Abstract
The potential of poly(ethylene oxide)-poly(propylene oxide) block copolymers Pluronic® F127 (PF127) and Tetronic® 304 (T304), 904 (T904) and 1307 (T1307) as components of solid self-(micro)emulsifying dosage forms, S(M)EDDS, was evaluated. The dependence of the self-associative properties of Tetronics on pH explained the low ability of the micelles to solubilize griseofulvin at acid pH (sevenfold increase) compared to at alkaline pH (12-fold). Blends of polyglycolyzed glycerides (Labrasol, Labrafac CC, and Labrafil M 1944CS) with each copolymer at two different weight ratios (80:20 and 60:40) were prepared, diluted in water, and characterized in terms of globule size, appearance and griseofulvin solubility. The blends with Labrasol led to microemulsions that are able to increase drug solubility up to 30-fold. SMEDD hard gelatine capsules filled with griseofulvin and Labrasol or Labrasol/copolymer 80:20 showed a remarkable increase in drug solubility and dissolution rate, particularly when T904, T1307 or PF127 was present in the blend. This effect was more remarkable when the volume of the dissolution medium was 200 ml (compared to 900 ml), which can be related to a higher stability of the microemulsion when there is a greater concentration of the copolymer and glyceride in the medium.
Similar content being viewed by others
References
C. W. Pouton. Formulation of poorly water-soluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system. Eur. J. Pharm Sci. 29:278–287 (2006).
R. N. Gursoy, and S. Benita. Self-emulsifying drug delivery systems (SMEDDS) for improved oral delivery of liphophilic drugs. Biomed. Pharmacother. 58:173–182 (2004).
F. S. Nielsen, E. Gibault, H. Ljusberg-Wahren, L. Arleth, J. S. Pedersen, and A. Müllertz. Characterization of prototype self-nanoemulsifying formulations of lipophilic compounds. J. Pharm. Sci. 96:876–892 (2007).
R. G. Strickley. Solubilizing excipients in oral and injectable formulations. Pharm. Res. 21:201–230 (2004).
W. Wu, Y. Wang, and L. Que. Enhanced bioavailability of silymarin by self-microemulsifying drug delivery system. Eur. J. Pharm. Biopharm. 63:288–294 (2006).
E. I. Taha, S. Al-Saidan, A. M. Samy, and M. A. Khan. Preparation and in vitro characterization of self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate. Int. J. Pharm. 285:109–119 (2004).
J. Y. Hong, J. K. Kim, Y. K. Song, J. S. Park, and C. K. Kim. A new self-emulsifying formulation of itraconazole with improved dissolution and oral absorption. J. Control Release. 110:332–338 (2006).
A. A. Date, and M. S. Nagarsenker. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int. J. Pharm. 329:166–172 (2007).
S. Nazzal, and M. A. Khan. Controlled release of a self-emulsifying formulation from a tablet dosage form: Stability assessment and optimization of some processing parameters. Int. J. Pharm. 315:110–121 (2006).
J. M. Newton, M. R. Pinto, and F. Podczeck. The preparation of pellets containing a surfactant or a mixture of mono- and di-glycerides by extrusion/spheronization. Eur. J. Pharm. Sci. 30:333–342 (2007).
A. Abdalla, and K. Mäder. Preparation and characterization of a self-emulsifying pellet formulation. Eur. J. Pharm. Biopharm. 66:220–226 (2007).
M. Serratoni, M. Newton, S. Booth, and A. Clarke. Controlled drug release from pellets containing water-insoluble drugs dissolved in a self-emulsifying system. Eur. J. Pharm. Biopharm. 65:94–98 (2007).
A. V. Kabanov, E. V. Batrakova, and V. Y. Alakhov. Pluronic® block copolymers for overcoming drug resistance in cancer. Adv. Drug Del. Rev. 54:759–779 (2002).
S. R. Croy, and G. S. Kwon. Polymeric micelles for drug delivery. Curr. Pharm. Des. 12:4669–4684 (2006).
M. F. Francis, M. Christea, and F. M. Winnik. Polymeric micelles for oral drug delivery: Why and how. Pure Appl. Chem. 76:1321–1335 (2004).
M. H. Dufresne, D. Le Garrec, V. Sant, J. C. Leroux, and M. Ranger. Preparation and characterization of water-soluble pH-sensitive nanocarriers for drug delivery. Int. J. Pharm. 277:81–90 (2004).
V. P. Torchilin. Block copolymer micelles as a solution for drug delivery problems. Expert Opin. Ther. Patents. 15:63–75 (2005).
G. Dumortier, J. L. Grossiord, F. Agnely, and J. C. Chaumeil. A review of poloxamer 407 pharmaceutical and pharmacological characteristics. Pharm. Res. 23:2709–2728 (2006).
