Saravana Perumal GOVINDAN, Senthamarai RAJAGOPALAN, Anbarasu KUMAR

Quality by design-based evaluation and optimization of ceftibuten flexible dispersible tablet design with high drug loading using Design-Expert software

There are challenges in developing dispersible tablets with a high drug loading of a waterinsolubledrug having flexibility, either as dispersible in water or as dispersible in the oral cavity beforeswallowing with overall acceptability. Overall acceptability is determined by the characteristics of the drugproduct and user acceptance. This study aimed to design and optimise the flexible dispersible tablets designusing a model drug, namely ceftibuten with the drug loading of about 72%w/w of targeted tablet weight,in a statistically significant manner using design-expert software. The significant effects of screened inputparameters on target responses were characterised based on the half-normal plot for the magnitude ofeffects, pareto chart for standardised effects, and variance analysis for the statistically significant model. Thecharacterised design was optimised using the response surface method (RSM). The optimised targetresponse was statistically confirmed based on the extent of statistical significance (very significant

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[1] Sharrif Z, Kirby D, Missaghi S, Rajabi-Siahboomi A, Maidment I. Patient-Centric Medicine Design: Key Characteristics of Oral Solid Dosage Forms that improve Adherence and Acceptance in Older People. Pharmaceutics. 2020; 12(10): 1-15. [CrossRef]
[2] Govindan S P, Senthamarai R, Anbarasu K. Design of Flexible Dispersible Tablet with high drug loading using quality by Design: Proof of Concept study using third generation Cephalosporins Model Drug. Research J Pharm Tech. 2021; 14(2): 705-714.
[3] Walsh J, Ranmal S R, Ernest T B, Liu F. Patient acceptability, safety and access: A balancing act for selecting ageappropriate oral dosage forms for paediatric and geriatric populations. Int J Pharm. 2018; 536(2): 547-562. [CrossRef]
[4] Logrippo S, Ricci G, Sestili M, Cespi M, Ferrara L, Palmieri G F, Ganzetti R, Bonacucina G, Blasi P. Oral drug therapy in elderly with dysphagia: between a rock and a hard place. Clin Interv Aging. 2017; 12: 241-251.
[5] Orubu E SF, Tuleu C. Medicines for children: flexible solid oral formulations. Bull World Health Organ. 2017; 95: 238- 240. [CrossRef]
[6] Hoppu, K. Time to change the paradigm of children's medicines from liquid formulations to flexible solid oraldosage forms. Ceylon Med J. 2016; 61(3): 93-95. [CrossRef]
[7] Liu F, Ranmal S, Batchelor H K, Gul M O, Ernest T B, Thomas I W, Flanagan T, Tuleu C. Patient-Centred Pharmaceutical Design to Improve Acceptability of Medicine: Similarities and Differences in Pediatric and Geriatric Populations. Drugs. 2014; 74(16):1871-1889. [CrossRef]
[8] Govindan S P, Senthamarai R, Anbarasu K. Refrigeration and the Shelf Life of Oral Cephalosporin Powder for Suspension Dosage Form: Review and Proposal. Int. J Emerg Technol. 2019; 10(2).376–383.
[9] International Conference on Harmonisation (ICH), 2009. ICH Harmonised Tripartite Guideline: Pharmaceutical Development Q8 (R2). https://database. ich.org/sites/default/files/Q8_R2_Guideline.pdf (accessed June 30, 2020).
[10] Quality by Design for ANDAs: An Example for Immediate-Release Dosage Forms. https://www.fda.gov/media/83664/download (accessed June 30, 2020).
[11] Dhoot A S, Fernandes G J, Naha A, Rathnanand M, Kumar L. Design of Experiments in Pharmaceutical Development. Pharm Chem J. 2019; 53(8): 730-735.
[12] Sangshetti J N, Deshpande M, Arote R, Zaheer Z, Shinde D B. Quality by design approach: Regulatory need. Arabian J Chem. 2017; 10(2): S3412-S3425. [CrossRef]
[13] Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation. https://www.fda.gov/media /81626/download (accessed June 30, 2020).
[14] Guidance for Industry Orally Disintegrating Tablets. https://www. fda.gov/media/70877/download (accessed June 30, 2020).
[15] Guidance for Industry Size, Shape, and other Physical Attributes of Generic Tablets and Capsules. https://www.fda.gov/media/87344/download (accessed June 30, 2020).
[16] Bircan Y, Çomoğlu T. Formulation technologies of orally fast disintegrating tablets. Marmara Pharm J. 2012; 16: 77- 81.
[17] Handbook for Experimenters Version 11.01. https://cdnm.statease.com/pubs/handbk_for_exp_sv.pdf (accessed June 7, 2019).
[18] Ceftibuten. https://www.accessdata.fda.gov/scripts /cder/dissolution/dsp_SearchResults.cfm (accessed June 7, 2019).
[19] Ali T, Ediz Y, Gülcin T. Ceftibuten Capsule Formulations. European Patent 3 031 450 A1; 2016 (accessed June 7, 2019).
[20] Cedax® (ceftibuten capsule) and (ceftibuten for oral suspension). https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/050685s011,050686s014IbI.pdf (accessed on June 7, 2019).
[21] Belissa E, Vallet T, Caget S L, Chevallier A, Chedhomme F X, Abdallah F, et al. Acceptability of oral liquid pharmaeutical products in older adults: palatability and swallowability issues. BMC Geriatrics. 2019; 19(344): 2-9. [CrossRef]
[22] European Medicines Agency (EMEA), 2012. Presentation-acceptability and palatability- methods available for assessment. https://www.ema.europa.eu/en/documents/presentation/presentation-acceptability-palatability- Methods-available-assessment_en.pdf (accessed May 3, 2020).
[23] Brniak W, Jachowicz R, Pelka P. The practical approach to the evaluation of methods used to determine the disintegration time of orally disintegrating tablets (ODTs). Saudi Pharm J. 2015; 23: 437-443. [CrossRef]
[24] Yoshita T, Uchida S, Namiki N. Clinical Disintegration Time of Orally Disintegrating Tablets Clinically Available Japan in Healthy Volunteers. Biol. Pharm. Bull. 2013; 36(9): 1488-1493.
[25] Kim J-II, Cho S-Min, Cui J-H, Cao Q-Ri, Oh E, Lee B-J. In Vitro and in Vivo Correlation of disintegration and bitter Taste masking using orally disintegrating tablet containing ion exchange resin-drug complex. Int J Pharm. 2013; 455: 31-39. [CrossRef]
[26] Callejo M J, Kostiuk-V Eugenia-M, Quijano-M R. Selection, training and validation of a sensory panel for bread analysis: Influence of cultivar on the quality of breads made from common wheat and spelt wheat. J Cereal Sci. 2015; 61: 55-62. [CrossRef]
[27] Ranmal S R, O’Brien F, Lopez F, Ruiz F, Orlu M, Tuleu C, et al. Methodologies for assessing the acceptability of oral formulations among children and older adults : a systematic review. Drug Discov Today. 2018; 23(4): 830-847. [CrossRef]