Login Register Cart 0
Generic placeholder image

Current Drug Therapy

Editor-in-Chief

ISSN (Print): 1574-8855
ISSN (Online): 2212-3903

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Formulation Development and Optimization of Blonanserin Liquid SMEDDS using D-Optimal Mixture Design

Author(s): Sohansinh Vaghela*, Sunita Chaudhary and Ankit Chaudhary

Volume 17, Issue 4, 2022

Published on: 06 July, 2022

Page: [266 - 280] Pages: 15

DOI: 10.2174/1574885517666220421125528

Price: $65

conference banner
Abstract

Background: Blonanserin is an atypical antipsychotic potent antagonist of dopamine-D2 and D3 receptors with low aqueous solubility BCS class II drugs.

Objective: The present research aims to develop and optimize the Blonanserin-loaded liquid selfmicro emulsifying drug delivery system (SMEDDS) to improve its in vitro drug release by D-optimal mixture design.

Methods: Saturation solubility of Blonanserin was checked in various oils, surfactants, and cosurfactants. The pseudo-ternary phase diagram was developed to identify the region of the microemulsion. Trial batches were designed to determine dependent and independent variables in the formulation. DOptimal Mixture design applies for optimization and minimized trials. The amount of oil(X1), surfactant( X2), and co-surfactant(X3) were selected as independent variables, and solubility(Y1) and in vitro percentage cumulative drug release(Y2) and size of globule(Y3) after 250 times dilution were selected as the dependant variable. The level of the independent variables in the design will be selected based on the drug's phase diagram, trial batches, and solubility. The developed SMEDDS was then evaluated for globule size, transparency, self-emulsification time, in vitro dissolution, and relative dissolution of the final formulation with marketed products and a pure drug.

Results: BLN shows the highest solubility in (1:1) Captex 200P: Capmul MCM (oil), Tween 20 (surfactant), and Ethanol (cosurfactant). Trial batches were shown at 1:9, 2:8, and 3:7 oil to surfactant and cosurfactant ratios suitable for optimization. Optimization using a D-optimal mixture design gives 11 run batches and the resulting surface and contour plot suggest the best design space. The optimized formula given by the mixture design of the target formulation had maximum drug solubility, maximum drug release, and minimum globule size. Optimized formula containing Blonanserin, Captex 200P: Capmul MCM (1:1) Mixture (23% v/v), Tween 80 (57% v/v), and Ethanol (20% v/v) having 94.72% in vitro diffusion within 30 min with 21 nm globule size. Optimized liquid SMEDDS have a higher in-vitro diffusion rate than marketed products and pure drugs.

Conclusion: Blonanserin liquid SMEDDS was successfully developed with high solubility, nanoglobule size, and improvement in in-vitro diffusion rate and vice versa for improvement in bioavailability of the drug.

Keywords: D-optimal mixture design, SMEDDS, in vitro diffusion, blonanserin, solubility enhancement, co-surfactant.

