The Development of Floating Multiple Unit Mini Tablets of Bosentan Using QbD: Characterisation and Pharmacokinetic Study

Author(s): Santosh Kumar Panda*, Manoranjan Sahu, Kahnu Charan Panigrahi, Chinam Niranjan Patra, Goutam Kumar Jena

Journal Name: Drug Delivery Letters

Volume 11 , Issue 2 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Multiple dosing is required for bosentan in order to achieve steady-state concentration. Hence formulating bosentan controlled release formulation could be an approach to solve this issue.

Objective: The objective is to develop floating multiple unit minitablets of bosentan using the Quality by design approach.

Methods: Failure mode effect analysis (FMEA) and Taguchi design are employed in order to screen highly critical factors. Box-Behnken design (BBD) was adopted for the process of optimization.

Results: The quantity of gelucire 39/01, HPMC K15 M, and sodium bicarbonate was found to be one of the significant factors using Taguchi design. The Box-Behnken design results in the optimised formulation showing floating lag time within 3 min, floating time of nearly 15 h, time to release 50% of drug of 3.6 h, time to release 90% of drug of 11h and better bioavailability compared to pure drug.

Conclusion: It can be concluded that floating multiple unit minitablet can be used as an encouraging approach for sustaining the drug release of bosentan.

Keywords: Bosentan, risk assessment, taguchi design, box-behnken design, bio-analytical study, solid state characterization, bioavailability.

