OPTIMIZATION OF FORMULATION OF SOLID DISPERSION OF FUROSEMIDE BY FACTORIAL DESIGN
DOI:
https://doi.org/10.22159/ijpps.2020v12i4.36428Keywords:
Furosemide, Dissolution, Hydrogen bonding, Solid dispersionAbstract
Objective: The present study aimed to improve the rate of dissolution of furosemide by solid dispersion technique.
Methods: Solid dispersion of furosemide was prepared by using hydrogel isolated from the seeds of Lepidium sativum as a novel carrier by the solvent evaporation method. Solid dispersion was evaluated to study the improvement in the rate of dissolution. Molecular dispersion of furosemide in the novel carrier was studied by DSC and FTIR studies. Solid dispersion was filled in capsules after stability studies and the formulation was optimized by adopting factorial design.
Results: Solid dispersion of furosemide exhibited dissolution improvement from 13.54 % (plain furosemide) to 69.12% (solid dispersion) in the first 60 min. Improvement in dissolution efficiency was found to be retained after stability studies. Capsules were filled with the formulation of solid dispersion using two different grades of lactose-α lactose monohydrate and anhydrous lactose and were found stable after stabilization studies.
Conclusion: The dissolution improvement of furosemide was attributed to its molecular dispersion in the novel carrier selected for this study. The recrystallization of furosemide was prevented due to intermolecular interaction between the novel carrier and furosemide. This was confirmed by FTIR. Evaluation of the dissolution data of factorial batches was analyzed by ANOVA. Analysis of the data revealed that selected levels of α lactose monohydrate and anhydrous lactose would be useful to navigate design space.
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Charalabidis A, Sfouni M, Christel Bergström C, Macheras P. The Biopharmaceutics Classification System (BCS) and the Biopharmaceutics Drug Disposition Classification System (BDDCS): beyond guidelines. Int J Pharm 2019;566;264-81.
Butler JM, Dressman JB. The developability classification system: Application of biopharmaceutics concepts to formulation development. J Pharm Sci 2010;99:4940-54.
Gurunath S, Pradeep Kumar S, Basavaraj NK, Patil PA. Amorphous solid dispersion method for improving oral bioavailability of poorly water-soluble drugs. J Pharm Res 2013;4:476-80.
Razmkhah S, Razavi SMA, Mohammadifar MA, Koocheki A, Ale MT. Stepwise extraction of Lepidium sativum seed gum: Physicochemical characterization and functional properties. Int J Biol Macromol 2016;88:543-64.
Srinarong P, Faber JH, Visser MR, Hinrichs WLJ, Frijlink HW. Strongly enhanced dissolution rate of fenofibrate solid dispersion tablets by incorporation of superdisintegrants. Eur J Pharm Biopharm 2009;73:154-61.
Vikas A Saharan, Vipin Kakkar, Mahesh Kataria, Manoj Gera, Pratim K Choudhury. Dissolution enhancement of drugs-part i: technologies and effect of carriers. J Health Res 2009;2:107-24.
Patel HH, Kardile D, Puvar AN, Prajapati RK, Patel MR. Lepidium sativum: natural superdisintegrant for fast dissolving technology. Int J Pharm Appl Sci 2011;2:56–62.
Jermain SV, Brough C, Williams RO. Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery–an update. Int J Pharm 2018;535:379-92.
Hebbink G, Dikhoff HJ. Chapter 5-application of lactose in the pharmaceutical industry evolutionary role. Health Effects and Applications; 2019. p. 175-229.
Petrovick PR, Jacob M, Gaudy D, Bassani VL, Guterres SS. Influence of adjuvants on the in vitro dissolution of hydrochlorothiazide from hard gelatin capsules. Int J Pharm 1991;76:49-53.
Kokilambigai KS, Laxmi KS. A QbD assisted spectro-photometric methods for the quantification of cefixime trihydrate using two oxidative coupling agents. Asian J Pharm Clin Res 2019;12:234-42.
Vasconcelos T, Marques S, Das Neves J, Sarmento B. Amorphous solid dispersions: Rational selection of a manufacturing process. Adv Drug Delivery Rev 2016;12:85-101.
U. S. P. National Formulary. Vol. 2; 2014. p. 3102-3.
Parfati N, Rani KC, Charles N, Geovanny V. Preparation and evaluation of Atenolol β-cyclodextrin orally disintegrating tablets using coprocessed crospovidone-sodium starch glycolate. Int J Appl Pharm 2018;10:190-4.
ICH Q8 (R2), Stability testing of new drug substances and products; 2003. Available from: http://www.ich.org [Last accessed on 10 Oct 2019].
De Muth JE. Factorial design: an introduction. In: Basic statistics and pharmaceutical statistical applications. New York: CRC Press; 2014. p. 269-308.
Bolton S, Bon C. Factorial designs. In: Pharmaceutical Statistics: Practical and Clinical Applications. New York: Marcel Dekker; 2009. p. 222-39.
Razmkhah S, Razavi SMA, Mohammadifar MA, Arash K, Ale MT. Stepwise extraction of Lepidium sativum seed gum: Physicochemical characterization and functional properties. Int J Bio Macromol 2016;88:553-64.
Behrouzian F, Razavi SMA, Phillips GO. Cress seed (Lepidium sativum) mucilage, an overview. Bio Ca Die Fib 2014;3:17-8.
Abdulrahman M, Fahad J, Khalid A. Furosemide. In: Florey K, Al-Badr AA, Forcier GA, Brittain HG, Grady LT. editors. Analytical profiles of drug substances. New Jersey: Academic Press, Inc; 1990. p. 153-84.
Dwi S, Retno S, Helmy Y, Riesta P. Preparation and characterization of Artesunate Nicotinamide cocrystal by Solvent evaporation and slurry method. Asian J Pharm Clin Res 2014;07:62-5.
Gupta SP. Tests of significance for small samples. In: Statistical methods. New Delhi: Sultan Chand and Sons; 1994. A.3.31-A.3.71.
Chan SY, Chung YY, Cheah XZ, Tan EYL, Quah J. The characterization and dissolution performances of spray-dried solid dispersion of ketoprofen in hydrophilic carriers. Asian J Pharm Sci 2015;10:372-85.
Jermain SV, Brough C, Williams RO. Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery–an update. Int J Pharm 2018;535:379-92.
Shirke SH, Shewale SB, Kulkarni AS, Aloorkar NH. Solid dispersion: a novel approach for poorly water soluble drugs. Int J Curr Pharm Res 2015;7:1-8.
Zhang D, Lee YC, Shabani Z, Lamm CF, Zhu W, Li Y, et al. Processing impact on the performance of solid dispersions. Int J Pharm 2018;142:1-13.
Hebbink G, Dikhoff HJ. Chapter 5-application of lactose in the pharmaceutical industry evolutionary role. In: Health Effects, and Applications; 2019. p. 175-229.
Kubbinga M, Moghani L, Langguth P. Novel insights into excipient effects on the biopharmaceutics of APIs from different BCS classes: lactose in solid oral dosage forms. Eur J Pharm Sci 2014;61:27-31.