Abstract

The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug-excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results. © American Association of Pharmaceutical Scientists 2008.
Original languageEnglish
Pages (from-to)651-659
Number of pages9
JournalAAPS PharmSciTech
Volume9
Issue number2
DOIs
Publication statusPublished - 06-2008

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Chitosan
in vivo studies
chitosan
Tablets
polymers
Polymers
drugs
phthalates
methylcellulose
pharmacokinetics
drug interactions
cellulose acetate
Pharmacokinetics
In Vitro Techniques
aceclofenac
differential scanning calorimetry
storage conditions
coatings
volunteers
confidence interval

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

@article{d6359efbf1d24c94a1494a57a7e85c43,
title = "Chitosan and enteric polymer based once daily sustained release tablets of aceclofenac: In Vitro and In Vivo studies",
abstract = "The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug-excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95{\%} confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results. {\circledC} American Association of Pharmaceutical Scientists 2008.",
author = "Srinivas Mutalik and Krishnan Manoj and Reddy, {Meka Sreenivasa} and Pralhad Kushtagi and Usha, {Achutha Nayak} and Parambil Anju and Ranjith, {Averineni Kumar} and Nayanabhirama Udupa",
note = "Cited By :20 Export Date: 10 November 2017 Correspondence Address: Mutalik, S.; Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India; email: ssmutalik@yahoo.com Chemicals/CAS: aceclofenac, 89796-99-6; cellacefate, 9004-38-0; chitosan, 9012-76-4; dodecyl sulfate sodium, 151-21-3; hydrochloric acid, 7647-01-0; hydroxypropylmethylcellulose phthalate, 9050-31-1; magnesium stearate, 557-04-0; microcrystalline cellulose, 39394-43-9, 51395-75-6; povidone, 9003-39-8; talc, 14807-96-6; cellulose, 61991-22-8, 68073-05-2, 9004-34-6; diclofenac, 15307-79-6, 15307-86-5; methylcellulose, 79484-92-7, 9004-67-5; aceclofenac, 89796-99-6; Anti-Inflammatory Agents, Non-Steroidal; cellulose acetate phthalate, 9004-38-0; Cellulose, 9004-34-6; Chitosan, 9012-76-4; Delayed-Action Preparations; Diclofenac, 15307-86-5; Drug Carriers; hydroxypropyl methylcellulose phthalate, 9050-31-1; Methylcellulose, 9004-67-5; Tablets, Enteric-Coated Tradenames: hifenac, Intas, India Manufacturers: Intas, India; Lupin Laboratories, India References: Parfitt, K., Analgesics, anti-inflammatory and antipyretics (1999) Martindale: The Complete Drug Reference, pp. 1-12. , In J. E. F. Reynolds (ed.) 32nd ed, Massachusetts; Kay, A.E., Alldred, A., Rheumatoid arthritis and osteoarthritis (2003) Clinical Pharmacy and Therapeutics, pp. 791-807. , In R. Walker, and C. Edwards (eds.) 3rd ed., Churchill Livingstone, London, UK; Moffet, A.C., Osselton, M.D., Widdop, B., (2006) Clarke' S Analysis of Drugs and Poisons, , 3rd ed., Pharmaceutical Press, London, UK; Rao, M.Y., Veni, J.K., Jayasagar, G., Formulation and evaluation of diclofenac sodium using hydrophilic matrices (2001) Drug. Dev. Ind. Pharm., 27, pp. 759-766; Maggi, L., Machiste, E.O., Torre, M.L., Conte, U., Formulation of biphasic release tablets containing slightly soluble drugs (1999) Eur. J. Pharm. Biopharm., 48, pp. 37-42; Chien, Y.W., Regulatory considerations in controlled release medication (1982) Novel Drug Delivery Systems, pp. 577-578. , In Y. W. Chien (ed.) Marcel Dekker, New York, NY; Mutalik, S., Naha, A., Usha, A.N., Preparation, in vitro, Preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac (2007) Arch. Pharm. Res., 30, pp. 222-234; George, M., Abraham, E.T., Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan - A review (2006) J. Controlled. Rel., 114, pp. 1-14; Fukuda, M., Nicholas, A.P., McGinity, J.W., Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum (2006) Int. J. Pharm., 310, pp. 90-100; Wang, K., Zhimin, H., Alginate-konjac glucomannan-chitosan beads as controlled release matrix (2001) Int. J. Pharm., 244, pp. 117-126; Barreiro-Iglesias, R., Coronilla, R., Concheiro, A., Alvarez-Lorenzo, C., Preparation of chitosan beads by simultaneous cross-linking/ insolubilisation in basic pH. Rheological optimisation and drug loading/ release behaviour (2005) Eur. J. Pharm. Sci., 24, pp. 77-84; Akbua, J., Use of chitosonium malate as a matrix in sustained-release tablets (1993) Int. J. Pharm., 89, pp. 19-24; Knapczyk, J., Antimycotic buccal and vaginal tablets with chitosan (1992) Int. J. Pharm., 88, pp. 9-14; Reddy, K.R., Mutalik, S., Reddy, S., Once-daily sustained-release matrix tablets of nicorandil: Formulation and in vitro evaluation (2003) AAPS PharmSciTech., 4, pp. E61; Agrawal, A.M., Neau, S.H., Bonate, P.L., Wet granulation fine particle ethylcellulose tablets: Effect of production variables and mathematical modeling of drug release (2003) AAPS PharmSci., 2. , Article 13; Chen, R., Takahashi, H., Okamoto, H., Danjo, K., Particle design of three-component system for sustained release using a 4-fluid nozzle spray-drying technique (2006) Chem. Pharm. Bull., 11, pp. 1486-1490; Silva, C.M., Ribeiro, A.J., Ferreira, D., Veiga, F., Insulin encapsulation in reinforced alginate microspheres prepared by internal gelation (2006) Eur. J. Pharm. Sci., 2, pp. 148-159; Aulton, M.E., Wells, T.I., (1988) Pharmaceutics-The Science of Dosage Form Design, , Churchill Livingstone, London, UK; (1996) Indian Pharmacopoeia. Ministry of Health and Family Welfare, 2. , Government of India Delhi, India: Controller of Publication; Joshi, B.V., Patil, V.B., Pokharkar, V.B., Compatibility studies between carbamazepine and tablet excipients using thermal and non-thermal methods (2002) Drug Dev. Ind. Pharm., 6, pp. 687-694; Kibbe, H.A., (2000) Hand Book of Pharmaceutical Excipients, , 3rd ed. American pharmaceutical association, Pharmaceutical press, London; Seitz, J.A., Mehta, S.P., Yeager, J.L., Tablet coating (1987) The Theory and Practice of Industrial Pharmacy, pp. 346-373. , In L. Lachman, H. A. Liberman, and J. L. Kanig (eds.) 3rd ed., Varghese Publishing House, Delhi, India; Banakar, U.V., Dissolution of modified release dosage forms (1992) Pharmaceutical Dissolution Testing, pp. 299-312. , In J. Swarbrick (ed.) Marcel Dekker, New York, NY; Palmieri, G.F., Michelini, S., Martino, P.D., Martelli, S., Polymers with pH-dependent solubility: Possibility of use in the formulation of gastro resistant and controlled-release matrix tablets. Drug (2000) Dev Ind Pharm., 26, pp. 837-845; Yomota, C., Miyazaki, T., Okada, S., Sustained-release effect of the direct compressed tablet based on chitosan and Na alginate (1994) Yakugaku Zasshi., 114, pp. 257-263; Grundy, J.S., Anderson, K.E., Rogers, J.A., Foster, R.T., Studies on dissolution testing of the nifedipine gastrointestinal therapeutic system. II. Improved in vitro-in vivo correlation using a two-phase dissolution test (1997) J. Control Release., 48, pp. 9-17; Negrin, C.M., Delgado, A., Llabres, M., Evora, C., In vivo-in vitro study of biodegradable methadone delivery systems (2001) Biomaterials, 22, pp. 563-570; Yang, X., Zhang, G., Li, W., Peng, B., Liu, Z., Pan, W., Design and evaluation of Jingzhiguanxin monolithic osmotic pump tablet (2006) Chem. Pharm. Bull., 4, pp. 465-469",
year = "2008",
month = "6",
doi = "10.1208/s12249-008-9075-3",
language = "English",
volume = "9",
pages = "651--659",
journal = "AAPS PharmSciTech",
issn = "1530-9932",
publisher = "American Association of Pharmaceutical Scientists",
number = "2",

}

TY - JOUR

T1 - Chitosan and enteric polymer based once daily sustained release tablets of aceclofenac: In Vitro and In Vivo studies

