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Journal of Pharmaceutical Investigation

, Volume 49, Issue 1, pp 161–172 | Cite as

In-vitro and pharmacodynamic characterization of solidified self microemulsified system of quetiapine fumarate

  • Harini Chowdary Vadlamudi
  • Prasanna Raju Yalavarthi
  • Tejeswari Nagaswaram
  • Arun Rasheed
  • Jaya Preethi Peesa
Original Article
  • 41 Downloads

Abstract

Quetiapine fumarate has possessed low solubility and extremely poor bioavailability, which restricts its oral administration. In order to address this concern, microemulsification technique was envisaged. Solubility of quetiapine was assessed in various liquid vehicles (oils, surfactants and cosurfactants) for the selection of carriers in self microemulsifying drug delivery system (SMEDDS) formulation. Microemulsion region was identified from the pseudoternary phase diagram. Quetiapine was loaded in preconcetrates of the predetermined microemulsion region. Quetiapine loaded SMEDDS were characterized for FTIR, pH, viscosity, zeta potential, and evaluated for drug content, in-vitro dissolution, in-vitro diffusion, and ex-vivo permeation. Optimized liquid SMEDDS were renewed into S-SMEDDS by adsorption and melt granulation technique. Formulated S-SMEDDS were characterized for micromeritics, DSC, SEM, and evaluated for drug content, reconstitution time, drug release, stability and anti-psychotic activity in animals for amphetamine induced stereotypy and swimming normalization test. The formulations of O11, O13, C6 and C10 liquid SMEDDS had shown drug release of 92, 94.16, 68.59 and 55.03% respectively at the end of 1 h. S-SMEDDS exhibited good micromeritics with a drug content of 80 to 90% and released drug up to 96%. AO13 of S-SMEDDS had 1.2 years of shelf life and exhibited better anti-psychotic activity owing to enhanced biomembrane permeation in the presence of tweens as surfactants. The spontaneous formation of microemulsion from adsorption based S-SMEDDS resulted in hasty drug release. Thus the results of the study indicated that self microemulsification of quetiapine and subsequent solidification is the better alternative in affording optimal pharmacotherapy of psychosis.

Keywords

Adsorption Isotropic Lipid-matrix Micelle Specific-surface Stereotypy Swimming-score 

Notes

Acknowledgements

The authors are thankful to M/s. Aurobindo Pharma Ltd., Hyderabad, for gratis of quetiapine fumarate.

Funding

The research received no specific grant from any funding agency in public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

The article content has no declarations of interest.

