An overview of techniques for multifold enhancement in solubility of poorly soluble drugs

1. Liu R, Li X, Lam KS. Combinatorial chemistry in drug discovery. Curr Opin Chem Biol. 2017;38:117-26.10.1016/j.cbpa.2017.03.017 Search in Google Scholar

2. Macarron R, Banks MN, Bojanic D, Burns DJ, Cirovic DA, Garyantes T, et al. Impact of high-throughput screening in biomedical research. Nat Rev Drug Discov. 2011;10(3):188-95.10.1038/nrd3368 Search in Google Scholar

3. Khanna I. Drug discovery in pharmaceutical industry: productivity challenges and trends. Drug Discov Today. 2012;17(19-20):1088-102.10.1016/j.drudis.2012.05.007 Search in Google Scholar

4. Gardner CR, Walsh CT, Almarsson Ö. Drugs as materials: valuing physical form in drug discovery. Nat. Rev. Drug Discov. 2004;3(11): 926-34.10.1038/nrd1550 Search in Google Scholar

5. Huang LF, Tong WQ. Impact of solid state properties on developability assessment of drug candidates. Adv Drug Deliv Rev. 2004;56(3): 321-34.10.1016/j.addr.2003.10.007 Search in Google Scholar

6. Lipinski CA. Drug-like properties and the causes of poor solubility and poor permeability. J Pharmacol Toxicol Methods. 2000;44(1): 235-49.10.1016/S1056-8719(00)00107-6 Search in Google Scholar

7. Kalepu S, Nekkanti V. Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sinica B. 2015; 5(5):442-53.10.1016/j.apsb.2015.07.003462944326579474 Search in Google Scholar

8. Serajuddin AT. Salt formation to improve drug solubility. Adv Drug Del Rev. 2007;59(7):603-16.10.1016/j.addr.2007.05.01017619064 Search in Google Scholar

9. Stella VJ, Nti-Addae KW. Prodrug strategies to overcome poor water solubility. Adv Drug Del Rev. 2007;59(7):677-94.10.1016/j.addr.2007.05.01317628203 Search in Google Scholar

10. Seedher N, Kanojia M. Co-solvent solubilization of some poorly-soluble antidiabetic drugs. Pharm Dev Tech. 2009;14(2):185-92.10.1080/1083745080249889419519190 Search in Google Scholar

11. Rangel-Yagui CO, Pessoa Jr A, Tavares LC. Micellar solubilization of drugs. J Pharm Pharm Sci. 2005;8(2):147-63. Search in Google Scholar

12. Sintra TE, Shimizu K, Ventura SP, Shimizu S, Lopes JC, Coutinho JA. Enhanced dissolution of ibuprofen using ionic liquids as catanionic hydrotropes. Phy Chem Chem Phy. 2018;20(3):2094-103.10.1039/C7CP07569C Search in Google Scholar

13. Loftsson T, Brewster ME. Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization. J Pharm Sci. 1996;85(10):1017-25.10.1021/js950534b Search in Google Scholar

14. Thakuria R, Delori A, Jones W, Lipert MP, Roy L, Rodríguez-Hornedo N. Pharmaceutical cocrystals and poorly soluble drugs. Int J Pharm. 2013;453(1):101-25.10.1016/j.ijpharm.2012.10.043 Search in Google Scholar

15. Leuner C, Dressman J. Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000;50(1):47-60.10.1016/S0939-6411(00)00076-X Search in Google Scholar

16. Shegokar R, Müller RH. Nanocrystals: industrially feasible multifunctional formulation technology for poorly soluble actives. Int J Pharm. 2010;399(1-2):129-39.10.1016/j.ijpharm.2010.07.044 Search in Google Scholar

17. Müller RH, Peters K. Nanosuspensions for the formulation of poorly soluble drugs: I. Preparation by a size-reduction technique. Int J Pharm. 1998;160(2):229-37.10.1016/S0378-5173(97)00311-6 Search in Google Scholar