AU - Mutalik, Srinivas

AU - Manoj, Krishnan

AU - Reddy, Meka Sreenivasa

AU - Kushtagi, Pralhad

AU - Usha, Achutha Nayak

AU - Anju, Parambil

AU - Ranjith, Averineni Kumar

AU - Udupa, Nayanabhirama

N1 - Cited By :20 Export Date: 10 November 2017 Correspondence Address: Mutalik, S.; Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576104, India; email: ssmutalik@yahoo.com Chemicals/CAS: aceclofenac, 89796-99-6; cellacefate, 9004-38-0; chitosan, 9012-76-4; dodecyl sulfate sodium, 151-21-3; hydrochloric acid, 7647-01-0; hydroxypropylmethylcellulose phthalate, 9050-31-1; magnesium stearate, 557-04-0; microcrystalline cellulose, 39394-43-9, 51395-75-6; povidone, 9003-39-8; talc, 14807-96-6; cellulose, 61991-22-8, 68073-05-2, 9004-34-6; diclofenac, 15307-79-6, 15307-86-5; methylcellulose, 79484-92-7, 9004-67-5; aceclofenac, 89796-99-6; Anti-Inflammatory Agents, Non-Steroidal; cellulose acetate phthalate, 9004-38-0; Cellulose, 9004-34-6; Chitosan, 9012-76-4; Delayed-Action Preparations; Diclofenac, 15307-86-5; Drug Carriers; hydroxypropyl methylcellulose phthalate, 9050-31-1; Methylcellulose, 9004-67-5; Tablets, Enteric-Coated Tradenames: hifenac, Intas, India Manufacturers: Intas, India; Lupin Laboratories, India References: Parfitt, K., Analgesics, anti-inflammatory and antipyretics (1999) Martindale: The Complete Drug Reference, pp. 1-12. , In J. E. F. Reynolds (ed.) 32nd ed, Massachusetts; Kay, A.E., Alldred, A., Rheumatoid arthritis and osteoarthritis (2003) Clinical Pharmacy and Therapeutics, pp. 791-807. , In R. Walker, and C. Edwards (eds.) 3rd ed., Churchill Livingstone, London, UK; Moffet, A.C., Osselton, M.D., Widdop, B., (2006) Clarke' S Analysis of Drugs and Poisons, , 3rd ed., Pharmaceutical Press, London, UK; Rao, M.Y., Veni, J.K., Jayasagar, G., Formulation and evaluation of diclofenac sodium using hydrophilic matrices (2001) Drug. Dev. Ind. Pharm., 27, pp. 759-766; Maggi, L., Machiste, E.O., Torre, M.L., Conte, U., Formulation of biphasic release tablets containing slightly soluble drugs (1999) Eur. J. Pharm. Biopharm., 48, pp. 37-42; Chien, Y.W., Regulatory considerations in controlled release medication (1982) Novel Drug Delivery Systems, pp. 577-578. , In Y. W. Chien (ed.) Marcel Dekker, New York, NY; Mutalik, S., Naha, A., Usha, A.N., Preparation, in vitro, Preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac (2007) Arch. Pharm. Res., 30, pp. 222-234; George, M., Abraham, E.T., Polyionic hydrocolloids for the intestinal delivery of protein drugs: Alginate and chitosan - A review (2006) J. Controlled. Rel., 114, pp. 1-14; Fukuda, M., Nicholas, A.P., McGinity, J.W., Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum (2006) Int. J. Pharm., 310, pp. 90-100; Wang, K., Zhimin, H., Alginate-konjac glucomannan-chitosan beads as controlled release matrix (2001) Int. J. Pharm., 244, pp. 117-126; Barreiro-Iglesias, R., Coronilla, R., Concheiro, A., Alvarez-Lorenzo, C., Preparation of chitosan beads by simultaneous cross-linking/ insolubilisation in basic pH. Rheological optimisation and drug loading/ release behaviour (2005) Eur. J. Pharm. Sci., 24, pp. 77-84; Akbua, J., Use of chitosonium malate as a matrix in sustained-release tablets (1993) Int. J. Pharm., 89, pp. 19-24; Knapczyk, J., Antimycotic buccal and vaginal tablets with chitosan (1992) Int. J. Pharm., 88, pp. 9-14; Reddy, K.R., Mutalik, S., Reddy, S., Once-daily sustained-release matrix tablets of nicorandil: Formulation and in vitro evaluation (2003) AAPS PharmSciTech., 4, pp. E61; Agrawal, A.M., Neau, S.H., Bonate, P.L., Wet granulation fine particle ethylcellulose tablets: Effect of production variables and mathematical modeling of drug release (2003) AAPS PharmSci., 2. , Article 13; Chen, R., Takahashi, H., Okamoto, H., Danjo, K., Particle design of three-component system for sustained release using a 4-fluid nozzle spray-drying technique (2006) Chem. Pharm. Bull., 11, pp. 1486-1490; Silva, C.M., Ribeiro, A.J., Ferreira, D., Veiga, F., Insulin encapsulation in reinforced alginate microspheres prepared by internal gelation (2006) Eur. J. Pharm. Sci., 2, pp. 148-159; Aulton, M.E., Wells, T.I., (1988) Pharmaceutics-The Science of Dosage Form Design, , Churchill Livingstone, London, UK; (1996) Indian Pharmacopoeia. Ministry of Health and Family Welfare, 2. , Government of India Delhi, India: Controller of Publication; Joshi, B.V., Patil, V.B., Pokharkar, V.B., Compatibility studies between carbamazepine and tablet excipients using thermal and non-thermal methods (2002) Drug Dev. Ind. Pharm., 6, pp. 687-694; Kibbe, H.A., (2000) Hand Book of Pharmaceutical Excipients, , 3rd ed. American pharmaceutical association, Pharmaceutical press, London; Seitz, J.A., Mehta, S.P., Yeager, J.L., Tablet coating (1987) The Theory and Practice of Industrial Pharmacy, pp. 346-373. , In L. Lachman, H. A. Liberman, and J. L. Kanig (eds.) 3rd ed., Varghese Publishing House, Delhi, India; Banakar, U.V., Dissolution of modified release dosage forms (1992) Pharmaceutical Dissolution Testing, pp. 299-312. , In J. Swarbrick (ed.) Marcel Dekker, New York, NY; Palmieri, G.F., Michelini, S., Martino, P.D., Martelli, S., Polymers with pH-dependent solubility: Possibility of use in the formulation of gastro resistant and controlled-release matrix tablets. Drug (2000) Dev Ind Pharm., 26, pp. 837-845; Yomota, C., Miyazaki, T., Okada, S., Sustained-release effect of the direct compressed tablet based on chitosan and Na alginate (1994) Yakugaku Zasshi., 114, pp. 257-263; Grundy, J.S., Anderson, K.E., Rogers, J.A., Foster, R.T., Studies on dissolution testing of the nifedipine gastrointestinal therapeutic system. II. Improved in vitro-in vivo correlation using a two-phase dissolution test (1997) J. Control Release., 48, pp. 9-17; Negrin, C.M., Delgado, A., Llabres, M., Evora, C., In vivo-in vitro study of biodegradable methadone delivery systems (2001) Biomaterials, 22, pp. 563-570; Yang, X., Zhang, G., Li, W., Peng, B., Liu, Z., Pan, W., Design and evaluation of Jingzhiguanxin monolithic osmotic pump tablet (2006) Chem. Pharm. Bull., 4, pp. 465-469

