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Comparison the solubility and dissolution rate effects of beta-cyclodextrin and gamma-cyclodextrin complexations of rosuvastatin calcium

Yıl 2024, Cilt: 28 Sayı: 3, 797 - 807, 28.06.2025

Dilara Örgül

Öz

The present work focuses on the inclusion complexations (ICs) of rosuvastatin calcium (RSV) with beta () ve gama () derivatives of native cyclodextrins (CDs) and investigate effects on improved solubility and dissolution rate. The phase solubility studies illustrated that RSV solubility increased in the presence of CD with a negative deviation that indicates AN type diagrams, while βCD showed Bs type, upon addition of βCD, an increase in the solubility of the drug was observed up to a particular point. ICs of RSV were prepared with β and CD by at 1:1, 1:2 and 1:4 different molar ratios by freeze drying method. FT-IR and DSC results revealed formation of ICs between RSV and CD. High drug loading efficiency was obtained for all ICs in the range of 99.41–101.84%. Water solubility studies showed that βCD ICs have increased solubility of RSV about 1.3 times regardless of CD ratios(p>0.05). As compared to βCD ICs, RSV solubility was significantly greater in CD ICs and increased up to 1.45, 1.72 and 2.00 fold at 1:1, 1:2 and 1:4 ratio, respectively. Conspicuously, RSV solubility increased with increasing ratio of CD(p<0.05). Compared dissolution profiles with pure RSV, all ICs showed improved dissolution rates and immediate release profiles. However multiple point comparison of dissolution profiles indicated that CD ICs have higher drug release. Particularly CD ICs at 1:4 ratio released the highest RSV with 95.12% at 3 min and 100% completion in 15 min. It is concluded that CD provided a better improvement on RSV solubility and dissolution rate than βCD.

Anahtar Kelimeler

Rosuvastatin calcium beta cyclodextrin gama cyclodextrin inclusion complexation dissolution rate solubility

