• Moon Rajkumar Department of Pharmaceutics, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Nanded - 431 606, Maharashtra,India.
  • Gattani Surendra Department of Pharmaceutics, School of Pharmacy, Swami Ramanand Teerth Marathwada University, Nanded - 431 606, Maharashtra,India.


 Objective: The objective of this study was to increase the solubility and dissolution rate of paliperidone (PAL) by preparing its nanocrystals using different hydrophilic carriers by antisolvent precipitation technique.

Methods: The nanoparticles (NP) were characterized for aqueous solubility, drug content, Fourier transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, particle size, and in vitro-in vivo analysis.

Results: The results showed improved solubility and dissolution rate of NPs when compared to pure drug and physical mixture (PM). Solubility data showed a linear graph giving an indication that there is a gradual increase in the solubility profile of the drug with an increase in concentration of the carriers. At highest concentration, the solubility of NPs with Plasdone S630, Povidone K-25, and PVP K-30 found to be increased by 12 folds, 9 folds and 6 folds, respectively, as compared to pure drug. The release profile of NPs with Plasdone S630 in terms of dissolution efficiency at 60 min (DE60), initial dissolution rate (IDR), amount release in 15 min (Q15 min), and time for 75% release (t75%) shows better results when compared to pure drug, PM, and also NPs with povidone 25 and povidone 30. In vivo study reveals that optimized NPs elicited significant induction of cataleptic behavior which is the indication of antipsychotic agent(s) effect.

Conclusion: The process antisolvent precipitation under constant stirring may be a promising method to produce stable PAL NPs with markedly enhanced solubility and dissolution rate due to nanonization with the increased surface area, improved wettability, and reduced diffusion pathway.

Keywords: Paliperidone, Nanocrystals, Dissolution, Plasdone S630, Povidone K25, Povidone K30.


1. Radtke M. Raw drug nanoparticles for the formulation of poorly soluble drugs. New Drugs 2001;3:62-8.
2. Lipinski C. Poor aqueous solubility: An industry wide problem in drug discovery. Am Pharm Rev 2002;5:82-5.
3. Patravale VB, Date AA, Kulkarni RM. Nanosuspensions: A promising drug delivery strategy. J Pharm Pharmacol 2004;56:827-40.
4. Rabinow BE. Nanosuspensions in drug delivery. Nat Rev Drug Discov 2004;3:785-96.
5. Wong SM, Kellaway IW, Murdan S. Enhancement of the dissolution rate and oral absorption of a poorly water soluble drug by formation of surfactant-containing microparticles. Int J Pharm 2006;317:61-8.
6. Dressman JB, Reppas C. In vitro-in vivo correlations for lipophilic, poorly water-soluble drugs. Eur J Pharm Sci 2000;11 Suppl 2:S73-80.
7. Kesisoglou F, Panmai S, Wu Y. Nanosizing–oral formulation development and biopharmaceutical evaluation. Adv Drug Deliv Rev 2007;59:631-44.
8. Bagul R, Mahajan V, Dhake A. New approaches in nanoparticulate drug delivery system-a review. Int J Curr Pharm Res 2012;4:29-38.
9. Banjare J. Application of nanotechnology in food technology and targeted drug therapy for prevention of obesity: An overview. J Crit Rev 2017;4:7-11.
10. Ruby JJ, Pandey VP. Chitosan nanoparticles as a nasal drug delivery for memantine hydrochloride. Int J Pharm Pharm Sci 2015;7:34-7.
11. Guo Z, Zhang M, Li H, Wang E, Kougouslos E. Effect of ultrasound on antisolvent crystallization process. J Cryst Growth 2005;273:555-63.
12. Louhi-Kultanen M, Karjalainen M, Rananen J, Huhtanen M, Kallas J. Crystallization of glycine with ultrasound. Int J Pharm 2006;320:23-9.
13. Dhumal RS, Biradar SV, Yamamura S, Paradkar AR, York P. Preparation of amorphous cefuroxime axetil nanoparticles by sonoprecipitation for enhancement of bioavailability. Eur J Pharm Biopharm 2008;70:109 15.
14. Verma S, Gokhale R, Burgess DJ. A comparative study of top-down and bottom-up approaches for the preparation of micro/nanosuspensions. Int J Pharm 2009;380:216-22.
15. Devalapally H, Chakilam A, Amiji MM. Role of nanotechnology in pharmaceutical product development. J Pharm Sci 2007;96:2547-65.
16. Galindo-Rodriguez S, Allémann E, Fessi H, Doelker E. Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods. Pharm Res 2004;21:1428-39.
17. Hancock BC, Zografi G. Characteristics and significance of the amorphous state in pharmaceutical systems. J Pharm Sci 1997;86:1-2.
18. Matteucci ME, Hotze MA, Johnston KP, Williams RO 3rd. Drug nanoparticles by antisolvent precipitation: Mixing energy versus surfactant stabilization. Langmuir 2006;22:8951-9.
19. Park SJ, Jeon SY, Yeo SD. Recrystallization of a pharmaceutical compound using liquid and supercritical antisolvents. INP Eng Chem Res 2006;45:2287-93.
20. Pattekari P, Zheng Z, Zhang X, Levchenko T, Torchilin V, Lvov Y, et al. Top-down and bottom-up approaches in production of aqueous nanocolloids of low solubility drug paclitaxel. Phys Chem Chem Phys 2011;13:9014-9.
21. Noyes AA, Whitney WR, The rate of solution of solid substances in their own solutions. J Am Chem Soc 1897;19:930-4.
22. Gattani S, Moon R. Formulation and in vitro evaluation of tablet containing gliclazide nanocrystals for solubility and dissolution enhancement using soluplus. Int J Pharm Sci Res 2018;9:133-9.22.
23. Abdulbaqi MR. Evaluation the effect of nanotechnology on pharmaceutical and biological properties of metronidazole. Int J Pharm Pharm Sci 2017;9:139-45.
24. Khisti RT, Deshpande LS, Chopde CT. The neurosteroid 3 alpha hydroxy-5 alpha-pregnan-20-one affects dopamine-mediated behavior in rodents. Psychopharmacology (Berl) 2002;161:120-8.
25. Ghorab M, Gardouh A, Gad S. Effect of viscosity, surfactant type and concentration on physicochemical properties of solid lipid nanoparticles. Int J Pharm Pharm Sci 2015;7:145-53.
26. Zhang HX, Wang JX, Zhang ZB, Le Y, Shen ZG, Chen JF, et al. Micronization of atorvastatin calcium by antisolvent precipitation process. Int J Pharm 2009;374:106-13.
27. Rogers TL, Gillespie IB, Hitt JE, Fransen KL, Crowl CA, Tucker CJ, et al. Development and characterization of a scalable controlled precipitation process to enhance the dissolution of poorly water-soluble drugs. Pharm Res 2004;21:2048-57.
28. Dawood NM, Hammid SN, Hussien AA. Formulation and characterization of lafutidine nanosuspension for oral drug delivery system. Int J App Pharm 2018;10:20-30.
135 Views | 292 Downloads
How to Cite
Rajkumar, M., and G. Surendra. “PREPARATION AND CHARACTERIZATION OF NANOCRYSTALS FOR SOLUBILITY AND DISSOLUTION RATE ENHANCEMENT OF PALIPERIDONE USING DIFFERENT HYDROPHILIC CARRIERS: IN VITRO-IN VIVO STUDY”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 4, Apr. 2018, pp. 393-8, doi:10.22159/ajpcr.2018.v11i4.24964.
Original Article(s)