Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: A preliminary study

R.K. Averineni, S.G. Sunderajan, S. Mutalik, U. Nayak, G. Shavi, K. Armugam, S.R. Meka, S. Pandey, U. Nayanabhirama

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m-1 S-2 and more than 2.5 kg/3 cm2, respectively. The percent drug content was 98.5 ± 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically. © 2009 Informa UK Ltd.
Original languageEnglish
Pages (from-to)199-207
Number of pages9
JournalPharmaceutical Development and Technology
Volume14
Issue number2
DOIs
Publication statusPublished - 2009

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Cheek
Motion Pictures
Fibrosis
Pharmaceutical Preparations
Tensile Strength
Swine
Pharmacokinetics
Therapeutics
Taurocholic Acid
Cyclooxygenase 2 Inhibitors
Chitosan
Mouth Mucosa
Dialysis
Healthy Volunteers
Polymers
Mucous Membrane
Weights and Measures
In Vitro Techniques
valdecoxib

Cite this

@article{359075e9c27d4b7faa6e5996dc86f265,
title = "Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: A preliminary study",
abstract = "The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m-1 S-2 and more than 2.5 kg/3 cm2, respectively. The percent drug content was 98.5 ± 1.3{\%}. The in vitro drug release from the selected formulation showed that about 69.34{\%} of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70{\%} and 54.39{\%}, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically. {\circledC} 2009 Informa UK Ltd.",
author = "R.K. Averineni and S.G. Sunderajan and S. Mutalik and U. Nayak and G. Shavi and K. Armugam and S.R. Meka and S. Pandey and U. Nayanabhirama",
note = "Cited By :29 Export Date: 10 November 2017 CODEN: PDTEF Correspondence Address: Averineni, R. K.; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576 104, Karnataka State, India; email: ranjith.kumar@manipal.edu Chemicals/CAS: chitosan, 9012-76-4; hydroxypropylmethylcellulose, 9004-65-3; taurocholic acid, 145-42-6, 59005-70-8, 81-24-3; valdecoxib, 181695-72-7; methylcellulose, 79484-92-7, 9004-67-5; Chitosan, 9012-76-4; Cyclooxygenase Inhibitors; Drug Carriers; Isoxazoles; Methylcellulose, 9004-67-5; Sulfonamides; Taurocholic Acid, 81-24-3; hypromellose, 8063-82-9; valdecoxib Tradenames: valus, Glenmark, India Manufacturers: Glenmark, India; Unichem, India References: Shojaei, A.H., Buccal mucosa as a route for systemic drug delivery: A review (1998) J. Pharm. Pharmaceut. Sci., 1, pp. 15-30; Joshi, M., Patravale, V., Formulation and evaluation of nanostructured lipid carrier (NLC)-based gel of valdecoxib (2006) Drug Dev. Ind. Pharmacy., 32, pp. 911-918; Sveinsson, S.J., Holbrook, P.W., Oral mucosa adhesive ointment containing liposomal corticosteroid (1993) Int. J. Pharm., 95, pp. 105-109; Schor, J.M., Davis, S.S., Nigalaye, A., Bolton, S., Sudarin transmucosal tablets (1983) Drug Dev. Ind. Pharm., 9, pp. 1359-1377; Ishida, M., Nambu, N., Nagai, T., Highly viscous gel ointment containing Carbopol for application to the oral mucosa (1983) Chem. Pharm. Bull., 31, pp. 4561-4564; Bremecker, K.D., Strempel, H., Klein, G., Novel concept for a mucosal adhesive ointment (1984) J. Pharm. Sci., 73, pp. 548-552; Sengodan, G., Vijayakumar, Mishra, D.N., Preparation, characterization and in vitro dissolution studies of solid systems of valdecoxib with chitosan (2006) Chem. Pharm. Bull., 54 (8), pp. 1102-1106; Blanco, M.D., Gomez, C., Olmo, R., Chitosan microspheres in PLG films as devices for cytarabine release (2000) Int. J. Pharm., 202, pp. 29-39; Anders, R., Merkle, H.P., Evaluation of laminated mucoadhesive films for buccal drug delivery (1989) Int. J. Pharm., 49, pp. 231-240; Guo, J.H., Bioadhesive polymer buccal films for buprenorphine controlled delivery: Formulation in vitro adhesion and release properties (1994) Drug Dev. Ind. Pharmacy., 20, pp. 2809-2821; Kohda, Y., Kobayashi, H., Baba, Y., Yuasa, H., Ozeki, T., Kanaya, Y., Sagara, E., Controlled release of lidocaine from buccal mucosa-adhesive films with solid dispersion (1997) Int. J. Pharm., 158, pp. 147-155; Wong, C.F., Yuen, K.H., Peh, K.K., Formulation