Kaynakça

  • [1] Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications Int J Pharm. 2011;420(1):1-10. https://doi.org/10.1016/j.ijpharm.2011.08.032
  • [2] Sarfraz RM, Ahmad M, Mahmood A, Minhas MU, Yaqoob A. Development and evaluation of rosuvastatin calcium based microparticles for solubility enhancement: an in vitro study. Adv Polym Technol. 2017;36(4):433-441. https://doi.org/10.2147/DDDT.S143712
  • [3] Rodriguez-Aller M, Guillarme D, Veuthey J-L, Gurny R. Strategies for formulating and delivering poorly water-soluble drugs. J Drug Deliv Sci Technol. 2015;30:342-351. https://doi.org/10.1016/j.jddst.2015.05.009
  • [4] Quirk J, Thornton M, Kirkpatrick P. Rosuvastatin calcium. Nat Rev Drug Discov. 2003;2(10):769-770. https://doi.org/10.1038/nrd1205
  • [5] Rosenson RS. Rosuvastatin: a new inhibitor of HMG-coA reductase for the treatment of dyslipidemia. Expert Rev Cardiovasc Ther. 2003;1(4):495-505. https://doi.org/10.1586/14779072.1.4.495
  • [6] Gonzalez R, Pena MA, Torres NS, Torrado G. Design, development, and characterization of amorphous rosuvastatin calcium tablets. PLoS One. 2022;17(3):e0265263. https://doi.org/10.1371/journal.pone.0265263
  • [7] Elsayed I, El-Dahmy RM, Elshafeey AH, Abd El Gawad NA, El Gazayerly ON. Tripling the bioavailability of rosuvastatin calcium through development and optimization of an in-situ forming nanovesicular system. Pharmaceutics. 2019;11(6):275. https://doi.org/10.3390/pharmaceutics11060275
  • [8] Kanikkannan N. Technologies to improve the solubility, dissolution and bioavailability of poorly soluble drugs. J Anal Pharm Res. 2018;7(1):00198. https://doi.org/10.15406/japlr.2018.07.00198
  • [9] Rumondor AC, Dhareshwar SS, Kesisoglou F. Amorphous solid dispersions or prodrugs: complementary strategies to increase drug absorption. J Pharm Sci. 2016;105(9):2498-2508. https://doi.org/10.1016/j.xphs.2015.11.004
  • [10] Serajuddin AT. Salt formation to improve drug solubility. Adv Drug Deliv Rev. 2007;59(7):603-616. https://doi.org/10.1016/j.addr.2007.05.010
  • [11] Elder DP, Holm R, De Diego HL. Use of pharmaceutical salts and cocrystals to address the issue of poor solubility. Int J Pharm. 2013;453(1):88-100. https://doi.org/10.1016/j.ijpharm.2012.11.028
  • [12] Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007;59(7):645-666. https://doi.org/10.1016/j.addr.2007.05.012
  • [13] Carneiro SB, Costa Duarte FÍ, Heimfarth L, Siqueira Quintans JS, Quintans-Júnior LJ, Veiga Júnior VFD, Neves de Lima ÁA. Cyclodextrin⁻drug ınclusion complexes: In vivo and ın vitro approaches. Int J Mol Sci. 2019;20(3):642.https://doi.org/10.3390/ijms20030642
  • [14] Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol. 2010;62(11):1607-1621. https://doi.org/10.1111/j.2042-7158.2010.01030.x
  • [15] Salústio PJ, Pontes P, Conduto C, Sanches I, Carvalho C, Arrais J, Marques HM. Advanced technologies for oral controlled release: cyclodextrins for oral controlled release. AAPS PharmSciTech. 2011;12(4):1276-1292. https://doi.org/10.1208/s12249-011-9690-2
  • [16] Adeoye O, Cabral-Marques H. Cyclodextrin nanosystems in oral drug delivery: A mini review. Int J Pharm. 2017;531(2):521-531. https://doi.org/10.1016/j.ijpharm.2017.04.050
  • [17] Jambhekar SS, Breen P. Cyclodextrins in pharmaceutical formulations I: Structure and physicochemical properties, formation of complexes, and types of complex. Drug Discov Today. 2016;21(2):356-362. https://doi.org/10.1016/j.drudis.2015.11.017
  • [18] Higuchi T. Phase‐solubility techniques. Adv Anal Chem Instr. 1965; 4: 117-212
  • [19] Ikeda H, Fukushige Y, Matsubara T, Inenaga M, Kawahara M, Yukawa M, Fujisawa M, Aki H. Improving water solubility of nateglinide by complexation of β-cyclodextrin. J Therm Anal Calorim. 2016; 123: 1847-1850. https://doi.org/10.1007/s10973-015-4714-x
