Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia

Poonam Mogal; Deeliprao Derle

doi:doi:10.11648/j.jddmc.20170303.12

| Peer-Reviewed

Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia

Poonam Mogal, Deeliprao Derle

Published in Journal of Drug Design and Medicinal Chemistry (Volume 3, Issue 3)

Received: 19 May 2017 Accepted: 21 June 2017 Published: 25 July 2017

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

In modern times, people are suffering from many mental health disorders like schizophrenia, bipolar disorders and many psychoses. Hence, it is essential to treat these mental disorders using medications as well as with assistance from caregivers for the social well being of person. This study was focussed on improving solubility & dissolution of poorly soluble drug Ziprasidone using different formulation approaches like solid dispersion & inclusion complexation. Different solubility enhancing techniques like physical mixing, solvent evaporation, microwave irradiation, lyophilization & spray drying were used for the along with four different polymers i.e Kollidon, Soluplus, Pluronic and HPβCD. The prepared formulations were evaluated for saturated solubility, dissolution, ATR, SEM, XRD, pharmacodynamic and pharmacokinetic in vivo study. The prepare formulations showed increment in solubility as well as dissolution. The order of solubility enhancement for the studied polymers was found to be of following order: Soluplus >HPβCD >Kollidon >Pluronic. In the pharmacodynamic study, the optimized solid dispersion showed the calming effect on mice when compared to pure Ziprasidone. The pharmacokinetic study demonstrated the increase in oral absorption of Ziprasidone in all prepared formulations and it followed the same order as that solubility & dissolution enhancement. The Soluplus-solid dispersion prepared by spray drying technique was found to be suitable in enhancing oral absorption with significant (p < 0.05) enhancement in Cmax & AUC than pure Ziprasidone. Hence, comparative study was helpful in increasing oral bioavailability Of Ziprasidone in choosing the suitable polymer with decreasing the dose and increasing patient adherence to therapy.

Published in	Journal of Drug Design and Medicinal Chemistry (Volume 3, Issue 3)
DOI	10.11648/j.jddmc.20170303.12
Page(s)	37-48
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Ziprasidone, Solubility, Kollidon, Soluplus, Pluronic, HPβCD, Solid Dispersion