and evaluation of controlled release Eudragit buccal films (1999) Int. J. Pharm., 178, pp. 11-22; Janes, K.A., Fresneau, M.P., Marazuela, A., Chitosan nanoparticles as delivery systems for doxorubicin (2001) J. Control Release., 73, pp. 255-267; Ruel, G.E., Chenite, A., Chaput, C., Characterization of thermosensitive chitosan gels for the sustained delivery of drugs (2000) Int. J. Pharm., 203, pp. 89-98; Muzarelli, R., Baldassarre, V., Conti, F., Biological activity of chitosan: Ultra structural study (1998) Biomaterials, 9, pp. 247-252; Senel, S., Ikinci, G., Kas, S., Chitosan films and hydrogels of cholhexidine gluconate for oral mucosal delivery (2000) Int. J. Pharm., 193, pp. 197-203; Ouchi, T., Banba, T., Fujimoto, M., Synthesis and antitumor activity of chitosan carrying 5-fluorouracil (1989) Makromol. Chem., 190, pp. 1817-1825; Jameela, S.R., Jayakrisnan, A., Glutaraldehyde cross-linked chitosan microspheres as a long acting biodegradable drug delivery vehicle: Studies on the in vitro release of mitoxantrone and in vivo degradation of microspheres in rat muscle (1995) Biomaterials, 16, pp. 769-775; Miwa, A., Ishibe, A., Nakano, M., Development of novel chitosan derivatives as micellar carriers of taxol (1998) Pharm. Res., 1, pp. 1844-1850; Micheal, T.J., Jame, H.S., Carlo, P., Nonsteroidal anti-inflammatory drugs as anticancer agent: Mechanistic, pharmacologic, and clinical issues (2002) J. Natl. Cancer. Inst., 94, pp. 252-266; Sawayangi, Y., Nambu, N., Nagai, T., Permeation of drugs through chitosan membranes (1982) Chem. Pharm. Bull., 30, pp. 3297-3301; Eouania, C., Piccerellea, P.H., Prinderrea, P., Bourretb, E., Joachima, J., In-vitro comparative study of buccal mucoadhesive performance of different polymeric films (2001) Euro. J. Pharm. Biopharm., 52, pp. 45-55; Peh, K.K., Wong, C.F., Polymeric films as vehicle for buccal delivery: Swelling, mechanical and bioadhesive properties (1999) J. Pharm. Pharm. Sci., 2, pp. 53-61; Parodi, B., Russo, E., Caviglioli, G., Cafaggi, S., Bignardi, G., Development and characterization of a buccoadhesive dosage form of oxycodone hydrochloride (1996) Drug Dev. Ind. Pharm., 22, pp. 445-450; Nakamura, F., Ohta, R., MacHida, Y., Nagai, T., In-vitro and in-vivo nasal mucoadhesion of some water-soluble polymers (1996) Int. J. Pharm., 134, pp. 173-181; Perioli, L., Ambrogi, P., Angelici, F., Ricci, M., Giovagnolia, S., Capuccellab, M., Rossia, C., Development of mucoadhesive patches for buccal administration of ibuprofen (2004) J. Control. Rel., 99, pp. 73-82; Lehr, C.M., Bouwstra, J.A., Schacht, E.H., Junginger, H.E., In-vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers (1992) Int. J. Pharm., 78, pp. 43-48; Panomsuk, S.P., Hatanaka, T., Aiba, T., Katayama, K., Koizumi, T., A study of the hydrophilic cellulose matrix: Effect of drugs on the swelling properties (1996) Chem. Pharm. Bull., 44, pp. 1039-1042; Bottenberg, P., Cleymaet, R., Muyncha, C.D., Remon, J.P., Coomans, D., Slop, D., Comparison of salivary fluoride concentration after administration of a bioadhesive slow-release tablet and a conventional fluoride tablet (1992) J. Pharm. Pharmacol., 44, pp. 684-686; Peppas, N.A., Mongia, N.K., Ultrapure poly (vinyl alcohol) with mucoadhesive drug delivery characteristics (1997) Eur. J. Pharm. Biopharm., 43, pp. 51-58; Zenriksen, I., Green, L., Smart, J.D., Smistad, G., Karlsen, J., Bioadhesion of hydrated chitosans: An in-vitro and in-vivo study (1996) Int. J. Pharm., 145, pp. 231-240; Peppas, N.A., Analysis of Fickian and non-Fickian drug release from polymers (1985) Pharmacut. Helv., 60, pp. 110-111; Rossi, S., Ferrari, F., Bonferoni, M.C., Caramella, C., Characterization of chitosan hydrochloride-mucin rheological interaction: Influence of polymer concentration and polymer:mucin weight ratio (2001) Eur. J. Pharm. Sci., 12 (479-485), pp. 208-215",
year = "2009",
doi = "10.1080/10837450802498928",
language = "English",
volume = "14",
pages = "199--207",
journal = "Pharmaceutical Development and Technology",
issn = "1083-7450",
publisher = "Informa Healthcare",
number = "2",