  • [20] Sadaquat H, Akhtar M. Comparative effects of β-cyclodextrin, HP-β-cyclodextrin and SBE 7-β-cyclodextrin on the solubility and dissolution of docetaxel via inclusion complexation. J Incl Phenom Macrocycl Chem. 2020; 96: 333-351. https://doi.org/10.1007/s10847-020-00977-0
  • [21] Shukla SK, Chan A, Parvathaneni V, Kanabar DD, Patel K, Ayehunie S, Muth A, Gupta V. Enhanced solubility, stability, permeation and anti-cancer efficacy of Celastrol-β-cyclodextrin inclusion complex. J Mol Liq. 2020; 318: 113936. https://doi.org/10.1016/j.molliq.2020.113936
  • [22] Al-Shdefat R, Anwer MK, Fayed MH, Alsulays BB, Tawfeek HM, Abdel-Rahman RF, Soliman GA. Preparation and evaluation of spray dried rosuvastatin calcium-PVP microparticles for the improvement of serum lipid profile. J Drug Deliv Sci Technol. 2020;55:101342. https://doi.org/10.1016/j.jddst.2019.101342
  • [23] Ângelo ML, Ruela ALM, Ferreira ACM, Ramos MVdF, Montanari CM, Silva LMd, Araujo MBd. Evaluating the discriminatory power of a dissolution assay for rosuvastatin calcium capsules: Solid-state properties and dissolution media. Braz J Pharm Sci. 2019;55:e17520. https://doi.org/10.1590/s2175-97902019000117520
  • [24] Li H, Zhang G, Wang W, Chen C, Jiao L, Wu W. Preparation, characterization, and bioavailability of host-guest ınclusion complex of ginsenoside re with gamma-cyclodextrin. Molecules. 2021; 26(23):7227. https://doi.org/10.3390/molecules26237227
  • [25] Szabó ZI, Orbán G, Borbás E, Csicsák D, Kádár S, Fiser B, Dobó M, Horváth P, Kiss E, Budai L, Dobos J, Pálla T, Őrfi L, Völgyi G, Tóth G. Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility. Heliyon. 2021;7(7):e07581. https://doi.org/10.1016/j.heliyon.2021.e07581
  • [26] Vyas A. Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes. J Incl Phenom Macrocycl Chem. 2013;76:37-46. https://doi.org/10.1007/s10847-012-0170-4
  • [27] Das S, Subuddhi U. Studies on the complexation of diclofenac sodium with β–cyclodextrin: Influence of method of preparation. J Mol Struct. 2015; 1099: 482-489. https://doi.org/10.1016/j.molstruc.2015.07.001
  • [28] Sapte S, Pore Y. Inclusion complexes of cefuroxime axetil with β-cyclodextrin: Physicochemical characterization, molecular modeling and effect of l-arginine on complexation. J Pharm Anal. 2016;6(5):300-306. https://doi.org/10.1016/j.jpha.2016.03.004
  • [29] Aleem O, Kuchekar B, Pore Y, Late S. Effect of beta-cyclodextrin and hydroxypropyl beta-cyclodextrin complexation on physicochemical properties and antimicrobial activity of cefdinir. J Pharm Biomed Anal. 2008;47(3):535-540. https://doi.org/10.1016/j.jpba.2008.02.006
  • [30] Ridhurkar DN, Ansari KA, Kumar D, Kaul NS, Krishnamurthy T, Dhawan S, Pillai R. Inclusion complex of aprepitant with cyclodextrin: evaluation of physico-chemical and pharmacokinetic properties. Drug Dev Ind Pharm. 2013;39(11):1783-1792.https://doi.org/10.3109/03639045.2012.737331
  • [31] Devasari N, Dora CP, Singh C, Paidi SR, Kumar V, Sobhia ME, et al. Inclusion complex of erlotinib with sulfobutyl ether-β-cyclodextrin: Preparation, characterization, in silico, in vitro and in vivo evaluation. Carbohydr. Polym. 2015;134:547-556. https://doi.org/10.1016/j.carbpol.2015.08.012
  • [32] Maqbool I, Akhtar M, Ahmad R, Sadaquat H, Noreen S, Batool A, Khan SU. Novel multiparticulate pH triggered delayed release chronotherapeutic drug delivery of celecoxib-β-cyclodextrin inclusion complexes by using Box-Behnken design. Eur J Pharm Sci. 2020;146:105254. https://doi.org/10.1016/j.ejps.2020.105254
  • [33] Tang P, Li S, Wang L, Yang H, Yan J, Li H. Inclusion complexes of chlorzoxazone with β-and hydroxypropyl-β-cyclodextrin: characterization, dissolution, and cytotoxicity. Carbohydr Polym. 2015; 131: 297-305. https://doi.org/10.1016/j.carbpol.2015.05.055

