Formulation of cyclodextrin inclusion complex-based orally disintegrating tablet of eslicarbazepine acetate for improved oral bioavailability

2016 ◽  
Vol 58 ◽  
pp. 826-834 ◽  
Author(s):  
Samixa Desai ◽  
Aditi Poddar ◽  
Krutika Sawant
2019 ◽  
Vol 15 (1) ◽  
pp. 22
Author(s):  
Nur Aini Purnamasari ◽  
Pratama Anggi Saputra

Nifedipine is widely used for managing hypertension. The challenges of developing nifedipine oral preparation are its low solubility and unpleasant taste. The purpose of developing the Oral Disintegrating Tablet (ODT) dosage form from the Nifedipine-β-cyclodextrin inclusion complex is to increase the solubility of nifedipine and mask the unpleasant taste of the drug. Specific target: use of a superdisintegrant combination to increase the solubility of nifedipine and mask the bitter taste. The method used in the formation of Nifedipine inclusion complex with β-cyclodextrin was kneading method. Making ODT was done by direct pressing method. Characterization of nifedipine-β-cyclodextrin inclusion complex was analyzed by FTIR and DSC. ODT was tested for the physical properties of the tablet and its solution. Test results for ODT physical properties were analyzed and compared with the literature. Data obtained from the dissolution test results calculated the concentration of the active substance dissolved at 20 minutes (Q20). The results showed that the formation of the Nifedipine-β-cyclodextrin inclusion complex increased solubility and masked the bitter taste. The combination of superdisintegrant Ac-Di-Sol-Crosspovidon accelerated the disintegration and dissolution time and improve the taste of Nifedipine ODT.


