Keywords
SBA-15
Dissolution rate enhancment
improved physical stability
drug release kinetics
mesoporous silica
How to Cite
Abstract
Objective: The objective of this research was to enhance the physical stability and the dissolution rate of cefdinir, a BCS class IV drug, characterized by low and variable bioavailability due to both its low solubility and low permeability.
Methods: Cefdinir was loaded into the mesoporous silica (SBA-15), by using the solvent immersion method starting from different organic solvents. And then formula (F3), which exhibited the highest loading percentage, was selected to study its drug release in media with different pH (1.2, 4.5, and 6.8), and has been fully characterized by using: Fourier Transform Infrared Spectroscopy (FT-IR) Spectroscopy, Differential Scanning Calorimetry, Powder X-ray Diffraction, and has been subjected to accelerated stability tests using different temperatures and relative humidity. Drug release kinetics were studied by using the following models: Probit, Gompertz, Weibull, and Logistic.
Results: The results showed a remarkable dissolution improvement of cefdinir from the loaded silica in comparison to the crystalline drug at the different studied media. Drug release behaviors were well simulated by the Weibull model for F3 in all studied media and for pure Cefdinir in phosphate buffer only, and by the Gompertz function for pure Cefdinir in HCl buffer and Acetate buffer. FTIR results showed hydrogen bonds formed between the drug and silica, DSC and PXRD results revealed the transformation of cefdinir into an amorphous form upon adsorption. Stability studies under different conditions revealed the ability of mesoporous silica to maintain the amorphous state of the drug, which has been formed upon adsorption, and to prevent re-organization in the crystal nucleus of the drug molecules.
Conclusion: Thus, loading cefdinir onto mesoporous silica can be used as a promising method to enhance drug dissolution, and maintain the physical stability of its amorphous form.
References
Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 2000; 50(1): 47-60. https://doi.org/10.1016/S0939-6411(00)00076-X
Amidon CJ, Lennernas GL, Shah H. A theoreical basis for a Biopharamcetics Drug Classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995; 12(3): 413-20. https://doi.org/10.1023/A:1016212804288
Markovic M, Zur M, Ragatsky H, Cvijić S, Dahan A. Bcs class iv oral drugs and absorption windows: Regional-dependent intestinal permeability of furosemide. Pharmaceutics 2020; 12(12): 1-16. https://doi.org/10.3390/pharmaceutics12121175
Wise R, Andrews JM, Thbornber D. The in-vitro activity of cefdinir (FK482), a new oral cephalosporin. J Antimicrob Chemother 1991; 28(2): 239-48. https://doi.org/10.1093/jac/28.2.239
Guay DRP. Cefdinir: An advanced-generation, broad- spectrum oral cephalosporin. Clin Ther 2002; 24(4): 473-89. https://doi.org/10.1016/S0149-2918(02)85125-6
Perry CM, Scott LJ. Cefdinir: a review of its use in the management of mild-to-moderate bacterial infections. Drugs 2004; 64(13): 1433-64. https://doi.org/10.2165/00003495-200464130-00004
Aleem O, Kuchekar B, Pore Y, Late S. Effect of β - cyclodextrin and hydroxypropyl β -cyclodextrin complexation on physicochemical properties and antimicrobial activity of cefdinir. J Pharm Biomed Anal 2008; 47(3): 535-40. https://doi.org/10.1016/j.jpba.2008.02.006
Sawant KK, Patel MH, Patel K. Cefdinir nanosuspension for improved oral bioavailability by media milling technique: formulation, characterization and in vitro-in vivo evaluations. Drug Dev Ind Pharm 2015; 1-11. https://doi.org/10.3109/03639045.2015.1104344
