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

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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.

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References

  • 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):69–91

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):189–196

    Article  CAS  Google Scholar 

  • 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):315–325

    Article  Google Scholar 

  • 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 15:863–869

    Article  Google Scholar 

  • Guan HJ, Dai J, Zhu XZ (2000) Atypical antipsychotic effects of quetiapine fumarate in animal models. Acta Pharmacol Sin 21(3):205–210

    CAS  PubMed  Google Scholar 

  • Gupta SK (2009) Drug screening methods—preclinical evaluation of new drugs, 2nd edn. Jaypee Publishers, Hyderabad, p 385

    Google Scholar 

  • 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

    Article  Google Scholar 

  • 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):10821–10833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):1213–1222

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):208–213

    Google Scholar 

  • Pooja A, Payal S, Dhaiwat P, Sonali D (2014) Quetiapine fumarate loaded solid lipid nanoparticles for improved oral bioavailability. Drug Deliv Lett 4(2):170–184

    Article  CAS  Google Scholar 

  • 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):1539–1547

    Article  CAS  Google Scholar 

  • 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):219–235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):399–405

    Article  CAS  Google Scholar 

  • Sander C, Holm P (2009) Porous magnesium aluminometasilicate tablets as carrier of a cyclosporine self-emulsifying formulation. AAPS Pharm Sci Tech 10(4):1388–1395

    Article  CAS  Google Scholar 

  • 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–E17

    Article  Google Scholar 

  • 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 91:196–207

    Article  CAS  PubMed  Google Scholar 

  • 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):606–612

    Article  CAS  PubMed  Google Scholar 

  • 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 4:110–115

    Article  CAS  Google Scholar 

  • Ücok A, Gaebel W (2008) Side effects of atypical antipsychotics: a brief overview. World Psychiatry 7(1):58–62

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):989–995

    Article  CAS  PubMed  Google Scholar 

  • 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 8:1–17

    Google Scholar 

  • 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):162–167

    Article  CAS  PubMed  Google Scholar 

  • 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):212–216

    Article  CAS  Google Scholar 

  • Wahlbeck K, Westman J, Nordentoft M (2011) Outcomes of Nordic mental health systems: life expectancy of patients with mental disorders. Br J Psychiatr 199:453–458

    Article  Google Scholar 

  • 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):15–23

    Article  CAS  PubMed  Google Scholar 

  • Yang D, Kulkarni R, Behme RJ (2007) Effect of the melt granulation technique on the dissolution characteristics of griseofulvin. Int J Pharm 329:72–80

    Article  CAS  PubMed  Google Scholar 

  • 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 10:3865–3878

    CAS  Google Scholar 

Download references

Acknowledgements

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

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

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Authors and Affiliations

  1. Department of Pharmaceutics, PES College of Pharmacy, Bangalore, 560050, India

    Harini Chowdary Vadlamudi

  2. Centre for Research Studies, Krishna University, Machilipatnam, 521001, India

    Harini Chowdary Vadlamudi & Jaya Preethi Peesa

  3. Pharmaceutics Division, Sri Padmavathi School of Pharmacy, Tirupati, 517503, India

    Prasanna Raju Yalavarthi & Tejeswari Nagaswaram

  4. Department of Chemistry, Al-Shifa College of Pharmacy, Poonthavanam, 679325, India

    Arun Rasheed

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  1. Harini Chowdary Vadlamudi
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  2. Prasanna Raju Yalavarthi
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  3. Tejeswari Nagaswaram
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  4. Arun Rasheed
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  5. Jaya Preethi Peesa
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Correspondence to Harini Chowdary Vadlamudi.

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Vadlamudi, H.C., Yalavarthi, P.R., Nagaswaram, T. et al. In-vitro and pharmacodynamic characterization of solidified self microemulsified system of quetiapine fumarate. J. Pharm. Investig. 49, 161–172 (2019). https://doi.org/10.1007/s40005-018-0397-1

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  • DOI: https://doi.org/10.1007/s40005-018-0397-1

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