DESIGN OF CONTROLLED RELEASE MUCOADHESIVE BUCCAL TABLETS OF IVABRADINE HCL USING SINTERING TECHNIQUE
Keywords:Sintering Technique, Mucoadhesive, Ivabradine, Controlled release
Objective: The objective of the present work was to study the use of the sintering technique, a relatively new concept in pharmaceutical sciences, in the development of mucoadhesive buccal tablets for ivabradine Hydrochloride.
Methods: The method consisted of blending drug, hydroxypropyl methylcellulose (HPMC K100M), carnauba wax, and other excipients followed by direct compression into tablets. The compressed fluffy matrices were sintered at two different constant temperatures like 50 °C and 60 °C for two different periods like 1.5 h and 3 h in a hot air oven. The effect of sintering on tensile strength, dissolution profile, and other parameters were studied. The drug-polymer-excipient compatibility was evaluated by Fourier transform Infrared (FTIR) and differential scanning calorimetric (DSC) studies.
Results: The sintering condition markedly affected the drug release properties, hardness, and friability of the tablets. Based on the f2 similarity factor value, Ex-vivo mucoadhesive strength, Ex-vivo residence time, and in vitro dissolution studies, formulation F3SD was selected as an optimized formulation. Drug release followed a non-Fickian diffusion mechanism with the Higuchi model release kinetics. Stability studies of mucoadhesive buccal tablets in normal human saliva indicated the stability of the drug and buccal tablet in the oral cavity. Stability studies as per ICH guidelines revealed that optimized formulation was stable on storage conditions.
Conclusion: The sintering technique provides a significant and convenient method for the development of a controlled release dosage form that can be used in the design of mucoadhesive buccal tablets of Ivabradine HCL.
Miller NS. The use of mucoadhesive polymers in buccal drug delivery. Ad Drug Delivery Rev 2005;57:1666-91.
Mario J, Lacan MB. Influence of hydroxyl propyl-β-cyclodextrin complexation on piroxicam release from buccoadhesive tablets. Eur J Pharm Sci 2004;21:251-60.
Harris, Robinson JR. Drug delivery via the mucous membrane of oral cavity. J Pharm Sci 1992;81:1-10.
Tocker G. A method to study the kinetic of oral mucosal drug absorption for solution. Chem Pharm Bull 1998;40:679-83.
Junginger HE, Hoogstrate JA, Verhoef JC. Recent advances in buccal drug delivery and absorption in vitro and in vivo studies. J Controlled Release 1999;62:149-59.
Shojael H. Buccal mucosa as route for systemic drug delivery–a review. J Pharm Sci 1998;1:15-30.
Shafi S, Chowdary KA, Shivappa N, Hangargekar S. Formulation and evaluation of sintered matrix tablets of diltiazem hydrochloride. Int J Appl Pharm 2011;3:16-9.
Rao MRP, Shivpuje S, Godbole R, Shirsath C. Design and evaluation of sustained release matrix tablet using sintering technique. Int J Pharm Pharm Sci 2016;8:115-21.
Mohanty C. Sintering technique in pharmaceutical sciences: a brief review. Int J Pharmatech 2011;3:799-806.
Gordon F Rushworth, Philippe Lambrakis, Stephen J Leslie. Ivabradine: a new rate-limiting therapy for coronary artery disease and heart failure. Adv Drug Safety 2010;1:1-10.
Janet Marianne Jackson. Ivabradine–a novel treatment for chronic stable angina. Drugs Context 2008;4:135–52.
Lodhi M, Dubey A, Narayan R, Prabhu P, Priya S. Formulation and evaluation of buccal film of Ivabradine hydrochloride for the treatment of stable angina pectoris. Int J Pharma Investing 2013;3:47-53.
Dattatreya BU, Hiremath SN, Rao KS, Pawar D. Formulation and in vitro evaluation of Buccoadhesive tablets contaning ketoconazole inclusion complex with β-cyclodextrins. Res J Pharm Tech 2009;2:396-404.
Bhamre V, Sherkar D, Derle D, Narkhede M. Stability study of stavudine sintered matrix tablet. Int Res J Pharm 2013;4:182-5.
Bottenberg P, Cleymaet R, Muynek CD, Remon JP, Coomans D, Slop D, et al. Development and testing of bioadhesive, fluoride-containing slow-release tablets for oral use. J Pharm Pharmacol 1991;43:457-64.
Kumar BP, Kavitha P, Devi KJ. Formulation design and evaluation of mucoadhesive buccal tablets of nitroglycerin. Int J Pharm Pharm Sci 2014;6:251-9.
Patel DM, Shah PM, Patel CN. Formulation and evaluation of bioadhesive buccal drug delivery of repaglinide tablets. Asian J Pharm 2012;6:171-9.
Mohanty C, Subrahmanyam KV, Jena TK, Sreekanth D. Use of sintering technique to sustain the release of atazanavir sulphate from gastro retentive floating matrix tablets. Am J Pharmatech Res 2015;5:587-607.
Bhowmik M, Baisya O, Deb J. Formulation and evaluation of sustained release matrix tablet of atenolol based on natural polymer. Res J Pharm Bio Chem Sci 2012;13:878-86.
Uhumwangho MU, Ramana Murthy KV. Release characteristics of diltiazem hydrochloride wax-matrix granules-thermal sintering effect. J Appl Sci Manage 2011;15:365-70.
Penjuri SCB, Damineni S, Ravouru N. Design and development of buccal mucoadhesive drug delivery system of perindopril. J Pharm Sci 2015;8:37-49.
Biswal B, Karna N, Bhavsar B. Formulation and evaluation of Repaglinide buccal tablet: ex vivo bioadhesion study and ex vivo permeability study. J Appl Pharm Sci 2014;4:96-103.
Velmurugan S, Srinivas P. Formulation and evaluation of losartan potassium mucoadhesive buccal tablets. Asian J Pharm Clin Res 2013;6:125-30.
Goud K, Desai H, Pramod Kumar TM. Preparation and evaluation of a novel buccal adhesive system. AAPS PharmSciTech 2004;5:1-9.
Rowe RC, Sheskey PJ, Quinn ME. Handbook of pharmaceutical excipients, 6th ed. London: Pharmaceutical Press; 2009.
Meka VS, Songa AS, Nail SR, Battu JR, Kukati L, Kolapalli VRN, et al. Thermal sintering: a novel technique in the design of gastro retentive floating tablets of proprannlol HCL and its evaluation. Invest Clin 2012;53:223-36.
Meka VS, Songa AS, Nail SR, Battu JR, Kolapalli VRN. Thermal sintering: a novel technique used in the design, optimization and biopharmaceutical evaluation of propranolol HCl gastric floating tablets. Drug Dev Ind Pharm 2014;40:33–45.