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Improvement in solubility and dissolution rate of 1, 2-dithiole-3-thiones upon complexation with beta-cyclodextrin and its hydroxypropyl and sulfobutyl ether-7 derivatives.
J Pharm Sci. 1999 Sep; 88(9):889-95.JP

Abstract

Inclusion complexes between beta-cyclodextrin derivatives and 1, 2-dithione-3-thiones were studied in aqueous solution and in the solid state. Phase solubility study was used to evaluate the complexation in solution, at 37 degrees C, of three cyclodextrins, i. e., beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD), sulfobutyl ether-7-beta-cyclodextrin (SBE7betaCD), and four 1,2-dithiole-3-thiones, i.e., the parent compound dithiolethione (DTT), dimethyldithiolethione (DMDTT), 5-phenyldithiolethione (5PDTT), and anetholetrithione (ATT). Stability constants of the DTT complexes with HPbetaCD and SBE7betaCD were also determined spectrophotometrically using a nonlinear least-squares methodology. Differential scanning calorimetry (DSC) and scanning electronic microscopy (SEM) were used to characterize spray-dried complexes formed between 5PDTT and SBE7betaCD, ATT and SBE7betaCD. Dissolution studies using the USP paddle method were carried out in water at 37 degrees C for both ATT and 5PDTT binary systems with HPbetaCD and SBE7betaCD. Solubility enhancements were much greater with the more lipophilic ATT and 5PDTT compared to DTT and DMDTT, whatever the cyclodextrin used, in the rank order SBE7betaCD > HPbetaCD >> betaCD. Stability constants obtained (between 120 and 12800 mol(-1)) were also the highest for the more lipophilic drugs and in the same rank order SBE7betaCD > HPbetaCD >> betaCD. Results obtained by UV spectrophotometry were in good agreement with those obtained by phase-solubility study. DSC thermograms of spray-dried complexes of ATT and 5PDTT with HPbetaCD and SBE7betaCD lacked the endothermal peak of pure drug peak which was found for the physical mixtures (107 degrees C and 125 degrees C for ATT and 5PDTT, respectively). Finally, dissolution profiles of spray-dried inclusion complexes studied displayed a faster dissolution rate compared to physical mixtures and pure drugs. The present study showed that complexation of 1,2-dithiole-3-thiones with beta-cyclodextrin derivatives resulted in an increase in solubility, allowing intravenous formulation for bioavailability and metabolism studies and an increase in the dissolution rate of the drugs, which should be of interest for oral absorption of these lipophilic compounds.

Authors+Show Affiliations

Laboratoire de Pharmacie Galénique et Biopharmacie and Laboratoire de Chimie Analytique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Rennes I, 35043 Rennes Cedex, France. Gilles.Dollo@univ-rennes1.frNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10479350

Citation

Dollo, G, et al. "Improvement in Solubility and Dissolution Rate of 1, 2-dithiole-3-thiones Upon Complexation With Beta-cyclodextrin and Its Hydroxypropyl and Sulfobutyl Ether-7 Derivatives." Journal of Pharmaceutical Sciences, vol. 88, no. 9, 1999, pp. 889-95.
Dollo G, Le Corre P, Chollet M, et al. Improvement in solubility and dissolution rate of 1, 2-dithiole-3-thiones upon complexation with beta-cyclodextrin and its hydroxypropyl and sulfobutyl ether-7 derivatives. J Pharm Sci. 1999;88(9):889-95.
Dollo, G., Le Corre, P., Chollet, M., Chevanne, F., Bertault, M., Burgot, J. L., & Le Verge, R. (1999). Improvement in solubility and dissolution rate of 1, 2-dithiole-3-thiones upon complexation with beta-cyclodextrin and its hydroxypropyl and sulfobutyl ether-7 derivatives. Journal of Pharmaceutical Sciences, 88(9), 889-95.
Dollo G, et al. Improvement in Solubility and Dissolution Rate of 1, 2-dithiole-3-thiones Upon Complexation With Beta-cyclodextrin and Its Hydroxypropyl and Sulfobutyl Ether-7 Derivatives. J Pharm Sci. 1999;88(9):889-95. PubMed PMID: 10479350.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Improvement in solubility and dissolution rate of 1, 2-dithiole-3-thiones upon complexation with beta-cyclodextrin and its hydroxypropyl and sulfobutyl ether-7 derivatives. AU - Dollo,G, AU - Le Corre,P, AU - Chollet,M, AU - Chevanne,F, AU - Bertault,M, AU - Burgot,J L, AU - Le Verge,R, PY - 1999/9/10/pubmed PY - 2000/7/19/medline PY - 1999/9/10/entrez SP - 889 EP - 95 JF - Journal of pharmaceutical sciences JO - J Pharm Sci VL - 88 IS - 9 N2 - Inclusion complexes between beta-cyclodextrin derivatives and 1, 2-dithione-3-thiones were studied in aqueous solution and in the solid state. Phase solubility study was used to evaluate the complexation in solution, at 37 degrees C, of three cyclodextrins, i. e., beta-cyclodextrin (betaCD), hydroxypropyl-beta-cyclodextrin (HPbetaCD), sulfobutyl ether-7-beta-cyclodextrin (SBE7betaCD), and four 1,2-dithiole-3-thiones, i.e., the parent compound dithiolethione (DTT), dimethyldithiolethione (DMDTT), 5-phenyldithiolethione (5PDTT), and anetholetrithione (ATT). Stability constants of the DTT complexes with HPbetaCD and SBE7betaCD were also determined spectrophotometrically using a nonlinear least-squares methodology. Differential scanning calorimetry (DSC) and scanning electronic microscopy (SEM) were used to characterize spray-dried complexes formed between 5PDTT and SBE7betaCD, ATT and SBE7betaCD. Dissolution studies using the USP paddle method were carried out in water at 37 degrees C for both ATT and 5PDTT binary systems with HPbetaCD and SBE7betaCD. Solubility enhancements were much greater with the more lipophilic ATT and 5PDTT compared to DTT and DMDTT, whatever the cyclodextrin used, in the rank order SBE7betaCD > HPbetaCD >> betaCD. Stability constants obtained (between 120 and 12800 mol(-1)) were also the highest for the more lipophilic drugs and in the same rank order SBE7betaCD > HPbetaCD >> betaCD. Results obtained by UV spectrophotometry were in good agreement with those obtained by phase-solubility study. DSC thermograms of spray-dried complexes of ATT and 5PDTT with HPbetaCD and SBE7betaCD lacked the endothermal peak of pure drug peak which was found for the physical mixtures (107 degrees C and 125 degrees C for ATT and 5PDTT, respectively). Finally, dissolution profiles of spray-dried inclusion complexes studied displayed a faster dissolution rate compared to physical mixtures and pure drugs. The present study showed that complexation of 1,2-dithiole-3-thiones with beta-cyclodextrin derivatives resulted in an increase in solubility, allowing intravenous formulation for bioavailability and metabolism studies and an increase in the dissolution rate of the drugs, which should be of interest for oral absorption of these lipophilic compounds. SN - 0022-3549 UR - https://www.unboundmedicine.com/medline/citation/10479350/Improvement_in_solubility_and_dissolution_rate_of_1_2_dithiole_3_thiones_upon_complexation_with_beta_cyclodextrin_and_its_hydroxypropyl_and_sulfobutyl_ether_7_derivatives_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-3549(15)50864-2 DB - PRIME DP - Unbound Medicine ER -