Preparation, in vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac

S. Mutalik, A. Naha, A.N. Usha, A.K. Ranjith, P. Musmade, K. Manoj, P. Anju, S. Prasanna

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

The objective of the present study was to develop "once daily" sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose-K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drug-excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, in vitro drug release and stability studies. Preclinical (anti-inflammatory, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45%) and MCC (30%) along with talc and magnesium stearate (1% w/w, each) (Tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with body weight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters.
Original languageEnglish
Pages (from-to)222-234
Number of pages13
JournalArchives of Pharmacal Research
Volume30
Issue number2
Publication statusPublished - 2007

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Tablets
Pharmacokinetics
Dissolution
Pharmaceutical Preparations
Lactose
Toxicity
aceclofenac
In Vitro Techniques
Drug Stability
Talc
Body Water
Excipients
Non-Steroidal Anti-Inflammatory Agents
Chemical analysis
Solubility
Drinking
Rats
Healthy Volunteers
Eating
Body Weight

Cite this

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title = "Preparation, in vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac",
abstract = "The objective of the present study was to develop {"}once daily{"} sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose-K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drug-excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, in vitro drug release and stability studies. Preclinical (anti-inflammatory, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45{\%}) and MCC (30{\%}) along with talc and magnesium stearate (1{\%} w/w, each) (Tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with body weight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters.",
author = "S. Mutalik and A. Naha and A.N. Usha and A.K. Ranjith and P. Musmade and K. Manoj and P. Anju and S. Prasanna",
note = "Cited By :58 Export Date: 10 November 2017 CODEN: APHRD Correspondence Address: Mutalik, S.; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka 576 104, India; email: srinivas.mutalik@manipal.edu Chemicals/CAS: aceclofenac, 89796-99-6; diclofenac, 15307-79-6, 15307-86-5; aceclofenac, 89796-99-6; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Diclofenac, 15307-86-5; Excipients; Tablets References: Alderman, D. A., A review of cellulose ethers in hydrophilic matrices for oral controlled dosage forms. Int. J. Pharm. Tech. Prod. Manuf., 3, 1-9 (1984); Amaral, M. H., Lobo, J. M., and Ferreira, D. C., Effect of hydroxypropyl methylcellulose and hydrogenated castor oil on naproxen release from sustained-release tablets. AAPS. PharmSciTech., 2, article 6: 1-8, (2001); Aulton, E.M., Pharmaceutics-The Science of Dosage Form Design (1990) ELBS/ Churchill Livingstone, , London; British Pharmacopoeia. The Stationary office, MHRA, British Pharmacopoeial Commission office, 1, London, (2005); Chien, Y.W., Regulatory considerations in controlled release medication (1982) Novel Drug Delivery Systems, pp. 577-578. , Chien, Y. W, Eds, Marcel Dekker, New York, pp; Ford, J.L., Rubinstein, M.H., Hogan, J.E., Formulation of sustained-release promethazine hydrochloride tablets using hydroxypropyl methylcellulose matrices (1985) Int. J. Pharm, 24, pp. 327-338; Indian Pharmacopoeia, Ministry of Health and Family Welfare, Government of India, Controller of Publications, 2, Delhi, (1996); Kay, A.E., Alldred, A., Rheumatoid Arthritis and Osteoarthritis (2003) Clinical Pharmacy and Therapeutics, pp. 791-807. , Walker, R, Edwards, C, ed, 3 rd ed, Churchill Livingstone, London, pp; Kuksal, A., Tiwary, A.K., Jain, N.K., Jain, S., Formulation and In Vitro, In Vivo Evaluation of Extendedrelease Matrix Tablet of Zidovudine: Influence of Combination of Hydrophilic and Hydrophobic Matrix Formers. AAPS. PharmSciTech., 1 (2006) Article, 1, pp. 1-9; Kulkarni, S.K., (1997) Handbook of experimental pharmacology, , 2nd edn, Vallabh Prakashan, New Delhi; Liebermann, H.A., Lachman, L., Schwartz, J.B., (1990) Pharmaceutical Dosage Forms: Tablets, 2, pp. 201-243. , Marcel Dekker, New York, pp; Lordi, G.N., Sustained release dosage forms (1991) The Theory and Practice of Industrial Pharmacy, pp. 442-454. , Lachman, L, Lieberman, H. A, Kanig, J. L, ed, 3rd ed, Varghese Publishing House, New Delhi, pp; Mahaguna, V., Talbert, R.L., Peters, J.I., Adams, S., Reynolds, T.D., Lam, F.Y.W., Influence of hydroxypropyl methylcellulose polymer on in vitro and in vivo performance of controlled release tablets containing alprazolam (2003) Eur. J. Pharm. Biopharm, 56, pp. 461-468; Mutalik, S., Hiremath, D., Formulation and evaluation of chitosan matrix tablets of nifedipine (2000) The Eastern. Pharmacist, 10, pp. 109-111; Mutalik, S., Paridhavi, K., Rao, M., Udupa, N., Analgesic and antipyretic effect of Solanum melongena (2003) Indian J. Pharmacol, 32, pp. 312-315; Mutalik, S., Sulochana, B., Chetana, M., Udupa, N., Uma Devi, P., Preliminary studies on acute and subacute toxicity studies of an antidiabetic herbal formulation, Dianex (2003) Indian J. Exptl. Biol, 4, pp. 316-320; Mutalik, S., Udupa, N., Formulation development, in vitro and in vivo evaluation of membrane controlled transdermal systems of glibenclamide (2005) J. Pharm. Pharmaceut. Sci, 1, pp. 26-38; Nellore, R.V., Rekhi, G.S., Hussain, A.S., Tillman, L.G., Augsburger, L.L., Development of metoprolol tartrate extended-release matrix tablet formulations for regulatory policy consideration (1998) J. Controlled. Rel, 50, pp. 247-256; Parfitt, K., Analgesics Anti-inflammatory and antipyretics (1999) Martindale: The Complete Drug Reference, pp. 2-12. , Reynolds, J. E. F, ed, 32nd ed, Massachusetts, pp; Reddy, R., Mutalik, S., Reddy, M.S., Once daily sustained release matrix tablets of nicorandil: Formulation and in vitro evaluation. AAPS. PharmSciTech., 4 (2003) Article, 61, pp. 1-9; Terashita, K., Imamura, K., Preparation of antipyretic analgesic by direct compression and its evaluation (2002) Chem. Pharm. Bull, 12, pp. 1542-1549; Vueba, M.L., Batista, D.C., Veiga, F., Sousa, J.J., Pina, M.E., Influence of cellulose ether polymers on ketoprofen release from hydrophilic matrix tablets (2004) Eur. J. Pharm. Biopharm, 1, pp. 51-59",
year = "2007",
language = "English",
volume = "30",
pages = "222--234",
journal = "Archives of Pharmacal Research",
issn = "0253-6269",
publisher = "Pharmaceutical Society of Korea",
number = "2",