18. Kotta S, Khan AW, Pramod K, Ansari SH, Sharma RK, Ali J. Exploring oral nanoemulsions for bioavailability enhancement of poorly water-soluble drugs. Expert Opin Drug Del. 2012;9(5):585-98.10.1517/17425247.2012.66852322512597 Search in Google Scholar

19. He CX, He ZG, Gao JQ. Microemulsions as drug delivery systems to improve the solubility and the bioavailability of poorly water-soluble drugs. Expert Opin Drug Del. 2010;7(4):445-60.10.1517/1742524100359633720201713 Search in Google Scholar

20. Hu J, Johnston KP, Williams III RO. Nanoparticle engineering processes for enhancing the dissolution rates of poorly water soluble drugs. Drug Dev Ind Pharm. 2004;30(3):233-45.10.1081/DDC-120030422 Search in Google Scholar

21. Miyazaki S, Nakano M, Arita T. A comparison of solubility characteristics of free bases and hydrochloride salts of tetracycline antibiotics in hydrochloric acid solutions. Chem Pharm Bull (Tokyo). 1975;23(6):1197-204.10.1248/cpb.23.1197241499 Search in Google Scholar

22. Agharkar S, Lindenbaum S, Higuchi T. Enhancement of solubility of drug salts by hydrophilic counterions: properties of organic salts of an antimalarial drug. J Pharm Sci. 1976;65(5):747-9.10.1002/jps.2600650533932950 Search in Google Scholar

23. Groo AC, De Pascale M, Voisin-Chiret AS, Corvaisier S, Since M, Malzert-Fréon A. Comparison of 2 strategies to enhance pyridoclax solubility: Nanoemulsion delivery system versus salt synthesis. Eur J Pharm Sci. 2016;97:218-226.10.1016/j.ejps.2016.11.02527916693 Search in Google Scholar

24. Sanphui P, Tothadi S, Ganguly S, Desiraju GR. Salt and cocrystals of sildenafil with dicarboxylic acids: solubility and pharmacokinetic advantage of the glutarate salt. Mol Pharm. 2013;10(12):4687-97.10.1021/mp400516b24168322 Search in Google Scholar

25. Nielsen LH, Gordon S, Holm R, Selen A, Rades T, Müllertz A. Preparation of an amorphous sodium furosemide salt improves solubility and dissolution rate and leads to a faster Tmax after oral dosing to rats. Eur J Pharm Biopharm. 2013;85(3 Pt B):942-51.10.1016/j.ejpb.2013.09.00224075980 Search in Google Scholar

26. Chiang PC, Wong H. Incorporation of physiologically based pharmacokinetic modeling in the evaluation of solubility requirements for the salt selection process: a case study using phenytoin. AAPS J. 2013;15(4):1109-18.10.1208/s12248-013-9519-x378722023943382 Search in Google Scholar

27. Nielsen AB, Frydenvang K, Liljefors T, Buur A, Larsen C. Assessment of the combined approach of N-alkylation and salt formation to enhance aqueous solubility of tertiary amines using bupivacaine as a model drug. Eur J Pharm Sci. 2005;24(1):85-93.10.1016/j.ejps.2004.09.01215626581 Search in Google Scholar

28. ElShaer A, Khan S, Perumal D, Hanson P, Mohammed AR. Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin. Curr Drug Deliv. 2011;8(4):363-72.10.2174/15672011179576792421453261 Search in Google Scholar

29. Jornada DH, dos Santos Fernandes GF, Chiba DE, De Melo TR, Dos Santos JL, Chung MC. The prodrug approach: a successful tool for improving drug solubility. Molecules. 2015;21(1):42.10.3390/molecules21010042627360126729077 Search in Google Scholar

30. Nielsen AB, Buur A, Larsen C. Bioreversible quaternary N-acyloxymethyl derivatives of the tertiary amines bupivacaine and lidocaine--synthesis, aqueous solubility and stability in buffer, human plasma and simulated intestinal fluid. Eur J Pharm Sci. 2005;24(5):433-40.10.1016/j.ejps.2004.12.00715784333 Search in Google Scholar