[1]
Dingemanse, J.; van Giersbergen, P.L.M. Clinical pharmacology of bosentan, a dual endothelin receptor antagonist. Clin. Pharmacokinet., 2004, 43(15), 1089-1115.
[http://dx.doi.org/10.2165/00003088-200443150-00003] [PMID: 15568889]
[2]
Bosentan | C27H29N5O6S - PubChem, https://pubchem.ncbi.nlm.nih.gov/compound/Bosentan Apr 10, 2020
[3]
Panigrahi, K.C.; Patra, C.N.; Jena, G.K.; Ghose, D.; Jena, J.; Panda, S.K.; Sahu, M. Gelucire: A versatile polymer for modified release drug delivery system. Futur. J. Pharm. Sci., 2018, 4(1), 102-108.
[http://dx.doi.org/10.1016/j.fjps.2017.11.001]
[4]
Jammula, S.; Patra, ChN.; Swain, S.; Panigrahi, K.C.K.C.; Nayak, S.; Dinda, S.C.S.C.; Rao, M.E.B.M.E.B.; Panigrahi, C.; Nayak, S.; Dinda, C.; Eswara, M.; Rao, B.; Charan Panigrahi, K.; Chandra Dinda, S.; Panigrahi, K.C.K.C.; Nayak, S.; Dinda, S.C.S.C.; Rao, M.E.B.M.E.B. Design and characterization of cefuroxime axetil biphasic floating minitablets. Drug Deliv., 2015, 22(1), 125-135.
[http://dx.doi.org/10.3109/10717544.2013.871603] [PMID: 24417642]
[5]
Faulhammer, E.; Llusa, M.; Wahl, P.R.; Paudel, A.; Lawrence, S.; Biserni, S.; Calzolari, V.; Khinast, J.G. Development of a design space and predictive statistical model for capsule filling of low-fill-weight inhalation products. Drug Dev. Ind. Pharm., 2016, 42(2), 221-230.
[http://dx.doi.org/10.3109/03639045.2015.1040416] [PMID: 26023991]
[6]
Buttini, F.; Rozou, S.; Rossi, A.; Zoumpliou, V.; Rekkas, D.M. The application of Quality by Design framework in the pharmaceutical development of dry powder inhalers. Eur. J. Pharm. Sci., 2018, 113, 64-76.
[http://dx.doi.org/10.1016/j.ejps.2017.10.042] [PMID: 29104067]
[7]
Nagaich, U. Pharmaceutical “quality by design” approach. J. Adv. Pharm. Technol. Res., 2018, 9(1), 1.
[http://dx.doi.org/10.4103/japtr.JAPTR_343_17] [PMID: 29441316]
[8]
Chudiwal, S.S.; Dehghan, M.H.G. Quality by design (QbD) approach for design and development of drug-device combination products: a case study on flunisolide nasal spray. Pharm. Dev. Technol., 2018, 23(10), 1077-1087.
[http://dx.doi.org/10.1080/10837450.2016.1236130] [PMID: 27616074]
[9]
Zhang, L.; Mao, S. Applications of quality by design (QbD) and its tools in drug delivery. Asian J. Pharm. Sci., 2016, 11(1), 144-145.
[http://dx.doi.org/10.1016/j.ajps.2015.11.084]
[10]
Sethi, S.; Mangla, B.; Kamboj, S.; Rana, V. A QbD approach for the fabrication of immediate and prolong buoyant cinnarizine tablet using polyacrylamide-g-corn fibre gum. Int. J. Biol. Macromol., 2018, 117, 350-361.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.05.178] [PMID: 29807074]
[11]
Panigrahi, K.C.; Patra, C.N.; Rao, M.E.B. Quality by design enabled development of oral self-nanoemulsifying drug delivery system of a novel calcimimetic cinacalcet hcl using a porous carrier: in vitro and in vivo characterisation. AAPS. Pharm. Sci. Tech., 2019, 20(5), 216.
[http://dx.doi.org/10.1208/s12249-019-1411-2] [PMID: 31172322]
[12]
Bansal, S.; Beg, S.; Asthana, A.; Garg, B.; Asthana, G.S.; Kapil, R.; Singh, B. QbD-enabled systematic development of gastroretentive multiple-unit microballoons of itopride hydrochloride. Drug Deliv., 2016, 23(2), 437-451.
[http://dx.doi.org/10.3109/10717544.2014.916771] [PMID: 24865292]
[13]
Kaljević, O.; Djuriš, J.; Djurić, Z.; Ibrić, S. Application of Failure Mode and Effects Analysis in Quality by Design Approach for Formulation of Carvedilol Compression Coated Tablets. J. Drug Deliv. Sci. Technol., 2016, 32, 56-63.
[http://dx.doi.org/10.1016/j.jddst.2016.02.004]
[14]
Chudiwal, V.S.; Shahi, S.; Chudiwal, S. Development of sustained release gastro-retentive tablet formulation of nicardipine hydrochloride using quality by design (QbD) approach. Drug Dev. Ind. Pharm., 2018, 44(5), 787-799.
[http://dx.doi.org/10.1080/03639045.2017.1413111] [PMID: 29198152]
[15]
Panigrahi, K.C.; Jena, J.; Jena, G.K.; Patra, C.N.; Rao, M.E.B. QBD-Based Systematic Development of Bosentan SNEDDS: Formulation, Characterization and Pharmacokinetic Assessment. J. Drug Deliv. Sci. Technol., 2018, 47, 31-42.
[http://dx.doi.org/10.1016/j.jddst.2018.06.021]
[16]