PY - 2008/6

Y1 - 2008/6

N2 - The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug-excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results. © American Association of Pharmaceutical Scientists 2008.

AB - The purpose of this study was to develop a once daily sustained release tablet of aceclofenac using chitosan and an enteric coating polymer (hydroxypropyl methylcellulose phthalate or cellulose acetate phthalate). Overall sustained release for 24 h was achieved by preparing a double-layer tablet in which the immediate release layer was formulated for a prompt release of the drug and the sustained release layer was designed to achieve a prolonged release of drug. The preformulation studies like IR spectroscopic and differential scanning calorimetry showed the absence of drug-excipient interactions. The tablets were found within the permissible limits for various physicochemical parameters. Scanning electron microscopy was used to visualize the surface morphology of the tablets and to confirm drug release mechanisms. Good equivalence in the drug release profile was observed when drug release pattern of the tablet containing chitosan and hydroxypropyl methylcellulose phthalate (M-7) was compared with that of marketed tablet. The optimized tablets were stable at accelerated storage conditions for 6 months with respect to drug content and physical appearance. The results of pharmacokinetic studies in human volunteers showed that the optimized tablet (M-7) exhibited no difference in the in vivo drug release in comparison with marketed tablet. No significant difference between the values of pharmacokinetic parameters of M-7 and marketed tablets was observed (p > 0.05; 95% confidence intervals). However the clinical studies in large scale and, long term and extensive stability studies at different conditions are required to confirm these results. © American Association of Pharmaceutical Scientists 2008.

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U2 - 10.1208/s12249-008-9075-3

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JF - AAPS PharmSciTech

SN - 1530-9932

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