t 1=2 ;

ð6Þ

where kH is the constant reflecting the design variables of the system. The kinetic release parameters were obtained from the following plots: drug release (in wt.%) vs. time for the zero-order kinetic model; ln of drug remaining (in wt.%) vs. time for first-order kinetic model; and drug release (in wt.%) vs. the square root of time for the Higuchi model. The mechanism of VB1 release was determined using the Korsmeyer– Peppas model (Siepmann and Peppas, 2001) (Eq. (7)): Mt =M ∞ ¼ Kt n ;

Fig. 6. Release profile of VB1 from the Mt in SGF (pH = 1.2): ♦ Al 0, ◊ Al 0.2, □ Al 0.5, ■ Al 0.7, ○ Al 1.0, ▲ Al1.6, Δ Al 1.8 and ● K 10.

3. Results and discussion 3.1. Mt synthesis The Mt samples were prepared under hydrothermal conditions using the controlled isomorphous substitution of magnesium cations in the octahedral positions of aluminium cations, whereby a series of samples with varying chemical compositions were obtained. The results of chemical analysis (Table 1) confirmed that the samples were synthesised with various degrees of substitution of magnesium for aluminium. Fig. 2 shows the diffraction patterns of the synthesised Mt samples and the natural Mt K10 (sample identifications are given in Table 1). Fig. 2 indicates that single-phase samples with Mt structure were obtained, as evidenced by the position of the characteristic reflection peaks 7–9° (d001), 19° (d110), 28° (d004), 35° (d201), and 60–62° ((d060) and (d330)) of 2θ. The peak at 2θ = 7–9° (d001) characterises the basal space between the layers in the Mt structure. Thus, the position of the peak of the magnesium Mt Al 0 diffraction pattern at angles 2θ = 9.2° corresponds to an interlayer distance of 9.6 Å. The peak position shifted for the Al 1.8 sample in the small-angle region of 2θ = 7.1°, which indicates an increase of the interlayer distance to 12.4 Å. For the most of the synthesised samples, the d001 peak is absent. The broadening and disappearance of the (d001) reflection peak are related to the loss of periodicity in the crystallographic lattice and indicate disordered packing (flakes) (Golubeva et al., 2013).

ð7Þ

where Mt/M∞ is the fraction of drug released at time t, K is the rate constant and n is the release exponent. Table 3 Sorption parameters of the Dubinin–Radushkevich model for the adsorption isotherms of VB1 onto Mt. Mt sample

Xm, mmol g−1

k, mol2 kJ−2

E, kJ mol−1

R2

Al 0 Al 0.2 Al 0.5 Al 0.7 Al 1.0 Al 1.6 Al 1.8 K 10

0.36 0.78 0.83 1.01 1.02 0.67 0.80 0.16

0.0054 0.0066 0.0056 0.0064 0.0032 0.0014 0.0027 0.0051

9.6 8.7 9.4 8.8 12.5 18.9 13.6 9.9

0.9894 0.9867 0.9957 0.9775 0.9987 0.9531 0.9891 0.9482

Fig. 7. Release profile of VB1 from the Mt in SIF (pH = 7.4): ♦ Al 0, ◊ Al 0.2, □ Al 0.5, ■ Al 0.7, ○ Al 1.0, ▲ Al1.6, Δ Al 1.8 and ● K 10.

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Fig. 8. Release profile of VB1 from the Mt Na2x(Al2(1–x),Mg2x)Si4O10(OH)2∙nH2O in SGF (♦) and SIF (■) at 420 min.

With the decrease in the Mg/Al ratio in the synthesised samples, a decrease in the reflection band intensity at 2θ = 60.6° (maximum intensity for the sample Al 0) to its complete disappearance and the appearance of a peak at 2θ = 62.3° are observed. For the samples in the middle of the series (Al 0.7), the presence of reflection peaks at both 2θ = 60.8° and 2θ = 62.3° is observed. These changes in the diffraction patterns indicate the conversion of the dioctahedral structure (2θ = 60.8°, d = 1.48 Å, (d330)) to trioctahedral (2θ = 62.3°, d = 1.52 Å, (d330)). The (d330) peak indicates the dioctahedral structure of the sample and the presence of vacancies in the octahedral layers, which are gradually occupied as the replacement of magnesium atoms to aluminium occurs. Compared to the synthesised samples, the commercial Mt K10 contains impurities of quartz and muscovite (Fig. 2). The average particle size of the synthesised Mt defined by XRPD using the Debye–Scherrer method was 40 ± 7 nm. SSA according to the low-temperature nitrogen adsorption data was in the range of 120–280 m2 g−1 (Table 1), and the predominant pore size was 5–7 nm.