}

Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: A preliminary study. / Averineni, R.K.; Sunderajan, S.G.; Mutalik, S.; Nayak, U.; Shavi, G.; Armugam, K.; Meka, S.R.; Pandey, S.; Nayanabhirama, U.

In: Pharmaceutical Development and Technology, Vol. 14, No. 2, 2009, p. 199-207.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Development of mucoadhesive buccal films for the treatment of oral sub-mucous fibrosis: A preliminary study

AU - Averineni, R.K.

AU - Sunderajan, S.G.

AU - Mutalik, S.

AU - Nayak, U.

AU - Shavi, G.

AU - Armugam, K.

AU - Meka, S.R.

AU - Pandey, S.

AU - Nayanabhirama, U.

N1 - Cited By :29 Export Date: 10 November 2017 CODEN: PDTEF Correspondence Address: Averineni, R. K.; Department of Pharmaceutics, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, 576 104, Karnataka State, India; email: ranjith.kumar@manipal.edu Chemicals/CAS: chitosan, 9012-76-4; hydroxypropylmethylcellulose, 9004-65-3; taurocholic acid, 145-42-6, 59005-70-8, 81-24-3; valdecoxib, 181695-72-7; methylcellulose, 79484-92-7, 9004-67-5; Chitosan, 9012-76-4; Cyclooxygenase Inhibitors; Drug Carriers; Isoxazoles; Methylcellulose, 9004-67-5; Sulfonamides; Taurocholic Acid, 81-24-3; hypromellose, 8063-82-9; valdecoxib Tradenames: valus, Glenmark, India Manufacturers: Glenmark, India; Unichem, India References: Shojaei, A.H., Buccal mucosa as a route for systemic drug delivery: A review (1998) J. Pharm. Pharmaceut. Sci., 1, pp. 15-30; Joshi, M., Patravale, V., Formulation and evaluation of nanostructured lipid carrier (NLC)-based gel of valdecoxib (2006) Drug Dev. Ind. Pharmacy., 32, pp. 911-918; Sveinsson, S.J., Holbrook, P.W., Oral mucosa adhesive ointment containing liposomal corticosteroid (1993) Int. J. Pharm., 95, pp. 105-109; Schor, J.M., Davis, S.S., Nigalaye, A., Bolton, S., Sudarin transmucosal tablets (1983) Drug Dev. Ind. Pharm., 9, pp. 1359-1377; Ishida, M., Nambu, N., Nagai, T., Highly viscous gel ointment containing Carbopol for application to the oral mucosa (1983) Chem. Pharm. Bull., 31, pp. 4561-4564; Bremecker, K.D., Strempel, H., Klein, G., Novel concept for a mucosal adhesive ointment (1984) J. Pharm. Sci., 73, pp. 548-552; Sengodan, G., Vijayakumar, Mishra, D.N., Preparation, characterization and in vitro dissolution studies of solid systems of valdecoxib with chitosan (2006) Chem. Pharm. Bull., 54 (8), pp. 1102-1106; Blanco, M.D., Gomez, C., Olmo, R., Chitosan microspheres in PLG films as devices for cytarabine release (2000) Int. J. Pharm., 202, pp. 29-39; Anders, R., Merkle, H.P., Evaluation of laminated mucoadhesive films for buccal drug delivery (1989) Int. J. Pharm., 49, pp. 231-240; Guo, J.H., Bioadhesive polymer buccal films for buprenorphine controlled delivery: Formulation in vitro adhesion and release properties (1994) Drug Dev. Ind. Pharmacy., 20, pp. 2809-2821; Kohda, Y., Kobayashi, H., Baba, Y., Yuasa, H., Ozeki, T., Kanaya, Y., Sagara, E., Controlled release of lidocaine from buccal mucosa-adhesive films with solid dispersion (1997) Int. J. Pharm., 158, pp. 147-155; Wong, C.F., Yuen, K.H., Peh, K.K., Formulation and evaluation of controlled release Eudragit buccal films (1999) Int. J. Pharm., 178, pp. 11-22; Janes, K.A., Fresneau, M.P., Marazuela, A., Chitosan nanoparticles as delivery systems for doxorubicin (2001) J. Control Release., 73, pp. 255-267; Ruel, G.E., Chenite, A., Chaput, C., Characterization of thermosensitive chitosan gels for the sustained delivery of drugs (2000) Int. J. Pharm., 203, pp. 89-98; Muzarelli, R., Baldassarre, V., Conti, F., Biological activity of chitosan: Ultra structural study (1998) Biomaterials, 9, pp. 247-252; Senel, S., Ikinci, G., Kas, S., Chitosan films and hydrogels of cholhexidine gluconate for oral mucosal delivery (2000) Int. J. Pharm., 193, pp. 197-203; Ouchi, T., Banba, T., Fujimoto, M., Synthesis and antitumor activity of chitosan carrying 5-fluorouracil (1989) Makromol. Chem., 190, pp. 1817-1825; Jameela, S.R., Jayakrisnan, A., Glutaraldehyde cross-linked chitosan microspheres as a long acting biodegradable drug delivery vehicle: Studies on the in vitro release of mitoxantrone and in vivo degradation of microspheres in rat muscle (1995) Biomaterials, 16, pp. 769-775; Miwa, A., Ishibe, A., Nakano, M., Development of novel chitosan derivatives as micellar carriers of taxol (1998) Pharm. Res., 1, pp. 1844-1850; Micheal, T.J., Jame, H.S., Carlo, P., Nonsteroidal anti-inflammatory drugs as anticancer agent: Mechanistic, pharmacologic, and clinical issues (2002) J. Natl. Cancer. Inst., 94, pp. 252-266; Sawayangi, Y., Nambu, N., Nagai, T., Permeation of drugs through chitosan membranes (1982) Chem. Pharm. Bull., 30, pp. 3297-3301; Eouania, C., Piccerellea, P.H., Prinderrea, P., Bourretb, E., Joachima, J., In-vitro comparative study of buccal mucoadhesive performance of different polymeric films (2001) Euro. J. Pharm. Biopharm., 52, pp. 45-55; Peh, K.K., Wong, C.F., Polymeric films as vehicle for buccal delivery: Swelling, mechanical and bioadhesive properties (1999) J. Pharm. Pharm. Sci., 2, pp. 53-61; Parodi, B., Russo, E., Caviglioli, G., Cafaggi, S., Bignardi, G., Development and characterization of a buccoadhesive dosage form of oxycodone hydrochloride (1996) Drug Dev. Ind. Pharm., 22, pp. 445-450; Nakamura, F., Ohta, R., MacHida, Y., Nagai, T., In-vitro and in-vivo nasal mucoadhesion of some water-soluble polymers (1996) Int. J. Pharm., 134, pp. 173-181; Perioli, L., Ambrogi, P., Angelici, F., Ricci, M., Giovagnolia, S., Capuccellab, M., Rossia, C., Development of mucoadhesive patches for buccal administration of ibuprofen (2004) J. Control. Rel., 99, pp. 73-82; Lehr, C.M., Bouwstra, J.A., Schacht, E.H., Junginger, H.E., In-vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers (1992) Int. J. Pharm., 78, pp. 43-48; Panomsuk, S.P., Hatanaka, T., Aiba, T., Katayama, K., Koizumi, T., A study of the hydrophilic cellulose matrix: Effect of drugs on the swelling properties (1996) Chem. Pharm. Bull., 44, pp. 1039-1042; Bottenberg, P., Cleymaet, R., Muyncha, C.D., Remon, J.P., Coomans, D., Slop, D., Comparison of salivary fluoride concentration after administration of a bioadhesive slow-release tablet and a conventional fluoride tablet (1992) J. Pharm. Pharmacol., 44, pp. 684-686; Peppas, N.A., Mongia, N.K., Ultrapure poly (vinyl alcohol) with mucoadhesive drug delivery characteristics (1997) Eur. J. Pharm. Biopharm., 43, pp. 51-58; Zenriksen, I., Green, L., Smart, J.D., Smistad, G., Karlsen, J., Bioadhesion of hydrated chitosans: An in-vitro and in-vivo study (1996) Int. J. Pharm., 145, pp. 231-240; Peppas, N.A., Analysis of Fickian and non-Fickian drug release from polymers (1985) Pharmacut. Helv., 60, pp. 110-111; Rossi, S., Ferrari, F., Bonferoni, M.C., Caramella, C., Characterization of chitosan hydrochloride-mucin rheological interaction: Influence of polymer concentration and polymer:mucin weight ratio (2001) Eur. J. Pharm. Sci., 12 (479-485), pp. 208-215

