Formulation, Optimization and Evaluation of Solid Dispersion of Deferasirox Using Factorial Design
Abstract
Deferasirox, an oral iron-chelating agent, is a poorly soluble drug (Biopharmaceutical Classification System class II) having insufficient solubility in physiological fluids resulting in low bioavailability of the drug. The idea behind the present study was to explore the prospects of solid dispersion as a prolific method to enhance the dissolution rate of drug using a water soluble polymer. The solid dispersion was prepared by the solvent evaporation technique using Polyvinyl pyrrolidone with different drug to carrier and solvent ratio. Formulations were characterized through attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD), and in vitro release studies. A 32 factorial design was implemented to obtain optimum solubility, % yield, and optimization of solid dispersion (SD) also quantitates the influence of PVP on the solubility and dissolution profile. Thedrug-to-carrier and solvent ratio was chosen as independent variable, while %yield, drug content, and saturation solubility were chosen as dependent variables. The results showed that the optimized formulation of SD-DFX was able to significantly enhance its solubility. The SD containing a dispersion of Deferasirox with PVP show an exceptional rise in the solubility. This study describes the development of solid dispersion that significantly improved the solubility and bioavailability of DFX. The FTIR studies indicate the interaction between the drug and polymer. The DSC and XRD analysis indicated that the drug was in an amorphous state when dispersed in the polymer. It is resolved that the SD method significantly improves the solubility and dissolution rate, which could also be exploit for other poorly water soluble drug candidates.
Keywords: Deferasirox , Polyvinyl pyrrolidone, solid dispersion, Factorial design, Solubility
Keywords:
Deferasirox, Polyvinyl pyrrolidone, solid dispersion, Factorial design, SolubilityDOI
https://doi.org/10.22270/jddt.v14i5.6526References
REFERENCES
Eisa AM, El-Megrab NA, El-Nahas HM. Formulation and Evaluation of fast dissolving tablets of haloperidol solid dispersion. SPJ, 2022 Sep 9. https://doi.org/10.9734/jpri/2022/v34i45A36353
ALKUFI HK, RASHID AM. Enhancement of the solubility of famotidine solid dispersion using natural polymer by solvent evaporation. Int J App Pharm. 2021;13(3):193-8. https://doi.org/10.22159/ijap.2021v13i3.40934
Iqbal A, Hossain S, Shamim A, Islam M, Siddique AT. Formulation, in vitro evaluation and characterization of atorvastatin solid dispersion. Trop. J. Pharm. Res. 2020 Nov 13;19(6):1131-8. https://doi.org/10.4314/tjpr.v19i6.2
Szabó E, Záhonyi P, Brecska D, Galata DL, Mészáros LA, Madarász L, et al. Comparison of amorphous solid dispersions of spironolactone prepared by spray drying and electrospinning: The influence of the preparation method on the dissolution properties. Mol Pharm. 2020 Dec 10;18(1):317-27. https://doi.org/10.1021/acs.molpharmaceut.0c00965 PMid:33301326 PMCid:PMC7788570
Farmoudeh A, Rezaeiroshan A, Abbaspour M, Nokhodchi A, Ebrahimnejad P. Solid dispersion pellets: an efficient pharmaceutical approach to enrich the solubility and dissolution rate of deferasirox, Biomed Res Int. 2020 Jun 23;2020. https://doi.org/10.1155/2020/8583540 PMid:32685534 PMCid:PMC7333047
Joe JH, Lee WM, Park YJ, Joe KH, Oh DH, Seo YG, et al. Effect of the solid-dispersion method on the solubility and crystalline property of tacrolimus. Int J Pharm. 2010 Aug 16;395(1-2):161-6. https://doi.org/10.1016/j.ijpharm.2010.05.023 PMid:20580799
Panizzon GP, Giacomini Bueno F, Ueda-Nakamura T, Nakamura CV, Dias Filho BP. Manufacturing different types of solid dispersions of bcs class IV polyphenol (daidzein) by spray drying: formulation and bioavailability. Pharmaceutics. 2019 Sep 25;11(10):492. https://doi.org/10.3390/pharmaceutics11100492 PMid:31557831 PMCid:PMC6835336
Yu D, Li J, Wang H, Pan H, Li T, Bu T, et al. Role of polymers in the physical and chemical stability of amorphous solid dispersion: A case study of carbamazepine. Eur J Pharm Sci. 2022 Feb 1;169:106086. https://doi.org/10.1016/j.ejps.2021.106086 PMid:34861411
Wani SU, Kakkar V, Gautam SP, Gangadharappa HV, Ali M, Masoodi MH, et al. Enhancing therapeutic potential of poor aqueous soluble herbal drugs through solid dispersion-an overview. Phytomedicine Plus. 2021 Nov 1;1(4):100069. https://doi.org/10.1016/j.phyplu.2021.100069
