Enhancement of dissolution rate and bioavailability of aceclofenac: A chitosan-based solvent change approach

S. Mutalik, P. Anju, K. Manoj, A.N. Usha

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

In this study the significant effect of chitosan on improving the dissolution rate and bioavailability of aceclofenac has been demonstrated by simple solvent change method. Chitosan was precipitated on aceclofenac crystals using sodium citrate as the salting out agent. The pure drug and the prepared co-crystals with different concentrations of chitosan (0.05-0.6%) were characterized in terms of solubility, drug content, particle size, thermal behaviour (differential scanning calorimetry, DSC), X-ray diffraction (XRD), morphology (scanning electron microscopy, SEM), in vitro drug release and stability studies. The in vivo performance was assessed by preclinical pharmacodynamic (analgesic and anti-inflammatory activity) and pharmacokinetic studies. The particle size of the prepared co-crystals was drastically reduced during the formulation process. The DSC showed a decrease in the melting enthalpy indicating disorder in the crystalline content. The XRD also revealed a characteristic decrease in crystallinity. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of aceclofenac from optimized crystal formulation was attributed to the wetting effect of chitosan, decreased drug crystallinity, altered surface morphology and micronization. The optimized co-crystals exhibited excellent stability on storage at accelerated conditions. The in vivo studies revealed that the optimized crystal formulation provided a rapid pharmacological response in mice and rats besides exhibiting improved pharmacokinetic parameters in rats. © 2007 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)279-290
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume350
Issue number1-2
DOIs
Publication statusPublished - 2008

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Chitosan
Biological Availability
Differential Scanning Calorimetry
Particle Size
X-Ray Diffraction
Pharmaceutical Preparations
Pharmacokinetics
Drug Stability
Non-Steroidal Anti-Inflammatory Agents
Electron Scanning Microscopy
Solubility
Freezing
Hot Temperature
Pharmacology
aceclofenac

