Inclusion complexes of tadalafil with natural and chemically modified β-cyclodextrins. I: Preparation and in-vitro evaluation |
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| Institution: | 1. Medical University of Gdansk, Department of Physical Chemistry, Hallera 107, 80-416 Gdansk, Poland;2. Trinity College Dublin, School of Pharmacy and Pharmaceutical Sciences, College Green, Dublin 2, Ireland;1. College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon 34134, South Korea;2. IL-YANG Pharmaceutical Co., 110, Hagal-ro, Giheung-gu, Yongin-si, Gyeonggi-do, South Korea;1. NANOTEC PSU Center of Excellence on Drug Delivery and Department of Pharmacology, Faculty of Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand;2. NANOTEC, National Science and Technology Development Agency (NSTDA), 111 Thailand Science Park, Thanon Phahonyothin, Tambon Khlong Nueng, Amphoe Khlong Luang, Pathum Thani 12120, Thailand;3. Drug and Cosmetic Research and Development Unit, School of Pharmacy, Walailak University, Thasala, Nakhon Si Thammarat 80161, Thailand;4. NANOTEC PSU Center of Excellence on Drug Delivery and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla 90112, Thailand;1. Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka, Aljouf region 72341, Saudi Arabia;2. Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;3. Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf region 72341, Saudi Arabia;4. Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka, Aljouf region, 72341, Saudi Arabia;5. Department of Basic Health Sciences, Preparatory Year, Princess Nourah Bint Abdurrahman University, Riyadh 11671, Saudi Arabia;6. Department of Pharmacy Practice, College of Pharmacy, Almaarefa University, Ad Diriyah, 13713, Saudi Arabia;7. Department of Pharmacognosy, College of Pharmacy, Jazan University, Jazan, Saudi Arabia;8. Substance Abuse and Toxicology Research Center, Jazan University, PO Box 114, Jazan, Saudi Arabia;1. State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650091, PR China;2. School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China;1. Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China;2. Research Center for Health and Nutrition, Shanghai University of Traditional Chinese Medicine, Shanghai, China;3. Pharmacy Department, Shanghai TCM-Integrated Hospital, Shanghai, China |
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| 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 β-cyclodextrins: hydroxypropyl-β-cyclodextrin (HP-β-CD) and heptakis-2,6-di-O-methyl]-β-cyclodextrin (DM-β-CD), in comparison with the natural β-cyclodextrin (β-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 Ap-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-β-CD > HP-β-CD > β-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-β-CD and DM-β-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-β-CD and DM-β-CD yielded better performance than the corresponding ones prepared using β-CD. In addition, the freeze-drying technique showed superior dissolution enhancement than other methods especially when combined with the β-CD derivatives. |
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