Tekade AR, Yadav JN. A review on solid dispersion and carriers used therein for solubility enhancement of poorly water soluble drugs. Adv Pharm Bull. 2020 Jul;10(3):359. https://doi.org/10.34172/apb.2020.044 PMid:32665894 PMCid:PMC7335980
Huang BB, Liu DX, Liu DK, Wu G. Application of solid dispersion technique to improve solubility and sustain release of emamectin benzoate. Molecules. 2019 Nov 26;24(23):4315. https://doi.org/10.3390/molecules24234315 PMid:31779169 PMCid:PMC6930457
Dabhade D, Wadher K, Bute S, Naidu N, Umekar M, Anantwar S. Preparation and Characterization of Artemether Solid Dispersion by Spray Drying Technique. J. drug deliv. ther. 2021 Mar 15;11(2):1-5. https://doi.org/10.22270/jddt.v11i2.4557
Jahangiri A, Khalilzad F, Barghi L. Dissolution improvement of binary solid dispersions of erlotinib prepared by one-step electrospray method. Biol Methods Protoc. 2022;7(1):bpac001. https://doi.org/10.1093/biomethods/bpac001 PMid:35111974 PMCid:PMC8801718
Jiang X, Zhao Y, Guan Q, Xiao S, Dong W, Lian S, et al. Amorphous solid dispersions of cyclosporine A with improved bioavailability prepared via hot melt extrusion: Formulation, physicochemical characterization, and in vivo evaluation.Eur J Pharm Sci. 2022 Jan 1;168:106036. https://doi.org/10.1016/j.ejps.2021.106036 PMid:34637896
Mustafa WW, Fletcher J, Khoder M, Alany RG. Solid dispersions of gefitinib prepared by spray drying with improved mucoadhesive and drug dissolution properties. AAPS PharmSciTech. 2022 Jan;23(1):1-2. https://doi.org/10.1208/s12249-021-02187-4 PMid:34984564 PMCid:PMC8816420
Mahajan A, Surti N, Patel P, Gheewala N, Patel A, Shah D. Optimization of formulation and process variables using central composite design for the production of nevirapine spray dried solid dispersion. Drying Technology. 2021 Jan 11:1-4. https://doi.org/10.1080/07373937.2021.1874408
Liw JJ, Teoh XY, Teoh AX, Chan SY. The Effect of Carrier-Drug Ratios on Dissolution Performances of Poorly Soluble Drug in Crystalline Solid Dispersion System. J Pharm Sci. 2022 Jan 1;111(1):95-101. https://doi.org/10.1016/j.xphs.2021.06.026 PMid:34174289
Patel P, Mahajan A, Thakor N. ENHANCEMENT OF SOLUBILITY AND DISSOLUTION OF CLOPIDOGREL BISULFATE BY SOLID DISPERSION IN COMBINATION WITH SURFACE ADSORBENT. Pharmacophore. 2020 Sep 1;11(5).
Iqbal A, Hossain S, Shamim A, Islam M, Siddique AT. Formulation, in vitro evaluation and characterization of atorvastatin solid dispersion. Trop. J. Pharm. Res. 2020 Nov 13;19(6):1131-8. https://doi.org/10.4314/tjpr.v19i6.2
Singh J, Walia M, Harikumar SL, Solubility enhancement by solid dispersion method: a review, Journal of drug delivery and Therapeutics. 2013;3(5):148-155. https://doi.org/10.22270/jddt.v3i5.632
Kovalevska IV, Ruban OM, Kutova OV, Levachkova JS. Optimization of the composition of solid dispersion of quercetin.
Yamashita K, Nakate T, Okimoto K, Ohike A, Tokunaga Y, Ibuki R, et al. Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm. 2003 Nov 28;267(1-2):79-91. https://doi.org/10.1016/j.ijpharm.2003.07.010 PMid:14602386
Asif AH, Desu PK, Alavala RR, Rao GS, Sreeharsha N, Meravanige G. Development, Statistical Optimization and Characterization of Fluvastatin Loaded Solid Lipid Nanoparticles: A 32 Factorial Design Approach. Pharmaceutics. 2022 Mar 8;14(3):584. https://doi.org/10.3390/pharmaceutics14030584 PMid:35335960 PMCid:PMC8948994
Lee JH, Jeong HS, Jeong JW, Koo TS, Kim DK, Cho YH, et al. The Development and Optimization of Hot-Melt Extruded Amorphous Solid Dispersions Containing Rivaroxaban in Combination with Polymers. Pharmaceutics. 2021 Mar 6;13(3):344. https://doi.org/10.3390/pharmaceutics13030344 PMid:33800741 PMCid:PMC8001048
Vasconcelos T, Prezotti F, Araújo F, Lopes C, Loureiro A, Marques S, et al. Third-generation solid dispersion combining Soluplus and poloxamer 407 enhances the oral bioavailability of resveratrol. Int J Pharm.. 2021 Feb 15;595:120245. https://doi.org/10.1016/j.ijpharm.2021.120245 PMid:33484925
Manzoor M, Raza SA, Asim MH, Bukhari NI, Arshad S, Zafar U. Safety and Pharmaceutical Evaluation of a Novel Natural Polymer, Ocicum, as Solubility and Dissolution Enhancer in Solid Dispersion. Pharmaceuticals. 2022 Jul 14;15(7):869. https://doi.org/10.3390/ph15070869 PMid:35890167 PMCid:PMC9321241
Nowak M, Gajda M, Baranowski P, Szymczyk P, Karolewicz B, Nartowski KP. Stabilisation and growth of metastable form II of fluconazole in amorphous solid dispersions. Pharmaceutics. 2019 Dec 20;12(1):12. https://doi.org/10.3390/pharmaceutics12010012 PMid:31877666 PMCid:PMC7023302
Published
PDF Downloads: 312
PDF Downloads: 34
How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).