- Email: [email protected]
Effect of temperature, pressure and depressurization rate on release profile of salicylic acid from contact lenses prepared by supercritical carbon dioxide impregnation
chemical engineering research and design 1 0 0 ( 2 0 1 5 ) 89–94
Contents lists available at ScienceDirect
Chemical Engineering Research and Design journal homepage: www.elsevier.com/locate/cherd
Effect of temperature, pressure and depressurization rate on release profile of salicylic acid from contact lenses prepared by supercritical carbon dioxide impregnation Yuta Yokozaki, Junichi Sakabe, Brendan Ng, Yusuke Shimoyama ∗ Department of Chemical Engineering, Tokyo Institute of Technology, 2–12–1 S1-33, Ookayama, Meguro-ku, Tokyo, 152-8550, Japan
a r t i c l e
i n f o
a b s t r a c t
Article history:
Supercritical CO2 was used for the impregnation of a contact lens with salicylic acid. The
Received 17 September 2014
supercritical CO2 impregnations were conducted at 308, 313 and 318 K from 9.0 to 15.0 MPa.
Received in revised form 20 April
The effects of the temperatures and pressures in the impregnation processing on the loaded
2015
amount of salicylic acid in the contact lenses were investigated. The loaded amounts of sal-
Accepted 7 May 2015
icylic acid increase with the decrease of temperature and increase of pressures. It is found
Available online 14 May 2015
that the loaded amounts of salicylic acid in the lenses are correlated with the solubilities
Keywords:
the aqueous solution at 310 K for 8 h was studied by the released amounts measured using
in supercritical CO2 . The release profile of the salicylic acid from the contact lenses into Supercritical CO2
ultraviolet-visible spectroscopy. The higher temperature and lower pressure in the impreg-
Impregnation
nation processing lead to the slow release rate of salicylic acid from the contact lenses.
Contact lens
The release profiles were investigated by changing the depressurization rate from 0.06 to
Release profile
0.18 MPa min−1 . The lower depressurization rate results in the higher release rate of the
Salicylic acid
salicylic acid from the lenses. The release profile of salicylic acid from the lenses into the
Loaded amount in lens
aqueous solution is modeled by using kinetic constant and release exponent parameter. The modeled results suggest that the release from the lenses occurred by the superimpositions of Fickian controlled and swelling controlled releases. © 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
1.
Introduction
Polymer composite with drug have been developed and attracted much attention as a potential drug delivery system in order to sustain drug releasing and reduce the drug dosage required for the therapeutic effect. The drug delivery system based on polymer-drug composite is prepared by the incorporation of drug into the matrix of polymer using organic solvent (Pingnatello et al., 2002; Nair et al., 2012). Drying is required for the removal of solvent from the polymer in preparation of the polymer-drug composite. The limitations of the preparation
∗
of the polymer-drug composite are the residual solvent and drying that may decompose the thermolabile drugs. Some research groups of (Braga et al., 2008, 2011; Costa et al., 2010a,b) has applied supercritical CO2 as solvent for the impregnation of the polymer with drugs due to the unique properties, such as the low surface tension, high diffusivity and non-toxic to human body. In supercritical CO2 process, CO2 is separated from the prepared polymer-drug composite easily by only the depressurization without heating. The impregnations of the chitosan derivatives with flurbiprofen and timolol maleate have been conducted by supercritical
Corresponding author. Tel.: +81 3 5734 3285; fax: +81 3 5734 3285. E-mail address: [email protected] (Y. Shimoyama).
http://dx.doi.org/10.1016/j.cherd.2015.05.008 0263-8762/© 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
90
chemical engineering research and design 1 0 0 ( 2 0 1 5 ) 89–94
solvent impregnation using CO2 and CO2 + ethanol mixture (Braga et al., 2008). The several species of the commercial contact lenses were used in the supercritical solvent impregnation (Costa et al., 2010a). The effects of the operation conditions of the impregnation on the release profile of the ophthalmic drugs were investigated. The silicone-based contact lenses were used for the impregnation in the supercritical solvent impregnation using CO2 + ethanol and CO2 + water mixtures (Costa et al., 2010b; Braga et al., 2011). Masmoudi et al. (2011) also studied the impregnation of the commercially available lenses with cefuroxime sodium in CO2 + ethanol mixture. These studies concluded that the supercritical solvent impregnation would be a tunable process for the preparation of the contact lenses with drug. The loaded drug amount in the lenses can be controlled easily by changing the operation conditions during the supercritical solvent impregnation. It is very important for the process design of the supercritical solvent impregnation to understand the mechanism of the impregnation with drug in supercritical CO2 . The relationship between the impregnation condition and the drug release mechanism from the contact lenses prepared by the supercritical solvent impregnation can be a fundamental and potential knowledge to achieve the controlled release of the ophthalmic drugs. In this work, we investigated the effects of the temperatures, pressures and depressurization rates in the supercritical solvent impregnation on the loaded amount of salicylic acid in Hilafilcon B, a commercial contact lens and the release profile of salicylic acid from the lenses. Salicylic acid in Fig. 1 was used as a model substance in this work due to inexpensive compound compared with anti-inflammatory and ophthalmic drugs. Also, salicylic acid molecule has the aromatic ring and carboxy group that are contained in the molecular structure of anti-inflammatory drug, such as flurbiprofen (Pingnatello et al., 2002) and dexamethasone (Kim et al., 2010) and ophthalmic drugs, such as ofloxacin (Yamazaki et al., 2013) and norfloxacin (González-Chomón et al., 2012). Hilafilcon B used in this work contains the monomer units of 2hydroxyethyl methacrylate and methacrylic acid, cross-linker ˜ ethyleneglycol dimethacrylate and N-vinylpyrrolidone (Yanez et al., 2011). It is thought that the carboxy groups in salicylic acid makes the interaction with the monomer units, 2-hydroxyethyl methacrylate, methacrylic acid and the crosslinker, ethyleneglycol dimethacrylate in Hilafilcon B as well anti-inflammatory and ophthalmic drug molecules. The loading amount of salicylic acid in Hilafilcon B was discussed using the solubility of salicylic acid in supercritical CO2 . The release profile of salicylic acid from Hilafilcon B prepared in supercritical CO2 into the aqueous solution is also studied. The effects of temperature, pressure and depressurization rate on the release profile were discussed by using a theoretical model with kinetic constant and release exponent parameter.
2.
Experimental
2.1.
