Drug Solubilization by Means of Partition/Association Equilibrium Using a Modified Nanosized Dendrimeric Biopolymer
- 37 Downloads
The objective of this study is to elucidate the combined effects of a novel type of material being investigated as a new excipient, an octenylsuccinate-modified dendrimer-like biopolymer (OS-DLB) and poloxamer (PLX), on the solubility of poorly water-soluble compounds. Phenytoin (PHT), griseofulvin (GSF), ibuprofen (IBU), and loratadine (LOR) were used as model compounds. Phase solubility measurements were conducted to determine the relative proportions of API, OS-DLB, and PLX that result in the most stable dendrimeric complexes. The solubilizing power of OS-DLB increases with increasing hydrophobicity of the solute. In the presence of PLX, the solubilization effect of OS-DLB is modestly accentuated for the most hydrophobic drugs (IBU and LOR) but has no effect on the least hydrophobic one (PHT). The maximum potentiation effect of PLX on the solubilizing properties of OS-DLB was observed for GSF, the drug of intermediate hydrophobicity. Three different types of solubilization profiles were obtained in the study. All three different profiles can be appropriately described by a single solubilization model, depending on the specific parameter values. The defining parameters of the model reflect the hydrophobicity of the drug on the one hand and, on the other hand, the inherent tendency of the drug (crystal lattice energy) toward crystallization.
KEY WORDSsolubility solid dispersion solution phase model excipients
We thank Prof. Yuan Yao’s laboratory for providing the DLB material used in the study.
Financial support from the Dane O. Kildsig Center for Pharmaceutical Processing Research (CPPR), Purdue Research Foundation, and the National Science Foundation (NSF DMR 1310475) is gratefully acknowledged.
- 1.Yalkowsky SH. Solubility and solubilization in aqueous media. New York: American Chemical Society; 1999.Google Scholar
- 10.Karagianni A, Kachrimanis K, Nikolakakis I. Co-amorphous solid dispersions for solubility and absorption improvement of drugs: composition, preparation, characterization and formulations for oral delivery. Pharmaceutics. 2018;10(3). https://doi.org/10.3390/pharmaceutics10030098.CrossRefGoogle Scholar
- 17.Connors K, Higuchi T. Phase solubility techniques. Adv Anal Chem Instrum. 1965;4:117–212.Google Scholar
- 18.Takacs-Novak K, Urac M, Horvath P, Volgyi G, Anderson BD, Avdeef A. Equilibrium solubility measurement of compounds with low dissolution rate by Higuchi’s facilitated dissolution method. A validation study. Eur J Pharm Sci. 2017;106:133–41. https://doi.org/10.1016/j.ejps.2017.05.064.CrossRefPubMedGoogle Scholar
- 19.Repta AJ. Alteration of apparent solubility through complexation. In: S.H. Yolkowsky, editor. Techniques of solubilization of drugs. New York: Marcell Dekker, Inc.; 1981.Google Scholar
- 20.Yalkowsky SH, Roseman TJ. Solubilization of drugs by cosolvents. In: Yalkowsky SH, editor. Techniques of solubilization of drugs. New York: Marcell Dekker, Inc.; 1981. p. Chapter 3.Google Scholar
- 23.Timasheff SN. Control of protein stability and reactions by weakly interacting cosolvents: the simplicity of the complicated. In: Di Cera E, editor. Advances in protein chemistry. San Diego, California: Academic Press; 1998. p. 355–432.Google Scholar
- 25.Attwood D, Elworthy PH, Lawrence MJ. Effect of structural variations of non-ionic surfactants on micellar properties and solubilization: surfactants with semi-polar hydrophobes. J Pharm Pharmacol. 1989;41(9):585–9. https://doi.org/10.1111/j.2042-7158.1989.tb06536.x.CrossRefPubMedGoogle Scholar
- 26.Lawrence MJ, Elworthy PH, Attwood D. The effect of modification on solubilisation and micellar properties of a non-ionic surfactant. J Pharm Pharmacol. 1985;37(S12):2P. https://doi.org/10.1111/j.2042-7158.1985.tb14074.x.CrossRefGoogle Scholar
- 27.Elworthy PH, Patel MS. Demonstration of maximum solubilization in a polyoxyethylene alkyl ether series of non-ionic surfactants. J Pharm Pharmacol. 1982;34(9):543–6. https://doi.org/10.1111/j.2042-7158.1982.tb04790.x.CrossRefPubMedGoogle Scholar