Yıl 2024, Cilt: 28 Sayı: 3, 797 - 807, 28.06.2025

Dilara Örgül

Öz

Kaynakça

  • [1] Kawabata Y, Wada K, Nakatani M, Yamada S, Onoue S. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications Int J Pharm. 2011;420(1):1-10. https://doi.org/10.1016/j.ijpharm.2011.08.032
  • [2] Sarfraz RM, Ahmad M, Mahmood A, Minhas MU, Yaqoob A. Development and evaluation of rosuvastatin calcium based microparticles for solubility enhancement: an in vitro study. Adv Polym Technol. 2017;36(4):433-441. https://doi.org/10.2147/DDDT.S143712
  • [3] Rodriguez-Aller M, Guillarme D, Veuthey J-L, Gurny R. Strategies for formulating and delivering poorly water-soluble drugs. J Drug Deliv Sci Technol. 2015;30:342-351. https://doi.org/10.1016/j.jddst.2015.05.009
  • [4] Quirk J, Thornton M, Kirkpatrick P. Rosuvastatin calcium. Nat Rev Drug Discov. 2003;2(10):769-770. https://doi.org/10.1038/nrd1205
  • [5] Rosenson RS. Rosuvastatin: a new inhibitor of HMG-coA reductase for the treatment of dyslipidemia. Expert Rev Cardiovasc Ther. 2003;1(4):495-505. https://doi.org/10.1586/14779072.1.4.495
  • [6] Gonzalez R, Pena MA, Torres NS, Torrado G. Design, development, and characterization of amorphous rosuvastatin calcium tablets. PLoS One. 2022;17(3):e0265263. https://doi.org/10.1371/journal.pone.0265263
  • [7] Elsayed I, El-Dahmy RM, Elshafeey AH, Abd El Gawad NA, El Gazayerly ON. Tripling the bioavailability of rosuvastatin calcium through development and optimization of an in-situ forming nanovesicular system. Pharmaceutics. 2019;11(6):275. https://doi.org/10.3390/pharmaceutics11060275
  • [8] Kanikkannan N. Technologies to improve the solubility, dissolution and bioavailability of poorly soluble drugs. J Anal Pharm Res. 2018;7(1):00198. https://doi.org/10.15406/japlr.2018.07.00198
  • [9] Rumondor AC, Dhareshwar SS, Kesisoglou F. Amorphous solid dispersions or prodrugs: complementary strategies to increase drug absorption. J Pharm Sci. 2016;105(9):2498-2508. https://doi.org/10.1016/j.xphs.2015.11.004
  • [10] Serajuddin AT. Salt formation to improve drug solubility. Adv Drug Deliv Rev. 2007;59(7):603-616. https://doi.org/10.1016/j.addr.2007.05.010
  • [11] Elder DP, Holm R, De Diego HL. Use of pharmaceutical salts and cocrystals to address the issue of poor solubility. Int J Pharm. 2013;453(1):88-100. https://doi.org/10.1016/j.ijpharm.2012.11.028
  • [12] Brewster ME, Loftsson T. Cyclodextrins as pharmaceutical solubilizers. Adv Drug Deliv Rev. 2007;59(7):645-666. https://doi.org/10.1016/j.addr.2007.05.012
  • [13] Carneiro SB, Costa Duarte FÍ, Heimfarth L, Siqueira Quintans JS, Quintans-Júnior LJ, Veiga Júnior VFD, Neves de Lima ÁA. Cyclodextrin⁻drug ınclusion complexes: In vivo and ın vitro approaches. Int J Mol Sci. 2019;20(3):642.https://doi.org/10.3390/ijms20030642
  • [14] Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins: basic science and product development. J Pharm Pharmacol. 2010;62(11):1607-1621. https://doi.org/10.1111/j.2042-7158.2010.01030.x
  • [15] Salústio PJ, Pontes P, Conduto C, Sanches I, Carvalho C, Arrais J, Marques HM. Advanced technologies for oral controlled release: cyclodextrins for oral controlled release. AAPS PharmSciTech. 2011;12(4):1276-1292. https://doi.org/10.1208/s12249-011-9690-2
  • [16] Adeoye O, Cabral-Marques H. Cyclodextrin nanosystems in oral drug delivery: A mini review. Int J Pharm. 2017;531(2):521-531. https://doi.org/10.1016/j.ijpharm.2017.04.050
  • [17] Jambhekar SS, Breen P. Cyclodextrins in pharmaceutical formulations I: Structure and physicochemical properties, formation of complexes, and types of complex. Drug Discov Today. 2016;21(2):356-362. https://doi.org/10.1016/j.drudis.2015.11.017
  • [18] Higuchi T. Phase‐solubility techniques. Adv Anal Chem Instr. 1965; 4: 117-212
  • [19] Ikeda H, Fukushige Y, Matsubara T, Inenaga M, Kawahara M, Yukawa M, Fujisawa M, Aki H. Improving water solubility of nateglinide by complexation of β-cyclodextrin. J Therm Anal Calorim. 2016; 123: 1847-1850. https://doi.org/10.1007/s10973-015-4714-x
