Abstract
Poly(N-acryloyl glycinamide) polymers are soluble in hot aqueous media that gel rapidly on cooling. This gelatin-like behavior was previously compared with drug delivery requirements. Slow releases were demonstrated in vitro using different model molecules and macromolecules and in vivo using methylene blue. Risperidone is a weak basic drug sparingly soluble in water frequently used to treat patients suffering of schizophrenia. A standard risperidone-poly(N-acryloyl glycinamide) hydrogel formulation was selected from which the drug was allowed to release comparatively in buffered and non-buffered isotonic media at 37 °C under pseudo sink conditions. Linear release was observed in pH = 7.4 phosphate buffer whereas in buffer-free 0.15 M NaCl, the release was initially faster than in the buffer but became rapidly slower as the pH increased from 6.8 to 8.2. These features were related to the ionization-dependent solubility of risperidone. In order to minimize the ionization and thus the solubility of the drug inside the hydrogel despite outside buffering at 7.4, Mg(OH2), a sparingly soluble mineral base, was added to the standard formulation. This addition resulted in a c.a. threefold increase of the zero-order release duration. The method should be applicable to other sparingly soluble weakly basic drugs.
References
Haas HC, Schuler NW. Thermally reversible homopolymer gel systems. J Polym Sci. 1964;2:1095–6.
Haas HC, Moreau RD, Schuler NW. Synthetic thermally reversible gel systems. II J Polym Sci Polym Phys Ed. 1967;5:915–27.
Haas HC, Chiklis CK, Moreau RD. Synthetic thermally reversible gel systems. III J Polym Sci Part A-1 Polym Chem. 1970;8:1131–45.
Boustta M, Colombo P-E, Vert M. Combination of poly(N-acryloyl glycinamide) with at least one active principle. PCT Int. Appl. (2013), WO 2013128373, A1 20130906.
Boustta M, Colombo P-E, Lenglet S, Poujol S, Vert M. Versatile UCST-based thermoresponsive hydrogels for loco-regional sustained drug delivery. J Control Release. 2014;174:1–6.
Bale S, Khurana A, Reddy AS, Singh M, Godugu C. Overview of therapeutic applications of microparticulate drug delivery systems. Crit. Rev. Ther. Drug Carrier Syst. 2016;33:309–61.
Bagratashvili VN, Bogorodskii SE, Egorov AM, Krotova LI, Popov VK, Sevast'yanov VI. Supercritical fluid fabrication of components for a sustained-release injectable risperidone dose form. Russian J Phys Chem B. 2016;10:1123–30.
Acharya G, Shin CS, Vedantham K, McDermott M, Rish T, Hansen K, Fu Y, Park K. A study of drug release from homogeneous PLGA microstructures. J Control Release. 2010;146(2):201–6.
Rabin C, Liang Y, Ehrlichman RS, Budhian A, Metzger KL, Winey KI, Majewski-Tiedeken C, Siegel SJ. In vitro and in vivo demonstration of risperidone implants in mice. Schizophr Res. 2008;98:66–78.
Amann LC, Gandal MJ, Lin R, Liang Y, Siegel SJ. In vitro–in vivo correlations of scalable PLGA-risperidone implants for the treatment of schizophrenia. Pharm Res. 2010;27:1730–7.
Taktak F, Bütün V. Novel zwitterionic ABA-type triblock copolymer for pH- and salt-controlled release of risperidone. Int J Polym Mater Polym Biomater. 2016;65:151–61.
Saha S, Sarkar P, Sarkar M, Giri B. Electroconductive smart polyacrylamide-polypyrrole (PAC-PPY) hydrogel: a device for controlled release of risperidone. RSC Adv. 2015;5:27665–73.
MHRA, Risperidone 0.5mg, 1mg, 2mg, 3mg, 4mg and 6mg Film-Coated Tablets, PL 29412/0002–7 report. http://www.mhra.gov.uk/home/groups/par/documents/websiteresources/con123334.pdf.
Hu Z, Liu Y, Yuan W, Wu F, Su J, Jin T. Effect of bases with different solubility on the release behavior of risperidone loaded PLGA microspheres. Coll Surf B Biointerfaces. 2011;86:206–11.
Olesen OV, Licht RW, Thomsen E, Bruun T, Viftrup JE, Linnet K. Serum concentrations and side effects in psychiatric patients during risperidone therapy. Ther Drug Monit. 1998;20:380–4.
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Authors are indebted to CNRS, University Montpellier and CNRS for financial supports.
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Boustta, M., Vert, M. A method to slow down the ionization-dependent release of risperidone loaded in a thermoresponsive poly(N-acryloyl glycinamide) hydrogel. Drug Deliv. and Transl. Res. 7, 460–464 (2017). https://doi.org/10.1007/s13346-017-0376-5
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DOI: https://doi.org/10.1007/s13346-017-0376-5