• ABHISHEK KANUGO SVKM NMIMS School of Pharmacy and Technology Management, Shirpur, Dhule, India 425405



Solubility enhancement, Liquisolid technique, Liquisolid-Pellet, Pellet, Extrusion-spheronization, Bioavailability


The current article aims with the introduction of newer solubility enhancing technique as Liquisolid-pellet. The majority of newly invented molecules comes under the biopharmaceutical classification system (BCS) Class II, IV indicating poor solubility and thereby poor bioavailability. Liquisolid Compaq is one of the solubility enhancement techniques used for improving solubility and dissolution of the molecule by incorporating non-volatile solvent followed by carrier and coating agents. However, this technique is only applicable to potent molecules as a higher dose resulted in inconvenience to the patient and difficult to swallow. Another drawback of this method is not suitable for pilot plant scale-up. Liquisolid pellet technique overcoming all limitations of Liquisolid Compaq and offers good compaction, flowability, dose accuracy, less gastric irritations, and better bioavailability. In the Liquisolid-Pellet technique, powdered material received from Liquisolid Compaq is further moistened with granulating fluid to provide enough plasticity. The material is subjected to extrusion using an extruder to generate extrudates. The extrudates are placed under the spheronizer to form spherical particles as Pellets. The pellets are mainly prepared by extrusion-spheronization and hence, articles elaborate details of extruders and spheronizers, their specifications as well as factors, which strongly impart processing. These pellets are filled in capsules according to their dose and utilized as an immediate release or sustained release. The literature related to this review was collected from Science Direct, PubMed, Google Scholar, Google, USPTO, etc. from 1998 to 2020 with the following key-words.


Download data is not yet available.


Tadikonda RR, Shatri N, Chella N. Use of the liquisolid compaq technique for improvement of the dissolution rate of valsartan. Acta Pharm Sin B 2012;2:502-8.

Gajjar AK, Savjani KT, Savjani JK. Drug solubility: importance and enhancement techniques. ISRN; 2012. p. 1-10.

Kalepu S, Nekkanti V. Insoluble drug delivery strategies: review of recent advances and business prospects. Acta Pharm Sin B 2015;5:442-53.

Hasan SM, Butt S. Directly compressed rosuvastatin calcium tablets that offer hydrotropic and micellar solubilization for improved dissolution rate and extent of drug release. Saudi Pharm J 2019;27:614-28.

Butania SB, Prajapata MD, Gohelb MC. Liquisolid: a promising technique to improve dissolution efficiency and bioavailability of poorly water-soluble nimodipine. J Drug Delivery Sci Tech 2019;53:101135.

Surti N, Pipaliya RM, Patel DS. Liquisolid tablets for dissolution enhancement of a hypolipidemic drug. Int J Pharm Sci 2015;77:290-8.

Bonthagarala B, Dasari V, Kotra V. Quality-by-design based development and characterization of pioglitazone loaded liquisolid compact tablets with improved biopharmaceutical attributes. J Drug Delivery Sci Tech 2019;51:345-55.

Brahmankar DM, Jaiswal SB. Bioavailability and bioequivalence: biopharmaceutics and pharmacokinetics a treatise: Vallabh prakashan; 2009. p. 349-62.

Kaarashima M, Ikeda Y, Sano N. Enhanced pulmonary absorption of poorly soluble itracontazole by micronized cocrystal dry powder formulations. Eur J Pharm Biopharm 2017;115:65-72.

Lee BJ, Kim D, Park C. Utilization of a fattigation platform gelatin-oleic acid sodium salt conjugate as a novel solubilizing adjuvant for poorly water-soluble drugs via self-assembly and nanonization. Int J Pharm 2020;575:118892.

Elisabeth B, Masmoudi Y, Mouahid A. Current situation and perspectives in drug formulation by using supercritical fluid technology. J Supercritical Fluids 2018;134:274-83.

Hu J, Johnston KP, Williams RO. Spray freezing into liquid particle enginnering technology to enhance the dissolution of poorly water drugs: organic solvent versus organic/aqueous co-solvent system. Eur J Pharm Sci 2003;20:295-303.

Zhang C, Zi P, Zhang C. Solubility and bioavailability enhancement study of lopinavir solid dispersion matrixed with a polymeric surfactant-soluplus. Eur J Pharm Sci 2019;134:233-45.

