• IYAN SOPYAN Department of Pharmaceutical and Technology of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia, Study Center of Dosage Form Development, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia
  • DOLIH GOZALI Department of Pharmaceutical and Technology of Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia
  • SANDRA MEGANTARA Department of Pharmaceutical Analysis and Medicinal Chemsitry, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia
  • RETNO WAHYUNINGRUM Department of Pharmacy, Faculty of Science and Technology, Universitas Sembilanbelas November, Kolaka, Indonesia
  • INSAN SUNAN KS Department of Pharmaceutical and Technology Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Bandung, Indonesia



Solubility, Drug, Techniques increase solubility


The most significant aspect of a drug's physicochemical nature is its solubility. If the medicine is in a dissolved form, it can dissolve and enter the membrane, resulting in a therapeutic effect. The pharmacokinetic phase of the drug in the body, which includes absorption, distribution, metabolism, and excretion, will be correlated with solubility. Some medications, however, have a low solubility. To obtain a therapeutic impact, an effort must be made to increase the drug's solubility. Based on the literature research, the goal of this paper is to explain approaches that can be utilized to improve solubility. In general, physical, chemical, and micelle formation efforts can all be used it to enhance solubility. Particle size reduction, crystal shape modification, and the utilization of matrices in the disperse phase are examples of physical alterations. pH adjustment, buffering, salt formation, complexation, and derivatization all are examples of chemical alterations. The employment of supercritical processes in solutions and also excipients such as surfactants, cosolvents, stabilizing solutions, and others are examples of how micelle formation can be modified.


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Lachman L, Lieberman H, Kanig JL. Teori dan praktek Farmasi Industri II (Edisi 3). Terjemahan Siti Suyatmi, Jakarta. UI Press; 2008. p. 110-2.

Gong Y, Grant DJW, Britain HG. Principles of solubility. In: New York: Springer; 2007.

Aulton ME, Taylor K. Aulton’s pharmaceutics: the design and manufacture of medicines. Elsevier Health Sciences; 2013. p. 302-5.

Van den Mooter G. The use of amorphous solid dispersions: A formulation strategy to overcome poor solubility and dissolution rate. Drug Discov Today Technol. 2012;9(2):e79-85. doi: 10.1016/j.ddtec.2011.10.002.

Al-Hamidi H, Edwards AA, Mohammad MA, Nokhodchi A. To enhance the dissolution rate of poorly water-soluble drugs: glucosamine hydrochloride as a potential carrier in solid dispersion formulations. Colloids Surf B Biointerfaces. 2010;76(1):170-8. doi: 10.1016/j.colsurfb.2009.10.030, PMID 19945828.

Alavijeh MS, Chishty M, Qaiser MZ, Palmer AM. Drug metabolism and pharmacokinetics, the blood-brain barrier, and central nervous system drug discovery. Neurorx. 2005;2(4):554-71. doi: 10.1602/neurorx.2.4.554, PMID 16489365.

Mehta M. Biopharmaceutics classification system (bcs). United Kingdom: John Wiley and Sons; 2017. p. 213.

Jaiswal SB, Shamsuddin SSS, Shehzad SS, Brahmankar DM. Pelletization in rotary shaker effect of equipment variables on pelletization of ferrous fumarate. Drug Dev Ind Pharm. 1995;21(18):2109-20. doi: 10.3109/03639049509065894.

Babu NJ, Nangia A. Solubility advantage of amorphous drugs and pharmaceutical cocrystals. Cryst Growth Des. 2011;11(7):2662-79. doi: 10.1021/cg200492w.

Savjani KT, Gajjar AK, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012;2012:195727. doi: 10.5402/2012/195727, PMID 22830056.

Gupta S, Sawarkar S, Ravikumar P. Solubility enhancement of poorly water-soluble protease inhibitor. Int J Pharm Sci Res. 2016;7:252-8.

Gozali D, Bahti HH, Soewandhi SN, Abdassah M. Pembentukan Kokristal antara kalsium atorvastatin dengan Isonikotinamid dan Karakterisasinya. Abstrak; 2012. Available from:

Indra I, Janah FM, Aryani R. Enhancing the solubility of ketoconazole via pharmaceutical cocrystal. J Phys.: Conf Ser. 2019;1179(1):012134. doi: 10.1088/1742-6596/1179/1/ 012134.

Yadava SK, Naik JB, Patil JS, Mokale VJ, Singh R. Enhanced solubility and bioavailability of lovastatin using stabilized form of self-emulsifying drug delivery system. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2015;481:63-71. doi: 10.1016/j.colsurfa.2015.04.026.

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. doi: 10.1016/j.ejpb.2013.09.002, PMID 24075980.

Law D, Wang W, Schmitt EA, Qiu Y, Krill SL, Fort JJ. Properties of rapidly dissolving eutectic mixtures of poly (ethylene glycol) and fenofibrate: the eutectic microstructure. J Pharm Sci. 2003;92(3):505-15. doi: 10.1002/jps.10324, PMID 12587112.

Anwar M, Warsi MH, Mallick N, Akhter S, Gahoi S, Jain GK, Talegaonkar S, Ahmad FJ, Khar RK. Enhanced bioavailability of nano-sized chitosan–atorvastatin conjugate after oral administration to rats. Eur J Pharm Sci. 2011;44(3):241-9. doi: 10.1016/j.ejps.2011.08.001, PMID 21864678.