References

[1]	WHO. Draft comprehensive mental health action plan 2013–2020. http://apps.who.int/gb/ebwha/pdf_fi les/WHA66/A66_10Rev1-en. pdf
[2]	WHO. (2008) mhGAP Mental Health Gap Action Programme: scaling up care for mental, neurological and substance use disorders. Geneva: World Health Organization.
[3]	Lee H, Tsai S, Lin H, Chen C (2006) The association between psychiatrist numbers and hospitalization costs for schizophrenia patients: a population-based study. Schizophr Res 81(2–3):283–290.
[4]	Rossler W, Salize H, Van J, Riecher-Rossler A (2005) Size of burden of schizophrenia and psychotic disorders. Eur Neuropsychopharmacol 15(4):399–409.
[5]	Zhai J., Guo X., Chen M., Zhao J., Su Z. (2013) An investigation of economic costs of schizophrenia in two areas of China International Journal of Mental Health Systems 7:26.
[6]	Chong H., Teoh S., Wu D., Kotirum S., Chiou C. Chaiyakunapruk N. (2016) Global economic burden of schizophrenia: a systematic review. Neuropsychiatric Disease and Treatment 12:357–373.
[7]	Davis J, Matalon L, Watanabe M. (1994) Depot antipsychotic drugs. Place in therapy. Drugs 47:741–773.
[8]	Dencker S. (1984) The risk/benefit ratio of depot neuroleptics: a Scandinavian perspective. J. Clin. Psychiatry 45, 22–27.
[9]	Barnes T, Curson D. (1994) Long-term depot antipsychotics. A risk–benefit assessment. Drug. Saf. 10: 464–479.
[10]	Ereshefsky L, Saklad S, Jann M. (1984) Future of depot neuroleptic therapy: pharmacokinetic and pharmacodynamic approaches. J. Clin. Psychiatry 45:50–59.
[11]	Heres S, Hamann J, Kissling W, Leucht S. (2006) Attitudes of psychiatrics toward antipsychotic depot medication. J. Clin. Psychiatry 67:1948–1953.
[12]	Szasz T: Where does psychiatry go? In: Ideology and Insanity. (1970) Essays on the Psychiatric Dehumanization of Man. Szasz T (Ed.). Anchor Books, New York, NY, USA, 213–238.
[13]	Olivares J, Pinal B., Cinos C. (2011) Comparison of long-acting antipsychotic injection and oral antipsychotics in schizophrenia Neuropsychiatry 1(3):275–289.
[14]	Stahl S., Shayegan, D., (2003) The psychopharmacology of ziprasidone: receptorbinding properties and real-world psychiatric practice. J. Clin. Psychiatry 64: 6–12.
[15]	Clinicaltrils.gov [Internet homepage] https://clinicaltrials.gov/ct2/results?term=ziprasidone&pg=2
[16]	O’ Neil M, Heckelman P, Koch C, Roman K, Kenny C, D’Arecca M. (2006) Ziprasidone Hydrochloride, In: The Merck Index – An encyclopedia of chemicals, drugs and biological, Merck Research Laboratory, Division of Merck & Co., Inc., Whitehouse Station, New Jersey, 14th Edition. 10307.
[17]	Sweetman S. (2009) Ziprasidone Hydrochloride, In: Martindale-The Complete Drug Reference, Pharmaceutical Press, London, and 36th Edition. 1036.
[18]	Miceli J, Wilner K, Swan S, Tensfeldt T. (2005) Pharmacokinetics, safety, and tolerability of intramuscular Ziprasidone in healthy volunteers, J Clin Pharmacol 45: 620–30.
[19]	Preskorn S. (2005) Pharmacokinetics and therapeutics of acute intramuscular ziprasidone, Clin Pharmacokinet, 44: 1117–33.
[20]	Miceli J, Smith M, Robarge L, Morse T, Laurent A. (2000) The effects of ketoconazole on ziprasidone pharmacokinetics —a placebo-controlled crossovers study in healthy volunteers, British Journal of Clinical Pharmacology 49(S1): 71–76.
[21]	Martini L, Crowley P. (2011) Controlling drug release in oral product development programs: An industrial Perspective: In Controlled release in oral drug delivery. Springer, New York 45-70.
[22]	Geodon® (Revised 2009) [U.S. Prescribing Information including Patient Summary of Information], Pfizer Inc.
[23]	Daniel, D. (2003) Tolerability of ziprasidone: an expanding perspective. J. Clin. Psychiatry 64, 40–49.
