BOX-BEHNKEN DESIGN FOR OPTIMIZATION OF FORMULATION VARIABLES FOR CONTROLLED RELEASE GASTRORETENTIVE TABLET OF VERAPAMIL HYDROCHLORIDE

INDURKHYA ARPNA; KHAN AHMED MASHEER

doi:10.22159/ijap.2023v15i1.46489

Authors

INDURKHYA ARPNA School of Pharmacy, DAVV, Indore, Madhya Pradesh 452020, India https://orcid.org/0000-0002-0346-5765
KHAN AHMED MASHEER School of Pharmacy, DAVV, Indore, Madhya Pradesh 452020, India https://orcid.org/0000-0003-3313-3451

DOI:

https://doi.org/10.22159/ijap.2023v15i1.46489

Keywords:

Box Behnken Design, Verapamil Hcl, Controlled release gastroretentive tablet

Abstract

Objective: To develop a Verapamil hydrochloride controlled release gastro-retentive (CRGR) tablet for once-daily dosing using the response surface Box-Behnken Design (BBD) approach for the improvement of bioavailability and reduction in dosing frequency to overcome the issues related to the conventional tablet formulation.

Methods: For the optimization, 3³Box-Behnken design was used. The independent variables were selected, the amount of Compritol 888 ATO (A), HPMC K15M (B), and Sodium bicarbonate (C). The dependent variables were Cumulative % drug release in 1.5 h (Q1.5), 8 h (Q8), 24 H (Q24) and floating lag time (FLT). Flow properties of pre-compressed powder, physical characteristics, drug content, floating lag time, total floating time and in vitro dissolution study of all formulation were assessed. In vitro dissolution study of optimized formulation that was prepared experimentally was performed and compared with predicted data obtained from the software. Drug release kinetics of the optimized formulation was also assessed to know the mechanism of drug release from the CRGR tablets.

Results: Responses of experimental runs were found as Q1.5: 12.78-33.62 (%), Q8: 43.03-64 (%), Q24: 78.77 to 103.57 (%) and floating lag time as 3.01 min to 5.08 min. The predicted optimized formula with the highest desirability value of 0.963 containing amount 126.030 mg, 160.00 mg and 80.955 mg of Compritol 888 ATO, HPMC K15M and Sodium biarbonate respectively was prepared and evaluated. The experimental values from optimized formulation were obtained as Q1.5: 23.397%, Q8; 57.744%, Q24: 97.150% and FLT: 3.12 min. Predicted and experimental results were found comparable for all the responses. The release data from the optimized formulation were best fitted in the Higuchi (r² = 0.999) and the Korsmeyer-Peppas ((r² = 0.998, n=0.54) model. The in vitro drug release studies indicated that the Verapamil hydrochloride gastroretentive tablet releases the drug in controlled manner for 24 h.

Conclusion: This study found that using Box-Behnken Design with the response and variable relation, it is possible to achieve an optimum formulation with desirable characteristics. This study also established the suitability of Compritol 888 ATO-HPMC K15M combination with Sodium bicarbonate to increase the gastric residence time tablet formulation had once-daily dosing of the Verapamil Hcl with improved bioavailability for effective management of hypertension.

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References

Al-Zoubi N, Alkhatib HS, Alobaidi G, Abdel Rahim S, Obeidat W, Malamataris S. Optimization of pH-independent chronotherapeutic release of verapamil HCl from three-layer matrix tablets. Int J Pharm. 2015;494(1):296-303. doi: 10.1016/j.ijpharm.2015.08.021, PMID 26276259.

Mathur V, Nagpal K, Singh SK, Mishra DN. Comparative release profile of sustained release matrix tablets of verapamil HCl. Int J Pharm Investig. 2013;3(1):60-5. doi: 10.4103/2230-973X.108965, PMID 23799207.

Mandal UK, Chatterjee B, Senjoti FG. Gastro-retentive drug delivery systems and their in vivo success: a recent update. Asian J Pharm Sci. 2016;11(5):575-84. doi: 10.1016/j.ajps.2016.04.007.

Tripathi J, Thapa P, Maharjan R, Jeong SH. Current state and future perspectives on gastroretentive drug delivery systems. Pharmaceutics. 2019;11(4):193. doi: 10.3390/ pharmaceutics11040193, PMID 31010054, PMCID PMC6523542.

Porwal A, Dwivedi H, Pathak K. Decades of research in drug targeting using gastroretentive drug delivery systems for antihypertensive therapy. Braz J Pharm Sci. 2017;53(3). doi: 10.1590/s2175-97902017000300173.

Muijsers RB, Curran MP, Perry CM. Fixed combination trandolapril/verapamil sustained-release: a review of its use in essential hypertension. Drugs. 2002;62(17):2539-67. doi: 10.2165/00003495-200262170-00014, PMID 12421112.

