Enhancing solubility of poorly aqueous soluble drugs: critical appraisal of techniques

Alshahrani SM, Lu W, Park JB, Morott JT, Alsulays BB, Majumdar S, Langley N et al (2015) Stability enhanced hot melt extruded amorphous solid dispersions via combination of Soluplus and HPMCAS-HF. AAPS PharmSciTech 16(4):824–834

Anderson KE, Siepmann JI (2008) Solubility in supercritical carbon dioxide: importance of the poynting correction and entrainer effects. J Phys Chem 112:11374–11380

Avdeef A (2007) Solubility of sparingly soluble ionizable drugs. Adv Drug Deliv Rev 59:568–590

Badawi A, El-Nabarawi MA, El-Setouhy DA, Alsammit SA (2011) Formulation and stability testing of itraconazole crystalline nanoparticles. AAPS PharmSciTech 12:811–820

Baker CGJ (1997) Industrial drying of foods. Springer Science and Business Media, New York

Balakrishan P, Lee BJ, Oh DH, Kim JO et al (2014) Enhanced oral bioavailability of dexibuprofen by a novel solid self-emulsifying drug delivery system (SEDDS). Eur J Pharm Biopharm 72:539–545

Bastami Z, Taheri A, Soltanpour S (2015) Formulation, optimization and characterization of gemfibrozil nanocrystals prepared by wet milling technique. Asian J Pharm 9(1):19–22

Breitenbach J (2002) Melt extrusion: from process to drug delivery technology. Eur J Pharm Biopharm 54:107–117

Breitenbach JR (2006) Melt extrusion can bring new benefits to HIV therapy: the example of Kaletra® tablets. Am J Drug Deliv 4:61–64

Bruce C, Fegely KA, Siahboomi AR, Mc Ginity JW (2007) Crystal growth formation in melt extrudates. Int J Pharm 341:162–172

Cal K, Sollohub K (2010) Spray drying technique I: hardware and process parameters. J Pharm Sci 99:575–586

Cansell F, Aymonier C, Loppinet-Serani A (2003) Review on material science and supercritical fluid. Curr Opin Solid State Mater Sci 7:331–340

Chan SY, Chung YY, Cheah XZ, Tan EY, Quah J (2016) The characterization and dissolution performances of spray dried solid dispersion of ketoprofen in hydrophilic carriers. Asian J Pharm Sci 10(5):372–385

Chen JF, Zhou MY, Shao L, Wang YY, Yun J, Chew NYK et al (2004) Feasibility of preparing nanodrugs by high-gravity reactive precipitation. Int J Pharm 269:267–274

Chen Y, Liu J, Zhao X, Xu H (2005) Oleanolic acid nanosuspensions: preparation, in-vitro characterization and enhanced hepatoprotective effect. J Pharm Pharmacol 57(2):259–264

Chen JM, Wang ZZ, Chaun BJ, Li S, Lu T-B (2012) Crystal engineering approach to improve the solubility of mebendazole. CrystEngComm 14:6221–6229

Cheney ML, Wyena DR, Shan N, Hanna M, Wojtas L, Zaworotko MJ (2010) Supramolecular architectures of meloxicam carboxylic acid co-crystals, a crystal engineering case study. Cryst Growth Des 10(10):4401–4413

Childs SL, Hardcastle KI (2007) Co-crystals of piroxicam with carboxylic acids. Cryst Growth Des 7:1291–1304

Childs SL, Chyall LJ, Dunlap JT, Smolenskaya VN, Stahly BC, Stahly GP (2004) Crystal engineering approach to forming cocrystals of amine hydrochlorides with organic acids. Molecular complexes of fluoxetine hydrochloride with benzoic, succinic, and fumaric acids. J Am Chem Soc 126(41):13335–13342

Date AA, Desai N, Dixit R, Nagarsenker M (2014) Self-nanoemulsifying drug delivery systems: formulation insights, applications and advances. Nanomedicine 5(10):1595–1616