31. Sanphui P, Tothadi S, Ganguly S, Desiraju GR. Salt and cocrystals of sildenafil with dicarboxylic acids: solubility and pharmacokinetic advantage of the glutarate salt. Mol Pharm. 2013;10(12):4687-97.10.1021/mp400516b Search in Google Scholar

32. Niethammer A, Gaedicke G, Lode HN, Wrasidlo W. Synthesis and preclinical characterization of a paclitaxel prodrug with improved antitumor activity and water solubility. Bioconjug Chem. 2001;12(3):414-20.10.1021/bc000122g Search in Google Scholar

33. Siddiqui A, McGuigan C, Ballatore C, Srinivasan S, De Clercq E, Balzarini J. Enhancing the aqueous solubility of d4T-based phosphoramidate prodrugs. Bioorg Med Chem Lett. 2000;10(4): 381-4.10.1016/S0960-894X(99)00701-5 Search in Google Scholar

34. Nielsen LS, Bundgaard H, Falch E. Prodrugs of thiabendazole with increased water-solubility. Acta Pharm Nord. 1992;4(1):43-9. Search in Google Scholar

35. Gualdesi MS, Ravetti S, Raviolo MA, Briñón MC. Preformulation studies of novel 5’-O-carbonates of lamivudine with biological activity: solubility and stability assays. Drug Dev Ind Pharm. 2014; 40(9):1246-52.10.3109/03639045.2013.814064 Search in Google Scholar

36. Hasabelnaby S, Goudah A, Agarwal HK, abd Alla MS, Tjarks W. Synthesis, chemical and enzymatic hydrolysis, and aqueous solubility of amino acid ester prodrugs of 3-carboranyl thymidine analogs for boron neutron capture therapy of brain tumors. Eur J Med Chem. 2012;55:325-34.10.1016/j.ejmech.2012.07.033 Search in Google Scholar

37. Mahfouz NM, Hassan MA. Synthesis, chemical and enzymatic hydrolysis, and bioavailability evaluation in rabbits of metronidazole amino acid ester prodrugs with enhanced water solubility. J Pharm Pharmacol. 2001;53(6):841-8.10.1211/0022357011776199 Search in Google Scholar

38. Jouyban, A. Review of the cosolvency models for predicting solubility of drugs in water-cosolvent mixtures. J Pharm Pharm Sci. 2008;11(1):32-58.10.18433/J3PP4K Search in Google Scholar

39. Kovacs K, Ancha M, Jane M, Lee S, Angalakurthi S, Negrito M, Rasheed S, Nwaneri A, Petrikovics I. Identification, solubility enhancement and in vivo testing of a cyanide antidote candidate. Eur J Pharm Sci. 2013;49(3):352-8.10.1016/j.ejps.2013.04.007 Search in Google Scholar

40. Nicoli S, Bilzi S, Santi P, Caira MR, Li J, Bettini R. Ethyl-paraben and nicotinamide mixtures: apparent solubility, thermal behavior and X-ray structure of the 1:1 co-crystal. J Pharm Sci. 2008;97(11):4830-9.10.1002/jps.21341 Search in Google Scholar

41. Takeichi Y, Kimura T. Improvement of aqueous solubility and rectal absorption of 6-mercaptopurine by addition of sodium benzoate. Biol Pharm Bull. 1994;17(10):1391-4.10.1248/bpb.17.1391 Search in Google Scholar

42. Siddiqui A, McGuigan C, Ballatore C, Srinivasan S, De Clercq E, Balzarini J. Enhancing the aqueous solubility of d4T-based phosphoramidate prodrugs. Bioorg Med Chem Lett. 2000;10(4):381-4.10.1016/S0960-894X(99)00701-5 Search in Google Scholar

43. Seedher N, Agarwal P. Various solvent systems for solubility enhancement of enrofloxacin. Indian J Pharm Sci. 2009;71(1):82-7.10.4103/0250-474X.51958281006120177468 Search in Google Scholar

44. Haq N, Siddiqui NA, Shakeel F. Solubility and molecular interactions of ferulic acid in various (isopropanol + water) mixtures. J Pharm Pharmacol. 2017;69(11):1485-94.10.1111/jphp.1278628722130 Search in Google Scholar