Chopra D, Suresh A, Mondal P. Improving solubility and intrinsic dissolution rate of ofloxacin API through salt formation via mechanochemical synthesis with diphenic acid. J Mol Str 2020;2:128806.

Saal C, Price D, Nair A. Incorporation of HPMCAS during loading of glibenclamide onto mesoporous silica improves dissolution and inhibits precipitation. Eur J Pharm Sci 2020;141:105113.

Lewis SA, Muvva A, Lakshman D. In vitro-in silico evaluation of apremilast solid dispersion prepared via corotating twin-screw extruder. J Drug Delivery Sci Tech 2020;59:101844.

Cevher E, Morina D, Sinani G. Oral tablet formulations containing cyclodextrin complexes of poorly water-soluble cefdinir to enhance its bioavailability. J Drug Delivery Sci Tech 2020;57:101742.

Jaehwi L, Kanghee J, Hyeongmin K. Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-emulsifying drug delivery systems. Asian J Pharm Sci 2020;15:336-46.

Ge L, Webster T, Han H. A soluplus/poloxamer 407-based self nanoemulsifying drug delivery system for the weakly basic drug carvedilol to improve its bioavailability. Nanomed Nanotech Bio Med 2020;27:102199.

Bergonzi MC, Righeschi C, Isacchi B. Enhanced curcumin permeability by SLN formulation: the PAMPA approach. Food Sci Tech 2016;66:475-83.

Vavia P, Shewalkar G. Solidified nanostructured lipid carrier for enhancing the oral bioavailability of ezetimibe. J Drug Delivery Sci Tech 2019;53:101211.

Jian Y, Xiaoyi, Lihua L. A cabazitaxel liposomes for increased solubility, enhanced antitumor effect and reduced systemic toxicity. Asian J Pharm Sci 2019;14:658-67.

Ali HS, Shah MR, Simjee SU. Desugn and development of permeation enhancer containing self-nanoemulsifung drug delivery system for ceftriazone sodium improved oral pharmacokinetics. J Mol Liq 2019;289:111098.

Lanao J M, Zarzuelo A, Maderuelo C. Enteric coating of oral solid dosage forms as a tool to improve drug bioavailability. Eur J Pharm Sci 2019;138:105019.

Li J, Wang R, Han J. Involvement of metabolism permeability in enhancing the oral bioavailability of curcumin in excipient free solid dispersions co-formed with piperine. Int J Pharm 2019;561:9-18.

Spireas S, Bolton SM. Liquisolid systems and methods of preparing same, U. S. Patent, 5,800,834; 1998.

Spireas S, Bolton SM. Liquisolid systems and methods of preparing same, U. S. Patent, 6,096,337; 2000.

Spireas S, Sadu S. Enhancement of prednisolone dissolution properties using liquisolid compacts. Int J Pharm 1998;166:177-88.

Nokhodchi A, Javadzadeh Y, Navimipour BJ. Liquisolid technique for dissolution rate enhancement of a high dose water-insoluble drug (carbamazepine). Int J Pharm 2007;341:26-34.

Tulsankar SL, Sayyad FJ, Kolap UB. Design and development of liquisolid compact of candesartan cilexetil to enhance dissolution. J Pharm Res 2013;7:381-8.

Lam M, Commandeur D, Nokhodchi A. The crusial effect of water and co-solvent on Liqui-Pellet pharmaceutical performance. Adv Powder Tech 2020;31:1903-14.

Lam M, Nokhodchi A, Ghafourian T. Liqui-pellet: the emerging next-generation oral dosage form which stems from Liquisolid concept in combination with Pelletization technology. AAPS 2019;20:231.

Lam M, Nokhodchi A, Ghafourian T. Liquisolid system and Liqui-mass system are not same. AAPS 2020;21:105.

Lam M, Nokhodchi A, Ghafourian T. Optimising the release rate of naproxen liqui-pellet: a new technology for emerging novel oral dosage form. Drug Delivery Tran Res 2020;10:43-58.

Ding P, Lu M, Wang D. Liquisolid technique and its applications in pharmaceuticals. Asian J Pharm Sci 2017;12:115-23.

Rohera BD, Mamidi KH, Mishra SM. Determination of maximum flowable liquid-loading potential of Neusilin US2 and investigation of compressibility and compactibility of its liquisolid blends with PEG 400. J Drug Delivery Sci Tech 2019;54:101285.

