Solid Dispersion as Strategy to Improve the Solubility of Poorly Water Soluble Drugs and their Utilization and Consideration during Formulation Development
Solid dispersions are most promising system to increase the solubility of poorly water soluble drugs. By using reduction in drug particle size in required specification, and due to that improving drug wettability, bioavailability may be todays need. Solid dispersion generally presented as amorphous products, mainly obtained by two major different methods, melting and solvent evaporation. Now days, surfactants have been included to stabilize the formulations, thus avoiding drug recrystallization and potentiating their solubility. New manufacturing processes to obtain solid dispersions have also been developed to reduce the drawbacks of the initial process. In this review, it is intended to discuss the consideration during formulation development also role of hydrophobic polymer for solubility enhancement various strategy to inhibit the recrystallization.
Keywords: Solid dispersion, recrystallization, solubility, bioavailability, dissolution rate, hydrophobic polymer.
2) Shejul A, Deshmane S, Biyani K, Modified Natural Carrier In Solid Dispersion For Enhancement Of Solubility of Poorly Water Soluble Drugs, Journal of Drug Delivery & Therapeutics; 2014; 4(1):111-116.
3) Kharkwal H, Bala K, Joshi DD, Katare DP, Bioavailability Enhancement of Curcuminoids using Natural Polymer, Scholars Research Library ,Der Pharmacia Lettre, 2012; 4(6):1698-1711
4) Pahwa R, Kataria U, Rana AC, Rao R, Nanda S, Solid Dispersion Technology: Recent Advancements In The Delivery Of Various Phytoconstituents, IJPSR, 2015; 6(2).
5) Yalkowsky SH, Perspective on improving passive human intestinalabsorption. J Pharm Sci 2012; 101(9):3047–3050.
6) Yan He, Chris Ho, Amorphous Solid Dispersions: Utilization And Challenges In Drug Discovery And Development, Journal Of Pharmaceutical Sciences 2015; 104:3237–3258.
7) George , Joseph L, Saini PM, Nair JV, Enhancing the bioavailability of poorly water soluble drug etoroxib using solid dispersion technique solid dispersion a method to improve bioavailability of poorly water soluble drug. IJPPR. 2016; 17-51.
8) Ngoa HV, Phuc K Nguyena, T V Voa, W Duanb, Van-Thanh Tranc, P H Tranb, T Tran, Hydrophilic-Hydrophobic Polymer Blend For Modulation Of Crystalline Changes And Molecular Interactions In Solid Dispersion, International Journal Of Pharmaceutics, 2016; 513:148–152.
9) Baghel S, Cathcart H, O'reilly NJ, Polymeric Amorphous Solid Dispersions: A Review Of Amorphization, Crystallization, Stabilization, Solid-State Characterization, And Aqueous Solubilization Of Biopharmaceutical Classification SystemClass II Drugs, Journal of Pharmaceutical Sciences, Published by Elsevier, 2016; 105:2527-2544.
10) Knop, K.; Hoogenboom, R.; Fischer, D.; Schubert, U.S. Poly (ethylene glycol) in Drug Delivery: Pros and Cons asWell as Potential Alternatives. Angew. Chem. Int. Ed. 2010; 49: 6288–6308.
11) Hildebrand, VHeydenreich, M Laschewsky, A Möller, H.M.; M Buschbaum, P Papadakis, D Wischerho, “Schizophrenic” self-assembly of dual thermoresponsive block copolymers bearing a zwitterionic and a non-ionic hydrophilic block. Polymer 2017; 122:347–357.
12) Willersinn, J Bogomolova, A Brunet Cabré, M Schmidt, Vesicles of double hydrophilic pullulan and poly(acrylamide) block copolymers: A combination of synthetic- and bio-derived blocks. Polym. Chem. 2017; 8:1244–1254.