45. Rangel-Yagui CO, Pessoa Jr A, Tavares LC. Micellar solubilization of drugs. J Pharm Pharm Sci. 2005;8(2):147-63. Search in Google Scholar

46. Zhang Z, Cui C, Wei F, Lv H. Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system. Drug Dev Ind Pharm. 2017;43(8):1276-82.10.1080/03639045.2017.131385728358225 Search in Google Scholar

47. Dugar RP, Gajera BY, Dave RH. Fusion method for solubility and dissolution rate enhancement of ibuprofen using block copolymer poloxamer 407. AAPS PharmSciTech. 2016;17(6):1428-40.10.1208/s12249-016-0482-626817763 Search in Google Scholar

48. Granero GE, Ramachandran C, Amidon GL. Dissolution and solubility behavior of fenofibrate in sodium lauryl sulfate solutions. Drug Dev Ind Pharm. 2005;31(9):917-22.10.1080/0363904050027210816306004 Search in Google Scholar

49. Varshosaz J, Ziaei V, Minaiyan M, Jahanian-Najafabadi A, Sayed-Tabatabaei L. Enhanced solubility, oral bioavailability and anti-osteoporotic effects of raloxifene HCl in ovariectomized rats by Igepal CO-890 nanomicelles. Pharm Dev Technol. 2018,30:1-12.10.1080/10837450.2018.142881529338533 Search in Google Scholar

50. Mennini N, Furlanetto S, Bragagni M, Ghelardini C, Di Cesare Mannelli L, Mura P. Development of a chitosan-derivative micellar formulation to improve celecoxib solubility and bioavailability. Drug Dev Ind Pharm. 2014;40(11):1494-502.10.3109/03639045.2013.83144023992553 Search in Google Scholar

51. Kim MS, Kim JS, Cho WK, Hwang SJ. Enhanced solubility and oral absorption of sirolimus using D-α-tocopheryl polyethylene glycol succinate micelles. Artif Cells Nanomed Biotechnol. 2013;41(2):85-91.10.3109/21691401.2012.74210023305536 Search in Google Scholar

52. Lapenna S, Bilia AR, Morris GA, Nilsson M. Novel artemisinin and curcumin micellar formulations: drug solubility studies by NMR spectroscopy. J Pharm Sci. 2009;98(10):3666-75.10.1002/jps.2168519199296 Search in Google Scholar

53. Balakrishnan A, Rege BD, Amidon GL, Polli JE. Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity. J Pharm Sci. 2004;93(8):2064-75.10.1002/jps.2011815236455 Search in Google Scholar

54. Tsuji A, Miyamoto E, Matsuda M, Nishimura K, Yamana T. Effects of surfactants on the aqueous stability and solubility of beta-lactam antibiotics. J Pharm Sci. 1982;71(12):1313-8.10.1002/jps.26007112037153876 Search in Google Scholar

55. Balasubramanian D, Srinivas V, Gaikar VG, Sharma MM. Aggregation behavior of hydrotropic compounds in aqueous solution. J Phy Chem. 1989;93(9):3865-70.10.1021/j100346a098 Search in Google Scholar

56. Madan JR, Kamate VJ, Dua K, Awasthi R. Improving the solubility of nevirapine using A hydrotropy and mixed hydrotropy based solid dispersion approach. Polim Med. 2017;47(2):83-90.10.17219/pim/77093 Search in Google Scholar

57. Beig A, Lindley D, Miller JM, Agbaria R, Dahan A. Hydrotropic Solubilization of Lipophilic Drugs for Oral Delivery: The Effects of Urea and Nicotinamide on Carbamazepine Solubility-Permeability Interplay. Front Pharmacol. 2016;7(379):1-8.10.3389/fphar.2016.00379507867427826241 Search in Google Scholar

58. Madan JR, Pawar KT, Dua K. Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy. Int J Pharm Investig. 2015;5(2):114-20.10.4103/2230-973X.153390438138825838997 Search in Google Scholar