3.2. VB1 intercalation VB1 intercalation into the Mt interlayer space was confirmed by the XRD data. A shift was observed from the angle 2θ = 7.55° (d001 = 11.7 Å), which characterises the basal space between the silicon–oxygen layers in the untreated Mt sample, to the smaller angle. The gradual increase in the VB1 concentration in the sample structure is correlated with the gradual shift of the d001 peak, which confirms the effective intercalation of VB1 into the interlayer space of Mt. Fig. 3 shows an example of an X-ray diffraction pattern for Mt Al 1.8 and for samples of the same composition with various VB1 contents.

Fig. 4 shows a plot of the amount of drug adsorbed by the Mt samples with various compositions as a function of the pH of the medium. From Fig. 4, it can be concluded that the VB1 adsorption by the synthetic Mt weakly depends on the pH of the solution in the pH range from 3.0 to 8.0. An exception is the region of pH = 2.0, at which a sharp decrease in the adsorption is observed, which is probably due to an excess of chloride ions in the solution and a reduction of the rate of the cationic exchange reaction between the interlayer cations in the structure of Mt and VB1 ions (Joshi et al., 2009). For the majority of the Mt compositions, a slight increase in the adsorption occurs with increasing pH up to 6.0, wherein the maximum of VB1 adsorption is observed. This influence of the pH on the adsorption can be explained by the VB1 structural conformations that occur at various H+ concentrations in the solution (Joshi et al., 2009) and by possible surface and textural changes in the Mt that occur in strongly acidic or alkaline media. The results obtained in this study indicate that the adsorbed amount of the drug depends on the composition and structure of the adsorbent rather than the medium composition. From the results shown in Fig. 4, it can be observed that the adsorption of VB1 depends on the chemical composition of the synthetic Mt. Mt compositions Al 0.2, 0.7 and 1.0 adsorb maximum VB1 amount in the pH range 4.0–8.0, Al 0.5 and 1.8 at pH = 5.0–7.0, Al 1.6 adsorbs in more broad range – from 3.0 to 8.0, for Al 0 this range shifts to more alkaline medium – to pH = 6.0–8.0. VB1 adsorption by natural Mt K 10 in more extent depends on the pH of the medium and generally K 10 adsorbs the drug in less extent comparing to synthetic samples practically in the entire pH range except for 6.0. As follows from Fig. 5, the dependence of the adsorbed drug amount as a function of the Mt composition is correlated with the character of the CEC changes, depending on Mt composition: to the greatest extent, VB1 is adsorbed by the samples characterised by the greatest CEC values. A comparison of the results obtained with the SSA data given in Table 1 does not show as clear a dependence as in the CEC case, which indicates the absence of the dependence on the pore and textural characteristics of the Mt. The results listed in Table 2 show that the Langmuir model fits the experimental isotherms better than the Freundlich model (maximum values of R 2 ) and that all of the R L values are in the range of 0.0005 to 0.0080, which indicates that the adsorption is a favourable process. The correspondence to the Langmuir model indicates that a monolayer adsorbate is formed on the Mt surface and that all adsorptive sites have equal energies and enthalpies (Langmuir, 1916). Additionally, Table 2 shows that the increase in the monolayer adsorption capacity Cm and Freundlich's constant KF reflects the adsorption behaviour represented in Fig. 5. The values of Cm and KF for K10 are far less than those for all of the synthetic samples. The values of n for all of the compositions are less than 1, indicating a high adsorption intensity (Gereli et al., 2006). The type of adsorption was estimated by the values of E from Dubinin–Radushkevich model. The data represented in Table 3 show that the ionic exchange process is favoured for all Mt samples.

Table 4 Kinetic-release parameters of VB1 release from the MMT in SGF. MMT sample

Al 0 Al 0.2 Al 0.5 Al 0.7 Al 1.0 Al 1.6 Al 1.8 K 10

Zero-order

First-order

Higuchi

Korsmeyer–Peppas

k0

R2

k1

R2

kH

R2

n

kKP

R2

0.6557 0.6509 0.9741 0.748 1.0032 0.3763 0.4961 0.6637

0.6029 0.8660 0.8914 0.9131 0.8516 0.8730 0.9412 0.9270

0.0129 0.0223 0.0348 0.0325 0.0410 0.0244 0.0152 0.0221

0.6251 0.9053 0.933 0.9496 0.8958 0.9033 0.9564 0.9482

0.1916 0.1807 0.2524 0.2260 0.2776 0.1221 0.1313 0.1757

0.8419 0.9683 0.9814 0.9534 0.9654 0.9618 0.9932 0.9823

0.5127 0.5416 0.7024 0.3423 0.533 0.4103 0.5226 0.5161

0.0460 0.0544 0.0402 0.1477 0.0844 0.0947 0.0400 0.0545

0.8082 0.9315 0.9585 0.9961 0.9590 0.9839 0.9853 0.9715

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Table 5 Kinetic-release parameters of VB1 release in SIF. MMT sample

