Development of Sublingual tablets of Bisoprolol Hemifumarate / Hydroxypropyl -β-Cyclodextrin Complex for Potential treatment of Angina Pectoris

Rasha Mohamed Kharshoum, Adel A Ali

Abstract


Fast-disintegrating tablet drug delivery is gaining an importance for drug delivery technology especially for geriatric and pediatric patient because of swallowing difficulties.   In certain diseases such as hypertension and angina pectoris therapy, taking a fast pharmacological response is of important criteria. Thus, the aim of the present work was to prepare a novel fast disintegrating Bisoprolol Hemifumarate (BH) tablet formulation for sublingual administration based on the use of 2-hydroxypropyl-βcyclodextrin (HP-βCD) which forms an inclusion complex with (BH) to improve the permeability of the drug to sublingual membrane, in addition to mask the taste of the drug through the inclusion complex.  Attempt has been made to prepare fast disintegrating tablets of (BH) using superdistintegrants like crosscarmellose sodium and crospovidone in concentration of (5%). Eight different formulae (B1-B8) with variation in tablet excipients were prepared by direct compression method using different mucoadhesive polymers such as chitosan and polyethylene glycol 6000 at different concentration (3% and 6%) for reduction the flushing action of saliva and to provide enough contact time for drug to be absorbed. The tablets were evaluated for the weight variation, hardness, friability, wetting time, disintegration time and dissolution study. The formulae B2 and B7 possessed the lowest disintegration time due to the presence of the high concentration of chitosan, which has some disintegration action, thus were subjected to a pharmacokinetic study using human volunteers. The bioavailability of B2 was significantly higher than that of the reference (Concor®) (p > 0.05).  Thus, the present investigations suggest that (BH) sublingual tablets allowed the rapid tablet disintegration, improved bioavailability and effective in emergency treatment of anginal pain and hypertension.


Keywords


Sublingual tablets, Bisoprolol Hemifumarate, 2-hydroxypropyl-ß-cyclodextrin, inclusion complex, Bioavailability

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References


. Shojaei AH. Buccal mucosa as a route for systemic drug delivery: a review. J Pharm Pharm Sci., 1998. 1(1): p. 15-30.

. Rajat Sharma MY. Formulation and Evaluation of Fast Disintegrating Sublingual Tablets of Glipizide: An Attempt to Treat Diabetic Coma. International Journal of ChemTech Research 2010. 2: 2026-2033.

. Sean C, and Sweetman A, "Martindale The Complete Drug Refrences" 35th edited by Phamaceutical Press, 2006. p875.

. Prichard BN. Bisoprolol: a new beta-adrenoceptor blocking drug. Eur. Heart J. Suppl 1M., 1987. 121(9).

. Challa R, Ahuja A, Ali J, and Khar RK. Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech , Article 34, 2005. 6(2): E329-E357.

. Nagarsenker MS, Meshram RN. Solid dispersion of hydroxypropyl beta-cyclodextrin and ketorolac: enhancement of in-vitro dissolution rates, improvement in anti-inflammatory activity and reduction in ulcerogenicity in rats. J. Pharm. Pharmacol., 2000. 52(8):949-956.

. Szejtli JS. Elimination of bitter, disgusting tastes of drugs and foods by cyclodextrins. Eur. J. Pharm. Biopharm, 2005. 61(3): 115-125.

. Szejtli J, Szente L. Elimination of bitter, disgusting tastes of drugs and foods by cyclodextrins. Eur J Pharm Biopharm, 2005. 61(3): 115-125.

. Fu Y, Jeong SH, Kimura S, Park K. Orally fast disintegrating tablets: developments, technologies, taste-making and clinical studies. Crit Rev Ther Drug Carrier Syst., 2004. 21: 433-476.

. Nagarsenker MS, Joshi MS. Celecoxib-cyclodextrin systems: characterization and evaluation of in vitro and in vivo advantage. Drug Dev. Ind. Pharm., 2005. 31(2):169-178.

. Kottke MK, Rudnic EM. Tablet Dosage Forms, in Modern Pharmaceutics, G.S. Banker, and Rhodes C.T., Editor. 2002, Marcel Dekker Inc.: New York. p. 437-511.

. Alderborn G. Tablets and compaction, in: Pharmaceutics the Science of Dosage Form Design, M.E. Aulton, Editor. 2002, Churchill Livingstone: Edinburgh. p. 397-439.

. Schiermeier S, Schmidt PC. Fast dispersible ibuprofen tablets. Eur J Pharm Sci, 2002. 15(3): 295-305.

. Braza AJ, Modamino PM , Lastrras CF, and Marino EL. Development ,validation and analytical error fuction of two chromotagraphic methods with fluorimetric detection for the determination of bisoprolol and metoprolol in human. Biomed.Chromatogr., 2002. 16: 517-522.

. Liu L and Zhu S. Preparation and characterization of inclusion complexes of prazosin hydrochloride with beta-cyclodextrin and hydroxypropyl-beta-cyclodextrin. J Pharm Biomed Anal, 2006. 40(1): 122-127.

. Jun SW, Kim MS, Kim JS, Park HJ, Lee S, Woo S. and Hwang SJ. Preparation and characterization of simvastatin/hydroxypropyl-β-cyclodextrin inclusion complex using supercritical antisolvent (SAS) process. . Eur. J. Pharm. Biopharm, 2007. 66(3):413-421.

. Glomot F, Benkerrour L, Duchêne D, and Poelman M. Inclusion of retinoic acid in β-cyclodextrin Int. J. Pharm. , 1989. 54(2): 175-179

. Leonardi D, Lamac MC, Salomn CJ. Development of prednisolone PEG 6000 fast release tablets from solid dispersions: solid state characterization, dissolution behavior and formulation parameters. AAPS Pharm Sci Tech., 2007. 8(4 ):Article 108.

. Mannila J, Järvinen T, Järvinen K, and Jarho P. Sublingual administration of Δ9-tetrahydrocannabinol/h-cyclodextrin complex increases the bioavailability of Δ9-tetrahydrocannabinol in rabbits. Life Sciences, 2006. 78: 911-1914

. Jacobsen J, Christrup L, and Jensen N. Medicated chewing gum: pros and cons Am J Drug Delivery, 2004. 2(2): p. 75-88.

. Loftsson T, Jarho P, Masson M, and Jarvinen T. Cyclodextrins in drug delivery. Exp. Opinion Drug Del, 2005. 2: 335-351.

. Senel S, Hincal A. Drug permeation enhancement via. buccal route: Possibilities and limitations. J. Control. Rel., 2001. 72:133-144.


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