Patil OA, et al. Formulation optimization and evaluation of Cefdinir nanosuspension using 23 Factorial design. Marmara Pharm J 2018; 22(4): 587-598. https://doi.org/10.12991/jrp.2018.101
Park J, et al. Preparation and pharmaceutical characterization of amorphous cefdinir using spray-drying and SAS-process. Int J Pharm 2010; 396: 239-45. https://doi.org/10.1016/j.ijpharm.2010.06.032
Morina D, Sessevmez M, Sinani G, Mülazımoğlu L, Cevher E. Oral tablet formulations containing cyclodextrin complexes of poorly water soluble cefdinir to enhance its bioavailability. J Drug Deliv Sci Technol 2020; 57: 101742. https://doi.org/10.1016/j.jddst.2020.101742
Chhayani RL, Chhayani RB, Patel D, Borkhataria CH. Development and Characterization of Self- Microemulsifying Drug Delivery System for Improvement of Bioavailability of Cefdinir. JPMC 2016; 2(1): 57-83. https://doi.org/10.21088/jpmc.2395.6615.2116.7
Cho HJ, et al. Cefdinir Solid Dispersion composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats. Molecules 2017; 22(280): 1-14. https://doi.org/10.3390/molecules22020280
Jain S, Jain S, Mishra A, Garg G, Modi RK. Formulation and characterization of fast disintegrating tablets containing Cefdinir solid dispersion. Int J Pharm Life Sci 2012; 3(12): 2190-99.
Maraie NK, Alhamdany AT, Radhi AA. Efficacy of compenation solid dispersion technology on dissolution performance of nalidixic acid and cefdinir. Asian J Pharm Clin Res 2017; 10(4): 394-401. https://doi.org/10.22159/ajpcr.2017.v10i4.16913
Prathibha B, Reddy DV, Reddy DS. Formulation and evalution of once a day tablet of cefdinir. Int J Pharm Technol 2014; 5(4): 115-6130.
Lakshmanarao P, et al. Enhancement of solubility and dissolution rate of cefdinir using solid dispersions. Indo Am J Pharm Res 2017; 4(3): 747-753.
Sharma S, Sher P, Badve S, Pawar AP. Absorption of Meloxicam on Porous Calcium Silicate: Characterization and tablet formulation. AAPS PharmSciTech 2005; 6(4): 618-25. https://doi.org/10.1208/pt060476
Maleki A, Kettiger H, Schoubben A, Rosenholm JM, Ambrogi V, Hamidi M. Mesoporous silica materials: From physico- chemical properties to enhanced dissolution of poorly water- soluble drugs. J Control Release 2017; 262: 329-47. https://doi.org/10.1016/j.jconrel.2017.07.047
Ambrogi V, et al. MCM-41 for furosemide dissolution improvement. Micropor Mesopor Mat 2012; 147(1): 343-49. https://doi.org/10.1016/j.micromeso.2011.07.007
Chircov C, et al. Mesoporous Silica Platforms with Potential Applications in Release and Adsorption of Active Agents. Molecules 2020; 25(17): 1-35. https://doi.org/10.3390/molecules25173814
Celer EP, Kruk M, Zuzek Y, Jaroniec M. Hydrothermal stability of SBA-15 and related ordered mesoporous silicas with plugged pores. J Mater Chem 2006; 16(27): 2824-33. https://doi.org/10.1039/b603723b
Cassiers K, et al. A detailed study of thermal, hydrothermal, and mechanical stabilities of a wide range of surfactant assembled mesoporous silicas. Chem Mater 2002; 14(5): 2317-24. https://doi.org/10.1021/cm0112892
Ma Y, Qi L, Ma J, Wu Y, Liu O, Cheng H. Large-pore mesoporous silica spheres: Synthesis and application in HPLC. Colloids Surfaces A Physicochem. Eng Asp 2003; 229(1-3): 1-8. https://doi.org/10.1016/j.colsurfa.2003.08.010
Ambrogi V, et al. Use of SBA-15 for furosemide oral delivery enhancement. Eur J Pharm Sci 2012; 46(1-2): 43-48. https://doi.org/10.1016/j.ejps.2012.02.004
Baka E, Comer JEA, Takács-Novák K. Stuy of equilibrium solubility measurement by saturation shake-flask method using hydrochlorothiazide as model compound. J Pharm Biomed Anal 2008; 46(2): 335-41. https://doi.org/10.1016/j.jpba.2007.10.030
Shah PB, Pundarikakshudu K. UV spectroscopic and colorimetric methods for the estimation of cefdinir in capsule dosage forms. Indian J Pharm Sci 2004; 66: 665-67.