Chemicals
Hilafilcon B, commercial soft contact lenses (SCLs) from Bausch & Lomb® , Medalist® One-Day Plus (Group 2 SCL, 59 wt% water content, 8.6 mm base curve, −0.25 D power, 14.2 mm diameter) was used. Hilafilcon B was in soaking solution for a commercial soft contact lens including sodium chloride and poloxamine. Salicylic acid was purchased from Wako Pure Chemical Industries, Ltd. The purity was higher than 99.5%.
Fig. 1 – Salicylic acid. Carbon dioxide was supplied from Fujii Bussan Co. Ltd. The purity was higher than 99.95%. Phosphate buffer solution with pH 6.86 from Wako Pure Chemical Industries, Ltd. was used as a solvent for salicylic acid release. Ultrapure water was also supplied from Wako Pure Chemical Industries, Ltd. and used as the medium for aqueous solution impregnation.
2.2. acid
Preparation of hilafilcon B composite with salicylic
2.2.1.
Supercritical CO2 impregnation
A schematic diagram of the experimental apparatus is shown in Fig. 2. This apparatus is composed of a CO2 supply part, a high-pressure cell and a trap part. The high-pressure cell was immersed in an air bath for controlling the desired temperature within ±0.1 K. The deviation of the pressure in the system during the impregnation was ±0.1 MPa. The volume of high-pressure cell was 170 ml, and the inside of the cell was partitioned into two parts by a petri dish. Three pieces of Hilafilcon B in 14.2 mm diameter wetted with the soaking solution for a commercial soft contact lens were set inside of the dish horizontally and the known amount of salicylic acid was set outside of the dish. The amount of salicylic acid introduced into the high-pressure cell was 0.088–0.700 g that was much greater than the saturated solubility in supercritical CO2 at the experimental temperatures and pressures 0.084–0.66 g L−1 (Gurdial and Foster, 1991). The petri dish was covered with a stainless steel mesh (0.2 mm of mesh size) not to contact salicylic acid directly to the surface of Hilafilcon B. Carbon dioxide from a gas cylinder was liquefied through a cooling unit. The liquefied CO2 was pressurized and supplied to the system by a feed pump. A back-pressure regulator was used for
Fig. 2 – Supercritical CO2 impregnation apparatus. (1) CO2 bottle; (2) dryer; (3) back pressure regulator; (4) pressure gauge; (5) cooling bath; (6) feed pump; (7) check valve; (8) pressure gauge; (9) high-pressure cell; (10) temperature control unit; (11) depressurization valve.
chemical engineering research and design 1 0 0 ( 2 0 1 5 ) 89–94
controlling the pressure in the system. The liquefied CO2 was introduced into the high-pressure cell at the desired temperature and attained to the supercritical state. The supercritical CO2 impregnations were conducted for 2 h. After the impregnation period, the system was depressurized at the various depressurization rates. The impregnated Hilafilcon B were then recovered from the high-pressure cell after the depressurization of the system. The recovered Hilafilcon B after the impregnation was dry. Then, Hilafilcon B were placed in 10 ml of the saturated salicylic acid aqueous solution using ultrapure water, 0.247 × 10−3 in mole fraction at 298 K (Nordström and Rasmuson, 2006) for 15 min in order to rehydrate Hilafilcon B. The rehydrated Hilafilcon B were recovered from the aqueous solution and the excess water on the Hilafilcon B surface was removed by the tissue paper before the test of the salicylic acid release.
2.2.2.
Aqueous solution impregnation
The aqueous solution impregnations of Hilafilcon B with salicylic acid were performed for the comparisons with those impregnated in supercritical CO2 . The Hilafilcon B was placed in 40 ml of salicylic acid saturated solution in ultrapure water. The concentration of salicylic acid in the solution was 2.2 × 10−3 g ml−1 . The impregnations in the aqueous solution were conducted for 2 h at 298 K. After the impregnations, the Hilafilcon B was recovered from the bottle of the aqueous solution and the excess water on the Hilafilcon B surface was removed by the tissue paper before the test of the salicylic acid release.
2.3. Characterization of hilafilcon B composite with salicylic acid 2.3.1.
Amount of salicylic acid in hilafilcon B
The composite prepared by the supercritical CO2 or aqueous solution impregnations was placed in 10 ml of the phosphate buffer solution at 298 K for 24 h in order to leach out the total amount of salicylic acid in Hilafilcon B. The samples were taken from the solution and analyzed by the UV–vis spectrophotometry for quantifying the amount of salicylic acid released from the Hilafilcon B. In this work, the total amounts of salicylic acid in Hilafilcon B are determined from the amount released into the phosphate aqueous solution for 24 h. The standard deviation of the amount of salicylic acid in Hilafilcon B was 0.06 × 10−4 g lens−1 .
Microstructure of hilafilcon B
The contact lenses with salicylic acid after the impregnation were cut by a razor and dried at 303 K. The cross section of the dried lens was observed by a Scanning Electron Microscope (SEM, KEYENCE, VE-8000).
3. Modeling of salicylic acid release from hilafilcon B The release profile of salicylic acid from the Hilafilcon B is assumed to the result from the two contributions: the initial instantaneous release of the adsorbed salicylic acid on the surface of Hilafilcon B and the release of the incorporated salicylic acid inside the hydrogel matrix of Hilafilcon B. The total amount of salicylic acid in the Hilafilcon B is given by the following equation: Mtot = Mads + Mdep
(1)
where, M denotes the amount of salicylic acid in Hilafilcon B. The superscripts tot, ads and dep mean the total amount, adsorbed amount on the surface and deposited amount inside the lenses, respectively. The adsorbed amount of salicylic acid at the surface of Hilafilcon B is obtained from the total amount in that prepared by the aqueous solution impregnation. It is assumed that the amount of salicylic acid from the rehydration solution to Hilafilcon B is almost the same as that adsorbed at the lens surface in aqueous solution impregnation. The deposited amount of salicylic acid inside Hilafilcon B can be calculated by discounting the adsorbed amounts using the Eq. (1). The amount of salicylic acid deposited inside the hydrogel matrix is modeled using the kinetic constant k and release exponent parameter n as follows (Korsmeyer et al., 1983; Ritger and Peppas, 1987).
