Mechanical, optical, and physicochemical properties of HPMC-based doxazosin mesylate orodispersible films
Keywords:Orodispersible films; Design of experiments; Doxazosin mesylate; FTIR; Mechanical properties; Desirability function
In this study, orodispersible films formed from hydroxypropyl methylcellulose (HPMC) E6 (2, 2.5, and 3%) and plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), containing doxazosin mesylate, were prepared by the solvent casting method and characterized. Design of experiments (DoE) was used as a statistical tool to facilitate the interpretation of the experimental data and allow the identification of optimal levels of factors for maximum formulation performance. Differential scanning calorimetry (DSC) curves and X-ray powder diffraction (XRPD) diffractograms showed doxazosin mesylate amorphization, probably due to complexation with the polymer (HPMC E6), and the glass transition temperature of the polymer was reduced by adding a plasticizer. Fourier transformed infrared (FTIR) spectroscopy results showed that the chemical structure of doxazosin mesylate was preserved when introduced into the polymer matrix, and the plasticizers, glycerin and PEG, affected the polymer matrix with high intensity. The addition of plasticizers increased the elongation at break and adhesiveness (Gly > PEG > PP), confirming the greater plasticizer effect of Gly observed in DSC and FTIR studies. Greater transparency was observed for the orodispersible films prepared using PP. The addition of citric acid as a pH modifier was fundamental for the release of doxazosin mesylate, and the desirability formulation had a release profile similar to that of the reference product.
Altiokka G. Voltammetric determination of doxazosin in tablets using rotating platinum electrode. J Pharm Biomed Anal. 2001;25(3-4):387-91.
ASTM D2582 - 16. In: Standard Test Method for Puncture-Propagation Tear Resistance of Plastic Film and Thin Sheeting [Internet]. Available from: https://www.astm.org/Standards/D2582.htm
ASTM D4541 - 17. In: Standard Test Method For Pull-Off Strength Of Coatings Using Portable Adhesion Testers [Internet]. Available from: https://www.astm.org/Standards/D4541.htm
ASTM D6132-13(2017). In: Standard Test Method for Nondestructive Measurement of Dry Film Thickness of Applied Organic Coatings Using an Ultrasonic Coating Thickness Gage [Internet]. Available from: https://www.astm.org/Standards/D6132.htm
Beuchat LR. Thermal Inactivation of Yeasts in Fruit Juices Supplemented with Food Preservatives and Sucrose. J Food Sci. 1982;47(5):1679-82.
Bharti K, Mittal P, Mishra B. Formulation and characterization of fast dissolving oral films containing buspirone hydrochloride nanoparticles using design of experiment. J Drug Deliv Sci Technol. 2019;49:420-32.
Biswas N, Guha A, Sahoo RK, Kuotsu K. Pulse release of doxazosin from hydroxyethylcellulose compression coated tablet: Mechanistic and in vivo study. Int J Biol Macromol. 2015;72:537-43.
Borges AF, Silva C, Coelho JFJJ, Simões S. Oral films: Current status and future perspectives: I-Galenical development and quality attributes. J Control Release 2015;28(206):1-19.
Candioti LV, de Zan MM, Cámara MS, Goicoechea HC. Experimental design and multiple response optimization. Using the desirability function in analytical methods development. Talanta. 2014;124:123-38.
Carvalho FC, Bruschi ML, Evangelista RC, Gremião MPD. Mucoadhesive drug delivery systems. Braz J Pharm Sci. 2010;46(1):1-17.
Cha KH, Tran TH, Kim MS, Kim JS, Park HJ, Park J, et al PH-independent sustained release matrix tablet containing doxazosin mesylate: Effect of citric acid. Arch Pharm Res. 2010;33(12):2003-9.
Chauhan K, Solanki R, Sharma S. A review on fast dissolving tablet. Int J Appl Pharm. 2018;10(6):1-7.