Yadav JK, Reddy KD, Jukanti R. Competence of raloxifene hydrochloride loaded liquisolid compacts for improved dissolution and intestinal permeation. J Drug Delivery Sci Tech 2015;30:232-41.

Elkordy AA, Tiong N. Effects of liquisolid formulations on dissolution of naproxen. Eur J Pharm Biopharm 2009;73:373-84.

Fahmy RH, Kassem MA. Enhancement of famotidine dissolution rate through liquisolid tablets formulation: in vitro and in vivo evaluation. Eur J Pharm Biopharm 2008;69:1003.

Gubbi SR, Jarag R. Formlation and characterization of atorvastatin calcium liquisolid compacts. Asian J Pharm Sci 2010;5:50-60.

Elkordy AA, Tan XN, Essa EA. Spironolactone release from liquisolid formulations prepared with capryol 90, solutol HS-15 and kollicoat SR 30 D as bon-volatile liquid vehicles. Eur J Pharm Biopharm 2013;83:203-23.

Leopold CS, Hentzchel CM, Alnaief M. Enhancement of griseofulvin release from liquisolid compacts. Eur J Pharm Biopharm 2012;80:130-5.

Barakat NS, El-Shazil G, Elkhodairy KA. Effect of type and concentration of release-retarding vehicles on the dissolution rate of diltiazem hydrochloride from liquisolid compact. J Drug Delivery Sci Tech 2012;22:189-95.

Pezzini BR, Sonaglio D. Liquisolid pellets: mixture experimental design assessment of critical quality attributes influencing the manufacturing performance via extrusion-spheronization. J Drug Delivery Sci Tech 2020;57:101630.

Pezzini BR, Espindola BD. Liquisolid pellets: a pharmaceutical technology strategy to improve the dissolution rate of ritonavir. Saudi Pharm J 2019;27:702-12.

Erkoboni DF. Extrusion/spheronization: pharmaceutical pelletization technology; Isaac Ghebre, Vol. 133. Marcel Dekkar; 2003. p. 277-318.

Mehta KA, Rekhi GS, Parikh DM. Extrusion/spheronization as a granulation technique: Handbook of pharmaceutical granulation technology; Taylor and Francis; 2005. p. 333-60. [Last accessed on 10 Jul 2020] [Last accessed on 10 Jul 2020] [Last accessed on 10 Jul 2020] [Last accessed on 10 Jul 2020]

Muley S, Nandgude T, Poddar S. Extrusion-spheronization a promising pelletization technique: in-depth review. Asian J Pharm Sci 2016;11:684-99.

Gustafsson CL, Johal HK, Newton JM. The influence of water content and drug solubility on the formulation of pellets by extrusion and spheronization. Eur J Pharm Sci 1999;8:147-52.

Dukic OA, Vervaet, Kleinebudde P. Production of pellets via extrusion-spheronization without the incorporation of microcrystalline cellulose: a critical review. Eur J Pharm Biopharm 2009;71:38-46.

Levis SR, Deasy PB. Production and evaluation of size reduced grades of microcrystalline cellulose. Int J Pharm 2001;213:13-24.

Rojas J, Correa D. Assessment of the production variables on the pelletization properties of microcrystalline cellulose II (MCCII). Int J Pharm Pharm Sci 2017;9:73-80.

Sonaglio D, Bataille B, Jacob M. Effects of extrusion and formulation parameters on the production of paracetamol-microcrystalline cellulose extrudates. Pharmaceutica Acta Helvetiae 1997;72:69-74.

Fielden KE, Newton JM, Rowe RC. Thermal studies on the interaction of water and microcrystalline cellulose. J Pharm Pharmacol 1988;40:674-8.

Mishra RV, Paldewar SG, Nandgude TD. An outline of variables in pelletization by extrusion-spheronization. Int J Appl Pharm 2020;12:39-44.

Dashevskiya A, Zoubaria G, Ali R. Water-soluble and insoluble polymers as binders for pellet preparation by extrusion-spheronization. J Drug Delivery Sci Tech 2019;49:1-5.

Pacheco RM, Souto C, Goyanes A. Co-processed MCC-eudragit e excipients for extrusion-spheronization. Eur J Pharm Biopharm 2011;79:658-63.



How to Cite




Review Article(s)