Cite this

@article{acc88778a5fc4d39904952273351727a,
title = "Enhancement of dissolution rate and bioavailability of aceclofenac: A chitosan-based solvent change approach",
abstract = "In this study the significant effect of chitosan on improving the dissolution rate and bioavailability of aceclofenac has been demonstrated by simple solvent change method. Chitosan was precipitated on aceclofenac crystals using sodium citrate as the salting out agent. The pure drug and the prepared co-crystals with different concentrations of chitosan (0.05-0.6{\%}) were characterized in terms of solubility, drug content, particle size, thermal behaviour (differential scanning calorimetry, DSC), X-ray diffraction (XRD), morphology (scanning electron microscopy, SEM), in vitro drug release and stability studies. The in vivo performance was assessed by preclinical pharmacodynamic (analgesic and anti-inflammatory activity) and pharmacokinetic studies. The particle size of the prepared co-crystals was drastically reduced during the formulation process. The DSC showed a decrease in the melting enthalpy indicating disorder in the crystalline content. The XRD also revealed a characteristic decrease in crystallinity. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of aceclofenac from optimized crystal formulation was attributed to the wetting effect of chitosan, decreased drug crystallinity, altered surface morphology and micronization. The optimized co-crystals exhibited excellent stability on storage at accelerated conditions. The in vivo studies revealed that the optimized crystal formulation provided a rapid pharmacological response in mice and rats besides exhibiting improved pharmacokinetic parameters in rats. {\circledC} 2007 Elsevier B.V. All rights reserved.",
author = "S. Mutalik and P. Anju and K. Manoj and A.N. Usha",
note = "Cited By :63 Export Date: 10 November 2017 CODEN: IJPHD Correspondence Address: Mutalik, S.; Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104 Karnataka, India; email: ssmutalik@yahoo.com Chemicals/CAS: aceclofenac, 89796-99-6; chitosan, 9012-76-4; aceclofenac, 89796-99-6; Anti-Inflammatory Agents, Non-Steroidal; Chitosan, 9012-76-4; Diclofenac, 15307-86-5; Solvents Manufacturers: Lupin Laboratories, India References: Agnihotri, S.A., Mallikarjuna, N.N., Aminabhavi, T.M., Recent advances on chitosan-based micro- and nanoparticles in drug delivery (2004) J. Control. Rel., 100, pp. 5-28; Anal, A.K., Stevens, W.F., Chitosan-alginate multilayer beads for controlled release of ampicillin (2005) Int. J. Pharm., 290, pp. 45-54; Babu, G.V.M.M., Prasad, C.D.S., Murthy, K.V.R., Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water-soluble drug nimodipine (2002) Int. J. Pharm., 234, pp. 1-17; Balakrishnan, A., Rege, B.D., Amidon, G.L., Polli, J.E., Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity (2004) J. Pharm. Sci., 93, pp. 2064-2075; Banakar, U.V., (1992) Pharmaceutical Dissolution Testing, 49. , Marcel Dekker, New York; Cai, K., Rechtenbachb, A., Haoa, J., Bosserta, J., Jandt, K.D., Polysaccharide-protein surface modification of titanium via a layer-by-layer technique: characterization and cell behaviour aspects (2005) Biomaterials, 26, pp. 5960-5971; Dupuis, G., LeHoux, J., Recovery of chitosan from aqueous acidic solutions by salting-out. Part 2. Use of salts of organic acids (2007) Carbohydrate Polym., 68, pp. 287-294; Fukuda, M., Peppas, N.A., McGinity, J.W., Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum (2006) Int. J. Pharm., 310, pp. 90-100; Gowda, K.V., Rajan, D.S., Mandal, U., Selvan, P.S., Sam Solomon, W.D., Bose, A., Sarkar, A.K., Chattaraj, T.K., Evaluation of bioequivalence of two formulations containing 100 mg of aceclofenac (2006) Drug Dev. Ind. Pharm., 32, pp. 1219-1225; Hel, P., Davis, S.S., Illum, L., Chitosan microspheres prepared by spray drying (1999) Int. J. Pharm., 187, pp. 53-65; Imai, T., Shiraishi, S., Saito, H., Otagiri, M., Interaction of indomethacin with low molecular weight chitosan, and improvements of some pharmaceutical properties of indomethacin by low molecular weight chitosans (1991) Int. J. Pharm., 67, pp. 11-20; Kapoor, A., Mujumdar, D.K., Yadav, M.R., Crystal forms of nimesulide-a sulfonanilide (non-steroidal anti-inflammatory drug) (1998) Indian J. Chem. B, 37, pp. 