Davis JB, Devack DL (1989) Droplet freezing method and apparatus. US Patent (US 4848094 A)

Devalapally H, Silchenko S, Zhou F, Mcdade J, Goloverda G, Owen A et al (2013) Evaluation of a nanoemulsion formulation strategy for oral bioavailability enhancement of danazol in rats and dogs. J Pharm Sci 102(10):3808–3815

Dinunzio JC, Martin ZFC, Mcginity JW (2012) Melt extrusion. In: Williams III, Watts RO, Miller AB DA (eds) Formulating poorly water soluble drugs. Springer, New York, pp 311–362

Dobry DE, Settell DM, Baumann JM, Ray RJ, Graham LJ, Beyerinck RA (2009) A model based methodology for spray drying process development. J Pharm Innov 4(3):133–142

Doney JA (2014) Carotenoids of enhanced bioavailability. US Patent (US 8613946 B2)

Dressman JB, Vertzoni M, Goumas K, Reppas C (2007) Estimating drug solubility in the gastrointestinal tract. Adv Drug Deliv Rev 59:591–602

Elder D, Holm R (2013) Aqueous solubility: Simple predictive methods (in silico, in vitro and biorelevant approaches). Int J Pharm 453:3–11

Faller B, Ertl P (2007) Computational approaches to determine drug solubility. Adv Drug Deliv Rev 59:533–545

Fleischmann SG (2003) Crystal engineering of the composition of pharmaceutical phases: multiple component crystalline solids involving carbamazepine. Cryst Growth Des 3:909–919

Geng NA, Chen JM, Li ZJ, Jiang L, Lu B (2013) Approach of crystallization to improve the solubility and photostability of tranilast. Cryst Growth Des 13(8):3546–3553

Ghanavati R, Taheri A, Homayouni A (2017) Anomalous dissolution behavior of celecoxib in PVP/Isomalt solid dispersions prepared using spray drier. Mater Sci Eng C 72(1):501–511

Girotra P, Singh SK, Nagpal K (2013) Supercritical fluid technology: a promising approach in pharmaceutical research. Pharm Dev Technol 18(1):22–38

Gonnade RJ (2015) Pharmaceutical co-crystals of gefitinib. US Patent (WO 2015170345 A1)

Good DJ, Rodriderz HN (2009) Solubility advantage of pharmaceutical co-crystals. Cryst Growth Des 9:2252–2264

Grace G, Murphy J, Rogers R (1974) Spray freezing apparatus and method US Patent (US 3788095 A)

He X, Pei L, Tong HY, Zheng Y (2011) Comparison of spray freeze drying and the solvent evaporation method for preparing solid dispersions of baicalein with Pluronic F68 to improve dissolution and oral bioavailability. AAPS PharmSciTech 12(1):104–113

Hecq J, Deleers M, Fanara D, Vranckx H (2005) Preparation and characterization of nanocrystals for solubility and dissolution rate enhancement of nifedipine. Int J Pharm 299(1):167–177

Henry S, Tonga HY, Zhen D, Wangc ZN, Chana HM, Changc QI, Leon CM, Lai B, Albert HL, Zhengpray Y (2011) Freeze drying with polyvinylpyrrolidone and sodium caprate for improved dissolution and oral bioavailability of oleanolic acid, a BCS Class IV compound. Int J Pharm 404:148–158

Hickey MB, Peterson ML, Scoppettuolo AL, Morrisette L, Vetter A et al (2007) Performance comparison of a co-crystal of carbamazepine with marketed product. Eur J Pharm Biopharm 67:112–119

Hildebrand JH, Scott RL (1950) The solubility of non-electrolytes. Reinhold Publishing, New York

Hu J, Rogers TL, Brown J, Young T, Johnston KP, Williams T (2006) Improvement of dissolution rates of poorly water soluble APIs using novel spray freezing into liquid technology. Pharm Res 19(9):1278–1284

