• PURNACHANDRA REDDY GUNTAKA Department of Pharmaceutics, GITAM Institute of Pharmacy, GITAM University, Rushikonda, Visakhapatnam, Andhra Pradesh, India.
  • SRINIVAS LANKALAPALLI Department of Pharmaceutics, GITAM Institute of Pharmacy, GITAM University, Rushikonda, Visakhapatnam, Andhra Pradesh, India.


Enhancement of the bioavailability of poorly water-soluble drugs is a challenging task in drug development. Currently 40% of new chemical entities are discovered as poorly water-soluble drugs. Solid dispersion is one of the best technology for improving solubility, dissolution rate, and bioavailability. Solid dispersion techniques are more useful for enhancing drug solubility for a combination of drug and inert carrier to improve wettability, reduced particle size, and converting amorphous particles. This article reviews various advantages, methods of solid dispersions, carriers used in solid dispersion, characterization, and marketed products.

Keywords: Bioavailability, Solubility, Dissolution, Carrier, Polymorphism.


1. Youn YS, Jung JY, Oh SH, Yoo SD, Lee KC. Improved intestinal delivery of salmon calcitonin by lys18-amine specific PEGylation: Stability, permeability, pharmacokinetic behavior and in vivo hypocalcemic efficacy. J Control Release 2006;114:334-42.
2. Ohara T, Kitamura S, Kitagawa T, Terada K. Dissolution mechanism of poorly water-soluble drug from extended release solid dispersion system with ethylcellulose and hydroxypropylmethylcellulose. Int J Pharm 2005;302:95-102.
3. Dhirendra K, Lewis S, Udupa N, Atin K. Solid dispersions: A review. Pak J Pharm Sci 2009;22:234-46.
4. Amidon GL, Lennernäs H, Shah VP, Crison JR. A theoretical basis for a biopharmaceutic drug classification: The correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm Res 1995;12:413-20.
5. Ad Noyes AA, Whitney WR. The rate of solution of solid substances in their own solutions J Am Chem Soc 1897;19:930-4.
6. Kapoor B, Kaur R, Kaur S. Solid dispersion: An evolutionary approach for solubility enhancement of poorly water soluble drugs. Int J Rec Adv Pharm Res 2012;2:1-16.
7. Lim SM, Pang ZW, Tan HY, Shaikh M, Adinarayana G, Garg S, et al. Enhancement of docetaxel solubility using binary and ternary solid dispersion systems. Drug Dev Ind Pharm 2015;41:1847-55.
8. Akiladevi D, Shanmugapandiyan P, Jebasingh D, Basak S. Preparation and evaluation of paracetamol solid dispersion technique. Int J Pharm Pharm Sci 2011;3:188-91.
9. Kushwaha A, Prajapati SK, Sharma B. Comparative study of acyclovir solid dispersion for bioavailability enhancement. Am J Pharm Tech Res 2011;1:179-201.
10. Chiou WL, Riegelman S. Preparation and dissolution characteristics of several fast-release solid dispersions of griseofulvin. J Pharm Sci 1969;58:1505-10.
11. Kanig JL. Properties of fused mannitol in compressed tablets. J Pharm Sci 1964;53:188-92.
12. Levy G. Effect of particle size on dissolution and gastrointestinal absorption rates of pharmaceuticals. Am J Pharm Sci Support Public Health 1963;135:78-92.
13. Urbanetz NA. Stabilization of solid dispersions of nimodipine and polyethylene glycol 2000. Eur J Pharm Sci 2006;28:67-76.
14. More SD, Sontakke SB. Solubility enhancement of gliclazide by solid dispersion method. Asian J Pharm Clin Res 2013;6:91-8.
15. Khazaal MN, Tarik AA, Abd AV. Efficacy of combination solid dispersion technology on dissolution performance of nalidixic acid and cefdinir. Asian J Pharm Clin Res 2017;1:394-401.
16. Dannenfelser RM, He H, Joshi Y, Bateman S, Serajuddin AT. Development of clinical dosage forms for a poorly water soluble drug I: Application of polyethylene glycol-polysorbate 80 solid dispersion carrier system. J Pharm Sci 2004;93:1165-75.
17. Chauhan B, Shimpi S, Paradkar A. Preparation and evaluation of glibenclamide-polyglycolized glycerides solid dispersions with silicon dioxide by spray drying technique. Eur J Pharm Sci 2005;26:219-30.