572-574; Kim, T., Shin, J., Lee, B., Enhanced dissolution and bioavailability of poorly water-soluble aceclofenac using solid dispersion system (2001) AAPS, Annual Meeting, Denver, , Colorado, USA, October 21-25; Kulkarni, S.K., (1997) Handbook of Experimental Pharmacology. second ed., , Vallabh Prakashan, New Delhi; Kumar, V.S.G., Mishra, D.N., Preparation, characterization and in vitro dissolution studies of solid systems of valdecoxib with chitosan (2006) Chem. Pharm. Bull., 54, pp. 1102-1106; Lu, Z., Steenekamp, J.H., Hamman, J.H., Cross-linked cationic polymer microparticles: effect of n-trimethyl chitosan chloride on the release and permeation of ibuprofen (2005) Drug Dev. Ind. Pharm., 31, pp. 311-317; Maestrelli, F., Zerrouk, N., Chemtob, C., Mura, P., Influence of chitosan and its glutamate and hydrochloride salts on naproxen dissolution rate and permeation across Caco-2 cells (2004) Int. J. Pharm., 271, pp. 257-267; Moneghini, M., Kikie, I., Voinovich, D., Perissutti, B., Filipovic-Grcic, J., Processing of carbamazepine-PEG 4000 solid dispersions with supercritical carbon dioxide: preparation, characterization and in vitro dissolution (2001) Int. J. Pharm., 222, pp. 129-138; Mura, P., Zerrouk, N., Mennini, N., Maestrelli, F., Chemtob, C., Development and characterization of naproxen-chitosan solid systems with improved drug dissolution properties (2003) Eur. J. Pharm. Sci., 19, pp. 67-75; Mutalik, S., Usha, A.N., Reddy, M.S., Ranjith, A.K., Pandey, S., Improved bioavailability of aceclofenac from spherical agglomerates: development, in vitro and preclinical studies (2007) Pak. J. Pharm. Sci., 3, pp. 218-226; Mutalik, S., Naha, A., Usha, N., Ranjith, A.K., Musmade, P., Manoj, K., Anju, P., Prasanna, S., Preparation, In vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac (2007) Arch. Pharm. Res., 30, pp. 222-234; Nijlen, T.V., Brennan, K., Mooter, V.G., Blaton, N., Kinget, R., Augustijns, P., Improvement of the dissolution rate of artemisinin by means of supercritical fluid technology and solid dispersions (2003) Int. J. Pharm., 254, pp. 173-181; Nokhodchi, A., The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (indomethacin) from liquisolid compacts (2005) J. Pharm. Pharmaceut. Sci., 8, pp. 18-25; Paradkar, A.R., Pawar, A.P., Chordiya, J.K., Patil, V.B., Ketkar, A.R., Spherical crystallization of celecoxib (2002) Drug Dev. Ind. Pharm., 28, pp. 1213-1220; Park, S., Choi, H., The effects of surfactants on the dissolution profiles of poorly water-soluble acidic drugs (2006) Int. J. Pharm., 321, pp. 35-41; Pennings, F.H., Kwee, B.L.S., Vromans, H., Influence of enzymes and surfactants on the disintegration behavior of cross-linked hard gelatin capsules during dissolution (2006) Drug Dev. Ind. Pharm., 32, pp. 33-37; Perrut, M., Jung, J., Leboeuf, F., Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes. Part I. Micronization of neat particles (2005) Int. J. Pharm., 288, pp. 3-10; Portero, A., Remunan-Lopez, Vila-Jato, J.L., Effect of chitosan and chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine (1998) Int. J. Pharm., 175, pp. 75-84; Rawlinson, C.F., Williams, A.C., Timmins, P., Grimsey, I., Polymer-mediated disruption of drug crystallinity (2007) Int. J. Pharm., 336, pp. 42-48; Rowe, R.C., Sheskey, P.J., Owen, S.C., (2006) Handbook of Pharmaceutical Excipients, , Pharmaceutical Press, London, United Kingdom; Shinozaki, H., Oguchi, T., Suzuki, S., Aoki, K., Sako, T., Morishita, S., Tozuka, Y., Yamamoto, K., Micronization and polymorphic conversion of tolbutamide and barbital by rapid expansion of supercritical solutions (2006) Drug Dev. Ind. Pharm., 32, pp. 877-891; Shu, X.Z., Zhu, K.J., Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure (2002) Int. J. Pharm., 233, pp. 217-225; Spence, J.K., Bhattachar, S.N., Wesley, J.A., Martin, P.J., Babu, S.R., Increased dissolution rate and bioavailability through comicronization with microcrystalline cellulose (2005) Pharm. Dev. Technol., 10, pp. 451-460; Zhang, M., Li, X.H., Gong, Y.D., Zhao, N.M., Zhang, X.F., Properties and biocompatibility of chitosan films modified by blending with PEG (2002) Biomaterials, 23, pp. 2641-2648",
year = "2008",
doi = "10.1016/j.ijpharm.2007.09.006",
language = "English",
volume = "350",
pages = "279--290",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