Al 0 Al 0.2 Al 0.5 Al 0.7 Al 1.0 Al 1.6 Al 1.8 K 10

Zero-order

First-order

Higuchi

Korsmeyer–Peppas

k0

R2

k1

R2

kH

R2

n

kKP

R2

0.1780 0.2408 0.2948 0.2902 0.1830 0.2708 0.3448 0.1581

0.8431 0.7924 0.8295 0.7530 0.9158 0.7195 0.8839 0.7851

0.0044 0.0062 0.0078 0.0076 0.0046 0.0074 0.0090 0.0039

0.8510 0.8032 0.8404 0.7663 0.9227 0.7374 0.8925 0.7915

0.0474 0.0650 0.0823 0.0792 0.0475 0.0747 0.0895 0.0425

0.9551 0.9204 0.9727 0.8941 0.9818 0.8727 0.9549 0.9060

0.5076 0.4400 0.3867 0.6203 0.3504 0.3917 0.5702 0.3591

0.0173 0.0327 0.0495 0.0197 0.0345 0.0509 0.0226 0.0317

0.9555 0.9452 0.9723 0.8737 0.9804 0.8908 0.9515 0.9276

3.3. In vitro release of VB1 Figs. 6–8 present the VB1-desorption results by the synthetic and natural (K10) Mt samples in the chosen media. The VB1 release depends on the chemical composition of the Mt and the pH of the medium. The dependence of the VB1 desorption amount on the Mt composition in SGF correlates with the compositional dependence of the adsorption: as the degree of substitution of magnesium for aluminium rises, a gradual increase in the VB1 release occurs up to the composition with an equal content of magnesium and aluminium (Al 1.0), and then a decrease in the VB1 release is observed (Fig. 8). Thus, the VB1-release amount varies from 25 wt.% (Al 0) to 54 wt.% (Al 1.0) in SGF. In SIF, the dependence is practically the same, except for Al 1.0, and the VB1 release is lower and varies from 10 wt.% (Al 0) to 19 wt.% (Al 1.6 and Al 0.5). The natural Mt K10 desorbs VB1 less than essentially all of the synthetic samples and reaches 11 wt.% and 37 wt.% in SIF and SGF, respectively. As shown in Tables 4 and 5, the Higuchi model is a better fit (maximal values of R2) for the release processes in both media. The value of n is used to characterise the various release mechanisms of the drug. Values of n of approximately 0.5 indicate a purely diffusioncontrolled mechanism (Fickian diffusion), n between 0.5 and 1.0 indicates anomalous transport kinetics (non-Fickian diffusion) and n less than 0.5 may be due to partial drug diffusion through a swollen matrix and solution-filled pores (Joshi et al., 2009). The values of the release exponent n differ for the various Mt, and there is no clear dependence on the Mt composition. In SGF from most of the synthetic Mt, VB1 releases by a diffusion-controlled mechanism (n = 0.51–0.54), but it also occurs to a lesser extent by other mechanisms. In SIF, VB1 release occurs primarily by a swelling-controlled mechanism (n = 0.35–0.44). The commercial Mt K10 liberates VB1 by Fickian diffusion in SGF (n = 0.52) and by a swelling-controlled mechanism in SIF (n = 0.36).

4. Conclusions A series of samples were synthesised with the Mt structure and the gradual substitution of Mg into the octahedral sheet of Al. The intercalation of VB 1 into synthetic Mt with various compositions (Na 2x (Al2(1–x),Mg2x )Si4 O 10 (OH) 2∙ nH2O, where 0 b x b 1) and its in vitro release from these matrices were investigated. It was established that the intercalation of VB1 depends primarily on the composition and cation-exchange capacity of Mt and, to a lesser extent, on the pH of the solution. The adsorption data were fitted with several common isotherms, but the best regression parameters were obtained for the Langmuir model. Adsorption type was determined as the cation-exchange reaction according to the Dubinin–Radushkevich model. The results indicate that synthetic Mt can be used as controlled-release carriers. Directed Mt synthesis makes it possible to obtain samples with various drug-release profiles in simulated gastric (SGF) and intestinal (SIF) fluids. The maximum amount of released VB1 reached 54 wt.% and 19 wt.% in SGF and SIF, respectively, for synthetic Mt. For natural Mt

