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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Formulation and Optimization of Trandolapril Oro-dispersible Tablets using the Quality by Design (QbD) Approach

Author(s): Ganesh Kumar* and Meenakshi Bhatt

Volume 20, Issue 9, 2023

Published on: 06 September, 2022

Page: [1194 - 1203] Pages: 10

DOI: 10.2174/1570180819666220429153102

Price: $65

Abstract

Introduction: This study aims to use a Quality by Design (QbD) approach to formulate and optimize Trandolapriloro-dispersible tablets. The central composite design tool was utilized to assess the scientific understanding of independent input variables and output responses to construct a design space for regulatory flexibility. Oro-dispersible Tablets (ODT) can also be used to deliver drugs directly to the oral mucosa, bypassing first-pass hepatic metabolism and potentially accelerating the process.

Methodology: The concentrations of super disintegrant and dry compressible binder were selected as independent variables. Disintegration time in seconds and % friability was selected as dependent variables. Polynomial equations were used to predict the quantitative effect of independent variables at various levels on response variables.

Results and Discussion: The pre-compression parameters suggested that the flow characteristics were quite excellent. All tablets prepared in the above experiments were evaluated for pharmaco-technical properties and found to be within the required limits using the direct compression method. The angle of repose of the dry blends from each formulation batch (F1 to F9) ranged from 29.03° to 33.67°. All formulation batches had a loose bulk density of 0.31 + 0.07 to 0.37 + 0.91 g/cm3 and a tapped density of 0.41+ 0.02 to 0.46+ 0.16 g/cm3, respectively. The compressibility index was determined to be between 1.65 + 0.17 to 19.93 + 0.47 . Hausner's ratio was between 1.14 + 0.88 to 1.19 + 0.32. The thickness of the tablets ranged from 2.07 + 0.54 to 2.52 + 0.12 mm. The tablets were found to have a hardness of 3.08 + 0.14 to 3.67 + 0.41 kg/cm2. The weight of the tablets prepared ranged from 50 + 0.09 to 52 + 0.56 mg on average. Tablet friability was 0.52 + 0.54 to 0.83 + 0.10 %, and the disintegration time ranged between 27 and 58 seconds. All of these parameters were found under the acceptable limit of pharmacopoeias. The increase of Crospovidone concentration decreased the disintegration time and increased % friability. Whereas increasing the concentration of microcrystalline cellulose increased the disintegration time and decreased the % friability. Contour plots clarified the link between independent and dependent variables. The most cost-effective batch was chosen based on these plots within the desired range because the actual and projected values suggested by the full model were very close to each other; the statistical model is mathematically valid.

Conclusion: The results showed that the proposed design for developing trandolapriloro-dispersible tablets with optimal properties was effective.

Keywords: Oro-dispersible Tablet, Crospovidine, MicrocrystallineCellulose, Quality by Design