Enhancement of dissolution rate and bioavailability of aceclofenac: A chitosan-based solvent change approach. / Mutalik, S.; Anju, P.; Manoj, K.; Usha, A.N.

In: International Journal of Pharmaceutics, Vol. 350, No. 1-2, 2008, p. 279-290.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Enhancement of dissolution rate and bioavailability of aceclofenac: A chitosan-based solvent change approach

AU - Mutalik, S.

AU - Anju, P.

AU - Manoj, K.

AU - Usha, A.N.

N1 - Cited By :63 Export Date: 10 November 2017 CODEN: IJPHD Correspondence Address: Mutalik, S.; Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576104 Karnataka, India; email: ssmutalik@yahoo.com Chemicals/CAS: aceclofenac, 89796-99-6; chitosan, 9012-76-4; aceclofenac, 89796-99-6; Anti-Inflammatory Agents, Non-Steroidal; Chitosan, 9012-76-4; Diclofenac, 15307-86-5; Solvents Manufacturers: Lupin Laboratories, India References: Agnihotri, S.A., Mallikarjuna, N.N., Aminabhavi, T.M., Recent advances on chitosan-based micro- and nanoparticles in drug delivery (2004) J. Control. Rel., 100, pp. 5-28; Anal, A.K., Stevens, W.F., Chitosan-alginate multilayer beads for controlled release of ampicillin (2005) Int. J. Pharm., 290, pp. 45-54; Babu, G.V.M.M., Prasad, C.D.S., Murthy, K.V.R., Evaluation of modified gum karaya as carrier for the dissolution enhancement of poorly water-soluble drug nimodipine (2002) Int. J. Pharm., 234, pp. 1-17; Balakrishnan, A., Rege, B.D., Amidon, G.L., Polli, J.E., Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity (2004) J. Pharm. Sci., 93, pp. 2064-2075; Banakar, U.V., (1992) Pharmaceutical Dissolution Testing, 49. , Marcel Dekker, New York; Cai, K., Rechtenbachb, A., Haoa, J., Bosserta, J., Jandt, K.D., Polysaccharide-protein surface modification of titanium via a layer-by-layer technique: characterization and cell behaviour aspects (2005) Biomaterials, 26, pp. 5960-5971; Dupuis, G., LeHoux, J., Recovery of chitosan from aqueous acidic solutions by salting-out. Part 2. Use of salts of organic acids (2007) Carbohydrate Polym., 68, pp. 287-294; Fukuda, M., Peppas, N.A., McGinity, J.W., Properties of sustained release hot-melt extruded tablets containing chitosan and xanthan gum (2006) Int. J. Pharm., 310, pp. 90-100; Gowda, K.V., Rajan, D.S., Mandal, U., Selvan, P.S., Sam Solomon, W.D., Bose, A., Sarkar, A.K., Chattaraj, T.K., Evaluation of bioequivalence of two formulations containing 100 mg of aceclofenac (2006) Drug Dev. Ind. Pharm., 32, pp. 1219-1225; Hel, P., Davis, S.S., Illum, L., Chitosan microspheres prepared by spray drying (1999) Int. J. Pharm., 187, pp. 53-65; Imai, T., Shiraishi, S., Saito, H., Otagiri, M., Interaction of indomethacin with low molecular weight chitosan, and improvements of some pharmaceutical properties of indomethacin by low molecular weight chitosans (1991) Int. J. Pharm., 67, pp. 11-20; Kapoor, A., Mujumdar, D.K., Yadav, M.R., Crystal forms of nimesulide-a sulfonanilide (non-steroidal anti-inflammatory drug) (1998) Indian J. Chem. B, 37, pp. 572-574; Kim, T., Shin, J., Lee, B., Enhanced dissolution and bioavailability of poorly water-soluble aceclofenac using solid dispersion system (2001) AAPS, Annual Meeting, Denver, , Colorado, USA, October 21-25; Kulkarni, S.K., (1997) Handbook of Experimental Pharmacology. second ed., , Vallabh Prakashan, New Delhi; Kumar, V.S.G., Mishra, D.N., Preparation, characterization and in vitro dissolution studies of solid systems of valdecoxib with chitosan (2006) Chem. Pharm. Bull., 54, pp. 1102-1106; Lu, Z., Steenekamp, J.H., Hamman, J.H., Cross-linked cationic polymer microparticles: effect of n-trimethyl chitosan chloride on the release and permeation of ibuprofen (2005) Drug Dev. Ind. Pharm., 31, pp. 311-317; Maestrelli, F., Zerrouk, N., Chemtob, C., Mura, P., Influence of chitosan and its glutamate and hydrochloride salts on naproxen dissolution rate and permeation across Caco-2 cells (2004) Int. J. Pharm., 271, pp. 257-267; Moneghini, M., Kikie, I., Voinovich, D., Perissutti, B., Filipovic-Grcic, J., Processing of carbamazepine-PEG 4000 solid dispersions with supercritical carbon dioxide: preparation, characterization and in vitro dissolution (2001) Int. J. Pharm., 222, pp. 129-138; Mura, P., Zerrouk, N., Mennini, N., Maestrelli, F., Chemtob, C., Development and characterization of naproxen-chitosan solid systems with improved drug dissolution properties (2003) Eur. J. Pharm. Sci., 19, pp. 67-75; Mutalik, S., Usha, A.N., Reddy, M.S., Ranjith, A.K., Pandey, S., Improved bioavailability of aceclofenac from spherical agglomerates: development, in vitro and preclinical studies (2007) Pak. J. Pharm. Sci., 3, pp. 218-226; Mutalik, S., Naha, A., Usha, N., Ranjith, A.K., Musmade, P., Manoj, K., Anju, P., Prasanna, S., Preparation, In vitro, preclinical and clinical evaluations of once daily sustained release tablets of aceclofenac (2007) Arch. Pharm. Res., 30, pp. 222-234; Nijlen, T.V., Brennan, K., Mooter, V.G., Blaton, N., Kinget, R., Augustijns, P., Improvement of the dissolution rate of artemisinin by means of supercritical fluid technology and solid dispersions (2003) Int. J. Pharm., 254, pp. 173-181; Nokhodchi, A., The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (indomethacin) from liquisolid compacts (2005) J. Pharm. Pharmaceut. Sci., 8, pp. 18-25; Paradkar, A.R., Pawar, A.P., Chordiya, J.K., Patil, V.B., Ketkar, A.R., Spherical crystallization of celecoxib (2002) Drug Dev. Ind. Pharm., 28, pp. 1213-1220; Park, S., Choi, H., The effects of surfactants on the dissolution profiles of poorly water-soluble acidic drugs (2006) Int. J. Pharm., 321, pp. 35-41; Pennings, F.H., Kwee, B.L.S., Vromans, H., Influence of enzymes and surfactants on the disintegration behavior of cross-linked hard gelatin capsules during dissolution (2006) Drug Dev. Ind. Pharm., 32, pp. 33-37; Perrut, M., Jung, J., Leboeuf, F., Enhancement of dissolution rate of poorly-soluble active ingredients by supercritical fluid processes. Part I. Micronization of neat particles (2005) Int. J. Pharm., 288, pp. 3-10; Portero, A., Remunan-Lopez, Vila-Jato, J.L., Effect of chitosan and chitosan glutamate enhancing the dissolution properties of the poorly water soluble drug nifedipine (1998) Int. J. Pharm., 175, pp. 75-84; Rawlinson, C.F., Williams, A.C., Timmins, P., Grimsey, I., Polymer-mediated disruption of drug crystallinity (2007) Int. J. Pharm., 336, pp. 42-48; Rowe, R.C., Sheskey, P.J., Owen, S.C., (2006) Handbook of Pharmaceutical Excipients, , Pharmaceutical Press, London, United Kingdom; Shinozaki, H., Oguchi, T., Suzuki, S., Aoki, K., Sako, T., Morishita, S., Tozuka, Y., Yamamoto, K., Micronization and polymorphic conversion of tolbutamide and barbital by rapid expansion of supercritical solutions (2006) Drug Dev. Ind. Pharm., 32, pp. 877-891; Shu, X.Z., Zhu, K.J., Controlled drug release properties of ionically cross-linked chitosan beads: the influence of anion structure (2002) Int. J. Pharm., 233, pp. 217-225; Spence, J.K., Bhattachar, S.N., Wesley, J.A., Martin, P.J., Babu, S.R., Increased dissolution rate and bioavailability through comicronization with microcrystalline cellulose (2005) Pharm. Dev. Technol., 10, pp. 451-460; Zhang, M., Li, X.H., Gong, Y.D., Zhao, N.M., Zhang, X.F., Properties and biocompatibility of chitosan films modified by blending with PEG (2002) Biomaterials, 23, pp. 2641-2648