Chonkar AD, Bhagawati ST, Udupa N. An Overview on Fast Dissolving Oral Films. Asian J Pharm Technol. 2015;5(3):129-37.
Coelho BP, Gaelzer MM, dos Santos Petry F, Hoppe JB, Trindade VMT, Salbego CG, et al Dual Effect of Doxazosin: Anticancer Activity on SH-SY5Y Neuroblastoma Cells and Neuroprotection on an In Vitro Model of Alzheimer’s Disease. Neurosci. 2019;404:314-32
Dedroog S, Pas T, Vergauwen B, Huygens C, Van den Mooter G. Solid-state analysis of amorphous solid dispersions: Why DSC and XRPD may not be regarded as stand-alone techniques. J Pharm Biomed Anal. 2020;178:112937.
Dinge A, Nagarsenker M. Formulation and evaluation of fast dissolving films for delivery of triclosan to the oral cavity. AAPS PharmSciTech. 2008;9(2):349-56.
Dixit RP, Puthli SP. Oral strip technology: Overview and future potential. J Control Release . 2009;139(2):94-107.
Farooq MA, Nóvoa H, Araújo A, Tavares SMOO. An innovative approach for planning and execution of pre-experimental runs for Design of Experiments. Eur Res Manag Bus Econ. 2016;22(3):155-61.
Faulkner JK, Himanen P, Karjalainen U, Saraste M. The pharmacokinetics and pharmacodynamics of doxazosin compared with atenolol during long-term double-blind treatment. Eur J Clin Pharmacol. 1987;31(6):685-93.
Gittings S, Turnbull N, Henry B, Roberts CJ, Gershkovich P. Characterisation of human saliva as a platform for oral dissolution medium development. Eur J Pharm Biopharm. 2015;91:16-24.
Goethals PL, Cho BR. Extending the Desirability Function to Account for Variability Measures in Univariate and Multivariate Response Experiments. Comput Ind Eng. 2012;62(2):457-68.
Grčman M, Vrečer F, Meden A. Some physico-chemical properties of doxazosin mesylate polymorphic forms and its amorphous state. J Therm Anal Calorim. 2002;68(2):373-87.
Hazzah HA, EL-Massik MA, Abdallah OY, Abdelkader H. Preparation and characterization of controlled-release doxazosin mesylate pellets using a simple drug layering-aquacoating technique. J Pharm Investig. 2013;43(4):333-42.
Karki S, Kim H, Na S-JJ, Shin D, Jo K, Lee J. Thin films as an emerging platform for drug delivery. Asian J Pharm Sci. 2016;11(5):559-74.
Khalilullah H, Khan S, Nomani MS, Ahmed B. Synthesis, characterization and antimicrobial activity of benzodioxane ring containing 1,3,4-oxadiazole derivatives. Arab J Chem. 2016;9(Suppl 2):S1029-S1035.
Krampe R, Sieber D, Pein-Hackelbusch M, Breitkreutz J. A new biorelevant dissolution method for orodispersible films. Eur J Pharm Biopharm. 2016;98:20-5.
Mahadevaiah, Shivakumara LR, Demappa T, Vasudev S. Mechanical and Barrier Properties of Hydroxy Propyl Methyl Cellulose Edible Polymer Films with Plasticizer Combinations. J Food Process Preserv. 2017;41(4):1-10.
Morales JO, McConville JT. Manufacture and characterization of mucoadhesive buccal films. Eur J Pharm Biopharm. 2011;77(2):187-99.
Munjal B, Suryanarayanan R. Applications of synchrotron powder X-ray diffractometry in drug substance and drug product characterization. TrAC Trends Anal Chem. 2021;136:116181.
Musazzi UM, Khalid GM, Selmin F, Minghetti P, Cilurzo F. Trends in the production methods of orodispersible films. Int J Pharm. 2020;576:118963.
Preis M, Knop K, Breitkreutz J. Mechanical strength test for orodispersible and buccal films. Int J Pharm . 2014;461(1-2):22-9.