[24]	Patel, N., Keck J. (2006) Ziprasidone: efficacy and safety in patients with bipolar disorder. Expert Rev. Neurotherapeutics 6: 1129–1138.
[25]	Zimbroff D., Allen M, Battaglia, J., Citrome, L., Fishkind A., Francis A., Herr Daniel, L., Hughes, D., Martel, M., Preval, H., Ross, R. (2005) Best clinical practice with ziprasidone IM: update after 2 years of experience. CNS Spectr. 10:1–15.
[26]	Greenberg W., Citrome L. (2007) Ziprasidone for schizophrenia and bipolar disorder: a review of the Clinical trials. CNS Drug Rev. 13:137–177.
[27]	Harrison, T., Scott, L. Ziprasidone: a review of its use in schizophrenia and schizoaffective disorder. CNS Drugs 20:1027–1052.
[28]	Bernardo, M., Azanza, J., Rubio-Terres, C., Rejas, J. (2006) Cost-effectiveness analysis of schizophrenia relapse prevention: an economic evaluation of the ZEUS (ziprasidone-extended-use-in-schizophrenia) study in Spanish. Clin. Drug Invest. 26:447–457.
[29]	Bernardo, M.,Azanza, JR., Rubio-Terres, C., Rejas, J. (2007) Cost-effectiveness analysis of the prevention of relapse of schizophrenia in the longitudinal study ziprasidone extended use in schizophrenia (ZEUS). Actas Esp. Psiquiatr. 35:259–262.
[30]	Bobes, J., Canas, F., Rejas, J., Mackell, J. (2004) Economic consequences of the adverse reactions related with antipsychotics: an economic model comparing tolerability of ziprasidone, olanzapine, risperidone, and haloperidol in Spain. Prog. Neuropsychopharmacol. Biol. Psychiatry 28: 1287–1297.
[31]	Miceli, J., Wilner, K., Hansen, R., Johnson, A., Apseloff, G., Gerber, N. (2000) Single- and multiple-dose pharmacokinetics of ziprasidone under nonfasting conditions in healthy male volunteers. Br. J. Clin. Pharmacol. 49: 5S–13S.
[32]	Lincoln J., Stewart Mark, E., Preskorn Sheldon, H. (2010) How sequential studies inform drug development: evaluating the effect of food intake on optimal bioavailability of ziprasidone. J. Psychiatr. Pract. 16:103–114.
[33]	Perkins, D. (2002) Predictors of noncompliance in patients with schizophrenia. J. Clin. Psychiatry 63: 1121–1128.
[34]	Stella, V., Nti-Addae, K. (2007) Prodrug strategies to overcome poor water solubility. Adv. Drug Deliv. Rev. 59: 677–694.
[35]	Babu, N., Nangia, A. (2011) Solubility advantage of amorphous drugs and pharmaceutical cocrystals. Cryst. Growth Des. 11:2662–2679.
[36]	Porter, C., Pouton, C., Cuine, J., Charman, W. (2008) Enhancing intestinal drug solubilization using lipid-based delivery systems. Adv. Drug Deliv. Rev. 60:673–691.
[37]	Tang J., Sun, J., He Z. (2007) Self-emulsifying drug delivery systems: strategy for improving oral delivery of poorly soluble drugs. Curr. Drug Ther. 2:85–93.
[38]	Brewster M., Loftsson, T. (2007) Cyclodextrins as pharmaceutical solubilizers. Adv. Drug Deliv. Rev. 59:645–666.
[39]	Friesen, D., Shanker, R., Crew M., Smithey, D., Curatolo, W, Nightingale, J. (2008) Hydroxypropyl methylcellulose acetate succinate-based spray-dried dispersions: an overview. Mol. Pharm. 5: 1003–1019
[40]	Usha Y., Angel T., Udupa, N. (2010) Nanotechnology: perspectives on solubility/bioavailability enhancement. Pharma Rev. 8:59–66.
[41]	Hong J. (2011) Effect of Cyclodextrin Derivation and Amorphous State of Complex on Accelerated Degradation of Ziprasidone. Journal of Pharmaceutical Sciences. 100(7); 2703-2716.
[42]	Kim Y. (1998) Inclusion complexation of ziprasidone mesylate with β -cyclodextrin sulfobutyl ether. J Pharm Sci. 87(12):1560–7.
[43]	Thombre A, Shah J, Sagawa K. (2012) In vitro and in vivo characterization of amorphous, nanocrystalline, and crystalline ziprasidone formulations. Int J Pharm 428:8–17.
[44]	Thombre A, Herbig S, Alderman J. (2011) Improved ziprasidone formulations with enhanced bioavailability in the fasted state and a reduced food effect. Pharm Res 28:3159–70.