Release profile
Hilafilcon B composite with the salicylic acid prepared by the supercritical CO2 or aqueous solution impregnations were immersed in 10 ml of the phosphate aqueous solution with pH 6.86 at 310 K with stirring for 8 h. The sample of 0.3 ml aliquots were collected at the predetermined time periods and replaced with the equivalent amount of the fresh phosphate aqueous solution. The frequencies of the sample collection were once every 10, 30 and 60 min at the release time 0–3, 3–6 and 6–8 h, respectively. The collected samples were diluted to 3 ml with the fresh phosphate aqueous solution. The released amounts of salicylic acid were determined from the analysis of the collected samples using UV–vis spectrophotometry (JASCO, model V-630, Japan) at 296 nm. The results of the release profile were determined from the average of the three samples at each condition.
2.3.2.
2.3.3.
91
dep
Mt
Mdep
= ktn
(2)
The subscript t is the release amount at time t. In this work, the kinetic constant k and release exponent parameter n were fitted to the first 60% release of salicylic acid deposited in Hilafilcon B.
4.
Results and discussion
4.1.
Aqueous solution impregnation
The release profiles of salicylic acid from Hilafilcon B composite prepared by the aqueous solution impregnation are shown in Fig. 3. In Fig. 3, it can be seen that Hilafilcon B composite prepared by the aqueous solution impregnation result in the profile that all the impregnated salicylic acid is released for 10 min. Furthermore, the amount of the salicylic acid impregnated into Hilafilcon B are 1.75 × 10−4 g in the one lens.
4.2.
Supercritical CO2 impregnation
4.2.1.
Effect of impregnation temperature
The release profiles of salicylic acid from Hilafilcon B composite prepared supercritical CO2 impregnation are presented in Fig. 4. Table 1 gives the total and deposited amount of salicylic acid in the lenses and the time taken for 60% release of the deposited salicylic acid. The kinetic constant and release exponent parameter are also presented in Table 1. To
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chemical engineering research and design 1 0 0 ( 2 0 1 5 ) 89–94
Fig. 3 – Release profile of salicylic acid from contact lens prepared by aqueous solution impregnation at 298 K.
Fig. 5 – Effect of impregnation pressure on release profile of salicylic acid from contact lenses prepared by supercritical CO2 impregnation at 313 K and depressurization rate 0.06 MPa min−1 . () 9.0 MPa; (䊉) 11.0 MPa; () 15.0 MPa.
Table 2 – Effect of impregnation pressure on experimental and modeled results of salicylic acid release from contact lenses at 313 K and depressurization rate 0.06 MPa min−1 . p (MPa) 9.0 11.0 15.0 a
b
Fig. 4 – Effect of impregnation temperature on release profile of salicylic acid from contact lenses prepared by supercritical CO2 impregnation at 11.0 MPa and depressurization rate 0.06 MPa min−1 . () 308 K; (䊉) 313 K; () 318 K. Table 1 – Effect of impregnation temperature on experimental and modeled results of salicylic acid release from contact lenses at 11 MPa and depressurization rate 0.06 MPa min−1 . T, K
308 313 318 a
b
S (g L−1 )a
0.47 0.34 0.22
t (min)b
62.7 79.5 101.8
Mtot × 104 , g lens−1 4.84 3.75 2.96
Mdep × 104 , g lens−1 3.09 2.00 1.21
k
0.062 0.032 0.075
n
0.55 0.67 0.61
Solubility of salicylic acid in supercritical carbon dioxide (Gurdial and Foster, 1991). Time taken for 60% release of deposited salicylic acid.
investigate the effect of temperature, the pressure and depressurization rate on the supercritical CO2 impregnation were fixed at 11 MPa and 0.06 MPa min−1 , respectively. As shown in Fig. 4, supercritical CO2 impregnation results in the release profile of salicylic acid slower than those prepared by the aqueous solution impregnation. The total amount of salicylic acid in the lenses increases with the decrease of the impregnation temperature. This is because the solubilities of salicylic acid in supercritical CO2 increase with decrease of the temperature
S (g L−1 )a 0.084 0.34 0.66
t (min)b 103.2 79.5 49.6
Mtot × 104 (g lens−1 ) 2.61 3.75 5.45
Mdep × 104 (g lens−1 ) 0.862 2.00 3.70
k
n
0.021 0.032 0.046
0.72 0.67 0.66
Solubility of salicylic acid in supercritical carbon dioxide (Gurdial and Foster, 1991). Time taken for 60% release of deposited salicylic acid.
at 11 MPa (Gurdial and Foster, 1991). The time taken for 60% release of the deposited salicylic acid also decreases with the decrease of the impregnation temperature as given in Table 1. The values of the release exponent parameters in Eq. (2) is between 0.5 and 1.0. This suggests that the salicylic acid releases from the lenses prepared by supercritical CO2 impregnation are resulted from the superimposition of Fickian controlled and hydrogel swelling controlled releases (Korsmeyer et al., 1983; Ritger and Peppas, 1987).
4.2.2.
Effect of impregnation pressure
Fig. 5 presents the release profiles of salicylic acid from the composite prepared supercritical CO2 impregnation. The total and deposited amount of salicylic acid in the lenses and the time taken for 60% release of the deposited salicylic acid are listed in Table 2. The kinetic constant and release exponent parameter are also presented in Table 2. To investigate the effect of pressure, the temperature and depressurization rate on the supercritical CO2 impregnation were fixed at 313 K and 0.06 MPa min−1 , respectively. The total amount of salicylic acid in the composite increases with the pressure. This is because the solubilities of salicylic acid in supercritical CO2 increase with pressure at constant temperature (Gurdial and Foster, 1991). The time taken for 60% release of the deposited salicylic acid decreases with the increase of pressure as given in Table 2. It is though that the solubility of salicylic acid in supercritical carbon dioxide is important to control the amount of that in the composite. The relationship between
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chemical engineering research and design 1 0 0 ( 2 0 1 5 ) 89–94
Table 3 – Effect of depressurization rate on experimental and modeled results of salicylic acid release from contact lenses at 313 K and 11.0 MPa. dp (MPa min−1 ) 0.06 0.12 0.18 a
b
Fig. 6 – Relationship between solubility of salicylic acid in supercritical CO2 (Gurdial and Foster, 1991) and total amount of salicylic acid in contact lenses.
the solubility in supercritical CO2 and the total amount of salicylic acid in the composites is shown in Fig. 6. There is the very strong correlation between the solubility in supercritical CO2 and the total amount of salicylic acid in the composites. The relationship between the solubility in supercritical CO2 C2
0.34 0.34 0.34
t (min)b 79.5 73.3 83.4
Mtot × 104 (g lens−1 ) 3.75 2.96 2.95
Mdep × 104 (g lens−1 ) 2.00 1.21 1.20
k
n
0.032 0.037 0.041
0.67 0.64 0.60
Solubility of salicylic acid in supercritical carbon dioxide (Gurdial and Foster, 1991). Time taken for 60% release of deposited salicylic acid.