References

  1. Briand LA, Gritton H, Howe WM, Young DA, Sarter M (2007) Modulators in concert for cognition: modulator interactions in the prefrontal cortex. Prog Neurobiol 83(2):69–91CrossRefGoogle Scholar
  2. Chowdary VH, Raju YP, Rao PS, Vandana KR, Jayasri V, Chowdary GT (2014) Formulation and pharmacodynamic evaluation of glibenclamide incorporated niosomal gel. Curr Drug Disc Tech 11(3):189–196CrossRefGoogle Scholar
  3. Chowdary VH, Raju YP, Basaveswara Rao MV, Jyotsna T, Vandana KR, Sundaresan CR (2016) Potential of microemulsified entacapone drug delivery systems in the management of acute Parkinson’s disease. J Acute Dis 5(4):315–325CrossRefGoogle Scholar
  4. Gershanik T, Benzeno S, Benita S (1988) Interaction of a selfemulsifying lipid drug delivery system with the inverted rat intestinal mucosa as a function of droplet size and surface charge. Pharm Res 15:863–869CrossRefGoogle Scholar
  5. Guan HJ, Dai J, Zhu XZ (2000) Atypical antipsychotic effects of quetiapine fumarate in animal models. Acta Pharmacol Sin 21(3):205–210Google Scholar
  6. Gupta SK (2009) Drug screening methods—preclinical evaluation of new drugs, 2nd edn. Jaypee Publishers, Hyderabad, p 385Google Scholar
  7. Jorgen GB, Oystein HG, Joar G, Eline BR, Maija K, Else-Marie L, Sigrid M, Lars T, Johan F (2012) Amphetamine-induced psychosis—a separate diagnostic entity or primary psychosis triggered in the vulnerable? BMC Psychiatry 12:221.  https://doi.org/10.1186/1471-244X-12-221 CrossRefGoogle Scholar
  8. Kim MS, Ha ES, Choo GH, Baek IH (2015) Preparation and in-vivo evaluation of a dutasteride-loaded solid-supersaturatable self-microemulsifying drug delivery system. Int J Mol Sci 16(5):10821–10833CrossRefGoogle Scholar
  9. Nanda Kishore R, Raju YP, Chowdary VH, Vandana KR, Rasheed A, Sushma M (2015) Solid self microemulsification of atorvastatin using hydrophilic carriers: a design. Drug Dev Ind Pharm 41(7):1213–1222CrossRefGoogle Scholar
  10. Obitte NC, Rohan LC, Adeyeye CM, Parniak MA, Esimone CO (2013) The utility of self-emulsifying oil formulation to improve the poor solubility of the anti HIV drug CSIC. AIDS Res Ther 10:14.  https://doi.org/10.1186/1742-6405-10-14 CrossRefGoogle Scholar
  11. Parvathi M, Prathyusha A, Kiran RSV, Raveendra Reddy J (2014) Preparation and evaluation of quetiapine fumarate microemulsions: a novel delivery system. Asian J Pharm Clin Res 7(1):208–213Google Scholar
  12. Pooja A, Payal S, Dhaiwat P, Sonali D (2014) Quetiapine fumarate loaded solid lipid nanoparticles for improved oral bioavailability. Drug Deliv Lett 4(2):170–184CrossRefGoogle Scholar
  13. Raju YP, Hyndavi N, Chowdary VH, Nair RS, Basha DJ, Tejeswari N (2017) In vitro assessment of non-irritant microemulsified voriconazole hydrogel system. Artif Cells Nanomed Biotechnol 45(8):1539–1547CrossRefGoogle Scholar
  14. Riedel M, Müller N, Strassnig M, Spellmann I, Severus E, Möller H-J (2007) Quetiapine in the treatment of schizophrenia and related disorders. Neuropsychiatr Dis Treat 3(2):219–235CrossRefGoogle Scholar
  15. Robert KM, Logue A, Stanford K, Xu M, Zhang M, Neil MR (2006) Dose–response analysis of locomotor activity and stereotypy in dopamine D3 receptor mutant mice following acute amphetamine. Synapse 60(5):399–405CrossRefGoogle Scholar
  16. Sander C, Holm P (2009) Porous magnesium aluminometasilicate tablets as carrier of a cyclosporine self-emulsifying formulation. AAPS Pharm Sci Tech 10(4):1388–1395CrossRefGoogle Scholar
  17. Shafiq-un-Nabi S, Shakeel F, Talegaonkar S (2007) Formulation development and optimization using nanoemulsion technique: a technical note. AAPS Pharm Sci Tech 8(2):E12–E17CrossRefGoogle Scholar
  18. Shah B, Khunt D, Misra M, Padh H (2016) Non-invasive intranasal delivery of quetiapine fumarate loaded microemulsion for brain targeting: formulation, physicochemical and pharmacokinetic consideration. Eur J Pharm Sci 91:196–207CrossRefGoogle Scholar
  19. Tang B, Cheng G, Gu JC, Xu H (2008) Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discov Today 13(13–14):606–612CrossRefGoogle Scholar
  20. Thushara Bindu D, Raju YP, Satyanarayana Rao P, Haritha K, Vandana KR, Vinesha V, Chowdary VH (2014) Pharmaceutical and pharmacodynamic evaluation of naproxen incorporated Aloe vera transgel. Drug Deliv Lett 4:110–115CrossRefGoogle Scholar
  21. Ücok A, Gaebel W (2008) Side effects of atypical antipsychotics: a brief overview. World Psychiatry 7(1):58–62CrossRefGoogle Scholar
  22. Vadlamudi HC, Yalavarthi PR, Basaveswarao MV, Rasheed A, Tejeswari N (2017) In vitro characterization studies of self-microemulsified bosentan systems. Drug Dev Ind Pharm 43(6):989–995CrossRefGoogle Scholar
  23. Van OJ, Linscott RJ, Myin-Germeys I, Delespaul P, Krabbendam LA (2008) Systematic review and meta-analysis of the psychosis continuum: evidence for a psychosis–proneness–persistence-impairment model of psychotic disorder. Psychol Med 8:1–17Google Scholar
  24. Vandana KR, Raju YP, Sundaresan CR, Raghava Naidu S, Chowdary VH (2014) In-vitro assessment and pharmacodynamics of nimesulide incorporated Aloe vera transemulgel. Curr Drug Discov Technol 11(2):162–167CrossRefGoogle Scholar
  25. Vinesha V, Raju YP, Sundaresan CR, Vandana KR, Thushara Bindu D, Haritha K, Chowdary VH (2013) In vitro and in vivo assessment of piroxicam incorporated Aloe vera transgel. Int J Pharm Invest 3(4):212–216CrossRefGoogle Scholar
  26. Wahlbeck K, Westman J, Nordentoft M (2011) Outcomes of Nordic mental health systems: life expectancy of patients with mental disorders. Br J Psychiatr 199:453–458CrossRefGoogle Scholar
  27. Wu X, Xu J, Huang X, Wen C (2011) Self- microemulsifying drug delivery system improves curcumin dissolution and bioavailability. Drug Dev Ind Pharm 37(1):15–23CrossRefGoogle Scholar
  28. Yang D, Kulkarni R, Behme RJ (2007) Effect of the melt granulation technique on the dissolution characteristics of griseofulvin. Int J Pharm 329:72–80CrossRefGoogle Scholar
  29. Yeom DW, Song YS, Kim SR (2015) Development and optimization of a self-microemulsifying drug delivery system for atorvastatin calcium by using d-optimal mixture design. Int J Nanomed 10:3865–3878Google Scholar

Copyright information

© The Korean Society of Pharmaceutical Sciences and Technology 2018

Authors and Affiliations

  • Harini Chowdary Vadlamudi
    • 1
    • 2
  • Prasanna Raju Yalavarthi
    • 3
  • Tejeswari Nagaswaram
    • 3
  • Arun Rasheed
    • 4
  • Jaya Preethi Peesa
    • 2
  1. 1.Department of PharmaceuticsPES College of PharmacyBangaloreIndia
  2. 2.Centre for Research StudiesKrishna UniversityMachilipatnamIndia
  3. 3.Pharmaceutics DivisionSri Padmavathi School of PharmacyTirupatiIndia
  4. 4.Department of ChemistryAl-Shifa College of PharmacyPoonthavanamIndia

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