18. Mizuno M, Hirakura Y, Yamane I, Miyanishi H, Yokota S, Hattori M, et al. Inhibition of a solid phase reaction among excipients that accelerates drug release from a solid dispersion with aging. Int J Pharm 2005;305:37-51.
19. Verreck G, Decorte A, Heymans K, Adriaensen J, Cleeren D, Jacobs A, et al. The effect of pressurized carbon dioxide as a temporary plasticizer and foaming agent on the hot stage extrusion process and extrudate properties of solid dispersions of itraconazole with PVP-VA 64. Eur J Pharm Sci 2005;26:349-58.
20. Wagh KS, Kale SS, Patil SK, Mali KD. Design and evaluation of bilayer tablets of glimepiride and metformin hydrochloride with combination of hydrophilic and hydrophobic polymers by hot melt extrusion. Asian J Pharm Clin Res 2014;7:300-4.
21. Hasegawa S, Hamaura T, Furuyama N, Kusai A, Yonemochi E, Terada K, et al. Effects of water content in physical mixture and heating temperature on crystallinity of troglitazone-PVP K30 solid dispersions prepared by closed melting method. Int J Pharm 2005;302:103-12.
22. Yoshihashi Y. Estimation of physical stability of amorphous solid dispersion using differential scanning calorimetry. J Therm Anal Calorim 2006;85:689-92.
23. Sri A, Latha RK. Formulation and evaluation of zolpidem tartrate layered tablets by melt granulation technique for treatment of insomnia. Asian J Pharm Clin Res 2018;1:139-47.
24. Mohanty S. Dissolution enhancement of seroquel by solid dispersion techniques. Asian J Pharm Clin Res 2016;2016:284-7.
25. Pouton CW. Formulation of poorly water-soluble drugs for oral administration: Physicochemical and physiological issues and the lipid formulation classification system. Eur J Pharm Sci 2006;29:278-87.
26. Dixit ND, Niranjan SK. A review: Solid dispersion. World J Pharm Pharm Sci 2014;3:238-57.
27. Singh J, Walia M, Harikumar SL. Solubility enhancement by solid dispersion method: A review. J Drug Deliv Ther 2013;3:148-55.
28. van Drooge DJ, Hinrichs WL, Visser MR, Frijlink HW. Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniques. Int J Pharm 2006;310:220-9.
29. Eriksson HJ, Hinrichs WL, van Veen B, Somsen GW, de Jong GJ, Frijlink HW, et al. Investigations into the stabilisation of drugs by sugar glasses: I. Tablets prepared from stabilised alkaline phosphatase. Int J Pharm 2002;249:59-70.
30. Seo A, Schaefer T. Melt agglomeration with polyethylene glycol beads at a low impeller speed in a high shear mixer. Eur J Pharm Biopharm 2001;52:315-25.
31. Vilhelmsen T, Eliasen H, Schaefer T. Effect of a melt agglomeration process on agglomerates containing solid dispersions. Int J Pharm 2005;303:132-42.
32. Hohman MM, Shin M, Rutledge G, Brennera MP. Electrospinning and electrically forced jets. II. Applications. Phys Fluids 2001;13:2221-36.
33. Neamnark A, Rujiravanit R, Supaphol P. Electrospinning of hexanoyl chitosan. Carbohydrate polymers. Int J Pharm 2006;66:298-305.
34. Zhang W, Yan E, Huang Z, Wang C, Xin Y, Zhao Q, et al. Preparation and study of PPV/PVA nanofibers via electrospinning PPV precursor alcohol solution. Eur Poly 2007;43:802-97.
35. Taki S, Badens E, Charbit G. Controlled release system formed by supercritical anti-solvent coprecipitation of a herbicide and a biodegradable polymer. J Supercrit Fluids 2001;21:61-70.
36. Dohrn R, Bertakis E, Behrend O, Voutsas E, Tassios D. Melting point depression by using supercritical CO2 for a novel melt dipersionmicronization process. J Mol Liq 2007;131-2:53-9.
37. Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. 6th ed. London: Pharmaceutical Press; 2009.