(Gurdial and Foster, 1991) in g L−1 and the total amount of salicylic acid in the composite in g lens−1 is given by the following equation. Mtot = 0.0005589y2 + 0.0001907
4.2.3.
Fig. 7 – Effect of depressurization rate on release profile of salicylic acid from contact lenses prepared by supercritical CO2 impregnation at 313 K and 11.0 MPa. () 0.06 MPa min−1 ; (䊉) 0.12 MPa min−1 ; () 0.18 MPa min−1 .
S (g L−1 )a
(3)
Effect of depressurization rate
The supercritical CO2 impregnations were performed at 313 K and 11 MPa by changing the depressurization rate, 0.06 to 0.18 MPa min−1 . The effects of the depressurization rate on the release profile of salicylic acid are studied as shown in Fig. 7. Table 3 gives the total and deposited amount of salicylic acid in the composites and the time taken for 60% release of the deposited drug. The kinetic constant and release exponent parameter are also presented in Table 3. The total amount of salicylic acid in the composite at the depressurization rate 0.06 MPa min−1 is higher than those in case of 0.12 and 0.18 MPa min−1 . It is thought that the higher depressurization rate leads to a rapid mass transfer of the CO2 impregnated in the hydrogel matrix to vapor phase. This rapid CO2 mass transfer seems to cause the transfer of salicylic acid impregnated in the hydrogel to outside of Hilafilcon B. The SEM pictures of the cross-section of the contact lenses depressurized at 0.06 and 0.18 MPa min−1 are shown in Fig. 8. As shown in Fig. 8, the higher depressurization rate leads to the destruction of the lenses due to the rapid mass transfer of the dissolved CO2 in the hydrogel.
5.
Conclusion
Supercritical CO2 impregnation was used for the preparation of Hilafilcon B with salicylic acid. The salicylic acid-loaded composites prepare by supercritical CO2 impregnation are
Fig. 8 – SEM observations of microstructure of contact lenses prepared by supercritical CO2 impregnation. Depressurization rate: (a) 0.06 MPa min−1 ; (b) 0.18 MPa min−1 .
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chemical engineering research and design 1 0 0 ( 2 0 1 5 ) 89–94
capable of the release profile slower than those by aqueous solution impregnation. The increase of the impregnation temperature results in the decrease of the amount of salicylic acid in the composite. The amount of salicylic acid in the composite increases with the impregnation pressures. These effects of the impregnation temperatures and pressure can be explained from the strong correlation between the solubility of salicylic acid in supercritical CO2 and amount of salicylic acid in the composites. The high depressurization rate results in the low amount of salicylic acid in the composites and the destruction of the microstructure of the lenses. The kinetic constant and release exponent parameter in the mass transfer equation were determined from the release data of salicylic acid from the composites. This modeling suggest that salicylic acid release from the composites prepared by supercritical CO2 impregnation can be conducted by the superimposition of Fickian controlled and hydrogel swelling controlled releases.
References Braga, M.E., Costa, V.P., Pereira, M.J.T., Fiadeiro, P.T., Gomes, A.P.A.R., Durate, C.M.M., de Sousa, H.C., 2011. Effects of operational conditions on the supercritical solvent impregnation of acetazolamide in Balafilcon A commercial contact lenses. Int. J. Pharm. 420, 231–243. Braga, M.E.M., Pato, M.T.V., Costa Silva, H.S.R., Ferreira, E.I., Gil, M.H., Durate, C.M.M., de Sousa, H.C., 2008. Supercritical solvent impregnation of ophthalmic drugs on chitosan derivatives. J. Supercrit. Fluids 44, 245–257. Costa, V.P., Braga, M.E.M., Guerra, J.P., Duarte, A.R.C., Duarte, C.M.M., Leite, E.O.B., Gil, M.H., de Sousa, H.C., 2010a. Development of therapeutic contact lenses using a supercritical solvent impregnation method. J. Supercrit. Fluids 52, 306–316. Costa, V.P., Braga, M.E.M., Duarte, C.M.M., Alvarez-Lorenzo, C., Concheiro, A., Gil, M.H., de Sousa, H.C., 2010b. Anti-glaucoma
drug-loaded contact lenses prepared using supercritical solvent impregnation. J. Supercrit. Fluids 53, 165–173. González-Chomón, C., Braga, M.E.M., de Sousa, H.C., Concheiro, A., Alvarez-Lorenzo, C., 2012. Antifouling flodable acrylic IOLs loaded with norfloxacin by aqueous soaking and by supercritical carbon dioxide technology. Eur. J. Pharm. Biopharm. 82, 383–391. ˜ Yanez, F., Martikainen, L., Braga, M.E.M., Alvarez-Lorenzo, C., Concheiro, A., Duarte, C.M.M., Gil, M.H., de Sousa, H.C., 2011. Supercritical fluid-assisted preparation of imprinted contact lenses for drug delivery. Acta Biomater. 7, 1019–1030. Gurdial, G.S., Foster, N.R., 1991. Solubility of o-hydroxybenzoic acid in supercritical carbon dioxide. Ind. Eng. Chem. Res. 30, 575–580. Kim, J., Peng, C.C., Chauhan, A., 2010. Extended release of dexamethasone from silicone-hydrogel contact lenses containing vitamin E. J. Control. Release 148, 110–116. Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P., Peppas, N.A., 1983. Mechanism of solute release from porous hydrophilic polymers. Int. J. Pharm. 15, 25–35. Masmoudi, Y., Azzouk, L.B., Forzano, O., Andre, J.M., Badens, E., 2011. Supercritical impregnation of intraocular lenses. J. Supercrit. Fluids 60, 98–105. Nair, K.L., Vidyanand, S., James, J., Kumar, G.S.V., 2012. Pilocarpine-loaded poly(DL-lactic-co-glycolic acid) nanoparticles as potential candidates for controlled drug delivery with enhanced ocular pharmacological response. J. Appl. Polym. Sci. 124, 2030–2036. Nordström, F.L., Rasmuson, Å.C., 2006. Solubility and melting properties of salicylic acid. J. Chem. Eng. Data 51, 1668–1671. Pingnatello, P., Bucolo, C., Spedalieri, G., Maltese, A., Puglisi, G., 2002. Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application. Biomaterials 23, 3247–3255. Ritger, P.L., Peppas, N.A., 1987. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J. Control. Release 5, 37–42. Yamazaki, Y., Matsunaga, T., Syohji, K., Arakawa, T., Sato, T., 2013. Effect of anionic/siloxy groups on the release of ofloxacin from soft contact lenses. J. Appl. Polym. Sci. 127, 5022–5027.
