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Inclusion complexes of tadalafil with natural and chemically modified beta-cyclodextrins. I: preparation and in-vitro evaluation.
Eur J Pharm Biopharm. 2008 Nov; 70(3):819-27.EJ

Abstract

The aim of this work was to investigate the inclusion complexation between tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5), and two chemically modified beta-cyclodextrins: hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and heptakis-[2,6-di-O-methyl]-beta-cyclodextrin (DM-beta-CD), in comparison with the natural beta-cyclodextrin (beta-CD) in order to improve the solubility and the dissolution rate of the drug in an attempt to enhance its bioavailability. Inclusion complexation was investigated in both the solution and the solid state. The UV spectral shift method indicated guest-host complex formation between tadalafil and the three cyclodextrins (CDs). The phase solubility profiles with all the used CDs were classified as A(p)-type, indicating the formation of higher order complexes. The complexation efficiency values (CE), which reflect the solubilizing power of the CDs towards the drug, could be arranged in the following order: DM-beta-CD>HP-beta-CD>beta-CD. Solid binary systems of tadalafil with CDs were prepared by kneading and freeze-drying techniques at molar ratios of 1:1, 1:3 and 1:5 (drug to CD). Physical mixtures were prepared in the same molar ratios for comparison. Physicochemical characterization of the prepared systems at molar ratio of 1:5 was studied using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and Fourier-transform infrared spectroscopy (FTIR). The results showed the formation of true inclusion complexes between the drug and both HP-beta-CD and DM-beta-CD using the freeze-drying method at molar ratio of 1:5. In contrast, crystalline drug was detectable in all other products. The dissolution of tadalafil from all the prepared binary systems was carried out to determine the most appropriate CD type, molar ratio, and preparation technique to prepare inclusion complexes to be used in the development of tablet formulation for oral delivery of tadalafil. The dissolution enhancement was increased on increasing the CD proportion in all the prepared systems. Both the CD type and the preparation technique played an important role in the performance of the system. Irrespective of the preparation technique, the systems prepared using HP-beta-CD and DM-beta-CD yielded better performance than the corresponding ones prepared using beta-CD. In addition, the freeze-drying technique showed superior dissolution enhancement than other methods especially when combined with the beta-CD derivatives.

Authors+Show Affiliations

Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Cairo, Egypt.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

18655829

Citation

Badr-Eldin, Shaimaa M., et al. "Inclusion Complexes of Tadalafil With Natural and Chemically Modified Beta-cyclodextrins. I: Preparation and In-vitro Evaluation." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 70, no. 3, 2008, pp. 819-27.
Badr-Eldin SM, Elkheshen SA, Ghorab MM. Inclusion complexes of tadalafil with natural and chemically modified beta-cyclodextrins. I: preparation and in-vitro evaluation. Eur J Pharm Biopharm. 2008;70(3):819-27.
Badr-Eldin, S. M., Elkheshen, S. A., & Ghorab, M. M. (2008). Inclusion complexes of tadalafil with natural and chemically modified beta-cyclodextrins. I: preparation and in-vitro evaluation. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 70(3), 819-27. https://doi.org/10.1016/j.ejpb.2008.06.024
Badr-Eldin SM, Elkheshen SA, Ghorab MM. Inclusion Complexes of Tadalafil With Natural and Chemically Modified Beta-cyclodextrins. I: Preparation and In-vitro Evaluation. Eur J Pharm Biopharm. 2008;70(3):819-27. PubMed PMID: 18655829.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inclusion complexes of tadalafil with natural and chemically modified beta-cyclodextrins. I: preparation and in-vitro evaluation. AU - Badr-Eldin,Shaimaa M, AU - Elkheshen,Seham A, AU - Ghorab,Mahmoud M, Y1 - 2008/07/04/ PY - 2008/04/10/received PY - 2008/06/12/revised PY - 2008/06/13/accepted PY - 2008/7/29/pubmed PY - 2009/1/24/medline PY - 2008/7/29/entrez SP - 819 EP - 27 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 70 IS - 3 N2 - The aim of this work was to investigate the inclusion complexation between tadalafil, a practically insoluble selective phosphodiesterase-5 inhibitor (PDE5), and two chemically modified beta-cyclodextrins: hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and heptakis-[2,6-di-O-methyl]-beta-cyclodextrin (DM-beta-CD), in comparison with the natural beta-cyclodextrin (beta-CD) in order to improve the solubility and the dissolution rate of the drug in an attempt to enhance its bioavailability. Inclusion complexation was investigated in both the solution and the solid state. The UV spectral shift method indicated guest-host complex formation between tadalafil and the three cyclodextrins (CDs). The phase solubility profiles with all the used CDs were classified as A(p)-type, indicating the formation of higher order complexes. The complexation efficiency values (CE), which reflect the solubilizing power of the CDs towards the drug, could be arranged in the following order: DM-beta-CD>HP-beta-CD>beta-CD. Solid binary systems of tadalafil with CDs were prepared by kneading and freeze-drying techniques at molar ratios of 1:1, 1:3 and 1:5 (drug to CD). Physical mixtures were prepared in the same molar ratios for comparison. Physicochemical characterization of the prepared systems at molar ratio of 1:5 was studied using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), and Fourier-transform infrared spectroscopy (FTIR). The results showed the formation of true inclusion complexes between the drug and both HP-beta-CD and DM-beta-CD using the freeze-drying method at molar ratio of 1:5. In contrast, crystalline drug was detectable in all other products. The dissolution of tadalafil from all the prepared binary systems was carried out to determine the most appropriate CD type, molar ratio, and preparation technique to prepare inclusion complexes to be used in the development of tablet formulation for oral delivery of tadalafil. The dissolution enhancement was increased on increasing the CD proportion in all the prepared systems. Both the CD type and the preparation technique played an important role in the performance of the system. Irrespective of the preparation technique, the systems prepared using HP-beta-CD and DM-beta-CD yielded better performance than the corresponding ones prepared using beta-CD. In addition, the freeze-drying technique showed superior dissolution enhancement than other methods especially when combined with the beta-CD derivatives. SN - 0939-6411 UR - https://www.unboundmedicine.com/medline/citation/18655829/Inclusion_complexes_of_tadalafil_with_natural_and_chemically_modified_beta_cyclodextrins__I:_preparation_and_in_vitro_evaluation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(08)00226-9 DB - PRIME DP - Unbound Medicine ER -