38. Fikentscher H, Herrle K. Polyvinylpyrrolidone. Mod Plast 1945;23:157-218.
39. Stubberud L, Arwidsson HG, Hjortsberg V, Graffner C. Water-solid interactions. III. Effect of glass transition temperature, tg, and processing on tensile strength of compacts of lactose and lactose/polyvinyl pyrrolidone. Pharm Dev Technol 1996;1:195-204.
40. Kolter K, Flick D. Structure and dry binding activity of different polymers, including kollidon VA 64. Drug Dev Ind Pharm 2000;26:1159-65.
41. Coppens KA. Hypromellose, ethylcellulose, and polyethylene oxide use in hot melt extrusion. Pharm Technol 2005;30:62-70.
42. 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;267:79-91.
43. Repka MA, McGinity JW. Influence of chlorpheniramine maleate on topical hydroxypropylcellulose films produced by hot-melt extrusion. Pharm Dev Technol 2001;6:297-304.
44. Chiou WL, Riegelman S. Pharmaceutical applications of solid dispersion systems. J Pharm Sci 1971;60:1281-302.
45. Vila-Jato JL, Blanco J, Alonso MJ. The effect of the molecular weight of polyethylene glycol on the bioavailability of paracetamol-polyethylene glycol solid dispersions. J Pharm Pharm 1986;38:126-8.
46. Shah NH, Lazarus JH, Sheth PR, Jarowski CI. Carboxymethylcellulose: Effect of degree of polymerization and substitution on tablet disintegration and dissolution. J Pharm Sci 1981;70:611-3.
47. Singh J. Effect of sodium carboxymethylcelluloses on the disintegration, dissolution and bioavailability of lorazepam from tablets. Drug Dev Ind Pharm 1992;18:375-83.
48. Dittgen M, Durrani M, Lehmann K. Acrylic polymers: A review of pharmaceutical applications. STP Pharm Sci 1997;7:403-37.
49. Nakamichi K. Method of Manufacturing Solid Dispersion. United States Patent No; 1994.
50. Sertsou G, Butler J, Hempenstall J, Rades T. Solvent change co-precipitation with hydroxypropyl methylcellulose phthalate to improve dissolution characteristics of a poorly water-soluble drug. J Pharm Pharmacol 2002;54:1041-7.
51. Black SN, Collier EA, Davey RJ, Roberts RJ. Structure, solubility, screening, and synthesis of molecular salts. J Pharm Sci 2007;96:1053-68.
52. Liao X, Krishnamurthy R, Suryanarayanan R. Influence of processing conditions on the physical state of mannitol – implications in freeze-drying. Pharm Res 2007;24:370-6.
53. Zhang H, Yao M, Morrison RA, Chong S. Commonly used surfactant, tween 80, improves absorption of P-glycoprotein substrate, digoxin, in rats. Arch Pharm Res 2003;26:768-72.
54. Yadav PS, Kumar V, Singh UP, Bhat HR, Mazumder B. Physicochemical characterization and in vitro dissolution studies of solid dispersions of ketoprofen with PVP K30 and d-mannitol. Saudi Pharm J 2013;21:77-84.
55. Bunaciu AA, Udri?tioiu EG, Aboul-Enein HY. X-ray diffraction: Instrumentation and applications. Crit Rev Anal Chem 2015;45:289-99.
56. Taylor LS, Zografi G. Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm Res 1997;14:1691-8.
57. De Meuter P, Rahier H, Van Mele B. The use of modulated temperature differential scanning calorimetry for the characterisation of food systems. Int J Pharm 1999;192:77-84.
58. Van Duong T, Van den Mooter G. The role of the carrier in the formulation of pharmaceutical solid dispersions. Part II: Amorphous carriers. Expert Opin Drug Deliv 2016;13:1681-94.
59. Qi S, Craig D. Recent developments in micro- and nanofabrication techniques for the preparation of amorphous pharmaceutical dosage forms. Adv Drug Deliv Rev 2016;100:67-84.
60. Paudel A, Van den Mooter G. Influence of solvent composition on the miscibility and physical stability of naproxen/PVP K 25 solid dispersions prepared by cosolvent spray-drying. Pharm Res 2012;29:251-70.
61. Li C, Yu DG, Williams GR, Wang ZH. Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process. PLoS One 2014;9:e92106.