[45]	Thombre A, Shamblin S, Malhotra B, Connor A, Wilding I, Caldwell W. (2015) Pharmacoscintigraphy studies to assess the feasibility of a controlled release formulation of ziprasidone. J Control Release 213:10–7.
[46]	Preskom S. (2005) Pharmacokinetics and therapeutics of acute intramuscular ziprasidone. Clin Pharmacokinet 44:1117–33.
[47]	NDA20-825. (2000) Clinical Pharmacology and Biopharmaceutics Review.
[48]	Miao Y, Chen G, Ren L, Pingkai O. (2016) Preparation and evaluation of ziprasidone-phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect. J Pharm Pharmacol. 68(2):185–94.
[49]	Dening T., Rao S., Thomas N., Prestidge C. (2016) Silica encapsulated lipid-based drug delivery systems for reducing the 5 fed/fasted variations of ziprasidone in vitro. European Journal of Pharmaceutics and Biopharmaceutics 1-10.
[50]	Setthacheewakul S, Mahattanadul S, Phadoongsombut N, Pichayakorn W, Wiwattanapatapee R. (2010) Development and evaluation of self-microemulsifying liquid and pellet formulations of curcumin and absorption studies in rats. Eur J Pharm Biopharm. 76: 475–85.
[51]	Marghade S, Musmade P., Moorkoth S. (2012) High-Performance Liquid Chromatographic Assay for Ziprasidone in Plasma Samples: Application to Pharmacokinetic Studies in Rats. Journal of Chromatographic Science 50:902–908.
[52]	Zakowiecki D, Cal K, Kaminski K, Adrjanowicz K, Swinder L, Kaminska E, (2015) The Improvement of the Dissolution Rate of Ziprasidone Free Base from Solid Oral Formulations. AAPS PharmSciTech 20(4):1–12.
[53]	Hamelin B, Allard S, Laplante L, Miceli J, Wilner K, Tremblay J. (1998) The effect of timing of a standard meal on the pharmacokinetics and pharmacodynamics of the novel atypical antipsychotic agent ziprasidone. Pharmacotherapy. 18(1):9–15.
[54]	Nagwa G., Amira Y. (2011) Synthesis of some oxindole derivatives as potential antipsychotic and anticonvulsant agents. International journal of pharmacy and pharmaceutical sciences. 3(3):213-219.
[55]	Kaminski K, Adrjanowicz K, Wojnarowska Z, Grzybowska K, Hawelek L, Paluch M. (2011) Molecular dynamics of the cryomilled base and hydrochloride ziprasidones by means of dielectric spectroscopy. J Pharm Sci. 100(7):2642–57.
[56]	Newa M, Bhandari K, Li D. (2007) Preparation, characterization and in vivo evaluation of ibuprofen binary solid dispersions with poloxamer 188. Int J Pharm 343:228–37.
[57]	Miao Y, Chen G, Ren L, Ouyang P. (2016) Preparation and evaluation of ziprasidone-phospholipid complex from sustained-release pellet formulation with enhanced bioavailability and no food effect. J Pharm Pharmacol. 68(2):185–94.
[58]	Hancock B, Parks M. (2000) What is the true solubility advantage for amorphous pharmaceuticals? Pharm Res. 17(4):397–404.
[59]	Poluri K., Mulpur E., Puttugunta S., Govada K. (2013) Formulation development and evaluation of novel oral soluble films of ziprasidone hydrochloride in the treatment of schizophrenia, Int J Pharm Pharm Sci.5(2): 600-608.
[60]	Hong, J., Shah, J., McGonagle, M. (2011) Effect of cyclodextrin derivation and amorphous state of complex on accelerated degradation of ziprasidone. J. Pharm. Sci. 100: 2703–2716.
[61]	Kim, Y., Oksanen, D., Massefski J., Blake, J., Duffy, E., Chrunyk, B. (1998) Inclusion complexation of ziprasidone mesylate with beta-cyclodextrin sulfobutyl ether. J. Pharm. Sci. 87:1560–1567.
[62]	Junghanns, J., Mueller, R. (2008) Nanocrystal technology, drug delivery and clinical applications. Int. J. Nanomed. 3:295–309.
[63]	Miceli J, Glue P, Alderman J, Wilner K. (2007) The effect of food on the absorption of oral ziprasidone. Psychopharmacol Bull. 40(3):58–68. 38.
[64]	Pfizer. (2011) Zeldox® (ziprasidone hydrochloride) capsules 20, 40, 60, and 80 mg- Product Monograph. Kirkland, Quebec, Canada.