Al-Badr AA, Alasseiri FA. Cefdinir. In: Profiles of Drug Substances, Excipients and Related Methodology Elsevier Inc. 2014; 39: 41-112. https://doi.org/10.1016/B978-0-12-800173-8.00002-7
Šoltys M, Kovačík P, Dammer O, Beránek J, Š těpánek F. Effect of solvent selection on drug loading and amorphisation in mesoporous silica particles. Int J Pharm 2019; 555: 19-27. https://doi.org/10.1016/j.ijpharm.2018.10.075
Albayati TM, Salih IK, Alazzawi HF. Synthesis and characterization of a modified surface of SBA-15 mesoporous silica for a chloramphenicol drug delivery system. Heliyon 2019; 5(10): e02539. https://doi.org/10.1016/j.heliyon.2019.e02539
Lakshmanarao P, Prasada Rao M, Krishnaveni T, Sukanya B, Lakshmi Priya P, Sai Krishna A. Enhancement of solubility and dissolution rate of cefdinir using solid dispersions. Indo Am J Pharm Sci 2017; 4: 747-53.
Tsong Y, Hammerstrom T, Chen JJ. Multipoint dissolution specification and acceptance sampling rule based on profile modeling and principal component analysis. J Biopharm Stat 1997; 7(3): 423-39. https://doi.org/10.1080/10543409708835198
Shah VP, Tsong Y, Sathe P, Liu JP. In vitro dissolution profile comparison- Statistics and analysis of the similarity factor, f2. Pharm Res 1998; 15(6): 889-96. https://doi.org/10.1023/A:1011976615750
Costa FO, Sousa JJS, Pais AACC, Formosinho SJ. Comparison of dissolution profiles of Ibuprofen pellets. J Control Release 2003; 89(2): 199-12. https://doi.org/10.1016/S0168-3659(03)00033-6
Langenbucher F. Letters to the Editor: Linearization of dissolution rate curves by the Weibull distribution. J Pharm Pharmacol 1972; 24(12): 979-81. https://doi.org/10.1111/j.2042-7158.1972.tb08930.x
Costa LJ. Modeling and comparison of dissolution profiles. Eur J Pharm Sci 2001; 13: 123-33. https://doi.org/10.1016/S0928-0987(01)00095-1
Zhang Yet al. DDSolver: An add-in program for modeling and comparison of drug dissolution profiles. AAPS J 2010; 12(3): 263-71. https://doi.org/10.1208/s12248-010-9185-1
Simionato LD, Petrone L, Baldut M, Bonafede SL, Segall AI. Comparison between the dissolution profiles of nine meloxicam tablet brands commercially available in Buenos Aires, Argentina. Saudi Pharm J 2018; 26(4): 578-84. https://doi.org/10.1016/j.jsps.2018.01.015
Mellaerts Ret al. Aging behavior of pharmaceutical formulations of itraconazole on SBA-15 ordered mesoporous silica carrier material. Micropor Mesopor Mat 2010; 130(1-3): 154-61. https://doi.org/10.1016/j.micromeso.2009.10.026
Belgic M. US 2013/0017156 A1.