Author(s):  
Nguyen Thi Thanh Binh ◽  
Ho Thi Quynh Xuan ◽  
Nguyen Thi Hai Yen

This study aims to ameliorate the water solubility of flurbiprofen by using β-cyclodextrin (β-CD). The drug/ligand 1:1 (M/M) stoichiometry was determined based on the effect of β-CD on the solubility of flurbiprofen. Several methods of preparing flurbiprofen/β-CD inclusion complex were investigated and a solvent method using hot water to dissolve the starting materials was selected. The selected method showed a lot of advantages such as high complexing ability, good product yield, simple and eco-friendly process. The obtained product was characterized using various analytical techniques such as high-performance liquid chromatography, differential scanning calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction and scanning electron microscopy. The product had a predominantly amorphous form with clathrate particles of about 2-7 µm in size, irregular edges and rough surfaces. The study results show that in the complexing process, flurbiprofen replaced water molecules located in the conical cavity of β-CD. The complex contained 19.91% flurbiprofen by mass with water solubility at 37°C was 1,100 µg/ml. The results also show that the complexing with β-CD significantly improved the water solubility of flurbiprofen by both speed and level. Keywords Flurbiprofen, β-cyclodextrin, inclusion complex, water solubility, preparation, characterization. References [1] K. Maroof, F. Zafar, H. Ali, S. Naveed, Flurbiprofen: a potent pain reliever, J. Bioequiv. Availab. 7(1) (2015) 056-058. https://doi.org/10.4172/jbb.1000214.[2] J.J. Thebault, G. Lagrue, C.E. Blatrix, L. Cheynier, R. Cluzan, Clinical pharmacology of flurbiprofen: a novel inhibitor of platelet aggregation, Curr. Med. Res. Opin. 5(1) (1977) 130-134. https://doi.org/10.1185/03007997709108990.[3] H. Geerts, Drug evaluation: (R)-flurbiprofen - an enantiomer of flurbiprofen for the treatment of Alzheimer's disease, Idrugs. 10(2) (2007) 121-133.[4] P.L. McGeer, M. Schulzer, E.G. McGeer, Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies, Neurology. 47(2) (1996) 425-432. https://doi.org/10.1212/WNL.47.2.425.[5] S. Meister, I. Zlatev, J. Stab, D. Docter, S. Baches, et al., Nanoparticulate flurbiprofen reduces amyloid-β 42 generation in an in vitro blood-brain barrier model, Alzheimers Res. Ther. 5(6) (2013) 51-63. https://doi.org/10.1186/alzrt225.[6] K.P. Townsend, D. Praticò, Novel therapeutic opportunities for Alzheimer’s disease: focus on nonsteroidal anti-inflammatory drugs, FASEB J. 19(12) (2005) 1592-1601. https://doi.org/10.1096/fj.04-3620rev.[7] C.K. Kim, Y.S. Yoon, J.Y. Kong, Preparation and evaluation of flurbiprofen dry elixir as a novel dosage form using a spray-drying technique, Int. J. Pharm. 120 (1995) 21-31. https://doi.org/10.1016/0378-5173(94)00375-F.[8] M.J. Habib, M.T. Phan, G. Owusu-Ababio, Dissolution profiles of flurbiprofen in phospholipid solid dispersions, Drug Dev. Ind. Pharm. 24 (1998) 1077-1082. https://doi.org/10.3109/03639049809089952.[9] D.H. Oh, Y.J. Park, J.H. Kang, C.S. Yong, H.G. Choi, Physicochemical characterization and in vivo evaluation of flurbiprofen-loaded solid dispersion without crystalline change, Drug. Deliv. 18 (2010) 46-53. https://doi.org/10.3109/10717544.2010.509365.[10] G.D. Gupta, S. Jain, N.K. Jain, Formulation of an aqueous injection of flurbiprofen, Pharmazie. 52 (1997) 709-712. https://doi.org/10.1080/10826079708005547.[11] K.W. Ambade, S.L. Jadhav, M.N. Gambhire, S.D. Kurmi, V.J. Kadam, K.R. Jadhav, Formulation and evaluation of flurbiprofen microemulsion, Curr. Drug Deliv. 5 (2008) 32–41[12] H.H. Baek, S.Y. Kwon, S.J. Rho, W.S. Lee, H.J. Yang, J.M. Hah, H.G. Choi, Y.R. Kim, C.S. Yong, Enhanced solubility and bioavailability of flurbiprofen by cycloamylose, Arch. Pharm. Res. 34 (2011) 391-397. https://doi.org/10.1007/s12272-011-0306-x.[13] A. Muraoka, T. Tokumura, Y. Machida, Evaluation of the bioavailability of flurbiprofen and its β-cyclodextrin inclusion complex in four different doses upon oral administration to rats, Eur. J. Pharm. Biopharm. 58(3) (2004) 667-671. https://doi.org/10.1016/j.ejpb.2004.03.030.[14] T. Tokumura, A. Muraoka, Y. Machida, Improvement of oral bioavailability of flurbiprofen from flurbiprofen/beta-cyclodextrin inclusion complex by action of cinnarizine, Eur. J. Pharm. Biopharm. 73 (2009) 202-204. https://doi.org/10.1016/j.ejpb.2009.04.018.[15] D. Li, M. Han, P. Balakrishnan, Y. Yan, D. Oh, et al., Enhanced oral bioavailability of flurbiprofen by combined use of micelle solution and inclusion compound, Arch. Pharm. Res. 33(1) (2010) 95-101. https://doi.org/10.1007/s12272-010-2231-9.[16] H. Arima, K. Motoyama, T. Irie, Recent findings on safety profiles of cyclodextrins, cyclodextrin conjugates, and polypseudorotaxanes, in: E. Bilensoy (Ed.), Cyclodextrins in Pharmaceutics, Cosmetics, and Biomedicine: Current and Future Industrial Applications, John Wiley & Sons Inc., Hoboken, 2011, pp. 91-122. https://doi.org/10.1002/9780470926819.ch5.[17] T.J. Grattan, Inclusion complexes of beta-cyclodextrin with flurbiprofen, ketoprofen and naproxen, International patent WO1995007104A1, March 16, 1995.[18] M. Cirri, C. Rangoni, F. Maestrelli, G. Corti, P. Mura, Development of fast-dissolving tablets of flurbiprofen-cyclodextrin complexes, Drug Dev. Ind. Pharm. 31(7) (2005) 697-707. https://doi.org/10.1080/03639040500253694.[19] M. Tirunagari, N. Mehveen, M.F. Qureshi, J.P. Sultana, V. Tirunagari (2012), Solubility Enhancement of Flurbiprofen using Different Solubilization Techniques, Int. J. Pharm. Pharm. Sci. 4(4) (2012) 97-100.[20] P. Saokham, C. Muankaew, P. Jansook, T. Loftsson, Solubility of cyclodextrins and drug/cyclodextrin complexes, Molecules. 23(5) (2018) 1161-1175. https://doi.org/10.3390/molecules23051161.[21] S. Pereva, T. Sarafska, S. Bogdanova, T. Spassov, Efficiency of “cyclodextrin-ibuprofen” inclusion complex formation, J. Drug Deliv. Sci. Tec. 35 (2016) 34-39. https://doi.org/10.1016/j.jddst.2016.04.006.[22] T.T.B. Nguyen, N.A. Dang, M.A. Tran, T.H. Nguyen, Validation of a high-performance liquid chromatographic method with diod array detection for the quantification of flurbiprofen in 100 mg film-coated tablet, VNU Journal of Science: Medical and Pharmaceutical Sciences. 33(2) (2017) 41-49. https://doi.org/10.25073/2588-1132/vnumps.4085.[23] T. Higuchi, K.A. Connors, Phase-solubility techniques, Adv. Anal. Chem. Instrum. 4 (1965) 117-122.    


Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 4089
Author(s):  
Katarzyna Betlejewska-Kielak ◽  
Elżbieta Bednarek ◽  
Armand Budzianowski ◽  
Katarzyna Michalska ◽  
Jan K. Maurin

Racemic ketoprofen (KP) and β-cyclodextrin (β-CD) powder samples from co-precipitation (1), evaporation (2), and heating-under-reflux (3) were analysed using X-ray techniques and nuclear magnetic resonance (NMR) spectroscopy. On the basis of NMR studies carried out in an aqueous solution, it was found that in the samples obtained by methods 1 and 2, there were large excesses of β-CD in relation to KP, 10 and 75 times, respectively, while the sample obtained by method 3 contained equimolar amounts of β-CD and KP. NMR results indicated that KP/β-CD inclusion complexes were formed and the estimated binding constants were approximately 2400 M−1, showing that KP is quite strongly associated with β-CD. On the other hand, the X-ray single-crystal technique in the solid state revealed that the (S)-KP/β-CD inclusion complex with a stoichiometry of 2:2 was obtained as a result of heating-under-reflux, for which the crystal and molecular structure were examined. Among the methods used for the preparation of the KP/β-CD complex, only method 3 is suitable.


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