Development, Evaluation and Optimization of Osmotic Controlled Tablets of Aceclofenac for Rheumatoid Arthritis Management

Author(s): Bijaya Ghosh*, Niraj Mishra, Preeta Bose, Moumita D. Kirtania.

Journal Name: Drug Delivery Letters

Volume 9 , Issue 1 , 2019

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Graphical Abstract:


Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and stiffness of joints, leading to severe immobility problems. The disease shows circadian variation and usually gets aggravated in early morning hours. Aceclofenac, a BCS Class II compound is routinely used in the treatment of pain and inflammation associated with rheumatoid arthritis. The objective of this study was to develop an osmotic delivery system of Aceclofenac that after administration at bedtime would deliver the drug in the morning hours.

Methods: A series of osmotically controlled systems of aceclofenac was developed by using lactose, sodium chloride and hydroxypropyl methylcellulose K100M as osmogens. Cellulose acetate (2% w/v in acetone) with varying concentrations of polyethylene glycol-400 was used as the coating polymer to create semi permeable membrane and dissolution was carried out in 290 mOsm phosphate buffer. Formulation optimization was done from four considerations: cumulative release at the end of 6 hours (lag time), cumulative release at the end of 7 hours (burst time), steady state release rate and completeness of drug release.

Results: A formulation having swelling polymer hydroxypropyl methylcellulose in the core and lactose and sodium chloride as osmogens, polyethylene glycol-400 (16.39 %) as pore former, with a coating weight of 5% was a close fit to the target release profile and was chosen as the optimum formulation.

Conclusion: Aceclofenac tablets containing lactose, HPMC and sodium chloride in the core, given a coating of cellulose acetate and PEG-400 (5% wt gain), generated a release profile for optimum management of rheumatoid arthritic pain.

Keywords: Aceclofenac, osmotic delivery, formulation, cellulose acetate, pore former, polyethylene glycol-400.

Keraliya, R.A.; Patel, C.; Patel, P.; Patel, V.; Soni, T.; Patel, R.C.; Patel, M.M. Osmotic drug delivery system as a part of modified release dosage form. ISRN Pharm., 2012, 2012, 528079.
Verma, R.K.; Krishna, D.M.; Garg, S. Formulation aspects in the development of osmotically controlled oral drug delivery systems. J. Control. Release, 2002, 79(1-3), 7-27.
Carmona, L.; Villaerde, V.; Hernandez, C.; Ballina, J.; Gbriel, R.; Laffon, A. The prevalence of rheumatoid arthritis in the general population of Spain. Rheumatology, 2002, 41, 88-95.
Choy, E. Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford), 2012, 51(Suppl. 5), v3-v11.
Tirnaksiz, F.; Arslan, S.A. A nonsteriodal anti-inflammatory drug: Aceclofenac, FABAD. J. Pharm. Sci., 2010, 35, 105-118.
Dooley, M.; Spencer, C.M.; Dunn, C.J. Aceclofenac a reappraisal of its use in the management of pain and rheumatic Disease. Drugs, 2001, 61, 1351-1378.
Shambim, L. In: Controlled release using bilayer osmotic tablet technology: Reducing theory to practice; Oral controlled release formulation design and drug delivery, theory to practice. , 2010. pp.129-151
Patel, K.N.; Mehta, T.A. Formulation design and characterization of an elementary osmotic pump tablet of flurbiprofen. PDA J. Pharm. Sci. Technol., 2014, 68(4), 333-346.
Jouyban, A.; Soltanpour, S. Solubility of pioglitazone hydrochorilde in binary and ternary mixtures of water, propylene glycol and polyethelene glycol 200, 400 and 600 at 298.2K. AAPS PharmSciTech, 2010, 11, 1713-1717.
Bolton, S.; Bon, C. Analysis of variance. In: Pharmaceutical Statistics Practical and Clinical Application; Informa healthcare: New York, USA. , 2008. pp. 182-189
Washington, N.; Washington, C.; Wilson, C.G. In: Physiological pharmaceutics: Barriers to Drug Absorption. Taylor & Francis editors. London, 2001. pp. 84.
Connell, E.L.; Fadda, H.M.; Basit, A.W. Gut instircts exploration in intestinal physiology and drug delivery. Int. J. Pharm., 2008, 364, 213-226.
Schiller, C.; Frohlich, C.P.; Grissmam, T.; Siegmund, W.; Monnikes, H.; Hoster, N.; Weitschies, W. Intestinal fluid volumes & transit of dosage forms an anessed by magnetic resonance imaging aliment. Pharmacol. Ther., 2005, 22, 971-979.
Bae, S.K.; Kim, S.H.; Lee, H.W.; Seong, S.J.; Shin, S.Y.; Lee, S.H.; Lim, M.S.; Yoon, Y.R.; Lee, H.J. Pharmacokinetics of a new once-daily controlled release formulation of aceclofenac in Korean healthy subjects compared with immediate release aceclofenac and the effect of food. Clin. Drug Investig., 2012, 32, 111-119.
Shakeel, F.; Faisal, M.S.; Shafiq, S. Comparative pharmacokinetic profile of aceclofenac from oral and transdermal application. J. Bioequiv. Availab, 2009. 1, 013-017
Sahoo, P.K.; Harleen, M. Investigation of release pattern of drug with low solubility through asymmetric membrane capsules. IJPS, 2013, 75, 205-210.
Alli, D.; Botton, S.; Gaylord, G.N. Hydroxypropyl methyl cellulose- anionic surfactant interactions in aqueous systems. J. Anim. Plant Sci., 1991, 42, 947-956.
Rowe, R.C.; Sheskey, P.J.; Quinn, M.E. Handbook of Pharmaceutical Excipients.In: RPS Publishing. Pharmaceutical Press. London., 2009. pp. 60030-7820

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Article Details

Year: 2019
Page: [29 - 36]
Pages: 8
DOI: 10.2174/2210303109666181203150830
Price: $58

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