Contents lists available at ScienceDirect
Chemical Engineering Research and Design journal homepage: www.elsevier.com/locate/cherd
Effect of temperature, pressure and depressurization rate on release profile of salicylic acid from contact lenses prepared by supercritical carbon dioxide impregnation Yuta Yokozaki, Junichi Sakabe, Brendan Ng, Yusuke Shimoyama ∗ Department of Chemical Engineering, Tokyo Institute of Technology, 2–12–1 S1-33, Ookayama, Meguro-ku, Tokyo, 152-8550, Japan
a r t i c l e
i n f o
a b s t r a c t
Article history:
Supercritical CO2 was used for the impregnation of a contact lens with salicylic acid. The
Received 17 September 2014
supercritical CO2 impregnations were conducted at 308, 313 and 318 K from 9.0 to 15.0 MPa.
Received in revised form 20 April
The effects of the temperatures and pressures in the impregnation processing on the loaded
2015
amount of salicylic acid in the contact lenses were investigated. The loaded amounts of sal-
Accepted 7 May 2015
icylic acid increase with the decrease of temperature and increase of pressures. It is found
Available online 14 May 2015
that the loaded amounts of salicylic acid in the lenses are correlated with the solubilities
Keywords:
the aqueous solution at 310 K for 8 h was studied by the released amounts measured using
in supercritical CO2 . The release profile of the salicylic acid from the contact lenses into Supercritical CO2
ultraviolet-visible spectroscopy. The higher temperature and lower pressure in the impreg-
Impregnation
nation processing lead to the slow release rate of salicylic acid from the contact lenses.
Contact lens
The release profiles were investigated by changing the depressurization rate from 0.06 to
Release profile
0.18 MPa min−1 . The lower depressurization rate results in the higher release rate of the
Salicylic acid
salicylic acid from the lenses. The release profile of salicylic acid from the lenses into the
Loaded amount in lens
aqueous solution is modeled by using kinetic constant and release exponent parameter. The modeled results suggest that the release from the lenses occurred by the superimpositions of Fickian controlled and swelling controlled releases. © 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
1.
Introduction
Polymer composite with drug have been developed and attracted much attention as a potential drug delivery system in order to sustain drug releasing and reduce the drug dosage required for the therapeutic effect. The drug delivery system based on polymer-drug composite is prepared by the incorporation of drug into the matrix of polymer using organic solvent (Pingnatello et al., 2002; Nair et al., 2012). Drying is required for the removal of solvent from the polymer in preparation of the polymer-drug composite. The limitations of the preparation
∗
of the polymer-drug composite are the residual solvent and drying that may decompose the thermolabile drugs. Some research groups of (Braga et al., 2008, 2011; Costa et al., 2010a,b) has applied supercritical CO2 as solvent for the impregnation of the polymer with drugs due to the unique properties, such as the low surface tension, high diffusivity and non-toxic to human body. In supercritical CO2 process, CO2 is separated from the prepared polymer-drug composite easily by only the depressurization without heating. The impregnations of the chitosan derivatives with flurbiprofen and timolol maleate have been conducted by supercritical
Corresponding author. Tel.: +81 3 5734 3285; fax: +81 3 5734 3285. E-mail address: [email protected] (Y. Shimoyama).
http://dx.doi.org/10.1016/j.cherd.2015.05.008 0263-8762/© 2015 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
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chemical engineering research and design 1 0 0 ( 2 0 1 5 ) 89–94
solvent impregnation using CO2 and CO2 + ethanol mixture (Braga et al., 2008). The several species of the commercial contact lenses were used in the supercritical solvent impregnation (Costa et al., 2010a). The effects of the operation conditions of the impregnation on the release profile of the ophthalmic drugs were investigated. The silicone-based contact lenses were used for the impregnation in the supercritical solvent impregnation using CO2 + ethanol and CO2 + water mixtures (Costa et al., 2010b; Braga et al., 2011). Masmoudi et al. (2011) also studied the impregnation of the commercially available lenses with cefuroxime sodium in CO2 + ethanol mixture. These studies concluded that the supercritical solvent impregnation would be a tunable process for the preparation of the contact lenses with drug. The loaded drug amount in the lenses can be controlled easily by changing the operation conditions during the supercritical solvent impregnation. It is very important for the process design of the supercritical solvent impregnation to understand the mechanism of the impregnation with drug in supercritical CO2 . The relationship between the impregnation condition and the drug release mechanism from the contact lenses prepared by the supercritical solvent impregnation can be a fundamental and potential knowledge to achieve the controlled release of the ophthalmic drugs. In this work, we investigated the effects of the temperatures, pressures and depressurization rates in the supercritical solvent impregnation on the loaded amount of salicylic acid in Hilafilcon B, a commercial contact lens and the release profile of salicylic acid from the lenses. Salicylic acid in Fig. 1 was used as a model substance in this work due to inexpensive compound compared with anti-inflammatory and ophthalmic drugs. Also, salicylic acid molecule has the aromatic ring and carboxy group that are contained in the molecular structure of anti-inflammatory drug, such as flurbiprofen (Pingnatello et al., 2002) and dexamethasone (Kim et al., 2010) and ophthalmic drugs, such as ofloxacin (Yamazaki et al., 2013) and norfloxacin (González-Chomón et al., 2012). Hilafilcon B used in this work contains the monomer units of 2hydroxyethyl methacrylate and methacrylic acid, cross-linker ˜ ethyleneglycol dimethacrylate and N-vinylpyrrolidone (Yanez et al., 2011). It is thought that the carboxy groups in salicylic acid makes the interaction with the monomer units, 2-hydroxyethyl methacrylate, methacrylic acid and the crosslinker, ethyleneglycol dimethacrylate in Hilafilcon B as well anti-inflammatory and ophthalmic drug molecules. The loading amount of salicylic acid in Hilafilcon B was discussed using the solubility of salicylic acid in supercritical CO2 . The release profile of salicylic acid from Hilafilcon B prepared in supercritical CO2 into the aqueous solution is also studied. The effects of temperature, pressure and depressurization rate on the release profile were discussed by using a theoretical model with kinetic constant and release exponent parameter.
2.
Experimental
2.1.