Lee EH. A practical guide to pharmaceutical polymorph screening and selection. Asian J Pharm Sci. 2014;9(4):163-75. doi: 10.1016/j.ajps.2014.05.002.

Bekers O, Uijtendaal EV, Beijnen JH, Bult A, Underberg WJM. Cyclodextrins in the pharmaceutical field. Drug Dev Ind Pharm. 1991;17(11):1503-49. doi: 10.3109/03639049109026630.

Valero M, Tejedor J, Rodriguez LJ. Encapsulation of nabumetone by means of-drug: (β-cyclodextrin) 2: Polyvinylpyrrolidone ternary complex formation. J Lumin. 2007;126(2):297-302. doi: 10.1016/j.jlumin.2006.07.028.

Salustio PJ, Feio G, Figueirinhas JL, Pinto JF, Cabral Marques HM. The influence of the preparation methods on the inclusion of model drugs in a β-cyclodextrin cavity. Eur J Pharm Biopharm. 2009;71(2):377-86. doi: 10.1016/j.ejpb.2008. 09.027, PMID 18977436.

Tong WQT, Wen H. Applications of complexation in the formulation of insoluble compounds. In: Water-insoluble drug formulation. CRC Press; 2008. p. 147-74.

Kumar P, Singh C. A study on solubility enhancement methods for poorly water-soluble drugs. Am J Pharmacol Sci. 2013;1(4):67-73. doi: 10.12691/ajps-1-4-5.

Huang Y, Dai WG. Fundamental aspects of solid dispersion technology for poorly soluble drugs. Acta Pharm Sin B. 2014;4(1):18-25. doi: 10.1016/j.apsb.2013.11.001, PMID 26579360.

Sridhar I, Doshi A, Joshi B, Wankhede V, Doshi J. Solid dispersions: an approach to enhance the solubility of poorly water-soluble drug. J Sci Innov Res. 2013;2:685-94.

Fudholi A. Disolusi dan pelepasan obat in vitro. Pustaka Pelajar Yogyakatra. 2013. p. 115.

Martin AM, Swarbrick J, Cammarata A, Farmasi Fisik, Terjemahan Yoshita. Jakarta: UI Press; 1990. p. 203-4.

Craig DQ. The mechanisms of drug release from solid dispersions in water-soluble polymers. Int J Pharm. 2002;231(2):131-44. doi: 10.1016/s0378-5173(01)00891-2, PMID 11755266.

Alonzo DE, Zhang GG, Zhou D, Gao Y, Taylor LS. Understanding the behavior of amorphous pharmaceutical systems during dissolution. Pharm Res. 2010;27(4):608-18. doi: 10.1007/s11095-009-0021-1, PMID 20151181.

Aakeröy CB, Salmon DJ. Building co-crystals with molecular sense and supramolecular sensibility. Cryst Eng Comm. 2005;7(72):439-48. doi: 10.1039/b505883j.

Sopyan I, Sari IM, K IS. Solid-state characterization of a novel physical interaction (paracetamol-chlorpheniramine maleate). Int J App Pharm 2018;10(1). doi: 10.22159/ijap.2018v10i1.22840.

Hairunnisa H, Sopyan I, Gozali D. Ko-kristal: nikotinamid sebagai koformer. JFB. 2019;10(2):113-22. doi: 10.52434/jfb.v10i2.652.

Sopyan I, Syah ISK, Nurhayti D, Budiman A. Improvement of simvastatin dissolution rate using derivative non-covaalent approach by solvent drop grinding method. Int J Appl Pharm. 2020;12:21-4.

Liu R, Drug WI. Formulation. 2nd ed. Vol. 686. CRC Press; 2008. p. 235.

Lin HL, Hsu PC, Lin SY. Theophylline–citric acid co-crystals are easily induced by DSC–FTIR microspectroscopy or different storage conditions. Asian J Pharm Sci. 2013;8(1):19-27. doi: 10.1016/j.ajps.2013.07.003.

Junghanns JU, Muller RH. Nanocrystal technology, drug delivery and clinical applications. Int J Nanomedicine. 2008;3(3):295-309. doi: 10.2147/ijn.s595, PMID 18990939.

Yadav SK, Mishra S, Mishra B. Eudragit-based nanosuspension of poorly water-soluble drug: formulation and in vitro–in vivo evaluation. AAPS PharmSciTech. 2012;13(4):1031-44. doi: 10.1208/s12249-012-9833-0, PMID 22893314.

Stott PW, Williams AC, Barry BW. Transdermal delivery from eutectic systems: enhanced permeation of a model drug, ibuprofen. J Control Release. 1998;50(1-3):297-308. doi: 10.1016/s0168-3659(97)00153-3, PMID 9685897.

Gaudin K, Langlois MH, Barbaud A, Boyer C, Millet P, Fawaz F, Dubost JP. Stability of artesunate in pharmaceutical solvents. J Pharm Biomed Anal. 2007;43(3):1019-24. doi: 10.1016/ j.jpba.2006.09.039, PMID 17084575.

Sharma S, Khinch MP, Sharma N, Agrawal D, Gupta MK. Approches to development of solid-self micron emulsifying drug delivery system: formulation technices and dosage form–a review. Asian J Pharm Res Dev. 2013;1:146-56.



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