Hu J, Ng YK, Dong Y, Shen S, Tan RB (2011) Continuous and scalable process for water re-dispersible nano-formulation of poorly aqueous soluble APIs by anti-solvent precipitation and spray-drying. Int J Pharm 411:198–204

Ikeda M, Sivadas N, Nolan F (2015) Solubility enhancement for hydrophobic drugs. PCT Patent (WO 2015078936 A1)

Ishwarya S, Stapley GF et al (2015) Spray-freeze drying: a novel approach for the drying of foods and bio products. Trends Food Sci Technol 41:161–181

Janssens S, Armas HN, Mooterm G (2008) Characterization of ternary solid dispersions of itraconazole, PEG 6000 and HPMC 2910. J Pharm Sci 97(6):2110–2120

Jiang T, Han N, Zhao B, Xie Y, Wang S (2012) Enhanced dissolution rate and oral bioavailability of simvastatin nanocrystal prepared by sonoprecipitation. Drug Dev Ind Pharm 38:1230–1239

Jung J, Perrut M (2001) Particle design using supercritical fluids: literature and patent survey. J Supercrit Fluids 20:179–219

Junghanns JUAH, Muller RH (2008) Nanocrystal technology, drug delivery and clinical applications. Int J Nanomed 3(3):295–310

Kalivoda A, Fischbach M, Kleinebudde P (2012) Application of mixture of polymeric carriers for dissolution enhancement of fenofibrate using hot melt extrusion. Int J Pharm 429(2):58–68

Kang JH, Oh DH, Oh Y, Yong CS, Choi H (2014) Effects of solid carriers on the crystalline properties, dissolution and bioavailability of flurbiprofen in solid self-nanoemulsifying drug delivery system (solid SNEDDS). Eur J Pharm Biopharm 80:289–297

Karki S, Friscic T, Fabian T, Jones W (2010) New solid forms of artemisinins obtained through co-crystallization. CrystEngComm 12:4038–4041

Keck CM, Muller RH (2006) Drug nanocrystals of poorly soluble drugs produced by high pressure homogenization. Eur J Pharm Biopharm 62(1):3–16

Kotta S, Khan AW, Parmod K, Ansari SH, Sharma RK, Ali J (2012) Exploring oral nanoemulsions for bioavailability enhancement of poorly water-soluble drugs. Expert Opin Drug Deliv 9(5):585–598

Kulthe VV, Chaudhari PD, Enein A (2014) Freeze dried amorphous dispersions for solubility enhancement of thermosensitive API having low molecular lipophilicity. Drug Res 64(9):493–498

Kumar S, Kalaiselvan R, Singh RB (2013) Dissolution enhanced controlled drug delivery system for poorly water soluble drugs. US Patent (WO 2013018050 A2)

Kumar VS, Venkata B, Rao K, Charyulu KS, Praveen C et al (2016) Cocrystal of agomelatine with phosphoric acid. US Patent (EP 2743255 B1)

Lawrence YU (1999) An integrated model for determining causes of poor oral drug absorption. Pharm Res 16(12):1883–1887

Leuenberger H (2002) Spray freeze drying- the process of choice for low water soluble drugs? J Nanopart 4:111–119

Leuner C, Dressman J (2000) Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm 50:47–60

Lipinski AC, Lombardo F, Dominy BW, Feeney PJ (2012) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 64:4–17

Lu B, Zhang D, Sheng W (1990) Solubility enhancement in supercritical solvents. Pure Appl Chem 62:2277–2285

Lu M, Guo Z, Li Y, Pang H, Lin L, Liu X, Pan X, Wu C (2014) Applications of hot melt extrusion for poorly water soluble drugs: limitations, advances and future prospectives. Curr Pharm Res 20(3):369–387

Maheshwari C, Andre V, Reddy LS, Roy L, Duarte T (2012) Tailoring aqueous solubility of a highly soluble compound via co-crystallization: effect of co-former ionization, pH max and solvent-solute interactions. CrystEngComm 33:4801–4811