Chemicals
Hilafilcon B, commercial soft contact lenses (SCLs) from Bausch & Lomb® , Medalist® One-Day Plus (Group 2 SCL, 59 wt% water content, 8.6 mm base curve, −0.25 D power, 14.2 mm diameter) was used. Hilafilcon B was in soaking solution for a commercial soft contact lens including sodium chloride and poloxamine. Salicylic acid was purchased from Wako Pure Chemical Industries, Ltd. The purity was higher than 99.5%.
Fig. 1 – Salicylic acid. Carbon dioxide was supplied from Fujii Bussan Co. Ltd. The purity was higher than 99.95%. Phosphate buffer solution with pH 6.86 from Wako Pure Chemical Industries, Ltd. was used as a solvent for salicylic acid release. Ultrapure water was also supplied from Wako Pure Chemical Industries, Ltd. and used as the medium for aqueous solution impregnation.
2.2. acid
Preparation of hilafilcon B composite with salicylic
2.2.1.
Supercritical CO2 impregnation
A schematic diagram of the experimental apparatus is shown in Fig. 2. This apparatus is composed of a CO2 supply part, a high-pressure cell and a trap part. The high-pressure cell was immersed in an air bath for controlling the desired temperature within ±0.1 K. The deviation of the pressure in the system during the impregnation was ±0.1 MPa. The volume of high-pressure cell was 170 ml, and the inside of the cell was partitioned into two parts by a petri dish. Three pieces of Hilafilcon B in 14.2 mm diameter wetted with the soaking solution for a commercial soft contact lens were set inside of the dish horizontally and the known amount of salicylic acid was set outside of the dish. The amount of salicylic acid introduced into the high-pressure cell was 0.088–0.700 g that was much greater than the saturated solubility in supercritical CO2 at the experimental temperatures and pressures 0.084–0.66 g L−1 (Gurdial and Foster, 1991). The petri dish was covered with a stainless steel mesh (0.2 mm of mesh size) not to contact salicylic acid directly to the surface of Hilafilcon B. Carbon dioxide from a gas cylinder was liquefied through a cooling unit. The liquefied CO2 was pressurized and supplied to the system by a feed pump. A back-pressure regulator was used for
Fig. 2 – Supercritical CO2 impregnation apparatus. (1) CO2 bottle; (2) dryer; (3) back pressure regulator; (4) pressure gauge; (5) cooling bath; (6) feed pump; (7) check valve; (8) pressure gauge; (9) high-pressure cell; (10) temperature control unit; (11) depressurization valve.
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controlling the pressure in the system. The liquefied CO2 was introduced into the high-pressure cell at the desired temperature and attained to the supercritical state. The supercritical CO2 impregnations were conducted for 2 h. After the impregnation period, the system was depressurized at the various depressurization rates. The impregnated Hilafilcon B were then recovered from the high-pressure cell after the depressurization of the system. The recovered Hilafilcon B after the impregnation was dry. Then, Hilafilcon B were placed in 10 ml of the saturated salicylic acid aqueous solution using ultrapure water, 0.247 × 10−3 in mole fraction at 298 K (Nordström and Rasmuson, 2006) for 15 min in order to rehydrate Hilafilcon B. The rehydrated Hilafilcon B were recovered from the aqueous solution and the excess water on the Hilafilcon B surface was removed by the tissue paper before the test of the salicylic acid release.
2.2.2.
Aqueous solution impregnation
The aqueous solution impregnations of Hilafilcon B with salicylic acid were performed for the comparisons with those impregnated in supercritical CO2 . The Hilafilcon B was placed in 40 ml of salicylic acid saturated solution in ultrapure water. The concentration of salicylic acid in the solution was 2.2 × 10−3 g ml−1 . The impregnations in the aqueous solution were conducted for 2 h at 298 K. After the impregnations, the Hilafilcon B was recovered from the bottle of the aqueous solution and the excess water on the Hilafilcon B surface was removed by the tissue paper before the test of the salicylic acid release.
2.3. Characterization of hilafilcon B composite with salicylic acid 2.3.1.
Amount of salicylic acid in hilafilcon B
The composite prepared by the supercritical CO2 or aqueous solution impregnations was placed in 10 ml of the phosphate buffer solution at 298 K for 24 h in order to leach out the total amount of salicylic acid in Hilafilcon B. The samples were taken from the solution and analyzed by the UV–vis spectrophotometry for quantifying the amount of salicylic acid released from the Hilafilcon B. In this work, the total amounts of salicylic acid in Hilafilcon B are determined from the amount released into the phosphate aqueous solution for 24 h. The standard deviation of the amount of salicylic acid in Hilafilcon B was 0.06 × 10−4 g lens−1 .
Microstructure of hilafilcon B
The contact lenses with salicylic acid after the impregnation were cut by a razor and dried at 303 K. The cross section of the dried lens was observed by a Scanning Electron Microscope (SEM, KEYENCE, VE-8000).
3. Modeling of salicylic acid release from hilafilcon B The release profile of salicylic acid from the Hilafilcon B is assumed to the result from the two contributions: the initial instantaneous release of the adsorbed salicylic acid on the surface of Hilafilcon B and the release of the incorporated salicylic acid inside the hydrogel matrix of Hilafilcon B. The total amount of salicylic acid in the Hilafilcon B is given by the following equation: Mtot = Mads + Mdep
(1)
where, M denotes the amount of salicylic acid in Hilafilcon B. The superscripts tot, ads and dep mean the total amount, adsorbed amount on the surface and deposited amount inside the lenses, respectively. The adsorbed amount of salicylic acid at the surface of Hilafilcon B is obtained from the total amount in that prepared by the aqueous solution impregnation. It is assumed that the amount of salicylic acid from the rehydration solution to Hilafilcon B is almost the same as that adsorbed at the lens surface in aqueous solution impregnation. The deposited amount of salicylic acid inside Hilafilcon B can be calculated by discounting the adsorbed amounts using the Eq. (1). The amount of salicylic acid deposited inside the hydrogel matrix is modeled using the kinetic constant k and release exponent parameter n as follows (Korsmeyer et al., 1983; Ritger and Peppas, 1987).
Release profile
Hilafilcon B composite with the salicylic acid prepared by the supercritical CO2 or aqueous solution impregnations were immersed in 10 ml of the phosphate aqueous solution with pH 6.86 at 310 K with stirring for 8 h. The sample of 0.3 ml aliquots were collected at the predetermined time periods and replaced with the equivalent amount of the fresh phosphate aqueous solution. The frequencies of the sample collection were once every 10, 30 and 60 min at the release time 0–3, 3–6 and 6–8 h, respectively. The collected samples were diluted to 3 ml with the fresh phosphate aqueous solution. The released amounts of salicylic acid were determined from the analysis of the collected samples using UV–vis spectrophotometry (JASCO, model V-630, Japan) at 296 nm. The results of the release profile were determined from the average of the three samples at each condition.
