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Development of Rizatriptan Mouth Dissolving Films:A Fast Absorbing Drug Delivery System for Effective Treatment of Migraine
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The aim of this investigation was to develop Rizatriptan (RIZ) mouth dissolving films (MDFs)and evaluate the effect of formulation variables like film thickness, plasticizers, film formers and solubilizing agents on physico-mechanical, chemical and drug release properties of MDFs. MDFs were prepared (using wet film applicator, a commercially scalable technique) using Hydroxy propyl methyl cellulose (HPMC) of different viscosity grades (E3, E5 and E15) as film former, PEG 400 and glycerol as plasticizers. FTIR studies showed no RIZ-excipient interactions in the MDF formulations. Photomicrographs together with DSC and X-RD studies confirmed the absence of RIZ recrystallization within the MDFs. MDFs of higher film thickness were brittle with low tensile strength values indicating an inverse relationship between film thickness and tensile strength. Whereas, increase in polymer viscosity increased the tensile strength of MDFs and about a 2.6fold increase in tensile strength was obtained with HPMC E15 MDFs compared to E3. In vitro drug release studies revealed that higher film thickness and polymer viscosities delayed the RIZ release from MDFs and the release was in the order of E3>E5>E15. Addition of solubilizing agents (PVP K30 and SLS) to the E3 formulations resulted in 2 and 1.43 fold faster RIZ release compared to formulations without them. Overall, F11 formulation (1% w/w RIZ+7.5% w/w HPMC E3+0.04% w/w PVP K30+0.5% w/w PEG 400) showed faster disintegration (within 8sec) and RIZ release rates (complete release was obtained in 60sec) compared to other formulations. The MDFs showed 98-102% RIZ content even after 6months time period indicating that the RIZ was stable in MDF formulations.
Keywords
Rizatriptan, Mouth Dissolving Films, Wet Film Applicator, Tensile Strength, Film Thickness, Polymer Viscosity.
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- Goadsby PJ, Lipton RB, Ferrari MD. Migraine: current understanding and treatment. N. Engl. J. Med. 2002; 346: 257-270.
- Moskowitz MA. The neurobiology of vascular head pain. Ann Neurol.1984; 16:157-168.
- Goadsby PJ, Edvinsson L, Ekman R. Release of vasoactive peptides in the extracerebral circulation of man and the cat during activation of the trigemino vascular system. Ann. Neurol.1988; 23:193-196.
- Goadsby PJ. The pharmacology of headache. Prog. Neurobiol.2000; 62:509-525.
- Akerman S, Holland P, Goadsby PJ. Diencephalic and brainstem mechanisms in migraine. Nat. Rev. Neurosci.2011; 12:570-584.
- Goldberg MR. Rizatriptan, a novel 5-HT1B/1D agonist for migraine; Single and multiple dose tolerability and pharmacokinetics in healthy subjects. J. Clin. Pharmacol.2000; 40:74-83.
- De Hoon JN, Willigers JM, Troost J, Struijker-Boudier HA, Van Bortel LM. Vascular effects of 5-HT1B/1D receptor agonists in patients with migraine headaches. Clin. Pharmacol. Ther.2000; 68:418-426.
- Tokola RA, Neuvonen PJ. Effect of migraine attacks on paracetamol absorption. Br. J. Clin. Pharmacol. 1984; 118:867-871.
- Cheng YS, Yeh HC, Guilmette RA, Simpson SQ, Cheng KH, Swift DL. Nasal deposition of ultrafine particles in human volunteers and its relationship to airways geometry. Aerosol. Sci. Technol.1996; 25:274-291.
- Raj TJ, Bharathi Ch, Kumar MS, Prabahar J, Kumar PN, Sharma HK, Parikh K. Identification, isolation and characterization of process related impurities in Rizatriptan benzoate. J. Pharm. Biomedical. Anal.2009; 49:156-162.
- Rathbone MJ, Drummond BK, Tucker IG. The oral cavity as a site for systemic drug delivery. Adv. Drug. Deliv. Rev.1994; 13:1-22.
- Liang AC, Chen LH. Fast-dissolving intraoral drug delivery systems.Expert.Opin.Ther.Pat.2001; 11:981-986.
- Patel AR, Prajapati DS, Raval JA. Fast dissolving films as a newer venture in fast dissolving dosage forms. Int. J. Drug. Dev. Res.2010; 2:232-246.
- Borsadia SB, Halloran DO, Osborne JL. Quick dissolving films-a novel approach to drug delivery.Drug.Deliv.Technol.2003;3:63-66.
- Cilurzo F, Cupone IE, Minghetti P, Selmin F, Montanari L. Fast dissolving films made of maltodextrins. Eur. J. Pharm. Biopharm.2008; 70:895-900.
- Arya A, Chandra A, Sharma V, Pathak K.Fast dissolving oral Films: An Innovative Drug Delivery System and Dosage Form.Int. J. Chem. Tech. Res.2010; 2:576-583.
- Karthikeyan D, Sanju S, Santhosh. Development of fast dissolving oral film containing of Rizatriptan Benzoate as an anti-migraine medication. Indo American Journal of Pharm Research.2013; 3:2642-2654.
- Prasana D K, Brahmaiah B, Sreekanth N, Nagalakshmi A. Formulation and evaluation of fast dissolving films of Rizatriptan. Int. J. Pharm. Res. Bio-Sci.2013; 2:298-305.
- Bhupinder B, Sartia J. Formulation and evaluation of fast dissolving sublingual films of Rizatriptan Benzoate. Int. J. Drug. Dev. Res.2012; 4:133-144.
- Na DH, Faraj J, Capan Y, Leung KP, DeLuca PP. Chewing gum of antimicrobial decapeptide (KSL) as a sustained antiplaque agent: Preformulation study. J. Controlled Release.2005; 107:122-130.
- El-Setouhy DA, El-Malak NSA. Formulation of a novel tianeptine sodium orodIspersible film. AAPS PharmSciTech.2010; 11:1018-1025.
- Choudhary DR, Patel VA, Patel HV, Kundawala AJ. Formulation and evaluation of quick dissolving film of Levocetirizinedihydrochloride. Int. J. Pharm. Technol.2011; 3:1740-1749.
- Gavaskar B, Kumar SV, Sharan G, Madhusudan Y. Overview on fast dissolving films. Int. J. Pharm.Pharm.Sci.2010; 2:29-33.
- Vidyadhara S, Sasidhar RL, Balakrishna T, Santha Vardhan M. Formulation of rizatriptan benzoate fast dissolving buccal films by emulsion evaporation technique. Int. J. Pharm. Investig.2015; 5:101-106.
- Lapidus H, Lording. Drug release from compressed hydrophilic matrices. J. Pharm.Sci.1966; 55:840-843.
- Higuchi T. Mechanism of sustained action medication. Theoretical analysis of rate of release solid drugs dispersed in solid matrices. J. Pharm.Sci.1963; 52:1145-1148.
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