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[1]
Nishi, T. A novel approach of fast dissolving film and their patients. Adv. Biol. Res. (Faisalabad), 2013, 7(2), 50-58.
[2]
Ketul, P. Patel, K.R.; Patel, M.R.; Patel, N.M. Fast dissolving films; A novel approach to oral drug delivery system. Int. J. Pharm. Teach. Pract., 2013, 4(2), 655-661.
[3]
Osterberg, R.; See, N. Toxicity of excipients- A Food and Drug Administration Perspective. Int. J. Toxicol., 2003, 22(5), 377-380.
[4]
Lachman, L; Liberman, H.; Kanig, J. The Theory and Practice of Industrial Pharmacy, (3rd ed.. ) , 346-373.
[5]
Indurwade, N.H.; Rajyaguru, T.H.; Nakhat, P.D. Fast Dissolving drug delivery systems: A brief overview. Indian Drugs, 2002, 39(8), 405-409.
[6]
CheinYie W. Oral drug delivery and delivery systems, 2nd ed; Marcel Dekker: New York, 1992.
[7]
Bi, Y.; Sunada, H.; Yonezawa, Y.; Danjo, K.; Otsuka, A.; Iida, K. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem. Pharm. Bull. (Tokyo), 1996, 44(11), 2121-2127.
[http://dx.doi.org/10.1248/cpb.44.2121] [PMID: 8945778]
[8]
Kaushik, D.; Dureja, H.; Saini, T.R. Mouth dissolving tablets: A review. Indian Drugs, 2004, 41(4), 187-193.
[9]
Tanmoy, G.; Amitava, G.; Devi, P. A review on new generation orodispersible tablet and its future prospective. Int. J. Pharm. Pharm. Sci., 2011, 3, 1-7.
[10]
Hirani, J.J.; Rathod, D.A.; Vadalia, K.R. Orally disintegrating tablets: A review. Trop. J. Pharm. Res., 2008, 8(2), 161-172.
[11]
Arora, P.; Arora, V. Orodispersible tablets: A comprehensive review. Int. J. Res. Dev. Pharm. Life Sci., 2013, 2, 270-284.
[12]
Mudgal, V.K.; Singhai, A.K. Orally disintegrating tablet: A review. Int. Res. J. Pharm., 2011, 2230-8407.
[13]
Chandrasekhar, R.; Hassan, Z.; Alhusban, F.; Smith, A.M.; Mohammed, A.R. The role of formulation excipients in the development of lyophilised fast-disintegrating tablets. Eur. J. Pharm. Biopharm., 2009, 72(1), 119-129.
[http://dx.doi.org/10.1016/j.ejpb.2008.11.011] [PMID: 19073253]
[14]
Jain, D.; Amul, M.A. Formulation & development of orodispersible tablet. Int J Pharm Eru., 2014, 4, 21-38.
[15]
Deepak, K. Orally disintegrating tablets. Tablets and Capsules, 2004, 7, 30-35.
[16]
Khan, T. Sayyed, N.; Siraj, S.; Afsar, S.; Ashish, K.; Aejaz, A. An approach for rapid disintegrating tablet: a review. Int. J. Res. Dev. Pharm. Res. Dev., 2011, 3(3), 170-183.
[17]
Pebley, W.S.; Jager, N.E.; Thompson, S.J. Rapidly disintegrating tablet. US Patent, 1994, 298-261.
[18]
ICH. Q8 (R2), Harmonised tripartite guideline, Pharmaceutical development. August 2009:9-24.
[19]
Khan, I.A.; Smillie, T. Implementing a “quality by design” approach to assure the safety and integrity of botanical dietary supplements. J. Nat. Prod., 2012, 75(9), 1665-1673.
[http://dx.doi.org/10.1021/np300434j] [PMID: 22938174]
[20]
Orlandini, S.; Pinzauti, S.; Furlanetto, S. Application of quality by design to the development of analytical separation methods. Anal. Bioanal. Chem., 2013, 405(2-3), 443-450.
[http://dx.doi.org/10.1007/s00216-012-6302-2] [PMID: 22941176]
[21]
Guay, D.R.P. Trandolapril: A newer angiotensin-converting enzyme inhibitor. Clin. Ther., 2003, 25(3), 713-775.
[http://dx.doi.org/10.1016/S0149-2918(03)80107-8] [PMID: 12852701]
[22]
Køber, L.; Torp-Pedersen, C.; Carlsen, J.E.; Bagger, H.; Eliasen, P.; Lyngborg, K.; Videbaek, J.; Cole, D.S.; Auclert, L.; Pauly, N.C. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N. Engl. J. Med., 1995, 333(25), 1670-1676.
[http://dx.doi.org/10.1056/NEJM199512213332503] [PMID: 7477219]
[23]
Stefan, R-I.; van Staden, J.F.; Aboul-Enein, H.Y. Detection of S-enantiomers of cilazapril, pentopril and trandolapril using a potentiometric, enantioselective membrane electrode. Electroanalysis, 1999, 11(3), 192-194.
[http://dx.doi.org/10.1002/(SICI)1521-4109(199903)11:3<192:AID-ELAN192>3.0.CO;2-O]
[24]
Zhang, L.; Yan, B.; Gong, X.; Yu, L.X.; Qu, H. Application of quality by design to the process development of botanical drug products: A case study. AAPS PharmSciTech, 2013, 14(1), 277-286.
[http://dx.doi.org/10.1208/s12249-012-9919-8] [PMID: 23297167]
[25]
Bezerra, M.A.; Santelli, R.E.; Oliveira, E.P.; Villar, L.S.; Escaleira, L.A. Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta, 2008, 76(5), 965-977.
[http://dx.doi.org/10.1016/j.talanta.2008.05.019] [PMID: 18761143]
[26]
Bhutani, H.; Kurmi, M.; Singh, S.; Beg, S.; Singh, B. Quality by design (QbD) in analytical sciences: An overview. Pharm. Times, 2014, 46(8), 71-75.
[27]
US Food and Drug Administration. Quality by design for ANDAs: an example for immediate-release dosage forms; HHS, 2012.
[28]
Chowhan, Z Pharmaceutical technology: Excipients and their functionality in drug product development. Pharm. Technol., 1993, 17(9), 72-82.
[29]
Liberman, H.A.; Lachman, L. In pharmaceutical dosage form: Tablets; Marcell Dekker Inc: New York, 1991, 2, pp. (1)209-215.
[30]
Banker, G.; Rhodes, C. Drug and pharmaceutical sciences: Modern pharmaceutics; Marcel Dekker Inc: New York, 2002, 3, pp. (2)333-394.
[31]
Seager, H. Drug-delivery products and the Zydis fast-dissolving dosage form. J. Pharm. Pharmacol., 1998, 50(4), 375-382.
[http://dx.doi.org/10.1111/j.2042-7158.1998.tb06876.x] [PMID: 9625481]

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