Alt, N.; Zhang, T.Y.; Motchnik, P.; Taticek, R.; Quarmby, V.; Schlothauer, T.; Beck, H.; Emrich, T.; Harris, R.J. Determination of critical quality attributes for monoclonal antibodies using quality by design principles. Biologicals, 2016, 44(5), 291-305.
[http://dx.doi.org/10.1016/j.biologicals.2016.06.005] [PMID: 27461239]
[17]
von Stosch, M.; Hamelink, J-M.; Oliveira, R. Hybrid modeling as a QbD/PAT tool in process development: an industrial E. coli case study. Bioprocess Biosyst. Eng., 2016, 39(5), 773-784.
[http://dx.doi.org/10.1007/s00449-016-1557-1] [PMID: 26879643]
[18]
FDA. Quality by Design for ANDAs : An Example for Immediate-Release Dosage Forms. Fda, 2012 April;, 1-107..
[http://dx.doi.org/10.1117/12.809118.]
[19]
Mandal, U.K.; Chatterjee, B.; Senjoti, F.G. Gastro-Retentive Drug Delivery Systems and Their in Vivo Success: A Recent Update. Asian J. Pharm. Sci., 2016, 11(5), 575-584.
[http://dx.doi.org/10.1016/j.ajps.2016.04.007]
[20]
Lopes, C.M.; Bettencourt, C.; Rossi, A.; Buttini, F.; Barata, P. Overview on gastroretentive drug delivery systems for improving drug bioavailability. Int. J. Pharm., 2016, 510(1), 144-158.
[http://dx.doi.org/10.1016/j.ijpharm.2016.05.016] [PMID: 27173823]
[21]
Qi, X.; Chen, H.; Rui, Y.; Yang, F.; Ma, N.; Wu, Z. Floating tablets for controlled release of ofloxacin via compression coating of hydroxypropyl cellulose combined with effervescent agent. Int. J. Pharm., 2015, 489(1-2), 210-217.
[http://dx.doi.org/10.1016/j.ijpharm.2015.05.007] [PMID: 25956047]
[22]
Singh, B.; Kaur, A.; Dhiman, S.; Garg, B.; Khurana, R.K.; Beg, S. QbD-Enabled Development of Novel Stimuli-Responsive Gastroretentive Systems of Acyclovir for Improved Patient Compliance and Biopharmaceutical Performance. AAPS PharmSciTech, 2016, 17(2), 454-465.
[http://dx.doi.org/10.1208/s12249-015-0367-0] [PMID: 26238805]
[23]
Alzaher, W.; Shaw, J.; Al-Kassas, R. Gastroretentive formulations for improving oral bioavailability of drugs-focus on microspheres and their production. Curr. Drug Deliv., 2016, 13(5), 646-661.
[http://dx.doi.org/10.2174/1567201812666151012113357] [PMID: 26456212]
[24]
Garg, N.K.; Sharma, G.; Singh, B.; Nirbhavane, P.; Tyagi, R.K.; Shukla, R.; Katare, O.P. Quality by Design (QbD)-enabled development of aceclofenac loaded-nano structured lipid carriers (NLCs): An improved dermatokinetic profile for inflammatory disorder(s). Int. J. Pharm., 2017, 517(1-2), 413-431.
[http://dx.doi.org/10.1016/j.ijpharm.2016.12.010] [PMID: 27956192]
[25]
Kumar Panda, S.; Sahu, M.; Charan Panigrahi, K.; Patra, C.N.; Santosh, M.; Panda, K. Systematic development with quality by design approach of effervescent floating multiple unit minitablets of metoprolol succinate using hydrophobic grade of gelucire. Indian J. Pharm. Educ. Res., 2019, 53(3s), s213-s224.
[http://dx.doi.org/10.5530/ijper.53.3s.90]
[26]
Chen, Y.C.; Ho, H.O.; Liu, D.Z.; Siow, W.S.; Sheu, M.T. Swelling/floating capability and drug release characterizations of gastroretentive drug delivery system based on a combination of hydroxyethyl cellulose and sodium carboxymethyl cellulose. PLoS One, 2015, 10(1), e0116914.
[http://dx.doi.org/10.1371/journal.pone.0116914] [PMID: 25617891]
[27]
Dudhipala, N.; Janga, K.Y. Lipid nanoparticles of zaleplon for improved oral delivery by Box-Behnken design: optimization, in vitro and in vivo evaluation. Drug Dev. Ind. Pharm., 2017, 43(7), 1205-1214.
[http://dx.doi.org/10.1080/03639045.2017.1304957] [PMID: 28274147]
[28]
Rahman, N.; Nasir, M. Application of Box-Behnken design and desirability function in the optimization of Cd(II) removal from aqueous solution using poly(o-phenylenediamine)/hydrous zirconium oxide composite: equilibrium modeling, kinetic and thermodynamic studies. Environ. Sci. Pollut. Res. Int., 2018, 25(26), 26114-26134.
[http://dx.doi.org/10.1007/s11356-018-2566-1] [PMID: 29971743]
[29]
Quality Guidelines : ICH, http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html [Accessed Dec 26, 2018];


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 11
ISSUE: 2
Year: 2021
Published on: 26 February, 2021
Page: [179 - 194]
Pages: 16
DOI: 10.2174/2210303111666210226142015
Price: $25

Article Metrics

PDF: 139