Pupe CG, do Carmo FA, de Sousa VP, Lopes M, Abrahim-Vieira B, Ribeiro AJ, et al Development of a doxazosin and finasteride transdermal system for combination therapy of benign prostatic hyperplasia. J Pharm Sci. 2013;102(11):4057-64.
Radebaugh GW, Murtha JL, Julian TN, Bondi JN. Methods for evaluating the puncture and shear properties of pharmaceutical polymeric films. Int J Pharm . 1988;45(1-2):39-46.
Ramaraj B, Nayak SK, Yoon KRJ. Poly(vinyl alcohol) and layered double hydroxide composites: Thermal and mechanical properties. Appl Polym Sci. 2010;116(3):1671-77.
Rani NS, Sannappa J, Demappa T, Mahadevaiah. Structural and ionic conductivity behavior in hydroxypropylmethylcellulose (HPMC) polymer films complexed with sodium iodide (NaI). AIP Conference Proceedings. 2013;1512(1):544-545.
Rowe RR, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. Sixth Edition. Revue des Nouvelles Technologies de l’Information. 2015.
Santana RF, Bonomo RCF, Gandolfi ORR, Rodrigues LB, Santos LS, dos Santos Pires AC, et al Characterization of starch-based bioplastics from jackfruit seed plasticized with glycerol. J Food Sci Technol. 2018;55(1):278-86.
Siddiqui MDN, Garg F, Sharma PK. A Short Review on “A Novel Approach in Oral Fast Dissolving Drug Delivery System and Their Patents.” Adv Biol Res. 2011;5(6):291-303.
Simionato LD, Petrone L, Baldut M, Bonafede SL, Segall AI. Comparison between the dissolution profiles of nine meloxicam tablet brands commercially available in Buenos Aires, Argentina. Saudi Pharm J. 2018;26(4):578-84.
Tuberoso CIG, Jerković I, Sarais G, Congiu F, Marijanović Z, Kuś PM. Color evaluation of seventeen European unifloral honey types by means of spectrophotometrically determined CIE-L*Cab*h(ab)° chromaticity coordinates. Food Chem. 2014;145:284-91.
Uhoraningoga A, Kinsella GK, Henehan GT, Ryan BJ. The goldilocks approach: A review of employing design of experiments in prokaryotic recombinant protein production. Bioengineering. 2018;5(89):1-27.
USP. U.S. Pharmacopoeia-National Formulary [USP 38 NF 33]. In: Rockville, Md: United States Pharmacopeial Convention. 2015.
Usui F, Maeda K, Kusai A, Nishimura K, Yamamoto K. Inhibitory effects of water-soluble polymers on precipitation of RS-8359. Int J Pharm . 1997;154(1):59-66.
Veiga F, Pecorelii C, Ribeiro LF, Pecorelii C, Ribeiro L. As Ciclodextrinas em Tecnologia Farmacêutica. 1a ed. MinervaCoimbra, editor. Coimbra; 2006.
Vincent J, Elliott H, Meredith P, Reid J. Doxazosin, an alpha 1-adrenoceptor antagonist: pharmacokinetics and concentration-effect relationships in man. Br J Clin Pharmacol. 1983;15(6):719-25.
Van Der Weerd J, Kazarian SG. Combined approach of FTIR imaging and conventional dissolution tests applied to drug release. J Control Release . 2004;98(2):295-305.
Wray PS, Clarke GS, Kazarian SG. Application of FTIR spectroscopic imaging to study the effects of modifying the pH microenvironment on the dissolution of ibuprofen from HPMC matrices. J Pharm Sci . 2011;100(11):4745-755.
Xie F, Ji S, Cheng Z. In vitro dissolution similarity factor (f2) and in vivo bioequivalence criteria, how and when do they match? Using a BCS class II drug as a simulation example. Eur J Pharm Sci . 2015;66:163-72.
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