Study on solubility improvement of lidocaine by ternary solid dispersion

doi:10.5246/jcps.2020.01.005

Abstract

Abstract:

In the present study, we aimed to probe the possibility of using mixed poloxamers as carriers to prepare ternary solid dispersion (SD) that facilitated solubility and dissolution rate of the poorly water soluble drug and compare with binary SD with single poloxamer. Lidocaine (LIC) was selected as a model drug, and poloxamer 188 (P188) and poloxamer 407 (P407) were utilized as single and mixed carriers. Depending on DSC and the dissolution testing, the appropriate ratio of SD prepared by melting method was optimized. Ternary and binary SD was characterized by DSC, XRD, SEM and FTIR. In vitro dissolution study, phase solubility study and saturated solubility study were performed to clarify solubilization from apparent phenomena and inherent reason. Moreover, stability study under different relative humidity (RH) was investigated. Physical characterizations of binary and ternary SD exhibited the formation of eutectic mixture and the presence of molecular interaction. Compared with the pure LIC, the dissolution rate and solubility of LIC in binary and ternary SDs were enhanced. The phase solubility study revealed an AL-type curve. Furthermore, the stability test indicated that ternary and binary SD was stable. The results of this study demonstrated that SD with mixed poloxamers could improve dissolution rate and solubility of poorly water-soluble drug.

Key words: Solubility, Lidocaine, Poloxamer, Solid dispersion

CLC Number:

R944

Supporting:

Wenling Fan, Yan Xu, Xinyi Zhang, Liuqing Di, Lei Li. Study on solubility improvement of lidocaine by ternary solid dispersion[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(1): 55-65.

References

[1] Baird, J.A.; Taylor, L.S. Evaluation of amorphous solid dispersion properties using thermal analysis techniques. Adv. Drug Deliv. Rev. 2012, 64, 396–421.

[2] Stella, V.J.; Nti-Addae, K.W. Prodrug strategies to overcome poor water solubility. Adv. Drug Deliv. Rev. 2007, 59, 677–694.

[3] Seo, J.H.; Park, J.B.; Choi, W.K.; Park, S.; Sung, Y.J.; Oh, E.; Bae, S.K. Improved oral absorption of cilostazol via sulfonate salt formation with mesylate and besylate. Drug Des. Devel. Ther. 2015, 9, 3961–3968.

[4] Serrano, D.R.; Gallagher, K.H.; Healy, A.M. Emerging nanonisation technologies: tailoring crystalline versus amorphous nanomaterials. Curr. Top. Med. Chem. 2015, 15, 2327–2340.

[5] Sekiguchi, K.; Obi, N. Studies on absorption of eutectic mixture. I. A comparison of the behavior of eutectic mixture of sulfathiazole and that of ordinary sulfathiazole in man. Chem. Pharm. Bull. 1961, 9, 866–872.

[6] Ma, Y.Z.; Gill, H.S. Coating solid dispersions on microneedles via a molten dip-coating method: development and in vitro evaluation for transdermal delivery of a water-insoluble drug. J. Pharm. Sci. 2014, 103, 3621–3630.

[7] Kawakami, K. Modification of physicochemical characteristics of active pharmaceutical ingredients and application of supersaturatable dosage forms for improving bioavailability of poorly absorbed drugs. Adv. Drug Deliv. Rev. 2012, 64, 480–495.

[8] Chaudhari, S.P.; Dugar, R.P. Application of surfactants in solid dispersion technology for improving solubility of poorly water soluble drugs. J. Drug Deliv. Sci. Technol. 2017, 41, 68–77.

[9] Nepal, P.R.; Han, H.K.; Choi, H.K. Enhancement of solubility and dissolution of coenzyme Q10 using solid dispersion formulation. Int. J. Pharm. 2010, 383, 147–153.

[10] Kolašinac, N.; Kachrimanis, K.; Homšek, I.; Grujić, B.; Ðurić, Z.; Ibrić, S. Solubility enhancement of desloratadine by solid dispersion in poloxamers. Int. J. Pharm. 2012, 436, 161–170.

[11] Vukićević, M.; Hegge, A.B.; Vulić, P.; Tønnesen, H.H. Poloxamer-based curcumin solid dispersions for ex tempore preparation of supersaturated solutions intended for antimicrobial photodynamic therapy. Pharm. Dev. Technol. 2015, 20, 863–871.

