Development and Optimization of Wax Matrix Tablets of Levetiracetam for Zero-order Controlled Release
Abstract
The major objective of this work was to develop once daily extended release tablets with zero order drug release for levetiracetam using wax matrix as the release retarding element. Extending drug release for highly water soluble drugs is always a challenge. In this work levetiracetam, a highly soluble drug was chosen for which extended release matrix tablets were developed using different waxes such as Compritol ATO 888, Imwitor 491, tristearin and cetylpalmitateas rate controlling materials taken in different amounts. PEG 6000 was used to regulate the availability of water inside the wax matrix and lactose was used as pore forming agent to aid the release of the drug from the wax matrix. Tablets were prepared by embedding the drug into the molten wax followed by its solidification, sieving, mixing with other excipients and finally compression. The prepared tablets were tested for hardness, tensile strength, friability, drug content and drug release studies. Type of wax, amount of wax and amount of PEG 6000 were optimized in order to achieve controlled drug release for about 24 hours. All the tablets showed good tensile strength in the range of 0.59-0.70 N/mm2, packing fraction in the range of 0.85-0.92 and friability in the range of 0.42-55% indicating their solid physical integrity. The drug release studies indicated thatthe tablets prepared with tristearin showed better control among the waxes taken. The tablets containing 150mg of tristearin, 50 mg of PEG 6000 and 50 mg of lactose showed controlled drug release for 24 h with zero-order release.
Keywords:
wax matrix, Pore former, Highlysoluble drugs, Zero-order controlled release, EmbedmentDOI
https://doi.org/10.25004/IJPSDR.2021.130302References
Patel R, Patel J. Novel technologies of oral controlled release drug delivery system. Sys Rev Pharm. 2010;1(2):128-132.
Kushal M, Monali M, DurgavathiM,Mittal P, Umesh S, Pragna S. oral controlled release drug delivery systems: An overview. Int Res J Pharm. 2013;4(3):70-76.
Nokhodchi A, Raja S, Patel P, Asare-Addo K. The role of oral controlled release matrix tablets in drug delivery systems. BioImpacts. 2012;2(4):175-187.
Petrusevska M, Berglez S, Krisch I, Legen I, Megusar K, Peternel L et al.Biowaiver monographs for immediate release solid oral dosageforms: Levetiracetam. J Pharm Sci.2015;104:2676–2687.
Cao QR, Kim TW, Lee BJ. Photoimages and the release characteristics of lipophilic matrix tablets containing highly water-soluble potassium citrate with high drug loadings. IntJPharm. 2007;339(1-2):19-24.
Nart V, Beringhs AO, França MT, de Espíndola B, Pezzini BR, Stulzer HK. Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs. Mater SciEng C. 2017;70:250-257.
Phaechamud T, Choncheewa C. Single and dual drug release patterns from shellac wax-lutrol matrix tablets fabricated with fusion and molding techniques. Indian JPharm Sci. 2015;77(1):62-74.
Yonezawa Y, Ishida S, Sunada H. Release from or through a wax matrix system. I. Basic release properties of the wax matrix system. Chem Pharm Bull. 2001;49(11):1448-1451.
Srikar G, Avula P, Koreddi S. Embedment technique: An alternative to wet granulation for bettercontrol of release of highly water soluble drugs–A case study with diltiazemHCl. Int J Pharm Pharm Sci. 2015;7(12):270-276.
Huang HP, Mehta SC, Radebaugh GW, Fawzi MB. Mechanism of drug release from an acrylic polymer‐wax matrix tablet. JPharmSci. 1994;83(6):795-797.
Mahajabeen A, Krishna EH, Surya RS. Formulation and evaluation of levetiracetamextended release tablets. World J Pharm Pharm Sci. 2015;4(4):1446-1461.
Singh S, Bhavesh S, Sanjaykumar N, SunilB. Formulation and evaluation of levetiracetam extendedrelease tablets. Int J Pharm Sci Nanotech. 2013;6(1):1958-1965.
Paliwal H, Goyal S, Rathore KS, Singla S, Daksh S. Formulation and evaluation of levetiracetam extended release tablets. Int J Pharm Sci Rev Res. 2016;41(1):260-266.
Srikar G, Gouthamib KS, Manasac B, Sirishad AS. Formulation optimization and characterization of amlodipine oral disintegrating tablets prepared by co-grinding technique. Der Pharm Lett. 2013;5(4):335-343.
Uhumwangho MU, Ogedebe JO, Osazuwa EQ. Effect of surfactants on the mechanical properties of acetaminophen-wax matrix tablets and its implication on dissolution profile. Ife J Sci. 2012;14(1):31-36.
Srikar G, Avula P, Annapurna S, Boola M. Development of extended release matrix tablets of felodipine through solid dispersions for better drug release profile by a 32 factorial design. Indian J PharmEdu Res. 2016;50(2S):S89-99.
Sivaneswari S, Karthikeyan E, Chandana PJ. Novel expandable gastro retentive system by unfolding mechanism of levetiracetam using simple lattice design–Formulation optimization and in vitro evaluation. Bull Fac Pharm Cairo Univ. 2017;55(1):63-72.
Sinko PJ. Martin’s physical pharmacy and pharmaceutical sciences. Wolter Kluwer and Lippincott Williams and Wilkins, 2011.
Yonezawa Y,Ishida S, Suzuki S,Sunada H. Release from or through a wax matrix System. IVgeneralized expression of the release process for a reservoir device tablet. Chem. Pharm. Bull. 2002;50(9):1219—1222.
D’souza AA. Shegokar R.Polyethylene glycol (PEG): A versatile polymer forpharmaceutical applications. Expert Opin Drug Deliv. 2016;13(9):1257-1275.
Robinson JR, Lee VHL. Controlled drug delivery – Fundamentals and Applications. Informa Healthcare, 2011.
Published