59. Maheshwari RK, Jagwani Y. Mixed hydrotropy: novel science of solubility enhancement. Indian J Pharm Sci. 2011;73(2):179-83.10.4103/0250-474X.91585 Search in Google Scholar

60. Coffman RE, Kildsig DO. Effect of nicotinamide and urea on the solubility of riboflavin in various solvents. J Pharm Sci. 1996;85(9):951-4.10.1021/js960012b8877885 Search in Google Scholar

61. Frank SG, Cho MJ. Phase solubility analysis and PMR study of complexing behavior of dinoprostone with beta-cyclodextrin in water. J Pharm Sci. 1978;67(12):1665-8.10.1002/jps.2600671207722476 Search in Google Scholar

62. Loftsson T, Duchêne D. Cyclodextrins and their pharmaceutical applications. Int J Pharm. 2007;329:1-11.10.1016/j.ijpharm.2006.10.04417137734 Search in Google Scholar

63. Budhwar V. Cyclodextrin Complexes: An approach to improve the physicochemical properties of drugs and applications of cyclodextrin complexes. Asian J Pharm. 2018;12(02). Search in Google Scholar

64. Azzi J, Danjou PE, Landy D, Ruellan S, Auezova L, Greige-Gerges H, et al. The effect of cyclodextrin complexation on the solubility and photostability of nerolidol as pure compound and as main constituent of cabreuva essential oil. Beilstein J Org Chem. 2017; 13:835-44.10.3762/bjoc.13.84543314428546841 Search in Google Scholar

65. Chi L, Liu R, Guo T, Wang M, Liao Z, Wu L, et al. Dramatic improvement of the solubility of pseudolaric acid B by cyclodextrin complexation: preparation, characterization and validation. Int J Pharm. 2015;479(2):349-56.10.1016/j.ijpharm.2015.01.00525575474 Search in Google Scholar

66. Vangara KK, Ali HI, Lu D, Liu JL, Kolluru S, Palakurthi S. SN-38-cyclodextrin complexation and its influence on the solubility, stability, and in vitro anticancer activity against ovarian cancer. AAPS PharmSciTech. 2014;15(2):472-82.10.1208/s12249-013-0068-5396948724477982 Search in Google Scholar

67. Zhang QF, Nie HC, Shangguang XC, Yin ZP, Zheng GD, Chen JG. Aqueous solubility and stability enhancement of astilbin through complexation with cyclodextrins. J Agric Food Chem. 2013; 61(1):151-6.10.1021/jf304398v Search in Google Scholar

68. Ansari MT, Iqbal I, Sunderland VB. Dihydroartemisinincyclodextrin complexation: solubility and stability. Arch Pharm Res. 2009;32(1):155-65.10.1007/s12272-009-1130-4 Search in Google Scholar

69. Klein S, Wempe MF, Zoeller T, Buchanan NL, Lambert JL, Ramsey MG, et al. Improving glyburide solubility and dissolution by complexation with hydroxybutenyl-beta-cyclodextrin. J Pharm Pharmacol. 2009;61(1):23-30.10.1211/jpp/61.01.0004 Search in Google Scholar

70. Latrofa A, Trapani G, Franco M, Serra M, Muggironi M, Fanizzi FP, et al. Complexation of phenytoin with some hydrophilic cyclodextrins: effect on aqueous solubility, dissolution rate, and anticonvulsant activity in mice. Eur J Pharm Biopharm. 2001; 52(1):65-73.10.1016/S0939-6411(01)00144-8 Search in Google Scholar

71. Cui L, Zhang Z, Sun E, Jia X, Qian Q. Effect of β-cyclodextrin complexation on solubility and enzymatic hydrolysis rate of icariin. J Nat Sci Biol Med. 2013;4(1):201-6.10.4103/0976-9668.107291363327823633863 Search in Google Scholar

72. Cui L, Zhang ZH, Sun E, Jia XB. Effect of β-cyclodextrin complexation on solubility and enzymatic conversion of naringin. Int J Mol Sci. 2012;13(11):14251-61.10.3390/ijms131114251350957823203062 Search in Google Scholar