« Previous Next »
[1]
Porter CJH, Trevaskis NL, Charman WN. Lipids and lipid-based formulations: Optimizing the oral delivery of lipophilic drugs. Nat Rev Drug Discov 2007; 6(3): 231-48.
[http://dx.doi.org/10.1038/nrd2197] [PMID: 17330072]
[2]
Feeney OM, Crum MF, McEvoy CL, et al. 50 Years of oral lipid-based formulations: Provenance, progress and future perspectives. Adv Drug Deliv Rev 2016; 101: 167-94.
[http://dx.doi.org/10.1016/j.addr.2016.04.007] [PMID: 27089810]
[3]
Hörter D, Dressman JB. Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev 1997; 25: 3-14.
[http://dx.doi.org/10.1016/S0169-409X(96)00487-5] [PMID: 11259834]
[4]
Pouton CW. Lipid formulations for oral administration of drugs: Non-emulsifying, self-emulsifying and ‘self-microemulsifying’ drug delivery systems. Eur J Pharm Sci 2000; 11(Suppl. 2): S93-8.
[http://dx.doi.org/10.1016/S0928-0987(00)00167-6] [PMID: 11033431]
[5]
Humberstone AJ, Charman WN. Lipid-based vehicles for the oral delivery of poorly water soluble drugs. Adv Drug Deliv Rev 1997; 25: 103-28.
[http://dx.doi.org/10.1016/S0169-409X(96)00494-2]
[6]
Pouton CW. Self-emulsifying drug delivery systems: Assessment of the efficiency of emulsification. Int J Pharm 1985; 27: 335-48.
[http://dx.doi.org/10.1016/0378-5173(85)90081-X]
[7]
Mohsin K, Shahba AA, Alanazi FK. Lipid based self emulsifying formulations for poorly water soluble drugs-An excellent opportunity. Indian J Pharm Educ Res 2012; 46: 88-96.
[8]
Pouton CW, Porter CJH. Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies. Adv Drug Deliv Rev 2008; 60(6): 625-37.
[http://dx.doi.org/10.1016/j.addr.2007.10.010] [PMID: 18068260]
[9]
Chong HY, Teoh SL, Wu DBC, Kotirum S, Chiou CF, Chaiyakunapruk N. Global economic burden of schizophrenia: A systematic review. Neuropsychiatr Dis Treat 2016; 12: 357-73.
[http://dx.doi.org/10.2147/NDT.S96649] [PMID: 26937191]
[10]
Kishi T, Matsuda Y, Nakamura H, Iwata N. Blonanserin for schizophrenia: Systematic review and meta-analysis of double-blind, randomized, controlled trials. J Psychiatr Res 2013; 47(2): 149-54.
[http://dx.doi.org/10.1016/j.jpsychires.2012.10.011] [PMID: 23131856]
[11]
Tenjin T, Miyamoto S, Ninomiya Y, et al. Profile of blonanserin for the treatment of schizophrenia. Neuropsychiatr Dis Treat 2013; 9: 587-94.
[http://dx.doi.org/10.2147/NDT.S34433] [PMID: 23766647]
[12]
Maddileti D, Swapna B, Nangia A. High solubility crystalline pharmaceutical forms of blonanserin. Cryst Growth Des 2014; 14: 2557-70.
[http://dx.doi.org/10.1021/cg500252c]
[13]
Iwata N, Ishigooka J, Kim WH, et al. Efficacy and safety of blonanserin transdermal patch in patients with schizophrenia: A 6-week randomized, double-blind, placebo-controlled, multicenter study. Schizophr Res 2020; 215: 408-15.
[http://dx.doi.org/10.1016/j.schres.2019.07.055] [PMID: 31471246]
[14]
Garcia E, Robert M, Peris F, Nakamura H, Sato N, Terazawa Y. The efficacy and safety of blonanserin compared with haloperidol in acute-phase schizophrenia. CNS Drugs 2009; 23: 615-25.
[http://dx.doi.org/10.2165/00023210-200923070-00006]
[15]
Takahashi S, Suzuki M, Uchiyama M. One-year follow-up study of psychotic patients treated with blonanserin: A case series. Asia-Pac Psychiatry 2013; 5(3): 164-7.
[http://dx.doi.org/10.1111/j.1758-5872.2012.00232.x] [PMID: 23857800]
[16]
Shaji J, Lodha S. Response surface methodology for the optimization of celecoxib self-microemulsifying drug delivery system. Indian J Pharm Sci 2008; 70(5): 585-90.