D. A. Chiappetta, and A. Sosnik. Poly(ethylene oxide)–poly(propylene oxide) block copolymer micelles as drug delivery agents: Improved hydrosolubility, stability and bioavailability of drugs. Eur. J. Pharm. Biopharm. 66:303–317 (2007).
J. Dong, J. K. Armstrong, B. Z. Chowdhry, and S. A. Leharne. Themodynamic modelling of the effect of pH upon aggregation transitions in aqueous solutions of the poloxamine T701. Thermochim. Acta. 417:201–206 (2004).
C. Alvarez-Lorenzo, J. Gonzalez-Lopez, M. Fernandez-Tarrio, I. Sandez-Macho, and A. Concheiro. Tetronic micellization, gelation and drug solubilization: Influence of pH and ionic strength. Eur. J. Pharm. Biopharm. 66:244–252 (2007).
L. Olivieri, M. Seiller, L. Bromberg, M. Besnard, T. N. Duong, and J. L. Grossiord. Optimization of a thermally reversible W/O/W multiple emulsion for shear-induced drug release. J. Control Release. 88:401–412 (2003).
C. R. E. Mansur, S. P. Barboza, G. Gonzales, and E. F. Lucas. Pluronic and tetronic polyols: study of their properties and performance in the destabilization of emulsions formed in the petroleum industry. J. Colloid Interf. Sci. 271:232–240 (2004).
F. Tirnaksiz, and O. Kalsin. A topical w/o/w multiple emulsions prepared with Tetronic 908 as a hydrophilic surfactant: Formulation, characterization and release study. J. Pharm. Pharmaceut. Sci. 8:299–315 (2005).
J. Y. Hong, J. K. Kim, Y. K. Song, J. S. Park, and C. K. Kim. A new self-emulsifying formulation of itraconazole with improved dissolution and oral absorption. J. Control. Release. 110:332–338 (2006).
C. Perreur, J. P. Habas, J. Peyrelasse, J. François, and A. Lapp. Rheological and small-angle neutron scattering studies of aqueous solutions of branched PEO-PPO-PEO copolymers, Part 1. Physical Rev. E. 63:031505 (2001).
M. Fernandez-Tarrio, C. Alvarez-Lorenzo, and A. Concheiro. Calorimetric approach to tetronic/water interactions. J. Thermal. Anal. Calor. 87:171–178 (2007).
R. Takano, K. Sugano, A. Higashida, Y. Hayashi, M. Machida, Y. Aso, and S. Yamashita. Oral absorption of poorly water-soluble drugs: computer simulation of fraction absorbed in humans from a miniscale dissolution test. Pharm. Res. 23:1144–1156 (2006).
C. O. Rangel-Yagui, A. Pessoa Jr., and L. C. T. Costa Tavares. Micellar solubilization of drugs. J. Pharm. Pharmaceut. Sci. 8:147–163 (2005).
P. Alexandridis, J. F. Holzwarth, and T. A. Hatton. A correlation for the estimation of critical micellization concentrations and temperatures of polyols in aqueous-solutions. J. Am. Oil Chem. Soc. 72:823–826 (1995).
A. Balakrishnari, B. D. Rege, G. Amidon, and J. E. Polli. Surfactant-mediated dissolution: contribution of solubility enhancement and relatively low micelle diffusivity. J. Pharm. Sci. 93:2064–2075 (2004).
N. R. Calafato, and G. Pico. Griseofulvin and ketoconazole solubilization by bile salts studied using fluorescence spectroscopy. Colloid. Surface B. 47:198–204 (2006).
M. Devani, M. Ashford, and D. Q. M. Craig. The emulsification and solubilization properties of polyglycolysed oils in self-emulsifying formulations. J. Pharm. Pharmacol. 56:307–316 (2004).
Z. Hu, R. Tawa, T. Konishi, N. Shibata, and K. Takada. A novel emulsifier, Labrasol, enhances gastrointestinal absorption of gentamicin. Life Sci. 69:2899–2910 (2001).
BASF, technical literature. Available at: http://www.basf.com/performancechemical/. Accessed October 22, 2007.
Acknowledgments
This work was financed by the Ministerio de Educación y Ciencia (SAF2005–01930) FEDER, and Xunta de Galicia (PGIDIT05BTF203011PR; equipment grant PGIDT01PX1203014IF), Spain. F. Yañez thanks MEC for a FPI fellowship. The authors thanks BASF Corporation for providing samples of Tetronic® varieties and to Gattefossé España S.A. for providing samples of polyglycolized glycerides.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fernandez-Tarrio, M., Yañez, F., Immesoete, K. et al. Pluronic and Tetronic Copolymers with Polyglycolyzed Oils as Self-Emulsifying Drug Delivery Systems. AAPS PharmSciTech 9, 471–479 (2008). https://doi.org/10.1208/s12249-008-9070-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1208/s12249-008-9070-8