  • [20] Sadaquat H, Akhtar M. Comparative effects of β-cyclodextrin, HP-β-cyclodextrin and SBE 7-β-cyclodextrin on the solubility and dissolution of docetaxel via inclusion complexation. J Incl Phenom Macrocycl Chem. 2020; 96: 333-351. https://doi.org/10.1007/s10847-020-00977-0
  • [21] Shukla SK, Chan A, Parvathaneni V, Kanabar DD, Patel K, Ayehunie S, Muth A, Gupta V. Enhanced solubility, stability, permeation and anti-cancer efficacy of Celastrol-β-cyclodextrin inclusion complex. J Mol Liq. 2020; 318: 113936. https://doi.org/10.1016/j.molliq.2020.113936
  • [22] Al-Shdefat R, Anwer MK, Fayed MH, Alsulays BB, Tawfeek HM, Abdel-Rahman RF, Soliman GA. Preparation and evaluation of spray dried rosuvastatin calcium-PVP microparticles for the improvement of serum lipid profile. J Drug Deliv Sci Technol. 2020;55:101342. https://doi.org/10.1016/j.jddst.2019.101342
  • [23] Ângelo ML, Ruela ALM, Ferreira ACM, Ramos MVdF, Montanari CM, Silva LMd, Araujo MBd. Evaluating the discriminatory power of a dissolution assay for rosuvastatin calcium capsules: Solid-state properties and dissolution media. Braz J Pharm Sci. 2019;55:e17520. https://doi.org/10.1590/s2175-97902019000117520
  • [24] Li H, Zhang G, Wang W, Chen C, Jiao L, Wu W. Preparation, characterization, and bioavailability of host-guest ınclusion complex of ginsenoside re with gamma-cyclodextrin. Molecules. 2021; 26(23):7227. https://doi.org/10.3390/molecules26237227
  • [25] Szabó ZI, Orbán G, Borbás E, Csicsák D, Kádár S, Fiser B, Dobó M, Horváth P, Kiss E, Budai L, Dobos J, Pálla T, Őrfi L, Völgyi G, Tóth G. Inclusion complexation of the anticancer drug pomalidomide with cyclodextrins: fast dissolution and improved solubility. Heliyon. 2021;7(7):e07581. https://doi.org/10.1016/j.heliyon.2021.e07581
  • [26] Vyas A. Preparation, characterization and pharmacodynamic activity of supramolecular and colloidal systems of rosuvastatin–cyclodextrin complexes. J Incl Phenom Macrocycl Chem. 2013;76:37-46. https://doi.org/10.1007/s10847-012-0170-4
  • [27] Das S, Subuddhi U. Studies on the complexation of diclofenac sodium with β–cyclodextrin: Influence of method of preparation. J Mol Struct. 2015; 1099: 482-489. https://doi.org/10.1016/j.molstruc.2015.07.001
  • [28] Sapte S, Pore Y. Inclusion complexes of cefuroxime axetil with β-cyclodextrin: Physicochemical characterization, molecular modeling and effect of l-arginine on complexation. J Pharm Anal. 2016;6(5):300-306. https://doi.org/10.1016/j.jpha.2016.03.004
  • [29] Aleem O, Kuchekar B, Pore Y, Late S. Effect of beta-cyclodextrin and hydroxypropyl beta-cyclodextrin complexation on physicochemical properties and antimicrobial activity of cefdinir. J Pharm Biomed Anal. 2008;47(3):535-540. https://doi.org/10.1016/j.jpba.2008.02.006
  • [30] Ridhurkar DN, Ansari KA, Kumar D, Kaul NS, Krishnamurthy T, Dhawan S, Pillai R. Inclusion complex of aprepitant with cyclodextrin: evaluation of physico-chemical and pharmacokinetic properties. Drug Dev Ind Pharm. 2013;39(11):1783-1792.https://doi.org/10.3109/03639045.2012.737331
  • [31] Devasari N, Dora CP, Singh C, Paidi SR, Kumar V, Sobhia ME, et al. Inclusion complex of erlotinib with sulfobutyl ether-β-cyclodextrin: Preparation, characterization, in silico, in vitro and in vivo evaluation. Carbohydr. Polym. 2015;134:547-556. https://doi.org/10.1016/j.carbpol.2015.08.012
  • [32] Maqbool I, Akhtar M, Ahmad R, Sadaquat H, Noreen S, Batool A, Khan SU. Novel multiparticulate pH triggered delayed release chronotherapeutic drug delivery of celecoxib-β-cyclodextrin inclusion complexes by using Box-Behnken design. Eur J Pharm Sci. 2020;146:105254. https://doi.org/10.1016/j.ejps.2020.105254
  • [33] Tang P, Li S, Wang L, Yang H, Yan J, Li H. Inclusion complexes of chlorzoxazone with β-and hydroxypropyl-β-cyclodextrin: characterization, dissolution, and cytotoxicity. Carbohydr Polym. 2015; 131: 297-305. https://doi.org/10.1016/j.carbpol.2015.05.055
Toplam 33 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular İlaç Dağıtım Teknolojileri
Bölüm Articles
Yazarlar