73. Ansari MJ. Formulation and physicochemical characterization of sodium carboxy methyl cellulose and [beta] cyclodextrin mediated ternary inclusion complexes of silymarin. Int J Pharm Sci Res. 2016; 7(3):984-90. Search in Google Scholar

74. Schultheiss N, Newman A. Pharmaceutical cocrystals and their physicochemical properties. Cryst Growth Des. 2009;9(6):2950-67.10.1021/cg900129f269039819503732 Search in Google Scholar

75. Bavishi DD, Borkhataria CH. Spring and parachute: How cocrystals enhance solubility. Prog Cryst Growth Charact Mater. 2016;62(3):1-8.10.1016/j.pcrysgrow.2016.07.001 Search in Google Scholar

76. Sanphui P, Rajput L. Tuning solubility and stability of hydrochlorothiazide co-crystals. Acta Crystallogr B Struct Sci Cryst Eng Mater. 2014;70(Pt1):81-90.10.1107/S205252061302691724441131 Search in Google Scholar

77. Keramatnia F, Shayanfar A, Jouyban A. Thermodynamic Solubility Profile of Carbamazepine-Cinnamic Acid Cocrystal at Different pH. J Pharm Sci. 2015;104(8):2559-65.10.1002/jps.2452526096952 Search in Google Scholar

78. Alhalaweh A, Roy L, Rodríguez-Hornedo N, Velaga SP. pH-dependent solubility of indomethacin-saccharin and carbamazepine-saccharin cocrystals in aqueous media. Mol Pharm. 2012;9(9):2605-12.10.1021/mp300189b22867056 Search in Google Scholar

79. Goud NR, Gangavaram S, Suresh K, Pal S, Manjunatha SG, Nambiar S, et al. Novel furosemide cocrystals and selection of high solubility drug forms. J Pharm Sci. 2012;101(2):664-80.10.1002/jps.2280522081478 Search in Google Scholar

80. Suresh K, Goud NR, Nangia A. Andrographolide: solving chemical instability and poor solubility by means of cocrystals. Chem Asian J. 2013;8(12):3032-41.10.1002/asia.20130085924027244 Search in Google Scholar

81. Huang Y and Dai WG. Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B. 2004;4(1):18-25.10.1016/j.apsb.2013.11.001459072126579360 Search in Google Scholar

82. Cho HJ, Jee JP, Kang JY, Shin DY, Choi HG, Maeng HJ, et al. Cefdinir Solid Dispersion Composed of Hydrophilic Polymers with Enhanced Solubility, Dissolution, and Bioavailability in Rats. Molecules. 2017;22(2). pii:E280.10.3390/molecules22020280615568128208830 Search in Google Scholar

83. Madgulkar A, Bandivadekar M, Shid T, Rao S. Sugars as solid dispersion carrier to improve solubility and dissolution of the BCS class II drug: clotrimazole. Drug Dev Ind Pharm. 2016;42(1):28-38.10.3109/03639045.2015.102468325874729 Search in Google Scholar

84. Kim SM, Pang ZW, Tan HY, Shaikh M, Adinarayana G, Garg S. Enhancement of docetaxel solubility using binary and ternary solid dispersion systems. Drug Dev Ind Pharm. 2015;41(11):1847-55.10.3109/03639045.2015.101481825721984 Search in Google Scholar

85. Lee SN, Poudel BK, Tran TH, Marasini N, Pradhan R, Lee YI, et al. A novel surface-attached carvedilol solid dispersion with enhanced solubility and dissolution. Arch Pharm Res. 2013;36(1):79-85.10.1007/s12272-013-0008-723328872 Search in Google Scholar

86. Onoue S, Kojo Y, Aoki Y, Kawabata Y, Yamauchi Y, Yamada S. Physicochemical and pharmacokinetic characterization of amorphous solid dispersion of tranilast with enhanced solubility in gastric fluid and improved oral bioavailability. Drug Metab Pharmacokinet. 2012;27(4):379-87.10.2133/dmpk.DMPK-11-RG-10122240843 Search in Google Scholar

