Solubility Enhancement of Carvedilol by Solid Dispersion Technique Using Sodium Alginate, Guar Gum, Xanthan Gum, and Locust Bean Gum as Polymers

https://doi.org/10.22146/ijc.77698

Iyan Sopyan(1*), Nurdiani Adiningsih(2), Sandra Megantara(3), Siska Sari Marvita(4)

(1) Department Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, Jl. Bandung-Sumedang KM 21, Sumedang 45363, West Java, Indonesia
(2) Department Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, Jl. Bandung-Sumedang KM 21, Sumedang 45363, West Java, Indonesia
(3) Department Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Padjadjaran University, Jl. Bandung-Sumedang KM 21, Sumedang 45363, West Java, Indonesia
(4) Department Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Padjadjaran University, Jl. Bandung-Sumedang KM 21, Sumedang 45363, West Java, Indonesia
(*) Corresponding Author

Abstract


Carvedilol (CVD) is a non-selective β-blocker. CVD is included in BCS class II. It has low water solubility. In this research, solid dispersion was used to increase the solubility and dissolution profile of CVD. In silico study using the ligand-ligand docking method. The preparation of solid dispersion using the kneading method with a weight ratio of 1:1, 1:2, 1:3, and 1:4, evaluation of solid dispersion includes solubility and dissolution. The best solid dispersion was characterized using FTIR, DSC, and PXRD. In silico study showed complexes CVD-SA, CVD-GG, CVD-XG and CVD-LBG have a hydrogen interaction. SA and XG were chosen as carriers in solid dispersion. CVD solid dispersion showed increased solubility in all samples, with the highest increase at 90.63 times at CVD: XG (1:4). The results of the dissolution profile obtained at 60 min are 64.95 ± 0.45% at pure CVD, 83.32 ± 1.19% at CVD:SA (1:4), and 72.56 ± 3.62% at CVD: XG (1:4). The FTIR spectrum indicates an interaction between CVD and SA. The thermogram indicated the amorphous drug, and the diffractogram showed a decrease in crystallinity. Solid dispersion is proven to increase the solubility and dissolution profile of CVD. Solid dispersion CVD: SA (1:4) showed the highest solubility and dissolution profile.


Keywords


carvedilol; BCS class II; solid dispersion

Full Text:

Full Text PDF


References

[1] Holford, N., 2016, Absorption and half-life, Transl. Clin. Pharmacol., 24 (4), 157–160.

[2] Arregui, J.R., Kovvasu, S.P., Kunamaneni, P., and Betageri, G.V., 2019, Carvedilol solid dispersion for enhanced oral bioavailability using rat model, J. Appl. Pharm. Sci., 9 (12), 042–050.

[3] Krstić, M., Manić, L., Martić, N., Vasiljević, D., Mračević, S.Đ., Vukmirović, S., and Rašković, A., 2020, Binary polymeric amorphous carvedilol solid dispersions: In vitro and in vivo characterization, Eur. J. Pharm. Sci., 150, 105343.

[4] Lee, S.N., Poudel, B.K., Tran, T.H., Marasini, N., Pradhan, R., Lee, Y.I., Lee, D.W., Woo, J.S., Choi, H.G., Yong, C.S., and Kim, J.O., 2013, A novel surface-attached carvedilol solid dispersion with enhanced solubility and dissolution, Arch. Pharmacal Res., 36 (1), 79–85.

[5] Liu, D., Xu, H., Tian, B., Yuan, K., Pan, H., Ma, S., Yang, X., and Pan, W., 2012, Fabrication of carvedilol nanosuspensions through the anti-solvent precipitation-ultrasonication method for the improvement of dissolution rate and oral bioavailability, AAPS PharmSciTech, 13 (1), 295–304.

[6] Hirlekar, R., and Kadam, V., 2009, Preparation and characterization of inclusion complexes of carvedilol with methyl-β-cyclodextrin, J. Inclusion Phenom. Macrocyclic Chem., 63 (3-4), 219–224.

[7] Zoghbi, A., Geng, T., and Wang, B., 2017, Dual activity of hydroxypropyl-β-cyclodextrin and water-soluble carriers on the solubility of carvedilol, AAPS PharmSciTech, 18 (8), 2927–2935.

[8] Shojaee, S.A., Rajaei, H., Hezave, A.Z., Lashkarbolooki, M., and Esmaeilzadeh, F., 2013, Experimental investigation and modeling of the solubility of carvedilol in supercritical carbon dioxide, J. Supercrit. Fluids, 81, 42–47.

[9] Fernandes, G.J., Kumar, L., Sharma, K., Tunge, R., and Rathnanand, M., 2018, A review on solubility enhancement of carvedilol—A BCS class II drug, J. Pharm. Innovation, 13 (3), 197–212.

[10] Sadr, M.H., and Nabipour, H., 2013, Synthesis and identification of carvedilol nanoparticles by ultrasound method, J. Nanostruct. Chem., 3 (1), 26.

[11] Shejul, A.A., Deshmahe, S., and Biyani, K., 2014, Modified natural carrier in solid dispersion for enhancement of solubility of poorly water soluble drugs, J. Drug Delivery Ther., 4 (1), 111–116.