Cite This Article

Plain Text BibTeX RIS

APA Style

Poonam Mogal, Deeliprao Derle. (2017). Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia. Journal of Drug Design and Medicinal Chemistry, 3(3), 37-48. https://doi.org/10.11648/j.jddmc.20170303.12

Copy | Download

ACS Style

Poonam Mogal; Deeliprao Derle. Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia. J. Drug Des. Med. Chem. 2017, 3(3), 37-48. doi: 10.11648/j.jddmc.20170303.12

Copy | Download

AMA Style

Poonam Mogal, Deeliprao Derle. Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia. J Drug Des Med Chem. 2017;3(3):37-48. doi: 10.11648/j.jddmc.20170303.12

Copy | Download

@article{10.11648/j.jddmc.20170303.12,
  author = {Poonam Mogal and Deeliprao Derle},
  title = {Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia},
  journal = {Journal of Drug Design and Medicinal Chemistry},
  volume = {3},
  number = {3},
  pages = {37-48},
  doi = {10.11648/j.jddmc.20170303.12},
  url = {https://doi.org/10.11648/j.jddmc.20170303.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20170303.12},
  abstract = {In modern times, people are suffering from many mental health disorders like schizophrenia, bipolar disorders and many psychoses. Hence, it is essential to treat these mental disorders using medications as well as with assistance from caregivers for the social well being of person. This study was focussed on improving solubility & dissolution of poorly soluble drug Ziprasidone using different formulation approaches like solid dispersion & inclusion complexation. Different solubility enhancing techniques like physical mixing, solvent evaporation, microwave irradiation, lyophilization & spray drying were used for the along with four different polymers i.e Kollidon, Soluplus, Pluronic and HPβCD. The prepared formulations were evaluated for saturated solubility, dissolution, ATR, SEM, XRD, pharmacodynamic and pharmacokinetic in vivo study. The prepare formulations showed increment in solubility as well as dissolution. The order of solubility enhancement for the studied polymers was found to be of following order: Soluplus >HPβCD >Kollidon >Pluronic. In the pharmacodynamic study, the optimized solid dispersion showed the calming effect on mice when compared to pure Ziprasidone. The pharmacokinetic study demonstrated the increase in oral absorption of Ziprasidone in all prepared formulations and it followed the same order as that solubility & dissolution enhancement. The Soluplus-solid dispersion prepared by spray drying technique was found to be suitable in enhancing oral absorption with significant (p < 0.05) enhancement in Cmax & AUC than pure Ziprasidone. Hence, comparative study was helpful in increasing oral bioavailability Of Ziprasidone in choosing the suitable polymer with decreasing the dose and increasing patient adherence to therapy.},
 year = {2017}
}

Copy | Download

TY  - JOUR
T1  - Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia
AU  - Poonam Mogal
AU  - Deeliprao Derle
Y1  - 2017/07/25
PY  - 2017
N1  - https://doi.org/10.11648/j.jddmc.20170303.12
DO  - 10.11648/j.jddmc.20170303.12
T2  - Journal of Drug Design and Medicinal Chemistry
JF  - Journal of Drug Design and Medicinal Chemistry
JO  - Journal of Drug Design and Medicinal Chemistry
SP  - 37
EP  - 48
PB  - Science Publishing Group
SN  - 2472-3576
UR  - https://doi.org/10.11648/j.jddmc.20170303.12
AB  - In modern times, people are suffering from many mental health disorders like schizophrenia, bipolar disorders and many psychoses. Hence, it is essential to treat these mental disorders using medications as well as with assistance from caregivers for the social well being of person. This study was focussed on improving solubility & dissolution of poorly soluble drug Ziprasidone using different formulation approaches like solid dispersion & inclusion complexation. Different solubility enhancing techniques like physical mixing, solvent evaporation, microwave irradiation, lyophilization & spray drying were used for the along with four different polymers i.e Kollidon, Soluplus, Pluronic and HPβCD. The prepared formulations were evaluated for saturated solubility, dissolution, ATR, SEM, XRD, pharmacodynamic and pharmacokinetic in vivo study. The prepare formulations showed increment in solubility as well as dissolution. The order of solubility enhancement for the studied polymers was found to be of following order: Soluplus >HPβCD >Kollidon >Pluronic. In the pharmacodynamic study, the optimized solid dispersion showed the calming effect on mice when compared to pure Ziprasidone. The pharmacokinetic study demonstrated the increase in oral absorption of Ziprasidone in all prepared formulations and it followed the same order as that solubility & dissolution enhancement. The Soluplus-solid dispersion prepared by spray drying technique was found to be suitable in enhancing oral absorption with significant (p < 0.05) enhancement in Cmax & AUC than pure Ziprasidone. Hence, comparative study was helpful in increasing oral bioavailability Of Ziprasidone in choosing the suitable polymer with decreasing the dose and increasing patient adherence to therapy.
VL  - 3
IS  - 3
ER  -

Copy | Download

Author Information

Poonam Mogal

Department of Pharmaceutics, M. V. P. S’ College of Pharmacy, Nashik, India
Deeliprao Derle

Department of Pharmaceutics, M. V. P. S’ College of Pharmacy, Nashik, India

Download PDF

Sections

Plain Text BibTeX RIS

APA Style

Poonam Mogal, Deeliprao Derle. (2017). Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia. Journal of Drug Design and Medicinal Chemistry, 3(3), 37-48. https://doi.org/10.11648/j.jddmc.20170303.12

Copy | Download

ACS Style

Poonam Mogal; Deeliprao Derle. Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia. J. Drug Des. Med. Chem. 2017, 3(3), 37-48. doi: 10.11648/j.jddmc.20170303.12

Copy | Download

AMA Style

Poonam Mogal, Deeliprao Derle. Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia. J Drug Des Med Chem. 2017;3(3):37-48. doi: 10.11648/j.jddmc.20170303.12