2.3.2.
2.3.3.
91
dep
Mt
Mdep
= ktn
(2)
The subscript t is the release amount at time t. In this work, the kinetic constant k and release exponent parameter n were fitted to the first 60% release of salicylic acid deposited in Hilafilcon B.
4.
Results and discussion
4.1.
Aqueous solution impregnation
The release profiles of salicylic acid from Hilafilcon B composite prepared by the aqueous solution impregnation are shown in Fig. 3. In Fig. 3, it can be seen that Hilafilcon B composite prepared by the aqueous solution impregnation result in the profile that all the impregnated salicylic acid is released for 10 min. Furthermore, the amount of the salicylic acid impregnated into Hilafilcon B are 1.75 × 10−4 g in the one lens.
4.2.
Supercritical CO2 impregnation
4.2.1.
Effect of impregnation temperature
The release profiles of salicylic acid from Hilafilcon B composite prepared supercritical CO2 impregnation are presented in Fig. 4. Table 1 gives the total and deposited amount of salicylic acid in the lenses and the time taken for 60% release of the deposited salicylic acid. The kinetic constant and release exponent parameter are also presented in Table 1. To
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Fig. 3 – Release profile of salicylic acid from contact lens prepared by aqueous solution impregnation at 298 K.
Fig. 5 – Effect of impregnation pressure on release profile of salicylic acid from contact lenses prepared by supercritical CO2 impregnation at 313 K and depressurization rate 0.06 MPa min−1 . () 9.0 MPa; (䊉) 11.0 MPa; () 15.0 MPa.
Table 2 – Effect of impregnation pressure on experimental and modeled results of salicylic acid release from contact lenses at 313 K and depressurization rate 0.06 MPa min−1 . p (MPa) 9.0 11.0 15.0 a
b
Fig. 4 – Effect of impregnation temperature on release profile of salicylic acid from contact lenses prepared by supercritical CO2 impregnation at 11.0 MPa and depressurization rate 0.06 MPa min−1 . () 308 K; (䊉) 313 K; () 318 K. Table 1 – Effect of impregnation temperature on experimental and modeled results of salicylic acid release from contact lenses at 11 MPa and depressurization rate 0.06 MPa min−1 . T, K
308 313 318 a
b
S (g L−1 )a
0.47 0.34 0.22
t (min)b
62.7 79.5 101.8
Mtot × 104 , g lens−1 4.84 3.75 2.96
Mdep × 104 , g lens−1 3.09 2.00 1.21
k
0.062 0.032 0.075
n
0.55 0.67 0.61
Solubility of salicylic acid in supercritical carbon dioxide (Gurdial and Foster, 1991). Time taken for 60% release of deposited salicylic acid.
investigate the effect of temperature, the pressure and depressurization rate on the supercritical CO2 impregnation were fixed at 11 MPa and 0.06 MPa min−1 , respectively. As shown in Fig. 4, supercritical CO2 impregnation results in the release profile of salicylic acid slower than those prepared by the aqueous solution impregnation. The total amount of salicylic acid in the lenses increases with the decrease of the impregnation temperature. This is because the solubilities of salicylic acid in supercritical CO2 increase with decrease of the temperature
S (g L−1 )a 0.084 0.34 0.66
t (min)b 103.2 79.5 49.6
Mtot × 104 (g lens−1 ) 2.61 3.75 5.45
Mdep × 104 (g lens−1 ) 0.862 2.00 3.70
k
n
0.021 0.032 0.046
0.72 0.67 0.66
Solubility of salicylic acid in supercritical carbon dioxide (Gurdial and Foster, 1991). Time taken for 60% release of deposited salicylic acid.
at 11 MPa (Gurdial and Foster, 1991). The time taken for 60% release of the deposited salicylic acid also decreases with the decrease of the impregnation temperature as given in Table 1. The values of the release exponent parameters in Eq. (2) is between 0.5 and 1.0. This suggests that the salicylic acid releases from the lenses prepared by supercritical CO2 impregnation are resulted from the superimposition of Fickian controlled and hydrogel swelling controlled releases (Korsmeyer et al., 1983; Ritger and Peppas, 1987).
4.2.2.
Effect of impregnation pressure
Fig. 5 presents the release profiles of salicylic acid from the composite prepared supercritical CO2 impregnation. The total and deposited amount of salicylic acid in the lenses and the time taken for 60% release of the deposited salicylic acid are listed in Table 2. The kinetic constant and release exponent parameter are also presented in Table 2. To investigate the effect of pressure, the temperature and depressurization rate on the supercritical CO2 impregnation were fixed at 313 K and 0.06 MPa min−1 , respectively. The total amount of salicylic acid in the composite increases with the pressure. This is because the solubilities of salicylic acid in supercritical CO2 increase with pressure at constant temperature (Gurdial and Foster, 1991). The time taken for 60% release of the deposited salicylic acid decreases with the increase of pressure as given in Table 2. It is though that the solubility of salicylic acid in supercritical carbon dioxide is important to control the amount of that in the composite. The relationship between
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Table 3 – Effect of depressurization rate on experimental and modeled results of salicylic acid release from contact lenses at 313 K and 11.0 MPa. dp (MPa min−1 ) 0.06 0.12 0.18 a
b
Fig. 6 – Relationship between solubility of salicylic acid in supercritical CO2 (Gurdial and Foster, 1991) and total amount of salicylic acid in contact lenses.
the solubility in supercritical CO2 and the total amount of salicylic acid in the composites is shown in Fig. 6. There is the very strong correlation between the solubility in supercritical CO2 and the total amount of salicylic acid in the composites. The relationship between the solubility in supercritical CO2 C2
0.34 0.34 0.34
t (min)b 79.5 73.3 83.4
Mtot × 104 (g lens−1 ) 3.75 2.96 2.95
Mdep × 104 (g lens−1 ) 2.00 1.21 1.20
k
n
0.032 0.037 0.041
0.67 0.64 0.60
Solubility of salicylic acid in supercritical carbon dioxide (Gurdial and Foster, 1991). Time taken for 60% release of deposited salicylic acid.
(Gurdial and Foster, 1991) in g L−1 and the total amount of salicylic acid in the composite in g lens−1 is given by the following equation. Mtot = 0.0005589y2 + 0.0001907
4.2.3.