87. 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;395(1-2):161-6.10.1016/j.ijpharm.2010.05.02320580799 Search in Google Scholar

88. Jung JY, Yoo SD, Lee SH, Kim KH, Yoon DS, Lee KH. Enhanced solubility and dissolution rate of itraconazole by a solid dispersion technique. Int J Pharm. 1999;187(2):209-18.10.1016/S0378-5173(99)00191-X Search in Google Scholar

89. Yuvaraja K, Khanam J. Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid. J Pharm Biomed Anal. 2014;96:10-20.10.1016/j.jpba.2014.03.019 Search in Google Scholar

90. Zoghbi A, Geng T, Wang B. Dual Activity of Hydroxypropyl-β-Cyclodextrin and Water-Soluble Carriers on the Solubility of Carvedilol. AAPS PharmSciTech. 2017;18(8):2927-35.10.1208/s12249-017-0769-2 Search in Google Scholar

91. Varshosaz J, Minayian M, Ahmadi M, Ghassami E. Enhancement of solubility and antidiabetic effects of Repaglinide using spray drying technique in STZ-induced diabetic rats. Pharm Dev Technol. 2017;22(6):754-63.10.3109/10837450.2016.1143001 Search in Google Scholar

92. Herbrink M, Schellens JHM, Beijnen JH, Nuijen B. Improving the solubility of nilotinib through novel spray-dried solid dispersions. Int J Pharm. 2017;529(1-2):294-302.10.1016/j.ijpharm.2017.07.010 Search in Google Scholar

93. Dhore PW, Dave VS, Saoji SD, Bobde YS, Mack C, Raut NA. Enhancement of the aqueous solubility and permeability of a poorly water soluble drug ritonavir via lyophilized milk-based solid dispersions. Pharm Dev Technol. 2017;22(1):90-102.10.1080/10837450.2016.1193193 Search in Google Scholar

94. Rai VK, Dwivedi H, Yadav NP, Chanotiya CS, Saraf SA. Solubility enhancement of miconazole nitrate: binary and ternary mixture approach. Drug Dev Ind Pharm. 2014;40(8):1021-9.10.3109/03639045.2013.801487 Search in Google Scholar

95. Shaikh SM, Avachat AM. Enhancement of solubility and permeability of Candesartan cilexetil by using different pharmaceutical interventions. Curr Drug Deliv. 2011;8(4):346-53.10.2174/156720111795767997 Search in Google Scholar

96. Li X, Yuan H, Zhang C, Chen W, Cheng W, Chen X, Ye X. Preparation and in-vitro/in-vivo evaluation of curcumin nanosuspension with solubility enhancement. J Pharm Pharmacol. 2016;68(8):980-8.10.1111/jphp.12575 Search in Google Scholar

97. Nanotechnology Drug Delivery Market (By Technology - Nanocrystals, Nanoparticles, Liposomes, Micelles, Nanotubes, and Others; By Application - Neurology, Oncology, Cardiovascular/Physiology, Anti-inflammatory/Immunology, Anti-infective, and Others) - Global Industry Analysis, Size, Share, Growth, Trends, and Forecast 2015-2023. Available at https://www.transparencymarketresearch.com/nanotechnology-drug-delivery.html accessed on 26/11/2018. Search in Google Scholar

98. Poste G, Papahadjopoulos D, and Vail WJ. Lipid vesicles as carriers for introducing biologically active materials into cells. Methods in Cell Biol. 1976;14:33-71.10.1016/S0091-679X(08)60468-9 Search in Google Scholar

99. Merisko-Liversidge E, Liversidge GG, and Cooper ER. Nanosizing: a formulation approach for poorly water-soluble compounds. Eur J Pharm Sci. 2004;18:113-20.10.1016/S0928-0987(02)00251-8 Search in Google Scholar

100. Rizvi SA, Saleh AM. Applications of nanoparticle systems in drug delivery technology. Saudi Pharma J. 2018;26(1):64-70.10.1016/j.jsps.2017.10.012578381629379334 Search in Google Scholar

101. Torchilin VP. Recent advances with liposomes as pharmaceutical carriers. Nature Rev Drug Disc. 2005;4(2):145.10.1038/nrd163215688077 Search in Google Scholar