Morissette SL, Almarsson O, Peterson ML, Remenar JF, Read MJ, Lemmo AV, Ellis S, Cima MJ, Gardner CR (2004) High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids. Adv Drug Deliv Rev 56(3):275–300

Moshashaee S, Bisrat M, Forbes RT, Quinn H, Nyqvist P (2003) Supercritical fluid processing of proteins: lysozyme precipitation from aqueous solution. J Pharm Pharmacol 55:85–192

Mujumdar AS (2014) Handbook of industrial drying, 4th edn. CRC Press, Boca Raton

Nanjwade BK, Derkar GK, Bechra HM, Manvi FV (2011) Design and characterization of nanocrystals of lovastatin for solubility and dissolution enhancement. J Nanomed Nanotechnol 2(2):14–22

Nasr A, Gardouh A, Ghorab M (2016) Novel solid self-nanoemulsifying drug delivery system (S-SNEDDS) for oral delivery of olmesartan medoxomil: design, formulation, pharmacokinetic and bioavailability evaluation. Pharmaceutics 8:20–29

Niwa T, Shimabara H, Kondo M, Danjo K (2010a) Design of porous microparticles with single-micron size by novel spray freeze-drying technique using four-fluid nozzle. Int J Pharm 382:88–97

Niwa T, Shimabara H, Kondo M, Danjo K (2010b) Novel spray freeze-drying technique using four-fluid nozzle: development of organic solvent system to expand its application to poorly water soluble drugs. Chem Pharm Bull 58(2):195–200

Ohyagi N, Ueda K, Higashi K, Yamamoto K, Kawakami K, Moiré K (2017) Synergetic role of hypromellose and methacrylic acid copolymer in the dissolution improvement of amorphous solid dispersions. J Pharm Sci. doi: 10.1016/j.xphs.2016.12.005

Palakodaty P, York P (1999) Phase behavioral effects on particle formation processes using supercritical fluids. Pharm Res 16:976–985

Park JH, Choi HK (2015) Enhancement of solubility and dissolution of cilostazol by solid dispersion technique. Arch Pharm Res 38:1336–1344

Park YJ, Ryu DS, Li QZ, Quan DH, Jo OH, Kim JO, Seo YG, Lee YL et al (2010) Physiochemical characterization of tacrolimus loaded solid dispersion with sodium carboxymethyl cellulose and sodium lauryl sulfate. Arch Pharm Res 32:893–898

Patel BB, Patel JK, Chakraborty S (2014) Review of patents and applications of spray drying in pharmaceutical, food and flavor industry. Recent Pat Drug Deliv Formul 8(1):63–78

Patel RB, Thakore SD, Patel MR (2016) Recent survey on patents on nanoemulsions. Curr Drug Deliv 13(6):857–881

Patole T, Deshpande A (2014) Co-crystallization: a technique for solubility enhancement. Int J Pharm Sci Res 5(9):3566–3576

Perrut M (2000) Supercritical fluid applications: industrial developments and economic issue. Ind Eng Chem Res 39:4531–4535

Rahman MA, Mujahid M, Hussain A, Iqbal Z (2016) Development and pharmacokinetic evaluation of spray-dried self-nanoemulsifying drug delivery system of sertraline. J Pharm Investig. doi: 10.1007/s40005-016-0263-y

Rao YM, Kumar MP, Apte S (2008) Formulation of nanosuspensions of albendazole for oral administration. Curr Nanosci 4(1):53–58

Repka MA, Battu SK, Upadhye SB, Thumma S, Crowley MM, Zhang F, Martin C, McGinity JW (2007) Pharmaceutical applications of hot-melt extrusion: part II. Drug Dev Ind Pharm 33:1043–1057

Repka MA, Majumdar S, Kumar BS, Srirangam R, Upadhye SB (2008) Applications of hot-melt extrusion for drug delivery. Expert Opin Drug Deliv 5:1357–1376

Reverchon E (1999) Supercritical anti-solvent precipitation of micro and nanoparticles. J Supercrit Fluids 15:1–21

