PART II: OPTIMIZATION OF ISOSORBIDE DINITRATE SUSTAINED RELEASE LAYER IN ANTIHYPERTENSIVE BILAYER TABLET

  • HARSH TRIVEDI Shree Swaminarayan Sanskar Pharmacy College, Zundal, Gandhinagar, Gujarat, India
  • KUNAL PATEL Shree Swaminarayan Sanskar Pharmacy College, Zundal, Gandhinagar, Gujarat, India
  • NISHANT A. OZA C. U. Shah University, Wadhwan City, Gujarat, India 363030
  • SWATI SAGAR C. U. Shah University, Wadhwan City, Gujarat, India 363030

Abstract

Objective: Aim of the present study was the optimization of the sustained release (SR) layer of isosorbide dinitrate (ISDN) 40 mg and compressed with the immediate-release (IR) layer of hydralazine hydrochloride (HHC) 25 mg to decrease the dosing frequency and development of a novel b. i. d dosage form.


Methods: Drug excipients compatibility study was carried out by FT-IR and a preliminary study was conducted for screening of polymer. The amount of HPMC K100M (X1) and the amount of Polyoxtm WSR303 (X2) were chosen as independent variables in 32full factorial designs. While % cumulative drug releases at 1 h (Q1) (Y1), % cumulative drug release at 2 h (Q2) (Y2), % cumulative drug release at 4 h (Q4) (Y3) and % cumulative drug release at 6 h (Q6) (Y4), were taken as dependent variables and statistically evaluation by using sigma plot 13.0. In the present study, according to the U. S. P. 2007 the following constraints were used for the selection of an optimized batch: Q1=15% to 30%, Q2=50% to 70%, Q4=65% to 85% and Q6>75%. To validate the evolved mathematical models, a checkpoint batch was selected from its desirability value.


Results: FT-IR spectra show that the drug and excipients were compatible with each other. The calculated F values found for Q1, Q2, Q4, and Q6 were 084.583, 038.188, 057.719, and 118.396, respectively. All Calculated F values are greater than the tabulated value for all dependent variables. Prepared checkpoint batch selected from its desirability value 1 and it gives a 93.40±1.29 % drug release within 6 h.


Conclusion: This bilayer formulation of anti-hypertensive drugs decreases the dosing frequency of HHC and ISDN.

Keywords: Bilayer tablet, 32 Full factorial design, Hydralazine hydrochloride, Isosorbide dinitrate, Sustained release layer

References

1. Jamie K, Rachael F, Katherine L, Tucker, Richard J, McManus. New approaches in hypertension management: a review of current and developing technologies and their potential impact on hypertension care. Curr Hypertens Rep 2019;21:1-8.
2. Taddei S. Combination therapy in hypertension: what are the best options according to clinical pharmacology principles and controlled clinical trial evidence? Am J Cardiovasc Drugs 2015;15:185-94.
3. Carmody MS, Anderson JR. BiDil (isosorbide dinitrate and hydralazine): a new fixed-dose combination of two older medications for the treatment of heart failure in black patients. Cardiol Rev 2007;15:46-53.
4. Cheng JW. A review of isosorbide dinitrate and hydralazine in the management of heart failure in black patients, with a focus on a new fixed-dose combination. Clin Ther 2006;28:666-78.
5. Momin S, Khan S, Ghadage D, Yadav A, Wagh A. Formulation and evaluation of bilayer tablets of propranolol hydrochloride. J Drug Delivery Ther 2017;7:50-7.
6. D Radhika, A Mohaideen, Manoj KR, Bhanu PS, Jahan Nur, Rahman H. Development of bi-layer tablets for immediate and controlled release of allicin. Int J Curr Pharm Res 2017;9:153-60.
7. Harika R, S Dineshmohan, Alluri Ramesh, VRM Gupta. Formulation and in vitro evaluation of bilayer tablets of nebivolol hydrochloride and nateglinide for the treatment of diabetes and hypertension. J Drug Delivery 2015:1-14. DOI:10.1155/2015/827859
8. SN Politis, P Colombo, G Colombo, DM Rekkas. Design of experiments (DoE) in pharmaceutical development. Drug Dev Ind Pharm 2017;43:889-901.
9. Kamble S, Poul B, Udapurkar P. Bilayer tablet of tramadol and gabapentin for combination pharmacotherapy of neuropathic pain: development and characterization. Int J Appl Pharm 2018;10:100-7.
10. Kulkarni AMT, Aloorkar N. Application of novel natural polymer for controlling the release of fenoverine from controlled release matrix tablets. Int J Appl Pharm 2017;9:1-9.
11. Karad BB, Shinde AD. Formulation and evaluation of an immediate-release tablet of levonorgestrel. Indo Am J Pharm Res 2017;7:471-9.
12. Kumar GH, Jaganathan K, Kumar RS, Perumal P. Formulation and in vitro evaluation of bilayer floating tablets of metformin hydrochloride and sitagliptin phosphate. Int J Adv Pharm 2012;2:64-81.
13. Sarfaraz Md, Reddy PKC, Udupi RH, Doddayya H. Formulation and in vitro evaluation of bilayer floating tablets of tramadol hydrochloride. Int J Drug Dev Res 2012;4:335-47.
14. Nivedithaa VR, Maanvizhi S. Formulation and evaluation of immediate-release combination tablet for cardiovascular diseases. Res J Life Sci Bioinf Pharm Chem Sci 2018;4:176-90.
15. Fridrun P. Theoretical and experimental investigations into the delamination tendencies of bilayer tablets. Int J Pharm 2011;408:102-12.
16. Neelima K, Prasad YR. Analytical method development and validation for simultaneous estimation of Hydralazine, Isosorbide dinitrate in bulk and tablet formulation by RP-HPLC. Int J Pharm Sci Res 2014;5:1290-4.
17. Kamble SR, Poul BN, Udapurkar PP. Fabrication and evaluation of bilayer floating tablet containing conventional ibuprofen and modified-release pregabalin for combination pharmacotherapy of neuropathic pain. Asian J Pharm 2016;10:290-9.
18. Saripilli R, Kudamala S, Murthy KVR. Development, formulation and evaluation of a bilayer gastric retentive floating tablets of ranitidine HCl and clarithromycin using natural polymers. Int J Pharm Pharm Sci 2017;9:164-77.
19. R Mazzeo, S Prati, M Quaranta, E Joseph, E Kendix, M Galeotti. Attenuated total reflection micro FTIR characterization of pigment–binder interaction in reconstructed paint films. Anal Bioanal Chem 2008;392:65-76.
20. Dnyaneshwar DG, Deshmukh MT, Solunke RS, Shete RV. Formulation and evaluation of antihypertensive bilayer tablets. Int J Pharm Sci Res 2019;10:4760-75.
21. Bolton S, Bon C. Pharmaceutical statistics: practical and clinical applications. 5th ed. Informa Healthcare; 2005. p. 472-93.
22. Mandlik SK, Dandgavhal HP. Enhancement of skin permeability of econazole nitrate using novel flexisomal nanocarriers by implementing quality by design (QbsD) approach. Int J Appl Pharm 2019;12:123-33.
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TRIVEDI, H., PATEL, K., OZA, N. A., & SAGAR, S. (2020). PART II: OPTIMIZATION OF ISOSORBIDE DINITRATE SUSTAINED RELEASE LAYER IN ANTIHYPERTENSIVE BILAYER TABLET. International Journal of Applied Pharmaceutics, 12(5), 219-226. https://doi.org/10.22159/ijap.2020v12i5.38098
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