Multicomponent crystals of fenofibric acid-L-proline with enhanced dissolution rate and antihyperlipidemic activity
Öz
The objectives of this study were to prepare and characterize a novel fenofibric acid-L prolin multicomponent crystals and to evaluate the improvement in dissolution rate and antihiperlipidemic activity of fenofibric acid when prepared in the multicomponent crystal formation. The solid-state characterization of the novel multicomponent crystal was performed by powder X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and Fourier transform-infrared (FT-IR) spectroscopy. The multicomponent crystals of fenofibric acid (FA) and L-prolin (PR) was prepared by solvent drop grinding method. Dissolution rate profiles were evaluated in phosphate buffer pH 6.8. To investigate the in vivo antihiperlipidemic activity, 16 male Swiss-Webster rat were injected with cholesterol-inductor solution 1%, following oral administration of intact fenofibric acid 9,45 mg/kg, physical mixture, and multicomponent crystals fenofibric acid- L-proline (equivalent to 9,45 mg/ kg fenofibric acid). The plasma level of cholesterol was determine with photometer. All data were analyzed with two-way ANOVA followed by Tukey HSD test (95% confidence interval). The results of the antihyperlipidemia test showed that the cholesterol levels of animals treated with multicomponen crystals FA-PR lower than the cholesterol levels of animals treated with fenofibric acid and physical mixture (significance <0,05). The Solubility and dissolution rate of multicomponent crystals FA-PR were also improved significantly compared to intact fenofibric acid.
Anahtar Kelimeler
Fenofibric acid L-Proline Multicomponen crystals Solubility Dissolution rate
Kaynakça
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- [18] Amidon GL, Lennernäs H, Shah V P, Crison JR. A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res: AAPS J. 1995; 12(3): 413–420. https://doi.org/10.1023/A:1016212804288
Öz
Kaynakça
- [1] Lipinski C, Poor aqueous solubility an industry wide problem in drug discovery. Am Pharm Rev. 2002; 5 (3): 82-85.
- [2] Kim K S, Kim J H, Jin S G, Kim DW, Kim D S, Kim JO, Yong C S, Cho KH, Li D X, Woo JS, Choi HG. Effect of magnesium carbonate on the solubility, dissolution and oral bioavailability of fenofibric acid powder as an alkalising solubilizer. Arch Pharm Res. 2016; 39(4): 531–538. https://doi.org/10.1007/s12272-015-0701-9
- [3] Yousaf A, M., Ramzan M, Shahzad Y, Mahmood T, Jamshaid M, Fabrication and in vitro characterization of fenofibric acid-loaded hyaluroNIC acid–polyethylene glycol polymeric composites with enhanced drug solubility and dissolution rate. Int J Polym Mater Polym Biomaterç 2019; 68(9): 510–515. https://doi.org/10.1080/00914037.2018.1466137
- [4] Long MA, Morris JB, Boyer M. Salt of fenofibric acid and pharmaceutical formulation. In: United States Patent. USA, 2007, pp 2(12).
- [5] Windriyati YN, Sumirtapura YC, Pamudji J S. Comparative in vitro and in vivo evaluation of fenofibric acid as an antihyperlipidemic drug. Turk J Pharm Sci. 2020; 17(2): 203–210 https://doi.org/10.4274%2Ftjps.galenos.2019.27147
- [6] Suhery WN, Sumirtapura YC, Pamudji JS, Mudhakir D. Development and characterization of self-nanoemulsifying drug delivery system (SNEDDS) formulation for enhancing dissolution of fenofibric acid. J Res Pharm. 2020; 24(5): 738–747. http://dx.doi.org/10.35333/jrp.2020.227
- [7] Putra OD, Furuishi T, Yonemochi E, Terada K, Uekusa H. Drug-drug multicomponent crystals as an effective technique to overcome weaknesses in parent drugs. Crys Growth Des. 2016;16(7): 3577–3581. https://doi.org/10.1021/acs.cgd.6b00639
- [8] Kotak U, Prajapati V, Solanki H, Jani G, Jha P. Co-crystallization technique-its rationale and recent progress. World J Pharm Pharm Sci. 2015; 4(04): 1484–1508.
- [9] Yamashita H, Hirakura, Y., Yuda, M., Teramura, T., & Terada, K. Detection of cocrystal formation based on binary phase diagrams using thermal analysis. Pharm Res. 2013; 30(1): 70–80. https://doi.org/10.1007/s11095-012-0850-1
- [10] Qiao N, Li M, Schlindwein W, Malek NA, Trappitt G. Pharmaceutical cocrystals; An overview. Int J Pharm. 2011; 419 (1-2): 1-11. https://doi.org/10.1016/j.ijpharm.2011.07.037
- [11] Manin AN, Voronin AP, Drozd KV, Manin NG, Bauer-Brandl A, Perlovich GL. Cocrystal screening of hydroxybenzamides with benzoic acid derivatives: A comparative study of thermal and solution-based methods. Eur J Pharm Sci. 2014: 65: 56-64. https://doi.org/10.1016/j.ejps.2014.09.003
- [12] Padrela L, de Azevedo E.G, Velaga SP. Powder X-ray diffraction method for the quantification of cocrystals in the crystallization mixture. Drug Dev Ind Pharm 2012; 38(8): 923-929.https://doi.org/10.3109/03639045.2011.633263
- [13] Chadha R, Bhalla Y, Nandan A, Chadha K, Karan M. Chrysin cocrystals: Characterization and evaluation. J Pharm BiomedAnaly. 2017; 134: 361-371. https://doi.org/10.1016/j.jpba.2016.10.020
- [14] Saha S, Rajput L, Joseph S, Mishra MK, Ganguly S, Desiraju GR. IR spectroscopy as a probe for C–H⋯X hydrogen bonded supramolecular synthons. CrystEngComm. 2015; 17(6): 1273-1290. http://dx.doi.org/10.1039/c4ce02034k
- [15] Mulye SP, Jamadar SA, Karekar PS, Pore YV, Dhawale SC. Improvement in physicochemical properties of ezetimibe using a crystal engineering technique. Powder Technol. 2012; 222: 131-138. https://doi.org/10.1016/j.powtec.2012.02.020
- [16] Nugrahani I, Utami D, Ibrahim S, Nugraha YP, Uekusa H. Zwitterionic cocrystal of diclofenac and L-proline: Structure determination, solubility, kinetics of cocrystallization, and stability study. Eur J Pharm Sci. 2018; 117: 185-176. https://doi.org/10.1016/j.ejps.2018.02.020
- [17] Vogel G. Drug Discovery and Evaluation Pharmacological Assays, Second Edition., Springer-Verley Berlin, Deidelbarg New York 2002.
- [18] Amidon GL, Lennernäs H, Shah V P, Crison JR. A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res: AAPS J. 1995; 12(3): 413–420. https://doi.org/10.1023/A:1016212804288
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Eczacılık ve İlaç Bilimleri (Diğer) |
| Bölüm | Articles |
| Yazarlar | |
| Yayımlanma Tarihi | 28 Haziran 2025 |
| Yayımlandığı Sayı | Yıl 2024 Cilt: 28 Sayı: 4 |