Rogers TL (2002) A novel particle engineering technology: spray freezing into liquid. Int J Pharm 242:271–280

Rogers TL, Nelsen AC, Sarkari M, Young TJ et al (2003) Enhanced aqueous dissolution of a poorly water soluble drug by novel particle engineering technology: spray freezing into liquid with atmospheric freezing. Pharm Res 20:485–493

Rogers TL, Nelsen AC, Hu J, Brown JN, Sarkari M et al (2004) A novel particle engineering technology to enhance dissolution of poorly water soluble drugs: spray-freezing into liquid. Eur J Pharm Biopharm 54:271–280

Ronco MP, Kluge J, Mazzotti M (2013) High pressure homogenization as a novel approach for the preparation of co-crystals. Cryst Growth Des 13(5):2013–2024

Roth W, Setnik B, Zietsch M, Burst A, Breitenbach J, Sellers E, Brennan D (2009) Ethanol effects on drug release from Verapamil Meltrex: an innovative melt extruded formulation. Int J Pharm 368:72–75

Sahu BP, Das MK (2014) Nanosuspension for enhancement of oral bioavailability of felodipine. Appl Nanosci 4:189–197

Sanphui P, Devi VK, Clara D, Malviya N, Ganguly S, Desiraju GR (2015) Co-crystals of hydrochlorothiazide: solubility and diffusion/permeability enhancements through drug-coformer interactions. Mol Pharm 12(5):1615–1622

Sareen S, Mathew G, Joseph L (2012) Improvement in solubility of poorly water soluble drugs by solid dispersion. Int J Pharm Investig 2(1):12–17

Sathigiri SK, Radhakrishan VK, Davis VA, Parsons DL et al (2012) Amorphous-state characterization of efavirenz-polymer hot-melt extrusion systems for dissolution enhancement. J Pharm Sci 101(9):3456–3464

Sauter C, Emin MA, Schuchmann HP, Tavman S (2008) Influence of hydrostatic pressure and sound amplitude on the ultrasound induced dispersion and de-agglomeration of nanoparticles. Ultrason Sonochem 15:517–523

Savjani JK (2015) Co crystallization: an approach to improve the performance characteristics of active pharmaceutical ingredients. Asian J Pharm 22:147–150

Schultheiss N, Newman A (2009) Pharmaceutical co-crystals and their physiochemical properties. Cryst Growth Des 9(6):2950–2967

Schultz S, Wagner G, Urban K, Ulrich J (2004) High-pressure homogenization as a process for emulsion formation. Chem Eng Technol 27(4):361–368

Serajuddin TM (2007) Salt formation to improve drug solubility. Adv Drug Deliv Rev 43:603–616

Shah S, Maddineni S, Lu J, Repka MA (2013) Melt extrusion with poorly soluble drugs. Int J Pharm 453:233–252

Sharma S, Sahni JK, Ali J, Baboota S (2014) Effect of high-pressure homogenization on formulation of TPGS loaded nanoemulsion of rutin: pharmacodynamic and antioxidant studies. Drug Deliv 22(4):541–551

Sihvonen M, Järvenpaa E, Hietaniemi V, Huopalahti R (1999) Advances in supercritical carbon dioxide technologies. Trends Food Sci Technol 10:217–222

Singh A, Mooter GVD (2015) Spray drying formulations of amorphous solid dispersions. Adv Drug Deliv Rev 100:27–50

Singh D, Sharma K, Bedi N (2017) Tacrolimus loaded liquid and solid self-microemulsion preconcentrates: development and evaluation. Drug Deliv Lett 7(1):24–38

Stahly GP (2007) Diversity in single- and multiple-component crystals. The search for prevalence of polymorphs and cocrystals. Cryst Growth Des 7:1007–1026

Stegemann S, Leveiller F, Franchi D, Jong DH, Linden H (2007) When poor solubility becomes an issue: from early stage to proof of concept. Eur J Pharm Sci 31:249–261

Svehring R (2008) Pharmaceutical particle engineering via spray drying. Pharm Res 25:999–1022