}

Preparation, in vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac. / Mutalik, S.; Naha, A.; Usha, A.N.; Ranjith, A.K.; Musmade, P.; Manoj, K.; Anju, P.; Prasanna, S.

In: Archives of Pharmacal Research, Vol. 30, No. 2, 2007, p. 222-234.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Preparation, in vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac

AU - Mutalik, S.

AU - Naha, A.

AU - Usha, A.N.

AU - Ranjith, A.K.

AU - Musmade, P.

AU - Manoj, K.

AU - Anju, P.

AU - Prasanna, S.

N1 - Cited By :58 Export Date: 10 November 2017 CODEN: APHRD Correspondence Address: Mutalik, S.; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal, Karnataka 576 104, India; email: srinivas.mutalik@manipal.edu Chemicals/CAS: aceclofenac, 89796-99-6; diclofenac, 15307-79-6, 15307-86-5; aceclofenac, 89796-99-6; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Diclofenac, 15307-86-5; Excipients; Tablets References: Alderman, D. A., A review of cellulose ethers in hydrophilic matrices for oral controlled dosage forms. Int. J. Pharm. Tech. Prod. Manuf., 3, 1-9 (1984); Amaral, M. H., Lobo, J. M., and Ferreira, D. C., Effect of hydroxypropyl methylcellulose and hydrogenated castor oil on naproxen release from sustained-release tablets. AAPS. PharmSciTech., 2, article 6: 1-8, (2001); Aulton, E.M., Pharmaceutics-The Science of Dosage Form Design (1990) ELBS/ Churchill Livingstone, , London; British Pharmacopoeia. The Stationary office, MHRA, British Pharmacopoeial Commission office, 1, London, (2005); Chien, Y.W., Regulatory considerations in controlled release medication (1982) Novel Drug Delivery Systems, pp. 577-578. , Chien, Y. W, Eds, Marcel Dekker, New York, pp; Ford, J.L., Rubinstein, M.H., Hogan, J.E., Formulation of sustained-release promethazine hydrochloride tablets using hydroxypropyl methylcellulose matrices (1985) Int. J. Pharm, 24, pp. 327-338; Indian Pharmacopoeia, Ministry of Health and Family Welfare, Government of India, Controller of Publications, 2, Delhi, (1996); Kay, A.E., Alldred, A., Rheumatoid Arthritis and Osteoarthritis (2003) Clinical Pharmacy and Therapeutics, pp. 791-807. , Walker, R, Edwards, C, ed, 3 rd ed, Churchill Livingstone, London, pp; Kuksal, A., Tiwary, A.K., Jain, N.K., Jain, S., Formulation and In Vitro, In Vivo Evaluation of Extendedrelease Matrix Tablet of Zidovudine: Influence of Combination of Hydrophilic and Hydrophobic Matrix Formers. AAPS. PharmSciTech., 1 (2006) Article, 1, pp. 1-9; Kulkarni, S.K., (1997) Handbook of experimental pharmacology, , 2nd edn, Vallabh Prakashan, New Delhi; Liebermann, H.A., Lachman, L., Schwartz, J.B., (1990) Pharmaceutical Dosage Forms: Tablets, 2, pp. 201-243. , Marcel Dekker, New York, pp; Lordi, G.N., Sustained release dosage forms (1991) The Theory and Practice of Industrial Pharmacy, pp. 442-454. , Lachman, L, Lieberman, H. A, Kanig, J. L, ed, 3rd ed, Varghese Publishing House, New Delhi, pp; Mahaguna, V., Talbert, R.L., Peters, J.I., Adams, S., Reynolds, T.D., Lam, F.Y.W., Influence of hydroxypropyl methylcellulose polymer on in vitro and in vivo performance of controlled release tablets containing alprazolam (2003) Eur. J. Pharm. Biopharm, 56, pp. 461-468; Mutalik, S., Hiremath, D., Formulation and evaluation of chitosan matrix tablets of nifedipine (2000) The Eastern. Pharmacist, 10, pp. 109-111; Mutalik, S., Paridhavi, K., Rao, M., Udupa, N., Analgesic and antipyretic effect of Solanum melongena (2003) Indian J. Pharmacol, 32, pp. 312-315; Mutalik, S., Sulochana, B., Chetana, M., Udupa, N., Uma Devi, P., Preliminary studies on acute and subacute toxicity studies of an antidiabetic herbal formulation, Dianex (2003) Indian J. Exptl. Biol, 4, pp. 