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and most importantly, patient compliance. Combinational therapy have been found to have various advantages over
monotherapy such as problem of dose-dependent side effects is minimized, a lowâ€‘dose combination of two different agents
reduces the dose-related risk, the addition of one agent may counteract some deleterious effects of the other, using low dosage of two different agents minimize the clinical and metabolic effects that occur with maximal dosage of individual component of the combined tablet. Multilayer tableting is getting increasing attention from a variety of industries for a variety of reasons viz. patent extension, therapeutic, and marketing attendance. To reduce capital investment, quite often existing, but modified tablet presses are used to develop and produce such tablets. Although the general tablet manufacturing principles remain the same, there is much more to consider, since making multilayer tablets involves multiple often incompatible products, additional equipment, and many formulation and operation challenges.
Key words: Bilayer matrix, combination therapy, multilayer tabletting, polytherapy
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Bankar GS, Anderson NR. Tablets. In: Leon L, Liberman HA, Kaing JL,
editors. The Theory and Practice of Industrial Pharmacy. 3rd ed. Varghese
Publishing House; 1987. p. 293 â€‘303.
Nangia A, Molloy T, Fahie BJ, Chopra SK. Novel regulated release
system based on geometric configuration. Proc Int Sym Con Rel Bio
Chidambaram N, Porter W, Flood K, Qiu Y. Formulation and
characterization of new layered diffusional matrices for zeroâ€‘order
sustained release. J Control Release 1998;52:149â€‘58.
Conte U, Maggi L, Columbo P, La Manna A. Multiâ€‘layered hydrophilic
matrices as constant release devices (Geomatrix Systems). J Control
Abdul S, Poddar SS. A flexible technology for modified release of drugs:
Multi layered tablets. J Control Release 2004;97:393â€‘405.
Podczeck F, Drake KR, Newton JM, Haririan I. The strength of biâ€‘layered
tablet. Eur J Pharm Sci 2006;29:361â€‘6.
Inman SJ, Briscoe BJ, Pitt KG. Topographic characterization of cellulose
bilayered tablets interfaces. Chem Eng Res Des 2007;85:1005â€‘12.
Jitendra R, Mohan A, Kalaskar G, Shrivastav VG, Yeole PG. Bilayer tablet
formulation of metformin hydrochloride and gliclazide: A novel approach
in the treatment of diabetes. Int J Pharma Res Dev 2009;1:1â€‘11.
Gunsel WC. Compressionâ€‘coated and layered tablets. In: Lieberman HA,
Lachman L, editors. Phramaceutical Dosage Forms: Tablets. Marcel Dekker.
Bogan RK. Treatment options for insomaniaâ€‘â€‘pharmacodynamics of
zolpidem extendedâ€‘release to benefit next day performance. Postgrad
Kulkarni A, Bhatia M. Development and evaluation of bilayer floating
tablets of atenolo and lovastatin for biphasic release profile. Iranian J
Pharm Res 2009;8:15â€‘25.
Nirmal J, Saisivam S, Peddanna C, Muralidharan S, Godwinkumar S,
Nagarajan M. Bilayer tablets of atorvastatin calcium and nicotinic acid:
Formulation and evaluation. Chem Pharm Bull (Tokyo) 2008;56:1455â€‘8.
Efentakis M, Peponaki C. Formulation study and evaluation of
matrix and threeâ€‘layer tablet sustained drug delivery systems based
on carbopols with isosorbite mononitrate. AAPS PharmSciTech
Phaechmud T. Variables influencing drug release from layered matrix
system comprising hydroxypropyl methylcellulose. AAPS PharmSciTech
LaForce C, Gentile DA, Skoner DP. A randomized, double blind,
parallel group, multicenter, placeboâ€‘controlled study of the safety and
efficacy of ER guaifensein/pseudoephedrine HCl for symptom relief
as an adjunctive therapy of antibiotic treatment of acute respiratory
infections. Postgrad Med 2008;120:53â€‘9.
Maggi L, Segale L, Conti S, Ochoa Machiste E, Conte U. Preparation
and evaluation of release characteristics of 3TabGum, a novel chewing
device. Eur J Pharm Sci 2005;4:487â€‘93.
Park CR, Munday DL. Development and evaluation of biphasic
buccal adhesive tablet for nicotine replacement therapy. Int J Pharm
Sungthongjeen S, Srimornsak P, Puttipipatkhachorn S. Design and
evaluation of floating multilayered coated tablets based on gas
formation. Eur J Pharm Biopharm 2008;69:255â€‘63.
Kale SS, Saste VS, Prajkta L, Ughade, Dheeraj T, Bhaviskar, et al. Bilayer
tablet: Review. Int J Pharm Sci Rev Res 2011;9:25â€‘30.
Available from: http://www.port/technology.com [Last accessed
on July 1, 2012].
The Indian Pharmacopoeia. 4th ed, Vol. 2. The Controller of Publication,
Govt. of India, Delhi, 1996. p. A82â€‘A85.
The United States Pharmacopoeia, United States Pharmacopoeial
Convention, Inc., Rockville: 2000. p. 1944.