Heikkilä Tet al. Evaluation of mesoporous TCPSi, MCM-41, SBA-15, and TUD-1 materials as API carriers for oral drug delivery. Drug Deliv 2007; 14(6): 337-47. https://doi.org/10.1080/10717540601098823
Hong S et al. High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: A comparison of spray drying versus solvent impregnation methods. Drug Deliv 2016; 23(1): 316-27. https://doi.org/10.3109/10717544.2014.913323
Salonen J et al. Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs. J Control Release 2005; 108(2-3): 362-74. https://doi.org/10.1016/j.jconrel.2005.08.017
Chaudhari SP, Gupte A. Mesoporous silica as a carrier for amorphous solid dispersion. Br J Pharm Res 2017; 16(6): 1- 19.
https://doi.org/10.9734/BJPR/2017/33553
Hillerström A, Andersson M, Samuelsson J, Van Stam J. Solvent strategies for loading and release in mesoporous silica. Colloid Interface Sci Commun 2014; 3: 5-8. https://doi.org/10.1016/j.colcom.2015.01.001
Eren ZS, Tunçer S, Gezer G, Yildirim LT, Banerjee S, Yilmaz A. Improved solubility of celecoxib by inclusion in SBA-mesoporous silica: Drug loading in different solvents and release. Micropor Mesopor Mat 2016; 235: 211-23. https://doi.org/10.1016/j.micromeso.2016.08.014
Tomasi J.Thirty years of continuum solvation chemistry: A review, and prospects for the near future. Theor Chem Acc 2004; 112: 184-03. https://doi.org/10.1007/s00214-004-0582-3
Fang R, Yang S, Wang Y, Qian H. Nanoscale Drug Delivery Systems: A Current Review on the Promising Paclitaxel Formulations for Future Cancer Therapy. Nano 2015; 10(5): 1-27. https://doi.org/10.1142/S1793292015300042
Server NE, and Law D. WO2005100368A2. 2006.
Cabri W, et al. Cefdinir: A comparative study of anhydrous vs. monohydrate form. Microstructure and tabletting behaviour. Eur J Pharm Biopharm 2006; 64(2): 212-21. https://doi.org/10.1016/j.ejpb.2006.05.007
Kiwilsza A, Mielcarek J, Pajzderska A, Waosicki J. Ordered mesoporous silica material SBA-15: Loading of new calcium channel blocker-lacidipine. J Microencapsul 2013; 30(1): 21- 27. https://doi.org/10.3109/02652048.2012.692401
Lepsy CS, Guttendorf RJ, Kugler AR, Smith DE. Effects of organic anion, organic cation, and dipeptide transport inhibitors on cefdinir in the isolated perfused rat kidney. Antimicrob Agents Chemother 2003; 47(2): 689-96. https://doi.org/10.1128/AAC.47.2.689-696.2003
Wang S. Ordered mesoporous materials for drug delivery. Micropor Mesopor Mat 2009; 117(1-2): 1-9. https://doi.org/10.1016/j.micromeso.2008.07.002
Yu LX, Wang JT, Hussain AS. Evaluation of USP apparatus 3 for dissolution testing of immediate-release products. AAPS PharmSci 2002; 4(1). https://doi.org/10.1208/ps040101
Lokhandwala H, Deshpande A, Deshpande S. Kinetic modeling and dissolution profiles comparison: an overview. Int J Pharma Bio Sci 2013; 4: 728-37.
Rengarajan GT, Enke D, Steinhart M, Beiner M. Stabilization of the amorphous state of pharmaceuticals in nanopores. J Mater Chem 2008; 18(22): 2537-39. https://doi.org/10.1039/b804266g
Andersson J, Rosenholm J, Areva S, Lindén M. Influences of material characteristics on ibuprofen drug loading and release profiles from ordered micro- and mesoporous silica matrices. Chem Mater 2004; 16(21): 4160-67. https://doi.org/10.1021/cm0401490
Genina N, Hadi B, Löbmann K. Hot Melt Extrusion as Solvent-Free Technique for a Continuous Manufacturing of Drug-Loaded Mesoporous Silica. J Pharm Sci 2018; 107(1): 149-55. https://doi.org/10.1016/j.xphs.2017.05.039
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