Copy | Download

@article{10.11648/j.jddmc.20170303.12,
  author = {Poonam Mogal and Deeliprao Derle},
  title = {Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia},
  journal = {Journal of Drug Design and Medicinal Chemistry},
  volume = {3},
  number = {3},
  pages = {37-48},
  doi = {10.11648/j.jddmc.20170303.12},
  url = {https://doi.org/10.11648/j.jddmc.20170303.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jddmc.20170303.12},
  abstract = {In modern times, people are suffering from many mental health disorders like schizophrenia, bipolar disorders and many psychoses. Hence, it is essential to treat these mental disorders using medications as well as with assistance from caregivers for the social well being of person. This study was focussed on improving solubility & dissolution of poorly soluble drug Ziprasidone using different formulation approaches like solid dispersion & inclusion complexation. Different solubility enhancing techniques like physical mixing, solvent evaporation, microwave irradiation, lyophilization & spray drying were used for the along with four different polymers i.e Kollidon, Soluplus, Pluronic and HPβCD. The prepared formulations were evaluated for saturated solubility, dissolution, ATR, SEM, XRD, pharmacodynamic and pharmacokinetic in vivo study. The prepare formulations showed increment in solubility as well as dissolution. The order of solubility enhancement for the studied polymers was found to be of following order: Soluplus >HPβCD >Kollidon >Pluronic. In the pharmacodynamic study, the optimized solid dispersion showed the calming effect on mice when compared to pure Ziprasidone. The pharmacokinetic study demonstrated the increase in oral absorption of Ziprasidone in all prepared formulations and it followed the same order as that solubility & dissolution enhancement. The Soluplus-solid dispersion prepared by spray drying technique was found to be suitable in enhancing oral absorption with significant (p < 0.05) enhancement in Cmax & AUC than pure Ziprasidone. Hence, comparative study was helpful in increasing oral bioavailability Of Ziprasidone in choosing the suitable polymer with decreasing the dose and increasing patient adherence to therapy.},
 year = {2017}
}

Copy | Download

TY  - JOUR
T1  - Use of Solid Dispersions and Inclusion Complexation for Enhancing Oral Bioavailability of Ziprasidone in Treating Schizophrenia
AU  - Poonam Mogal
AU  - Deeliprao Derle
Y1  - 2017/07/25
PY  - 2017
N1  - https://doi.org/10.11648/j.jddmc.20170303.12
DO  - 10.11648/j.jddmc.20170303.12
T2  - Journal of Drug Design and Medicinal Chemistry
JF  - Journal of Drug Design and Medicinal Chemistry
JO  - Journal of Drug Design and Medicinal Chemistry
SP  - 37
EP  - 48
PB  - Science Publishing Group
SN  - 2472-3576
UR  - https://doi.org/10.11648/j.jddmc.20170303.12
AB  - In modern times, people are suffering from many mental health disorders like schizophrenia, bipolar disorders and many psychoses. Hence, it is essential to treat these mental disorders using medications as well as with assistance from caregivers for the social well being of person. This study was focussed on improving solubility & dissolution of poorly soluble drug Ziprasidone using different formulation approaches like solid dispersion & inclusion complexation. Different solubility enhancing techniques like physical mixing, solvent evaporation, microwave irradiation, lyophilization & spray drying were used for the along with four different polymers i.e Kollidon, Soluplus, Pluronic and HPβCD. The prepared formulations were evaluated for saturated solubility, dissolution, ATR, SEM, XRD, pharmacodynamic and pharmacokinetic in vivo study. The prepare formulations showed increment in solubility as well as dissolution. The order of solubility enhancement for the studied polymers was found to be of following order: Soluplus >HPβCD >Kollidon >Pluronic. In the pharmacodynamic study, the optimized solid dispersion showed the calming effect on mice when compared to pure Ziprasidone. The pharmacokinetic study demonstrated the increase in oral absorption of Ziprasidone in all prepared formulations and it followed the same order as that solubility & dissolution enhancement. The Soluplus-solid dispersion prepared by spray drying technique was found to be suitable in enhancing oral absorption with significant (p < 0.05) enhancement in Cmax & AUC than pure Ziprasidone. Hence, comparative study was helpful in increasing oral bioavailability Of Ziprasidone in choosing the suitable polymer with decreasing the dose and increasing patient adherence to therapy.
VL  - 3
IS  - 3
ER  -

Copy | Download