Risperidone oral disintegrating mini-tablets: A robust-product for pediatrics

Open access


This study was aimed at developing risperidone oral disintegrating mini-tablets (OD-mini-tablets) as age-appropriate formulations and to assess their suitability for infants and pediatric use. An experimental Box-Behnken design was applied to assure high quality of the OD-mini-tablets and reduce product variability. The design was employed to understand the influence of the critical excipient combinations on the production of OD-mini-tablets and thus guarantee the feasibility of obtaining products with dosage form uniformity. The variables selected were mannitol percent in Avicel (X1), swelling pressure of the superdisintegrant (X2), and the surface area of Aerosil as a glidant (X3). Risperidone-excipient compatibilities were investigated using FTIR and the spectra did not display any interaction. Fifteen formulations were prepared and evaluated for preand post-compression characteristics. The prepared ODmini- tablet batches were also assessed for disintegration in simulated salivary fluid (SSF, pH 6.2) and in reconstituted skimmed milk. The optimized formula fulfilled the requirements for crushing strength of 5 kN with minimal friability, disintegration times of 8.4 and 53.7 s in SSF and skimmed milk, respectively. This study therefore proposes the risperidone OD-mini-tablet formula having robust mechanical properties, uniform and precise dosing of medication with short disintegration time suitable for pediatric use.

1. P. Lennartz and J. B. Mielck, Minitabletting: Improving the compactability of paracetamol powder mixtures, Int. J. Pharm. 173 (1998) 75-85; DOI: 10.1016/S0378-5173(98)00206-3.

2. I . Stoltenberg and J. Breitkreutz, Orally disintegrating mini-tablets (odmts) - a novel solid oral dosage form for paediatric use, Eur. J. Pharm. Biopharm. 78 (2011) 462-469; DOI: 10.1016/j.ejpb. 2011.02.005.

3. K. Wening and J. Breitkreutz, Oral drug delivery in personalized medicine: Unmet needs and novel approaches, Int. J. Pharm. 404 (2011) 1-9; DOI: 10.1016/j.ijpharm.2010.11.001.

4. D . L. Munday, A comparison of the dissolution characteristics of theophylline from film coated granules and mini-tablets, Drug Dev. Ind. Pharm. 20 (1994) 2369-2379; DOI: 10.3109/03639049409042643.

5. M. L. Huang, A. Van Peer, R. Woestenborghs, R. De Coster, J. Heykants, A. A. Jansen, Z. Zylicz, H. W. Visscher and J. H. Jonkman, Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects, Clin. Pharmacol. Ther. 54 (1993) 257-268; DOI:10.1038/clpt.1993.146.

6. ICH(Q4b) Guideline, General chapters, Annex 6, Step 4. Evaluation and recommendation of pharmacopeial texts for use in the ICH regions on uniformity of dosage units, in: Group, I.E.W. (ed.), ICH Harmonised Tripartite Guideline J.FDA , EMA, US. FDA , USA. 2014; Available from: http:// www.ich.org/fileadmin/Public_Web_Site/ICH_Products/Guidelines/Quality/Q4B/Step4/Q4B_ Guideline.pdf; last access date July 23, 2015.

7. S. Khan, P. Kataria, P. Nakhat and P. Yeole, Taste masking of ondansetron hydrochloride by polymer carrier system and formulation of rapid-disintegrating tablets, AAPS PharmSciTech. 8 (2007) E127-E133; DOI: 10.1208/pt0802046.

8. I . Mutlu and E. Oktay, Characterization of 17-4 PH stainless steel foam for biomedical applications in simulated body fluid and artificial saliva environments, Mater. Sci. Eng. C, Mater. Biol. Appl. 33 (2013) 1125-1131; DOI: 10.1016/j.msec.2012.12.004.

9. J . S. P. Daniel, I. P. Veronez, L. L. Rodrigues, M. G. Trevisan and J. S. Garcia, Risperidone - solidstate characterization and pharmaceutical compatibility using thermal and non-thermal techniques, Thermochim. Acta 568 (2013) 148-155; DOI: 10.1016/j.tca.2013.06.032.

10. R . Canitano and V. Scandurra, Risperidone in the treatment of behavioral disorders associated with autism in children and adolescents, Neuropsychiatr. Dis. Treat. 4 (2008) 723-730; DOI: 10.2147/ ND T.S1450.

11. C. C. Sun, Mechanism of moisture induced variations in true density and compaction properties of microcrystalline cellulose, Int. J. Pharm. 346 (2008) 93-101; DOI: 10.1016/j.ijpharm.2007.06.017.

12. J . G. Osorio and F. J. Muzzio, Effects of powder flow properties on capsule filling weight uniformity, Drug Dev. Ind. Pharm. 39 (2013) 1464-1475; DOI: 10.3109/03639045.2012.728227.

13. D . Otter, Milk: Physical and Chemical Properties, in Encyclopedia of Food Sciences and Nutrition (Ed. B. Caballero, L. C. Trugo, P. M. Finglas), 2nd ed., Academic Press, Oxford 2003, pp. 3957-3963.

14. M. B. Almeida, J. A. Almeida, M. E. Moreira and F. R. Novak, Adequacy of human milk viscosity to respond to infants with dysphagia: Experimental study, J. Appl. Oral Sci. 19 (2011) 554-559; DOI: 10.1590/S1678-77572011000600003.

15. W. H. Schwarz, The rheology of saliva, J. Dent. Res. 66 (1987) 660-666; DOI: 10.1177/00220345870660S209.

16. R . Pabari and Z. Ramtoola, Effect of a disintegration mechanism on wetting, water absorption, and disintegration time of orodispersible tablets, J. Young Pharm. 4 (2012) 157-163; DOI: 10.4103/0975-1483.100021.

17. A . M. Juppo, Relationship between breaking force and pore structure of lactose, glucose and mannitol tablets, Int. J. Pharm. 127 (1996) 95-102; DOI: 10.1016/0378-5173(95)04203-2.

Acta Pharmaceutica

The Journal of Croatian Pharmaceutical Society

Journal Information

IMPACT FACTOR 2018: 1,405
5-year IMPACT FACTOR: 1,701

CiteScore 2018: 1.47

SCImago Journal Rank (SJR) 2018: 0.314
Source Normalized Impact per Paper (SNIP) 2018: 0.637

Cited By


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 378 275 12
PDF Downloads 172 142 8