K10, these values reached 37 wt.% and 11 wt.%, respectively. Thus, the optimal compositions of the drug carriers can be selected. All samples studied show good intercalation abilities in a wide pH range. Additionally, Mt with compositions of x = 0.65 and 0.5 can be considered effective drug carriers with controlled release in gastric fluid. The Mt compositions with x = 0.1 and 0.2 can be used in the case in which controlled release in intestinal fluid is required. Acknowledgments The authors gratefully acknowledge the financial support provided by the Russian Foundation for Basic Research (RFBR), grant 14-0300235 a. References Annadurai, G., Ling, L.Y., Lee, J.F., 2008. Adsorption of reactive dye from an aqueous solution by chitosan: isotherm, kinetic and thermodynamic analysis. J. Hazard. Mater. 152, 337–346. Calabrese, I., Cavallaro, G., Scialabba, C., Licciardi, M., Merli, M., Sciascia, L. Turco, Liveri, M.L., 2013. Nanodevices for the colon metronidazole delivery. Int. J. Pharm. 457, 224–236. Chang, P.-H., Jiang, W.-T., Zhaohui, L., Chung-Yih, K., Jiin-Shuh, J., Chen, W.-R., Lv, G., 2014. Mechanism of amitriptyline adsorption on Ca-montmorillonite (SAz-2). J. Hazard. Mater. 277, 44–52. Dash, S., Murthy, P.N., Nath, L., Chowdhury, P., 2010. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol. Pharm. 67, 217–223. Dong, Y., Feng, S.-S., 2005. Poly(d, l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs. Biomaterials 26, 6068–6076. Dubinin, M.M., Radushkevich, L.V., 1947. Equation of the Characteristic Curve of Activated Charcoal. Proc. USSR Acad. Sci. Phys. Chem. Sect. 55, 331. Freundlich, H.M.F., 1906. Over the adsorption in solution. Z. Phys. Chem. 57, 385–471. Gereli, G., Seki, Y., Kusoglu, I., Yurdakoc, K., 2006. Equilibrium and kinetics for the sorption of promethazine hydrochloride onto K10 montmorillonite. J. Colloid Interface Sci. 299, 155–162. Golubeva, O.Yu., Ternovaya, N.Yu., Kostyreva, T.G., Drozdova, I.A., Mokeev, M.V., 2013. Synthetic nanoclays with montmorillonite structure: obtaining, structure and physicochemical properties. Glas. Phys. Chem. 39, 533–539. Higuchi, T., 1963. Mechanism of sustained action medication: theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci. 52, 1145–1148. Hoyo, C., Rives, V., Vicente, M.A., 1996. Thermal studies of pharmaceutical clay systems. Part II. Sepiolite-based systems. Thermochim. Acta 286, 105–117. Iliescu, R.I., Andronescu, E., Voicu, G., Ficai, A., Covaliu, C.I., 2011. Hybrid materials based on montmorillonite and citostatic drugs: preparation and characterization. Appl. Clay Sci. 52, 62–68. Joshi, G.V., Patel, H.A., Kevadiya, B.D., Bajaj, H.C., 2009. Montmorillonite intercalated with vitamin B1 as drug carrier. Appl. Clay Sci. 45, 248–253. Kevadiya, B.D., Joshi, G.V., Mody, H.M., Bajaj, H.C., 2011. Biopolymer–clay hydrogel composites as drug carrier: host–guest intercalation and in vitro release study of lidocaine hydrochloride. Appl. Clay Sci. 52, 364–367. Kevadiya, et al., 2012. Montmorillonite/poly-(e-caprolactone) composites as versatile layered material: reservoirs for anticancer drug and controlled release property. Eur. J. Pharm. Sci. 47, 265–272. Kollar, T., Palinko, I., Konya, Z., Kiricsi, I., 2003. Intercalating amino acid guests into montmorillonite host. J. Mol. Struct. 651–653, 335–340. Langmuir, I., 1916. The constitution and fundamental properties of solids and liquids. J. Am. Chem. Soc. 38, 2221–2295. Lee, Y.-H., Kuo, T.-F., Chen, B.-Y., Feng, Y.-K., Wen, Y.-R., Lin, W.-C., Lin, F.H., 2005. Toxicity assessment of montmorillonite as a drug carrier for pharmaceutical applications: yeast and rats model. Biomed. Eng. Appl. Basis Commun. 17, 72–78. Lin, F.H., Lee, Y.-H., Jian, C.H., Wong, J.M., Shieh, M.J., Wang, C.Y., 2002. A study of purified montmorillonite intercalated with 5-fluorouracil as drug carrier. Biomaterials 23, 1981–1987.

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