Tabbakhian M, Hasanzadeh F, Tavakoli N, Jamshidian D (2014) Dissolution enhancement of glibenclamide by solid dispersion: solvent evaporation versus a supercritical fluid-based solvent-anti solvent technique. Res Pharm Sci 9(5):337–350

Talegaonkar S, Farhan JA, Khar RK, Shadab A, Khan ZI (2014) Microemulsions: a novel approach to enhanced drug delivery. Recent Pat Drug Deliv Formul 2:238–257

Tan J, Smith AJ, Shytle RD (2017) Lithium co-crystals and an additional neuropsychiatric agent for treatment of neuropsychiatric disorders. US Patent (US 9603869 B2)

Tang BO, Cheng G, Chun GJ, Xu H (2008) Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discov Today 13:606–612

Teleki A, Alder C (2016) Formulation of sparingly soluble compounds by hot melt extrusion. US Patent (EP 3079670 A1)

Thakuria R, Delori M, Jones W, Lipert MP, Roy L et al (2013) Pharmaceutical co-crystals and poorly soluble drugs. Int J Pharm 453:101–125

Truong DH, Tran TH, Ramasamy T, Choi JY, Lee HH, Moon Cr, Choi HG, Yong CS, Kim JO (2015) Development of solid self-emulsifying formulation for improving the oral bioavailability of erlotinib. AAPS PharmSciTech 17(2):466–473

Tubesha J, Bakar ZA, Ismail M (2013) Characterization and stability evaluation of thymoquinone nanoemulsions prepared by high-pressure homogenization. J Nanomater. doi: 10.1155/2013/453290

Venkataraman C, Pawar AA (2013) Method and a system for producing thermolabile nanoparticles with controlled properties and nanoparticles matrices made thereby. US Patent (US 20130035279 A1)

Venkataraman C, Pawar AA (2015) Method and a system for producing thermolabile nanoparticles with controlled properties and nanoparticle matrices thereby. US Patent (US9066882 B2)

Wang Y, Zheng Y, Zhang L, Wang QZhang D (2013) Stability of nanosuspensions in drug delivery. J Control Release 172(3):1126–1141

Wanning S, Suvekrup R, Lamprecht A (2015) Pharmaceutical spray-freeze drying. Int J Pharm 488:136–153

Warashina S, Kusaki F, Kikuchi K, Obara S, Mariyama N (2015) Composition of hot melt extrusion method for preparing hot melt extrusion product using same. US Patent (US 20140357681 A1)

Wilson M, Williams MA, Jones DS, Andrews GP (2012) Hot melt extrusion technology and pharmaceutical applications. Ther Deliv 3(6):787–797

Yadav AV, Shete AS, Dabke AP, Kulkarni PV, Sakhare SS (2009) Co-crystals: a novel approach to modify the physiochemical properties of active pharmaceutical ingredients. Ind J Pharm Sci 71(4):359–370

Yadollahi R, Vasilev K, Simovic S (2015) Nanosuspension technologies for delivery of poorly water soluble drugs. J Nanomater 12:1–13

Yalkowsky SH (1999) Solubility and solubilization in aqueous media. American Chemical Society, Oxford University Press, New York

Yasugi T, Takeuchi H, Kawashima Y (2008) Particle design of poorly water soluble drug substances using supercritical fluid technologies. Adv Drug Deliv Rev 60:388–398

Yi T, Wan J, Xu H, Yang X (2007) A new solid self-microemulsifying formulation prepared by spray drying to improve the oral bioavailability of poorly water soluble drugs. Eur J Pharm Biopharm 70:439–444

Yu LX, Lionberger RA, Raw AS, D’Costa R, Wu H, Hussain AS (2004) Applications of process analytical technology to crystallization processes. Adv Drug Deliv Rev 56:349–369

Yu J, Johnston KP, Williams RO (2006) Spray freezing into liquid versus spray freeze drying: influence of atomization on protein aggregation and biological activity. Eur J Pharm Sci 27:9–18