Singh BN, Kim KH. Floating drug delivery systems an approach to
oral controlled drug delivery via gastric retention. J Control Release
Atram SC, Udavant YK, Salunke RJ, Neb GB, Shahi SR, Gulecha BS, et al.
Formulation and evaluation of bilayer tablet containing Metoprolol
succinate and Amlodipine besylate as a model drug for anti hypertensive
therapy. J Pharm Res 2009;2:1335â€‘47.
Jamunadhevi V, Sahoo PK, Kailasam P. Formulation and in vitro evaluation
of biâ€‘layer tablet of cyclobenzaprine hydrochloride ER and diclofenac
potassium IRâ€‘ A novel fixed dose combination. Int J Res Pharm Sci
Swamy PV, Kinagi MB, Biradar SS, Gada SN, Shilpa H. Formulation design
and evaluation of bilayer buccal tablets of granisetron hydrochloride.
Ind J Pharm Edu Res 2011;45:242â€‘7.
Pattanayak DP, Dinda SC. Bilayer tablet formulation of metformin HCl
and glimepiride: A novel approach to improve therapeutic efficacy. Int
J Drug Discov Herb Res 2011;1:1â€‘4.
Jain J, Marya BH, Mittal RP, Patel M. Formulation and evaluation of
indomethacin bilayer sustained release tablets. Int J PharmTech Res
Mohindeen S, Jyothi B, Pavani S, Satyanarayana T, Kumar SP, Krishna NS.
Formulation and evaluation of bilayered tablets of metformin
hydrochloride and atorvastatin calcium. Int J Pharm Sci Rev Res
Kumar GV, Babu KA, Ramasanay C. Formulation and evaluation of
bilayered tablets of cefixime trihydrate and dicloxacillin sodium. Int J
PharmTech Res 2011;3:613â€‘8.
Jadhav RT, Patil PH, Patil PR. Formulation and evaluation of bilayered
tablets of piracetam and vinpocetine. J Chem Pharm Res 2011;3:423â€‘31.
Rajendran NN, Natarajan R, Subhashini R, Patel H. Formulation and
evaluation of sustained release bilayer tablets of metformin HCl and
pioglitazone HCl. Int J Curr Pharm Res 2011;3:118â€‘22.
Shirsand SB, Swamy PV, Keshavshetti GG. Design and evaluation of
atenolol bilayer buccal tablets. RGUHS J Pharm Sci 2011;1:4â€‘10.
Parmar CK, Pednekar PP. Development and evaluation of bilayer tablets
of cefuroxime axetil and potassium clavulanate. Int J Pharm Res Dev
Musle K, Payghan SA, Disuza JI. Fomulation, evaluation and development
of bilayer tablet. Int J Pharm Res Dev 2011;3:80â€‘7.
Remya PN, Damodharan N, Kumar CV. Formulation and evaluation of
bilayered tablets of ibuprofen and methocarbamol. Int J PharmTech
Gohel MC, Parikh RK, Nagori SA, Jethwa BA. Fabrication and evaluation
of biâ€‘layer tabletcontaining conventional paracetamol and modified
diclofenac sodium. Indian J Pharm Sci 2010;72:191â€‘6.
Ramesh DS, Guruvaiah, Harani A. Formulation and evaluation of bilayer
sustained release matrix tablets of Metformin HCl and Pioglitazone.
Amerâ€‘Euras J Sci Res 2010;5:176â€‘82.
Naeem MA, Mahmood A, Khan SA, Shahiq Z. Development and evaluation
of controlledrelease bilayer tablets containing microencapsulated
tramadol and acetaminophen. Trop J Pharm Res 2010;9:347â€‘54.
Rathod RT, Misra D. FDC of montelukast with levocetirizine: Focus on
bilayer technology. J Indian Med Assoc 2009;107:562â€‘4.
Kadam VV, Waghmare MU, Venkatpurwar VP, Pokharkar VB. Preparation
and evaluation of glipizideâ€‘metformin HCl sustained release bilayer
tablet [online]. 2009 [Last cited on 2009 Sep 15]. Available from: http://
accessed on 2011 Jul 1].
Friedl T, Schepky G, inventors; Boehringer Ingelheim USA
Corporation, assignee. Bilayer pharmaceutical tablet comprising
telmisartan and a diuretic and preparation thereof. US patent
A1. 2009 Sept 10.
Bakuridze AD, Maglakelidze GM, Kurdiani NG, Tsagarejshvili NT,
Berashvili DT. Technology of vitamins containing double layer
suppositories. Georgian Med News 2008;158:49â€‘51.
Ouali A, Azad AK, inventors; Pharmascience Inc, assignee. Stabilized
pharmaceutical composition of nonsteroidal antiinflammatory agent
and a prostaglandin. WO 2000/056339. 2007 Jan 03.
Kohlrausch A, inventor; Boehringer Ingelheim International GmbH,
assignee. Bilayer tablet of telmisartan and simvastatin. US patent
A1. 2006 Apr 13.
Deâ€‘fang O, Shuâ€‘fang N, Jin M, Xingâ€‘gang Y, Zhiâ€‘quan S, Weiâ€‘san P.
Compound metformin/glipizide bilayer extended release tablets:
Development and in vitro release. 2005;14:169â€‘72.