102. Ansari MJ, Ahmed MM, Anwer MK, Jamil S, Alailaiwe A, Alshetaili AS, et al. Formulation and characterization of fluconazole loaded olive oil nano-emulsions. Indo Am J Pharm Sci. 2017, 4 (04), 852-60. Search in Google Scholar

103. Ansari MJ. Factors Affecting Preparation and Properties of Nanoparticles by Nanoprecipitation Method. Indo Am. J. P. Sci. 2017; 4(12):4854-8. Search in Google Scholar

104. Omolo CA, Kalhapure RS, Agrawal N, Rambharose S, Mocktar C, Govender T. Formulation and Molecular Dynamics Simulations of a Fusidic Acid Nanosuspension for Simultaneously Enhancing Solubility and Antibacterial Activity. Mol Pharm. 2018;15(8): 3512-26.10.1021/acs.molpharmaceut.8b0050529953816 Search in Google Scholar

105. Aditya NP, Yang H, Kim S, Ko S. Fabrication of amorphous curcumin nanosuspensions using β-lactoglobulin to enhance solubility, stability, and bioavailability. Colloids Surf B Biointerfaces. 2015;127:114-21.10.1016/j.colsurfb.2015.01.02725660094 Search in Google Scholar

106. Kassem MAA, ElMeshad AN, Fares AR. Enhanced Solubility and Dissolution Rate of Lacidipine Nanosuspension: Formulation Via Antisolvent Sonoprecipitation Technique and Optimization Using Box-Behnken Design. AAPS PharmSciTech. 2017;18(4):983-96.10.1208/s12249-016-0604-127506564 Search in Google Scholar

107. Telange DR, Patil AT, Pethe AM, Fegade H, Anand S, Dave VS. Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. Eur J Pharm Sci. 2017;108:36-49.10.1016/j.ejps.2016.12.00927939619 Search in Google Scholar

108. Lee JS, Hong DY, Kim ES, Lee HG. Improving the water solubility and antimicrobial activity of silymarin by nanoencapsulation. Colloids Surf B Biointerfaces. 2017;154:171-7.10.1016/j.colsurfb.2017.03.00428340483 Search in Google Scholar

109. Arunkumar R, Prashanth KVH, Manabe Y, Hirata T, Sugawara T, Dharmesh SM, Baskaran V. Biodegradable Poly (Lactic-co-Glycolic Acid)-Polyethylene Glycol Nanocapsules: An efficient carrier for improved solubility, bioavailability, and anticancer property of lutein. J Pharm Sci. 2015;104(6):2085-93.10.1002/jps.2443625824524 Search in Google Scholar

110. Groo AC, De Pascale M, Voisin-Chiret AS, Corvaisier S, Since M, Malzert-Fréon A. Comparison of 2 strategies to enhance pyridoclax solubility: Nanoemulsion delivery system versus salt synthesis. Eur J Pharm Sci. 2017;97:218-26.10.1016/j.ejps.2016.11.02527916693 Search in Google Scholar

111. Han M, He CX, Fang QL, Yang XC, Diao YY, Xu DH, He QJ, Hu YZ, Liang WQ, Yang B, Gao JQ. A novel camptothecin derivative incorporated in nano-carrier induced distinguished improvement in solubility, stability and anti-tumor activity both in vitro and in vivo. Pharm Res. 2009;26(4):926-35.10.1007/s11095-008-9795-919048358 Search in Google Scholar

112. Bolko K, Zvonar A, Gašperlin M. Mixed lipid phase SMEDDS as an innovative approach to enhance resveratrol solubility. Drug Dev Ind Pharm. 2014;40(1):102-9.10.3109/03639045.2012.74988823301796 Search in Google Scholar

113. Nandi I, Bari M, Joshi H. Study of isopropyl myristate microemulsion systems containing cyclodextrins to improve the solubility of 2 model hydrophobic drugs. AAPS PharmSciTech. 2003;4(1):E10.10.1208/pt040110275030612916919 Search in Google Scholar