Prinderre P, Sauzet C, Fuxen C. Advances in gastro retentive drug-delivery systems. Expert Opin Drug Deliv. 2011;8(9):1189-203. doi: 10.1517/17425247.2011.592828, PMID 21671821.

Das S, Kaur S, Rai VK. Gastro-retentive drug delivery systems: a recent update on clinical pertinence and drug delivery. Drug Deliv Transl Res. 2021;11(5):1849-77. doi: 10.1007/s13346-020-00875-5, PMID 33403646.

Sopyan I, Gozali D, Sriwidodo GRK, Guntina RK. Design-expert software (DOE): an application tool for optimization in pharmaceutical preparations formulation. Int J App Pharm. 2022;14(4):55-63. doi: 10.22159/ijap.2022v14i4.45144.

Zhang L, Mao S. Application of quality by design in the current drug development. Asian J Pharm Sci. 2017;12(1):1-8. doi: 10.1016/j.ajps.2016.07.006. PMID 32104308.

Tak JW, Gupta B, Thapa RK, Woo KB, Kim SY, Go TG. Preparation and optimization of immediate release/sustained release bilayered tablets of loxoprofen using Box-Behnken design. AAPS PharmSciTech. 2017;18(4):1125-34. doi: 10.1208/s12249-016-0580-5, PMID 27401334.

Kamala Kumari PV, Yarraguntla SR, Sharmila M, Harika V. Application of box-behnken design for formulation parameters of eslicarbazepine tablets. Indian J Pharm Sci. 2021;83(3):575-83. doi: 10.36468/pharmaceutical-sciences.808.

Yoshida MI, Gomes EC, Soares CD, Cunha AF, Oliveira MA. Thermal analysis applied to verapamil hydrochloride characterization in pharmaceutical formulations. Molecules. 2010;15(4):2439-52. doi: 10.3390/molecules15042439, PMID 20428054.

Mali AD, Bathe RS. Development and evaluation of gastroretentive floating tablets of a quinapril HCl by direct compression technique. Int J Pharm Pharm Sci. 2017;9(8):35-46. doi: 10.22159/ijpps.2017v9i8.12463.

Rapolu K, Sanka K, Vemula PK, Aatipamula V, Mohd AB, Diwan PV. Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design. Drug Dev Ind Pharm. 2013;39(12):1928-35. doi: 10.3109/03639045.2012.699068, PMID 22762132.

Chudiwal VS, 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):787-99. doi: 10.1080/03639045.2017.1413111, PMID 29198152.

Vidyadhara S, Sasidhar RL, Nagaraju R. Design and development of polyethylene oxide based matrix tablets for verapamil hydrochloride. Indian J Pharm Sci. 2013;75(2):185-90. PMID 24019567, PMCID PMC3757857.

Gattani SG, Londhe SG, Chalikwar SS, Amrutkar JR. Formulation and evaluation of gastroretentive drug delivery of verapamil hydrochloride. Eur J Parenter Pharm. 2010;15(4):125.

Patel A, Modasiya M, Shah D, Patel V. Development and in vivo floating behavior of verapamil HCl intragastric floating tablets. AAPS PharmSciTech. 2009;10(1):310-5. doi: 10.1208/s12249-009-9210-9, PMID 19296224, PMCID PMC2663699.

Sagar S, Srinivas L. Development and evaluation of raft forming gastro retentive floating drug delivery system of nizatidine by design of experiment. Int J App Pharm. 2022;14(2):242-51. doi: 10.22159/ijap.2022v14i2.43728.

Kadivar A, Kamalidehghan B, Javar HA, Davoudi ET, Zaharuddin ND, Sabeti B. Formulation and in vitro, in vivo evaluation of effervescent floating sustained-release imatinib mesylate tablet. PLOS ONE. 2015;10(6):e0126874. doi: 10.1371/journal.pone.0126874. PMID 26035710.

Gu X, Fediuk DJ, Simons FE, Simons KJ. Evaluation and comparison of five matrix excipients for the controlled release of acrivastine and pseudoephedrine. Drug Dev Ind Pharm. 2004;30(10):1009-17. doi: 10.1081/ddc-200040237, PMID 15595567.

Barakat NS, Elbagory IM, Almurshedi AS. Controlled-release carbamazepine matrix granules and tablets comprising lipophilic and hydrophilic components. Drug Deliv. 2009;16(1):57-65. doi: 10.1080/10717540802518157, PMID 19555310.

Li FQ, Hu JH, Deng JX, Su H, Xu S, Liu JY. In vitro controlled release of sodium ferulate from compritol 888 ATO-based matrix tablets. Int J Pharm. 2006 Nov 6;324(2):152-7. doi: 10.1016/j.ijpharm.2006.06.006. PMID 16837152.