62. Yousaf AM, Mustapha O, Kim DW, Kim DS, Kim KS, Jin SG, et al. Novel electrosprayed nanospherules for enhanced aqueous solubility and oral bioavailability of poorly water-soluble fenofibrate. Int J Nanomedicine 2016;11:213-21.
63. Craig DQ. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm 2002;231:131-44.
64. Gupta SS, Parikh T, Meena AK, Mahajan N, Vitez I, Serajuddin ATM, et al. Effect of carbamazepine on viscoelastic properties and hot melt extrudability of soluplus ®. Int J Pharm 2015;478:232-9.
65. Ghosh I, Vippagunta R, Li S, Vippagunta S. Key considerations for optimization of formulation and melt-extrusion process parameters for developing thermosensitive compound. Pharm Dev Technol 2012;17:502-10.
66. Shah S, Maddineni S, Lu J, Repka MA. Melt extrusion with poorly soluble drugs. Int J Pharm 2013;453:233-52.
67. Fule RA, Meer TS, Sav AR, Amin PD. Dissolution rate enhancement and physicochemical characterization of artemether and lumefantrine solid dispersions. Int J Drug Deliv 2012;4:95-106.
68. Papageorgiou GZ, Bikiaris D, Karavas E, Politis S, Docoslis A, Park Y, et al. Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation. AAPS J 2006;8:E623-31.
69. Li B, Konecke S, Wegiel LA, Taylor LS, Edgar KJ. Both solubility and chemical stability of curcumin are enhanced by solid dispersion in cellulose derivative matrices. Carbohydr Polym 2013;98:1108-16.
70. Friesen DT, Shanker R, Crew M, Smithey DT, Curatolo WJ, Nightingale JA, et al. Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: An overview. Mol Pharm 2008;5:1003-19.
71. Agrawal AM, Dudhedia MS, Patel AD, Raikes MS. Characterization and performance assessment of solid dispersions prepared by hot melt extrusion and spray drying process. Int J Pharm 2013;457:71-81.
72. Paudel A, Worku ZA, Meeus J, Guns S, Van den Mooter G. Manufacturing of solid dispersions of poorly water soluble drugs by spray drying: Formulation and process considerations. Int J Pharm 2013;453:253-84.
73. Zhang J, Huang Y, Liu D, Gao Y, Qian S. Preparation of apigenin nanocrystals using supercritical antisolvent process for dissolution and bioavailability enhancement. Eur J Pharm Sci 2013;48:740-7.
74. Xu M, Zhang C, Luo Y, Xu L, Tao X, Wang Y, et al. Application and functional characterization of POVACOAT, a hydrophilic co-polymer poly(vinyl alcohol/acrylic acid/methyl methacrylate) as a hot-melt extrusion carrier. Drug Dev Ind Pharm 2014;40:126-35.
75. Zidan AS, Rahman Z, Sayeed V, Raw A, Yu L, Khan MA, et al. Crystallinity evaluation of tacrolimus solid dispersions by chemometric analysis. Int J Pharm 2012;423:341-50.
76. Modi A, Tayade P. Enhancement of dissolution profile by solid dispersion (kneading) technique. AAPS Pharm Sci Tech 2006;7:68.
77. Biswal S, Sahoo J, Murthy PN, Giradkar RP, Avari JG. Enhancement of dissolution rate of gliclazide using solid dispersions with polyethylene glycol 6000. AAPS Pharm Sci Tech 2008;9:563-70.
78. Ali W, Williams AC, Rawlinson CF. Stochiometrically governed molecular interactions in drug: Poloxamer solid dispersions. Int J Pharm 2010;391:162-8.
79. Mehta S, Joseph NM, Feleke F, Palani S. Improving solubility of BCS class II drugs using solid dispersion. J Drug Deliv Ther 2014;4:7-13.
80. Micheli L, Radoi A, Guarrina R, Massaud R, Bala C, Moscone D, et al. Disposable immunosensor for the determination of domoic acid in shellfish. Biosens Bioelectron 2004;20:190-6.
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How to Cite
GUNTAKA, P. R., and S. LANKALAPALLI. “SOLID DISPERSION - A NOVEL APPROACH FOR BIOAVAILABILITY ENHANCEMENT OF POORLY WATER-SOLUBLE DRUGS IN SOLID ORAL DOSAGE FORMS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 2, Jan. 2019, pp. 17-26, doi:10.22159/ajpcr.2019.v12i2.29157.
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