[http://dx.doi.org/10.4103/0250-474X.45395] [PMID: 21394253]
[17]
Cho W, Kim MS, Kim JS, et al. Optimized formulation of solid self-microemulsifying sirolimus delivery systems. Int J Nanomedicine 2013; 8: 1673-82.
[http://dx.doi.org/10.2147/IJN.S43299] [PMID: 23641156]
[18]
Yeom DW, Song YS, Kim SR, et al. Development and optimization of a self-microemulsifying drug delivery system for atorvastatin calcium by using D-optimal mixture design. Int J Nanomedicine 2015; 10: 3865-77.
[http://dx.doi.org/10.2147/IJN.S83520] [PMID: 26089663]
[19]
Azeem A, Rizwan M, Ahmad FJ, et al. Nanoemulsion components screening and selection: A technical note. AAPS PharmSciTech 2009; 10(1): 69-76.
[http://dx.doi.org/10.1208/s12249-008-9178-x] [PMID: 19148761]
[20]
Wadhwa J, Nair A, Kumria R. Self emulsifying therapeutic system: A potential approach for delivery of lipophilic drugs. Braz J Pharm Sci 2011; 47: 447-66.
[http://dx.doi.org/10.1590/S1984-82502011000300003]
[21]
Chen H, Chang X, Weng T, et al. A study of microemulsion systems for transdermal delivery of triptolide. J Control Release 2004; 98(3): 427-36.
[http://dx.doi.org/10.1016/j.jconrel.2004.06.001] [PMID: 15312998]
[22]
Mahdi ES, Sakeena MH, Abdulkarim MF, Abdullah GZ, Sattar MA, Noor AM. Effect of surfactant and surfactant blends on pseudoternary phase diagram behavior of newly synthesized palm kernel oil esters. Drug Des Devel Ther 2011; 5: 311-23.
[http://dx.doi.org/10.2147/DDDT.S15698] [PMID: 21792294]
[23]
More H, Hazare A. Practical Pharmaceutics (Physical Pharmacy). 1st ed. Manas Prakashan 2004.
[24]
Villar AMS, Naveros BC, Campmany ACC, Trenchs MA, Rocabert CB, Bellowa LH. Design and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for enhanced dissolution of gemfibrozil. Int J Pharm 2012; 431(1-2): 161-75.
[http://dx.doi.org/10.1016/j.ijpharm.2012.04.001] [PMID: 22498011]
[25]
Patel G, Shelat P, Lalwani A. Statistical modeling, optimization and characterization of solid self-nanoemulsifying drug delivery system of lopinavir using design of experiment. Drug Deliv 2016; 23(8): 3027-42.
[http://dx.doi.org/10.3109/10717544.2016.1141260] [PMID: 26882014]
[26]
Dening TJ, Rao S, Thomas N, Prestidge CA. Montmorillonite-lipid hybrid carriers for ionizable and neutral poorly water-soluble drugs: Formulation, characterization and in vitro lipolysis studies. Int J Pharm 2017; 526(1-2): 95-105.
[http://dx.doi.org/10.1016/j.ijpharm.2017.04.063] [PMID: 28456653]
[27]
Jaiswal P, Aggarwal G, Harikumar SL, Singh K. Development of self-microemulsifying drug delivery system and solid-self-microemulsifying drug delivery system of telmisartan. Int J Pharm Investig 2014; 4(4): 195-206.
[http://dx.doi.org/10.4103/2230-973X.143123] [PMID: 25426441]
[28]
Shah A, Thool P, Sorathiya K, Prajapati H, Dalrymple D, Serajuddin ATM. Effect of different polysorbates on development of self-microemulsifying drug delivery systems using medium chain lipids. Drug Dev Ind Pharm 2018; 44(2): 215-23.
[http://dx.doi.org/10.1080/03639045.2017.1386202] [PMID: 29057677]
[29]
Prajapati HN, Dalrymple DM, Serajuddin ATM. A comparative evaluation of mono, di- and triglyceride of medium chain fatty acids by lipid/surfactant/water phase diagram, solubility determination and dispersion testing for application in pharmaceutical dosage form development. Pharm Res 2012; 29: 285-305.
[http://dx.doi.org/10.1007/s11095-011-0541-3]

Rights & Permissions Print Cite
Article Metrics
8
© 2024 Bentham Science Publishers | Privacy Policy