PY - 2009

Y1 - 2009

N2 - The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m-1 S-2 and more than 2.5 kg/3 cm2, respectively. The percent drug content was 98.5 ± 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically. © 2009 Informa UK Ltd.

AB - The objective of the present study was to develop the mucoadhesive buccal film of valdecoxib for the treatment of oral sub mucous fibrosis, a localized buccal disease. Valdecoxib, a novel COX-2 inhibitor has been reported to be used in various osteopathic and rheumatoid conditions as oral therapy. The films were made out of chitosan and HPMC K4M as polymers. Sodium taurocholate was used as a permeation enhancer. All the formulations were examined for film thickness, swelling properties, drug content, weight variation, in vitro release studies, bioadhesive force, tensile strength, diffusion studies using pig mucosa and pharmacokinetic study in healthy male volunteers. Prepared films were thin, flexible, smooth and transparent. Bioadhesive force and tensile strength of the optimized formulation were found to be 75 ± 4 kg m-1 S-2 and more than 2.5 kg/3 cm2, respectively. The percent drug content was 98.5 ± 1.3%. The in vitro drug release from the selected formulation showed that about 69.34% of the drug payload was released up to 6 hours. The drug permeation through the dialysis sac and pig buccal mucosa was found to be 62.70% and 54.39%, respectively. Pharmacokinetic studies of the buccal mucoadhesive film showed that the drug was released locally at the target site of action, and a very small amount might have absorbed systemically. © 2009 Informa UK Ltd.

U2 - 10.1080/10837450802498928

DO - 10.1080/10837450802498928

M3 - Article

VL - 14

SP - 199

EP - 207

JO - Pharmaceutical Development and Technology

JF - Pharmaceutical Development and Technology

SN - 1083-7450

IS - 2

ER -