316-320; Mutalik, S., Udupa, N., Formulation development, in vitro and in vivo evaluation of membrane controlled transdermal systems of glibenclamide (2005) J. Pharm. Pharmaceut. Sci, 1, pp. 26-38; Nellore, R.V., Rekhi, G.S., Hussain, A.S., Tillman, L.G., Augsburger, L.L., Development of metoprolol tartrate extended-release matrix tablet formulations for regulatory policy consideration (1998) J. Controlled. Rel, 50, pp. 247-256; Parfitt, K., Analgesics Anti-inflammatory and antipyretics (1999) Martindale: The Complete Drug Reference, pp. 2-12. , Reynolds, J. E. F, ed, 32nd ed, Massachusetts, pp; Reddy, R., Mutalik, S., Reddy, M.S., Once daily sustained release matrix tablets of nicorandil: Formulation and in vitro evaluation. AAPS. PharmSciTech., 4 (2003) Article, 61, pp. 1-9; Terashita, K., Imamura, K., Preparation of antipyretic analgesic by direct compression and its evaluation (2002) Chem. Pharm. Bull, 12, pp. 1542-1549; Vueba, M.L., Batista, D.C., Veiga, F., Sousa, J.J., Pina, M.E., Influence of cellulose ether polymers on ketoprofen release from hydrophilic matrix tablets (2004) Eur. J. Pharm. Biopharm, 1, pp. 51-59

PY - 2007

Y1 - 2007

N2 - The objective of the present study was to develop "once daily" sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose-K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drug-excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, in vitro drug release and stability studies. Preclinical (anti-inflammatory, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45%) and MCC (30%) along with talc and magnesium stearate (1% w/w, each) (Tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with body weight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters.

AB - The objective of the present study was to develop "once daily" sustained release tablets of aceclofenac by direct compression using hydroxypropyl methylcellulose-K4M (HPMC). The solubility studies of aceclofenac were conducted to select suitable dissolution media. The drug-excipient mixtures were subjected to preformulation studies. The tablets were subjected to physicochemical, in vitro drug release and stability studies. Preclinical (anti-inflammatory, analgesic, pharmacokinetic and toxicity studies) and clinical pharmacokinetic studies were conducted for optimized tablets. Based on the preformulation results, microcrystalline cellulose (MCC), dicalcium phosphate and spray dried lactose (SDL) were selected as directly compressible vehicles. Because of the incompatibility with aceclofenac, SDL was excluded from the study. The physicochemical properties of tablets were found within the limits. By comparing the dissolution profiles with the marketed product, the tablet containing HPMC (45%) and MCC (30%) along with talc and magnesium stearate (1% w/w, each) (Tablet B7) was considered as a better formulation. This tablet exhibited almost similar drug release profile in different dissolution media as that of marketed tablet. Tablet B7 was stable in accelerated conditions for 6 months. The composition of this tablet showed almost similar preclinical pharmacological activities compared to marketed tablet composition and did not exhibit any toxicity in rats and mice with respect to tested haematological and biochemical parameters along with body weight, food and water intake. The pharmacokinetic study in healthy human volunteers indicated that B7 tablet produced an extended drug release of drug upto 24 h as that of marketed product with almost identical pharmacokinetic parameters.

M3 - Article

VL - 30

SP - 222

EP - 234

JO - Archives of Pharmacal Research

JF - Archives of Pharmacal Research

SN - 0253-6269

IS - 2

ER -