[12] Borba, P.A.A., Pinotti, M., de Campos, C.E.M., Pezzini, B.R., and Stulzer, H.K., 2016, Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs, Carbohydr. Polym., 137, 350–359.

[13] Siraj, N.S., Athar, S.H., Khan, G.J., Raza, S., and Ansari, M.A., 2019, Review on solid dispersion of poor water soluble drug by using natural polymers, Pharma Innovation J., 8 (1), 631–636.

[14] Guan, J., Liu, Q., Zhang, X., Zhang, Y., Chokshi, R., Wu, H., and Mao, S., 2018, Alginate as a potential diphase solid dispersion carrier with enhanced drug dissolution and improved storage stability, Eur. J. Pharm. Sci., 114, 346–355.

[15] Kaza, R., Raju, Y.P., and Nagaraju, R., 2013, Dissolution enhancement of valsartan using natural polymers by solid dispersion technique, Pharm. Lett., 5 (2), 126–134.

[16] Nagpal, M., Kaur, L., Chander, J., and Sharma, P., 2016, Dissolution enhancement of domperidone fast disintegrating tablet using modified locust bean gum by solid dispersion technique, J. Pharm. Technol. Res. Manage., 4 (1), 1–11.

[17] Siswandi, S., Rusdiana, T., and Levita, J., 2015, Virtual screening of co-formers for ketoprofen co-crystallization and the molecular properties of the co-crystal, J. Appl. Pharm. Sci., 5 (6), 078–082.

[18] Yuvaraja, K., and Khanam, J., 2014, Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid, J. Pharm. Biomed. Anal., 96, 10–20.

[19] Prado, L.D., Rocha, H.V.A., Resende, J.A.L.C., Ferreira, G.B., and de Figuereido Teixeira, A.M.R., 2014, An insight into carvedilol solid forms: Effect of the supramolecular interactions on the dissolution profiles, CrystEngComm, 16 (15), 3168–3179.

[20] Eesam, S., Bhandaru, J.S., Naliganti, C., Bobbala, R.K., and Akkinepally, R.R., 2020, Solubility enhancement of carvedilol using drug–drug cocrystallization with hydrochlorothiazide, Future J. Pharm. Sci., 6 (1), 77.

[21] Fernandes, G.J., Rathnanand, M., and Kulkarni, V., 2019, Mechanochemical synthesis of carvedilol cocrystals utilizing hot melt extrusion technology, J. Pharm. Innovation, 14 (4), 373–381.

[22] Thenge, R., Patel, R., Kayande, N., and Mahajan, N., 2020, Co-crystals of carvedilol: Preparation, characterization and evaluation, Int. J. Appl. Pharm., 12 (1), 42–49.

[23] Sathisaran, I., and Dalvi, S.V., 2018, Engineering cocrystals of poorlywater-soluble drugs to enhance dissolution in aqueous medium, Pharmaceutics, 10 (3), 108.

[24] Saputri, K.E., Fakhmi, N., Kusumaningtyas, E., Priyatama, D., and Santoso, B., 2016, Docking molekular potensi anti diabetes melitus tipe 2 turunan zerumbon sebagai inhibitor aldosa reduktase dengan Autodock-Vina, Chim. Nat. Acta, 4 (1), 16–20.

[25] Sharma, A., Jain, C.P., and Tanwar, Y.S., 2013, Preparation and characterization of solid dispersions of carvedilol with poloxamer 188, J. Chil. Chem. Soc., 58 (1), 1553–1557.

[26] Sharma, U., Joshi, A., Vyas, N., Malviya, S., and Kharia, A., 2017, Solubility enhancement of clopidogrel bisulfate by solid dispersion technique using carboxymethylcellulose sodium and xanthan gum, J. Drug Delivery Ther., 7 (7), 35–37.

[27] Rajeswari, S., Bhanu, K., Panda, S., Swain, R.P., Murthy, K.V.R., and Kudamala, S., 2016, Solid dispersions: An evergreen solubility enhancement technique for hydrophobic drugs, J. Chem. Pharm. Res., 8 (4), 1218–1228.

[28] Luo, C., Wu, W., Lou, S., Zhao, S., and Yang, K., 2020, Improving the in vivo bioavailability and in vitro anti-inflammatory activity of tanshinone IIA by alginate solid dispersion, J. Drug Delivery Sci. Technol., 60, 101966.

[29] Beattie, K., Phadke, G., and Novakovic, J., 2013, Carvedilol, Profiles Drug Subst., Excipients, Relat. Methodol., 38, 113–157.



DOI: https://doi.org/10.22146/ijc.77698

Article Metrics

Abstract views : 1832 | views : 941


Copyright (c) 2023 Indonesian Journal of Chemistry

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

 


Indonesian Journal of Chemistry (ISSN 1411-9420 /e-ISSN 2460-1578) - Chemistry Department, Universitas Gadjah Mada, Indonesia.

Web
Analytics View The Statistics of Indones. J. Chem.