A QbD assisted modified release formulation of Midodrine Hydrochloride for management of long-term hypotension
Abstract
Midodrine Hydrochloride (MDH) is primarily utilized for the treatment of orthostatic hypotension. The main objective of this research work is to study the effect of the ratio of Methocel 4M to 100M, PVP K-30, and magnesium stearate in extended-release (ER) layer of bilayer tablets of MDH. Bilayer tablets of MDH were optimized by the design of experiment (DoE) using response surface face centre (α = 1), the central composite design having three independent variables at three levels. Bilayer tablets of MDH were administered once a day to reduce dosing frequency and improve patient compliance. Midodrine Hydrochloride tablets contain a drug layer and extended-release layer, which is further compressed into bilayer tablets. Based on the results of in-vitro %drug release it can be concluded that the ratio of Methocel 4M to 100M in MDH bilayer tablets shows a significant impact on % drug release whereas the concentration of PVP K-30 and concentration of magnesium stearate does not shows significant impact on % drug release. As the increase in the ratio of Methocel 4M to 100M, increase in the % drug release and as a decrease in the ratio of Methocel 4M to 100M, decrease in the % drug release. The optimized formulation of MDH bilayer tablets with 6% of Methocel 4M as an extended-release polymer, 24% of Methocel 100M as an extended-release polymer, 5% of PVP K-30 as a binder and 0.5% of magnesium stearate as a lubricant exhibits extended drug release up to 12 hours.
Keywords:
Quality by Design, Central Composite Design, Modified release, Bilayer tablet, Midodrine Hydrochloride (MDH), Sustained hypotension.DOI
https://doi.org/10.25004/IJPSDR.2021.130510References
Samir J, Paresh B, Mukesh S, Mukesh R. A Review on Extended Release Drug Delivery System. W Jour of Pharma Research. 2015; 4(8):724-747.
Rohan D, Gowda D, Nawaz M, Deepak N. Bi-layer tablets- an emerging trend: a review. Int. J Pharm Sci and research. 2011; 2(10):2534- 2544.
Wilding I, Coupe A, Davis S. The role of gamma scintigraphy in oral drug delivery, Adv. Drug Deliv Rev. 1991; 7:87– 117.
Hamed B, Bharani S, Sepideh S A review on extended release matrix tablet. J Pharma Res. 2016; 15(4): 147-152.
Vishwakarma A, Mogal R, Pawar A. Bi-Layer Tablet - A New Ways in Oral Drug Delivery System. 2014; 6(5):1416-1428.
https://en.wikipedia.org/wiki/Orthostatic_hypotension. [cited 2018 Aug 11].
Barber D, Rogers S, Fredrickson M, Able A. Spinal Cord. 2000; 38, 109-111
Karen J, Lynda R, Michelle I. A Review of its Therapeutic Use in the Management of Orthostatic Hypotension. Drugs & Aging 1998; 12 (1):75-86.
Ko J, Park H, Park Y, Hwang S, Park J. Chitosan microparticle preparation for controlled drug release by response surface methodology. J Microencapsul 2003;20:791 7.
Bose A, Wong TW, Singh N. Formulation development and optimization of sustained release matrix tablet of Itopride HCl by response surface methodology and its evaluation of release kinetics. Saudi Pharm J 2013;21:201 13.
Monajjemzadeh F, Hamishehkar H, Zakeri Milani P, Farjami A, Valizadeh H. Design and optimization of sustained release divalproex sodium tablets with response surface methodology. AAPS PharmSciTech 2013;14:245 53.
Dhillon GS, Kaur S, Sarma SJ, Brar SK. Recent development in applications of important biopolymer chitosan in biomedicine, pharmaceuticals and personal care products. Curr Tissue Eng 2013;2:20 40.
Yue S, Su Fang T, Li Qin G. Optimization of release of salicylic acid calibrator tablets in flow through cell with central composite design. Chin J Pharm Anal 2009;29:1243 7.
Politis SN, Colombo P, Colombo G, Rekkas DM. Design of experiments (DoE) in pharmaceutical development. Drug Dev Ind Pharm. 2017; 43(6):889-901.
Gujral G, Kapoor D, Jaimini M. An updated review on design of experiment (DoE) in pharmaceuticals. J Drug Deliv Ther. 2018; 8(3):147-152.
Sunitha R, Krishna M, Dillip K, Muhammad F. Formulation development and evaluation of extended release bi-layer tablets of anti asthmatic drug-zileuton. Int J of Pharm and Bio Sci. 2018; 8(1): 227-236.
Avinash B, Sonali N, Jadhav R, Saudager R. Bilayer tablet technology: An overview. Int. J ChemTech Res. 2017; 10(5):595-603.
Marie W, Karin L, Erik V, Anna S, Stefan U. Oral based controlled release formulations using poly(acrylic acid) microgels. Drug dev and Ind Phar. 2009;35(8):922-929.
Published
Abstract Display: 520 
PDF Downloads: 544 