Dilara Örgül 0000-0002-8947-4995

Yayımlanma Tarihi 28 Haziran 2025
Yayımlandığı Sayı Yıl 2024 Cilt: 28 Sayı: 3

Kaynak Göster

APA Örgül, D. (2025). Comparison the solubility and dissolution rate effects of beta-cyclodextrin and gamma-cyclodextrin complexations of rosuvastatin calcium. Journal of Research in Pharmacy, 28(3), 797-807.
AMA Örgül D. Comparison the solubility and dissolution rate effects of beta-cyclodextrin and gamma-cyclodextrin complexations of rosuvastatin calcium. J. Res. Pharm. Haziran 2025;28(3):797-807.
Chicago Örgül, Dilara. “Comparison the Solubility and Dissolution Rate Effects of Beta-Cyclodextrin and Gamma-Cyclodextrin Complexations of Rosuvastatin Calcium”. Journal of Research in Pharmacy 28, sy. 3 (Haziran 2025): 797-807.
EndNote Örgül D (01 Haziran 2025) Comparison the solubility and dissolution rate effects of beta-cyclodextrin and gamma-cyclodextrin complexations of rosuvastatin calcium. Journal of Research in Pharmacy 28 3 797–807.
IEEE D. Örgül, “Comparison the solubility and dissolution rate effects of beta-cyclodextrin and gamma-cyclodextrin complexations of rosuvastatin calcium”, J. Res. Pharm., c. 28, sy. 3, ss. 797–807, 2025.
ISNAD Örgül, Dilara. “Comparison the Solubility and Dissolution Rate Effects of Beta-Cyclodextrin and Gamma-Cyclodextrin Complexations of Rosuvastatin Calcium”. Journal of Research in Pharmacy 28/3 (Haziran 2025), 797-807.
JAMA Örgül D. Comparison the solubility and dissolution rate effects of beta-cyclodextrin and gamma-cyclodextrin complexations of rosuvastatin calcium. J. Res. Pharm. 2025;28:797–807.
MLA Örgül, Dilara. “Comparison the Solubility and Dissolution Rate Effects of Beta-Cyclodextrin and Gamma-Cyclodextrin Complexations of Rosuvastatin Calcium”. Journal of Research in Pharmacy, c. 28, sy. 3, 2025, ss. 797-0.
Vancouver Örgül D. Comparison the solubility and dissolution rate effects of beta-cyclodextrin and gamma-cyclodextrin complexations of rosuvastatin calcium. J. Res. Pharm. 2025;28(3):797-80.