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Ternary systems of naproxen with hydroxypropyl-beta-cyclodextrin and aminoacids.
Int J Pharm. 2003 Jul 24; 260(2):293-302.IJ

Abstract

The purpose of the present study was to investigate the combined effect of hydroxypropyl-beta-cyclodextrin and different aminoacids (L-lysine, LYS; L-valine, VAL; L-iso-leucine, LEU; and L-arginine, ARG) on the solubility of naproxen, a poorly water-soluble anti-inflammatory drug. Aqueous solubilities of naproxen in binary and ternary systems with hydroxypropyl-beta-cyclodextrin and each aminoacid were determined. The pH was measured in all solubility studies and its role on drug solubility variation was evaluated. Arginine was the most effective aminoacid in improving drug solubility and the only one which showed a synergistic effect when used in combination with hydroxypropyl-beta-cyclodextrin. In contrast, some reduction with respect to the theoretical drug solubility (i.e. the sum of the solubilities in the presence of cyclodextrin and aminoacid separately) was observed in ternary combinations with the other aminoacids. This occurred also in the case of lysine, despite the higher solubility of its ternary system in comparison with the binary cyclodextrin complex at pH 7. Phase-solubility experiments showed that the ternary system with arginine (pH approximately 7) exhibited a stability constant 3.6 times higher and was about 5.5 times more effective in improving drug solubility than the binary complex in buffered (pH approximately 7) aqueous solutions. These results demonstrated that the high increase in the drug solubility shown by ternary systems with arginine was not simply due to a favorable pH change but to multicomponent complex formation. Solid products of naproxen with hydroxypropyl-beta-cyclodextrin, and/or arginine, prepared by different methods, were characterized by Differential Scanning Calorimetry (DSC), Hot Stage Microscopy (HSM) and Scanning Electron Microscopy (SEM).

Authors+Show Affiliations

Department of Pharmaceutical Sciences, University of Florence, Via G. Capponi 9, 50121 Firenze, Italy. mura@unifi.itNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12842348

Citation

Mura, Paola, et al. "Ternary Systems of Naproxen With Hydroxypropyl-beta-cyclodextrin and Aminoacids." International Journal of Pharmaceutics, vol. 260, no. 2, 2003, pp. 293-302.
Mura P, Maestrelli F, Cirri M. Ternary systems of naproxen with hydroxypropyl-beta-cyclodextrin and aminoacids. Int J Pharm. 2003;260(2):293-302.
Mura, P., Maestrelli, F., & Cirri, M. (2003). Ternary systems of naproxen with hydroxypropyl-beta-cyclodextrin and aminoacids. International Journal of Pharmaceutics, 260(2), 293-302.
Mura P, Maestrelli F, Cirri M. Ternary Systems of Naproxen With Hydroxypropyl-beta-cyclodextrin and Aminoacids. Int J Pharm. 2003 Jul 24;260(2):293-302. PubMed PMID: 12842348.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ternary systems of naproxen with hydroxypropyl-beta-cyclodextrin and aminoacids. AU - Mura,Paola, AU - Maestrelli,Francesca, AU - Cirri,Marzia, PY - 2003/7/5/pubmed PY - 2003/9/27/medline PY - 2003/7/5/entrez SP - 293 EP - 302 JF - International journal of pharmaceutics JO - Int J Pharm VL - 260 IS - 2 N2 - The purpose of the present study was to investigate the combined effect of hydroxypropyl-beta-cyclodextrin and different aminoacids (L-lysine, LYS; L-valine, VAL; L-iso-leucine, LEU; and L-arginine, ARG) on the solubility of naproxen, a poorly water-soluble anti-inflammatory drug. Aqueous solubilities of naproxen in binary and ternary systems with hydroxypropyl-beta-cyclodextrin and each aminoacid were determined. The pH was measured in all solubility studies and its role on drug solubility variation was evaluated. Arginine was the most effective aminoacid in improving drug solubility and the only one which showed a synergistic effect when used in combination with hydroxypropyl-beta-cyclodextrin. In contrast, some reduction with respect to the theoretical drug solubility (i.e. the sum of the solubilities in the presence of cyclodextrin and aminoacid separately) was observed in ternary combinations with the other aminoacids. This occurred also in the case of lysine, despite the higher solubility of its ternary system in comparison with the binary cyclodextrin complex at pH 7. Phase-solubility experiments showed that the ternary system with arginine (pH approximately 7) exhibited a stability constant 3.6 times higher and was about 5.5 times more effective in improving drug solubility than the binary complex in buffered (pH approximately 7) aqueous solutions. These results demonstrated that the high increase in the drug solubility shown by ternary systems with arginine was not simply due to a favorable pH change but to multicomponent complex formation. Solid products of naproxen with hydroxypropyl-beta-cyclodextrin, and/or arginine, prepared by different methods, were characterized by Differential Scanning Calorimetry (DSC), Hot Stage Microscopy (HSM) and Scanning Electron Microscopy (SEM). SN - 0378-5173 UR - https://www.unboundmedicine.com/medline/citation/12842348/Ternary_systems_of_naproxen_with_hydroxypropyl_beta_cyclodextrin_and_aminoacids_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378517303002655 DB - PRIME DP - Unbound Medicine ER -