[12] Medarević, D.P.; Kachrimanis, K.; Mitrić, M.; Djuriš, J.; Djurić, Z.; Ibrić, S. Dissolution rate enhancement and physicochemical characterization of carbamazepine-poloxamer solid dispersions. Pharm. Dev. Technol. 2016, 21, 268–276.

[13] Song, C.K.; Yoon, I.S.; Kim, D.D. Poloxamer-based solid dispersions for oral delivery of docetaxel: Differential effects of F68 and P85 on oral docetaxel bioavailability. Int. J. Pharm. 2016, 507, 102–108.

[14] Khatri, P.; Shah, M.K.; Patel, N.; Jain, S.; Vora, N.; Lin, S.S. Preparation and characterization of pyrimethamine solid dispersions and an evaluation of the physical nature of pyrimethamine in solid dispersions. J. Drug Deliv. Sci. Technol. 2018, 45, 110–123.

[15] Tambe, A.; Pandita, N. Enhanced solubility and drug release profile of boswellic acid using a poloxamer-based solid dispersion technique. J. Drug Deliv. Sci. Technol. 2018, 44, 172–180.

[16] Kabanov, A.V.; Alakhov, V.Y. Pluronic block copolymers in drug delivery: from micellar nanocontainers to biological response modifiers. Crit. Rev. Ther. Drug Carrier. Syst. 2002, 19, 1–72.

[17] Lakshman, J.P.; Cao, Y.; Kowalski, J.; Serajuddin, A.T. Application of melt extrusion in the development of a physically and chemically stable high-energy amorphous solid dispersion of a poorly water-soluble drug. Mol. Pharm. 2008, 5, 994–1002.

[18] Marsac, P.J.; Li, T.L.; Taylor, L.S. Estimation of drug-polymer miscibility and solubility in amorphous solid dispersions using experimentally determined interaction parameters. Pharm. Res. 2009, 26, 139–151.

[19] Xu, M.; Zhang, C.G.; Luo, Y.F.; Xu, L.S.; Tao, X.G.; Wang, Y.J.; He, H.B.; Tang, X. Application and functional characterization of POVACOAT, a hydrophilic co-polymer poly(vinyl alcohol/acrylic acid/methyl methacrylate) as a hot-melt extrusion carrier. Drug Dev. Ind. Pharm. 2014, 40, 126–135.

[20] Newa, M.; Bhandari, K.H.; Li, D.X.; Kwon, T.H.; Kim, J.A.; Yoo, B.K.; Woo, J.S.; Lyoo, W.S.; Yong, C.S.; Choi, H.G. Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188. Int. J. Pharm. 2007, 343, 228–237.

[21] Kreidel, R.N.; Duque, M.D.; Serra, C.H.R.; Velasco, M.V.R.; Baby, A.R.; Kaneko, T.M.; Consiglieri, V.O. Dissolution enhancement and characterization of nimodipine solid dispersions with poloxamer 407 or PEG 6000. J. Dispers. Sci. Technol. 2012, 33, 1354–1359.

[22] Brouwers, J.; Brewster, M.E.; Augustijns, P. Supersaturating drug delivery systems: the answer to solubility-limited oral bioavailability? J. Pharm. Sci. 2009, 98, 2549–2572.

[23] Seo, S.W.; Han, H.K.; Chun, M.K.; Choi, H.K. Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier. Int. J. Pharm. 2012, 424, 18–25.

[24] Urbanetz, N.A. Stabilization of solid dispersions of nimodipine and polyethylene glycol 2000. Eur. J. Pharm. Sci. 2006, 28, 67–76.

[25] Newman, A.W.; Reutzel-Edens, S.M.; Zografi, G. Characterization of the “hygroscopic” properties of active pharmaceutical ingredients. J. Pharm. Sci. 2008, 97, 1047–1059.

[26] Liu, J.; Cao, F.; Zhang, C.; Ping, Q.N. Use of polymer combinations in the preparation of solid dispersions of a thermally unstable drug by hot-melt extrusion. Acta Pharm. Sin. B. 2013, 3, 263–272.