13) Xie Z, Chen D, Jiang D, X Zhang, Y Liu, H Liu, Stimuli-Responsive Double Hydrophilic Block Copolymer Micelles with Switchable Catalytic Activity. Macromolecules 40, 3538–3546, 2007
14) Rudolph, T Crotty, S V Lühe, M Pretzel, D Schubert, U Schacher, Synthesis and Solution Properties of Double Hydrophilic Poly(ethylene oxide)-block-poly(2-ethyl-2-oxazoline) (PEO-b-PEtOx) Star Block Copolymers. Polymers, 5, 1081, 2013
15) Schulte, V A Díez, M Möller, M Lensen, Surface Topography Induces Fibroblast Adhesion on Intrinsically Nonadhesive Poly(ethylene glycol) Substrates. Biomacromolecules 10, 2795–2801, 2009
16) F Wu, Y Bai, L Peng, X Zhang, H Zhang, Y An, P Wang, S Ma, G Ba, Facile preparation of hyperbranched glycopolymers via an AB3 inimer promoted by a hydroxy/cerium(iv) redox process. Polym. Chem. 2018, 9, 5024–5031, 2018
17) McCormick, C L Lowe, Aqueous RAFT polymerization: Recent developments in synthesis of functional water-soluble (co) polymers with controlled structures. Acc. Chem. Res. 2004, 37, 312–325
18) Zhou D. et al., A calorimetric investigation of thermodynamic and molecular mobility contributions to the physical stability of two pharmaceutical glasses. J. Pharm. Sci. 96, 71–83, 2007.
19) Yoshioka M., Crystallization of indomethacin from the amorphousstate below and above its glass transition temperature. J. Pharm. Sci. 83, 1700–1705,68,1994
20) Gunawan L., Structural relaxation of acetaminophen glass. Pharm. Res.23, 967–979,2006.
21) Shmeis, RA A mechanistic investigation of an amorphous pharmaceutical and its solid dispersions, part I: a comparative analysis by thermally stimulated depolarization current and differential scanning calorimetry. Pharm.Res. 21, 2025–2030,2004
22) Taylor L.S. and Zografi, Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm. Res.14, 1691–1698,1997
23) Vasanthavada, Phase behavior of amorphous molecular dispersions I: Determination of the degree and mechanism of solid solubility. Pharm. Res. 21, 1598–1606,2004.
24) Vasanthavada, Phase behavior of amorphous molecular dispersions II: Role of hydrogen bonding in solid solubility and phase separation kinetics. Pharm. Res. 22, 440–448,2005
25) Schachter D.M. et al,Solid state NMR perspective of drug-polymer solid solutions: a model system based on poly(ethylene oxide). Int. J. Pharm. 281, 89–101,2004
26) Vippagunta S.R. et al.,Factors affecting the formation of eutectic solid dispersions and their dissolution behavior. J. Pharm. Sci. 96, 294–304,2006
27) Teberekidis V.I. and Sigalas, Theoretical study of hydrogen bond interactions of felodipine with polyvinylpyrrolidone and polyethyleneglycol. THEOCHEM 803, 29–38,2006
28) Van den Mooter, G. et al.,Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. Eur. J. Pharm. Sci. 12, 261–269,2001
29) Weuts, I. et al.,Salt formation in solid dispersions consisting of polyacrylic acid as a carrier and three basic model compounds resulting in very high glass transition temperatures and constant dissolution properties upon storage. Eur. J. Pharm. Sci. 25, 387–393,2005
30) Bhugra C. et al.,Prediction of the onset of crystallization of amorphous sucrose below the calorimetric glass transition temperature from correlations with mobility. J. Pharm. Sci. 2007; 96:1258–1269.
31) Lohani X, Cooper H, XJin X, Nissley BP, Manser K, L H Rakes, J Cummings, S E Fauty, A Bak, Physicochemical properties, form, and formulation selection strategy for a biopharmaceutical classification system class II preclinical drug candidate. J Pharm Sci 103(10):3007–3021, 2014
32) Zheng W, Jain A, Papoutsakis D, Dannenfelser RM, Panicucci R, Garad S, Selection of oral bioavailability enhancing formulations during drug discovery. Drug Dev Ind Pharm 2012; 38(2):235–247.
33) Yalkowsky SH, Solubility and solubilization in aqueous media. New York, NY: Oxford University Press, Inc,1999
34) Yalkowsky SH, He Y, Jain P, Handbook of aqueous solubility data. 2nd ed. Boca Raton, FL: CRC Press,2009
35) Alonzo DE, Zhang GZ, Zhou D, Gao Y, Taylor LS, Understanding the behavior of amorphous pharmaceutical systems during dissolution. Pharm Res 2009; 27(4):608–618.
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