Fig. 7 – Effect of depressurization rate on release profile of salicylic acid from contact lenses prepared by supercritical CO2 impregnation at 313 K and 11.0 MPa. () 0.06 MPa min−1 ; (䊉) 0.12 MPa min−1 ; () 0.18 MPa min−1 .
S (g L−1 )a
(3)
Effect of depressurization rate
The supercritical CO2 impregnations were performed at 313 K and 11 MPa by changing the depressurization rate, 0.06 to 0.18 MPa min−1 . The effects of the depressurization rate on the release profile of salicylic acid are studied as shown in Fig. 7. Table 3 gives the total and deposited amount of salicylic acid in the composites and the time taken for 60% release of the deposited drug. The kinetic constant and release exponent parameter are also presented in Table 3. The total amount of salicylic acid in the composite at the depressurization rate 0.06 MPa min−1 is higher than those in case of 0.12 and 0.18 MPa min−1 . It is thought that the higher depressurization rate leads to a rapid mass transfer of the CO2 impregnated in the hydrogel matrix to vapor phase. This rapid CO2 mass transfer seems to cause the transfer of salicylic acid impregnated in the hydrogel to outside of Hilafilcon B. The SEM pictures of the cross-section of the contact lenses depressurized at 0.06 and 0.18 MPa min−1 are shown in Fig. 8. As shown in Fig. 8, the higher depressurization rate leads to the destruction of the lenses due to the rapid mass transfer of the dissolved CO2 in the hydrogel.
5.
Conclusion
Supercritical CO2 impregnation was used for the preparation of Hilafilcon B with salicylic acid. The salicylic acid-loaded composites prepare by supercritical CO2 impregnation are
Fig. 8 – SEM observations of microstructure of contact lenses prepared by supercritical CO2 impregnation. Depressurization rate: (a) 0.06 MPa min−1 ; (b) 0.18 MPa min−1 .
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capable of the release profile slower than those by aqueous solution impregnation. The increase of the impregnation temperature results in the decrease of the amount of salicylic acid in the composite. The amount of salicylic acid in the composite increases with the impregnation pressures. These effects of the impregnation temperatures and pressure can be explained from the strong correlation between the solubility of salicylic acid in supercritical CO2 and amount of salicylic acid in the composites. The high depressurization rate results in the low amount of salicylic acid in the composites and the destruction of the microstructure of the lenses. The kinetic constant and release exponent parameter in the mass transfer equation were determined from the release data of salicylic acid from the composites. This modeling suggest that salicylic acid release from the composites prepared by supercritical CO2 impregnation can be conducted by the superimposition of Fickian controlled and hydrogel swelling controlled releases.
References Braga, M.E., Costa, V.P., Pereira, M.J.T., Fiadeiro, P.T., Gomes, A.P.A.R., Durate, C.M.M., de Sousa, H.C., 2011. Effects of operational conditions on the supercritical solvent impregnation of acetazolamide in Balafilcon A commercial contact lenses. Int. J. Pharm. 420, 231–243. Braga, M.E.M., Pato, M.T.V., Costa Silva, H.S.R., Ferreira, E.I., Gil, M.H., Durate, C.M.M., de Sousa, H.C., 2008. Supercritical solvent impregnation of ophthalmic drugs on chitosan derivatives. J. Supercrit. Fluids 44, 245–257. Costa, V.P., Braga, M.E.M., Guerra, J.P., Duarte, A.R.C., Duarte, C.M.M., Leite, E.O.B., Gil, M.H., de Sousa, H.C., 2010a. Development of therapeutic contact lenses using a supercritical solvent impregnation method. J. Supercrit. Fluids 52, 306–316. Costa, V.P., Braga, M.E.M., Duarte, C.M.M., Alvarez-Lorenzo, C., Concheiro, A., Gil, M.H., de Sousa, H.C., 2010b. Anti-glaucoma
drug-loaded contact lenses prepared using supercritical solvent impregnation. J. Supercrit. Fluids 53, 165–173. González-Chomón, C., Braga, M.E.M., de Sousa, H.C., Concheiro, A., Alvarez-Lorenzo, C., 2012. Antifouling flodable acrylic IOLs loaded with norfloxacin by aqueous soaking and by supercritical carbon dioxide technology. Eur. J. Pharm. Biopharm. 82, 383–391. ˜ Yanez, F., Martikainen, L., Braga, M.E.M., Alvarez-Lorenzo, C., Concheiro, A., Duarte, C.M.M., Gil, M.H., de Sousa, H.C., 2011. Supercritical fluid-assisted preparation of imprinted contact lenses for drug delivery. Acta Biomater. 7, 1019–1030. Gurdial, G.S., Foster, N.R., 1991. Solubility of o-hydroxybenzoic acid in supercritical carbon dioxide. Ind. Eng. Chem. Res. 30, 575–580. Kim, J., Peng, C.C., Chauhan, A., 2010. Extended release of dexamethasone from silicone-hydrogel contact lenses containing vitamin E. J. Control. Release 148, 110–116. Korsmeyer, R.W., Gurny, R., Doelker, E., Buri, P., Peppas, N.A., 1983. Mechanism of solute release from porous hydrophilic polymers. Int. J. Pharm. 15, 25–35. Masmoudi, Y., Azzouk, L.B., Forzano, O., Andre, J.M., Badens, E., 2011. Supercritical impregnation of intraocular lenses. J. Supercrit. Fluids 60, 98–105. Nair, K.L., Vidyanand, S., James, J., Kumar, G.S.V., 2012. Pilocarpine-loaded poly(DL-lactic-co-glycolic acid) nanoparticles as potential candidates for controlled drug delivery with enhanced ocular pharmacological response. J. Appl. Polym. Sci. 124, 2030–2036. Nordström, F.L., Rasmuson, Å.C., 2006. Solubility and melting properties of salicylic acid. J. Chem. Eng. Data 51, 1668–1671. Pingnatello, P., Bucolo, C., Spedalieri, G., Maltese, A., Puglisi, G., 2002. Flurbiprofen-loaded acrylate polymer nanosuspensions for ophthalmic application. Biomaterials 23, 3247–3255. Ritger, P.L., Peppas, N.A., 1987. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J. Control. Release 5, 37–42. Yamazaki, Y., Matsunaga, T., Syohji, K., Arakawa, T., Sato, T., 2013. Effect of anionic/siloxy groups on the release of ofloxacin from soft contact lenses. J. Appl. Polym. Sci. 127, 5022–5027.