PART I: OPTIMIZATION OF HYDRALAZINE HYDROCHLORIDE IMMEDIATE RELEASE LAYER IN ANTIHYPERTENSIVE BILAYER TABLET
Keywords:Bilayer tablet, 32 Full factorial design, Immediate release, Hydralazine hydrochloride, Isosorbide dinitrate
Objective: Aim of the present study was the optimization of the immediate release (IR) layer containing hydralazine hydrochloride (HHC) 25 mg and compressed with a sustained-release (SR) layer of isosorbide dinitrate (ISDN) 40 mg to decrease the dosing frequency.
Methods: In this study, Drug-excipients compatibility study was carried out by FT-IR and a preliminary trial was conducted for screening of super disintegrating agents. The amount of sodium starch glycolate (SSG) (X1) and the amount of ac-di-sol® (X2) was chosen as independent variables in 32 full factorial design while wetting time (WT) (Y1), disintegration time (DT) (Y2) and In vitro drug release at 15 min (Q15) (Y3) were taken as dependent variables. Multiple linear regression analysis, ANOVA, and graphical representation of the influence of factor by 3D plots were performed by using sigma plot 13.0. In the present study, the following constraints were used for the selection of an optimized batch: WT<16 s, DT<25 s, and Q15>90%. 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 WT, DT, and Q15 were 045.559, 077.100 and 278.760, respectively. All Calculated F values are greater than tabulated values for all dependent variables. Prepared checkpoint was selected from its desirability value 0.935 and it gives a 100% drug release within 30 min.
Conclusion: These results confirm that the prepared HHC 25 mg IR layer is used for rapid control of hypertension.
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.
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.
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.
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.
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.
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.
Harika R, S Dinesh Mohan, 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
SN Politis, P Colombo, G Colombo, DM Rekkas. Design of experiments (DoE) in pharmaceutical development. Drug Dev Ind Pharm 2017;43:889-901.
Balaji R, Asra F, Babu MS. Formulation development and evaluation of immediate-release tablets of telmisartan. World J Pharm Pharm Sci 2017;6:659-73.
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.
Karad BB, Shinde AD. Formulation and evaluation of an immediate-release tablet of levonorgestrel. Indo Am J Pharm Res 2017;7:471-9.
Devender C, Dinesh K. Bilayer tablet tendered immediate release of paracetamol and sustained release of ibuprofen for quick onset of action against pain and fever. Asian J Pharm Clin Res 2019;12:166-74.
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.
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.
Fridrun P. Theoretical and experimental investigations into the delamination tendencies of bilayer tablets. Int J Pharm 2011;408:102-12.
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.
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.
Karim S, Bosu A, Biswas A, Laboni FR, Julie AS, Rashid MHO. Effect of sodium starch glycolate on the formulation of fexofenadine hydrochloride immediate-release tablets by direct compression method. J Sci Res 2018;10:31-8.
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.
Dnyaneshwar DG, Deshmukh MT, Solunke RS, Shete RV. Formulation and evaluation of antihypertensive bilayer tablet. Int J Pharm Sci Res 2019;10:4760-75.
Bolton S, Bon C. Pharmaceutical statistics: practical and clinical applications. 5th ed. Informa Healthcare; 2005. p. 472-93.
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.