PY - 2008

Y1 - 2008

N2 - In this study the significant effect of chitosan on improving the dissolution rate and bioavailability of aceclofenac has been demonstrated by simple solvent change method. Chitosan was precipitated on aceclofenac crystals using sodium citrate as the salting out agent. The pure drug and the prepared co-crystals with different concentrations of chitosan (0.05-0.6%) were characterized in terms of solubility, drug content, particle size, thermal behaviour (differential scanning calorimetry, DSC), X-ray diffraction (XRD), morphology (scanning electron microscopy, SEM), in vitro drug release and stability studies. The in vivo performance was assessed by preclinical pharmacodynamic (analgesic and anti-inflammatory activity) and pharmacokinetic studies. The particle size of the prepared co-crystals was drastically reduced during the formulation process. The DSC showed a decrease in the melting enthalpy indicating disorder in the crystalline content. The XRD also revealed a characteristic decrease in crystallinity. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of aceclofenac from optimized crystal formulation was attributed to the wetting effect of chitosan, decreased drug crystallinity, altered surface morphology and micronization. The optimized co-crystals exhibited excellent stability on storage at accelerated conditions. The in vivo studies revealed that the optimized crystal formulation provided a rapid pharmacological response in mice and rats besides exhibiting improved pharmacokinetic parameters in rats. © 2007 Elsevier B.V. All rights reserved.

AB - In this study the significant effect of chitosan on improving the dissolution rate and bioavailability of aceclofenac has been demonstrated by simple solvent change method. Chitosan was precipitated on aceclofenac crystals using sodium citrate as the salting out agent. The pure drug and the prepared co-crystals with different concentrations of chitosan (0.05-0.6%) were characterized in terms of solubility, drug content, particle size, thermal behaviour (differential scanning calorimetry, DSC), X-ray diffraction (XRD), morphology (scanning electron microscopy, SEM), in vitro drug release and stability studies. The in vivo performance was assessed by preclinical pharmacodynamic (analgesic and anti-inflammatory activity) and pharmacokinetic studies. The particle size of the prepared co-crystals was drastically reduced during the formulation process. The DSC showed a decrease in the melting enthalpy indicating disorder in the crystalline content. The XRD also revealed a characteristic decrease in crystallinity. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with pure drug. The considerable improvement in the dissolution rate of aceclofenac from optimized crystal formulation was attributed to the wetting effect of chitosan, decreased drug crystallinity, altered surface morphology and micronization. The optimized co-crystals exhibited excellent stability on storage at accelerated conditions. The in vivo studies revealed that the optimized crystal formulation provided a rapid pharmacological response in mice and rats besides exhibiting improved pharmacokinetic parameters in rats. © 2007 Elsevier B.V. All rights reserved.

U2 - 10.1016/j.ijpharm.2007.09.006

DO - 10.1016/j.ijpharm.2007.09.006

M3 - Article

VL - 350

SP - 279

EP - 290

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -