In vitro Studies of Mucoadhesiveness and Release of Nicotinamide Oral Gels Prepared from Bioadhesive Polymers
The aim of the present study was to evaluate the
mucoadhesion and the release of nicotinamide gel formulations using
in vitro methods. An agar plate technique was used to investigate the
adhesiveness of the gels whereas a diffusion apparatus was employed
to determine the release of nicotinamide from the gels. In this
respect, 10% w/w nicotinamide gels containing bioadhesive
polymers: Carbopol 934P (0.5-2% w/w), hydroxypropylmethyl
cellulose (HPMC) (4-10% w/w), sodium carboxymethyl cellulose
(SCMC) (4-6% w/w) and methylcellulose 4000 (MC) (3-5% w/w)
were prepared. The gel formulations had pH values in the range of
7.14 - 8.17, which were considered appropriate to oral mucosa
application. In general, the rank order of pH values appeared to be
SCMC > MC4000 > HPMC > Carbopol 934P. Types and
concentrations of polymers used somewhat affected the
adhesiveness. It was found that anionic polymers (Carbopol 934 and
SCMC) adhered more firmly to the agar plate than the neutral
polymers (HPMC and MC 4000). The formulation containing 0.5%
Carbopol 934P (F1) showed the highest release rate. With the
exception of the formulation F1, the neutral polymers tended to give
higher relate rates than the anionic polymers. For oral tissue
treatment, the optimum has to be balanced between the residence
time (adhesiveness) of the formulations and the release rate of the
drug. The formulations containing the anionic polymers: Carbopol
934P or SCMC possessed suitable physical properties (appearance,
pH and viscosity). In addition, for anionic polymer formulations,
justifiable mucoadhesive properties and reasonable release rates of
nicotinamide were achieved. Accordingly, these gel formulations
may be applied for the treatment of oral mucosal lesions.
[1] A. H. Shojaei, "Buccal mucosa as a route for systemic drug delivery: a
review," J. Pharm. Pharm. Sci., vol. 1, pp 15-30, Jan. 1998.
[2] D. N. Thorburn and M. M. Ferguson, "Topical corticosteroids and
lesions of the oral mucosa," Adv. Drug Deliv. Rev., vol. 13, pp. 135-
149, Jan. 1994.
[3] C. S. Sweetman, Martindale: The Complete Drug Reference. 34 th ed.
London: The Pharmaceutical Press, 2005, pp. 1441-1442.
[4] U. R. Hengge, T. Ruzicka, R. A. Schwartz, and M. J. Cork, "Adverse
effects of topical glucocorticosteroids," J. Am. Acad. Dermatol., vol. 4,
pp. 1-15, Jan. 2006.
[5] S. J. Sveinsson and W. P. Holbrook, "Oral mucosal adhesive ointment
containing liposomal corticosteroid," Int. J. Pharm., vol. 95, pp.105-109,
June 1993.
[6] N. Otte, C. Borelli, and H. C. Korting, "Nicotinamide-biologic actions of
an emerging cosmetic ingredient." Int. J. Cos. Sci., vol. 27, pp. 255-261,
Oct. 2005.
[7] N. M. Niren, "Pharmacologic doses of nicotinamide in the treatment of
inflammatory skin conditions: a review," Cutis, vol. 77 (1 Suppl.),
pp.11-16, Jan. 2006.
[8] Expert Group on Vitamins and Minerals. Safe Upper Levels for
Vitamins and Minerals. United Kingdom: Food Standards Agency, 2003,
pp. 52-61.
[9] J. I. Rader, R. J. Calvert, and J.N. Hathcock, "Hepatic toxicity of
unmodified and time -release preparations of niacin," Am J. Med., vol.
92, pp. 77-81, Jan. 1992.
[10] A. R. Shalita, J. G. Smith, L. C. Parish, M. S. Sofman, and D. K.
Chalker, "Topical nicotinamide compared with clindamycin gel in the
treatment of inflammatory acne vulgaris," Int. J. Dermatol., vol. 34, pp.
434-437, June 1995.
[11] D. L. Bissett and J. E. Oblong, "Cosmeceutical vitamins: Vitamin B,".
in Procedures in Cosmetic Dermatology Series: Cosmeceuticals, Z. D.
Draelos, Ed. Philadelphia: Elsevir Saunders, 2005, pp. 57-62.
[12] T. Hakozaki, L. Minwalla, J. Zhuang, M. Chhoa, A. Matsubara, K.
Miyamoto, A. Greatens, G. G. Hillebrand, D. L. Bissett, and R. E.
Biossy., "The effect of nicotinamide on reducing cutaneous
hyperpigmentation and suppression of melanosome transfer," Br. J.
Dermatol., vol. 147, pp. 20-31, July 2002.
[13] F. C. Kull, Jr., and F. A. Voelker, "Method of promoting healing," U.S.
Patent 4725609, Feb. 16, 1988.
[14] R. B. Gandhi and J. R. Robinson, "Oral cavity as a site for bioadhesive
drug delivery," Adv. Drug Deliv. Rev., vol. 13, pp. 43-74, Jan. 1994.
[15] R. L. Dunn, "Polymeric matrices," in Polymeric Drugs and Drug
Delivery Systems, R. L. Dunn, and R. M. Ottenbrite, Eds. Washington,
DC: American Chemical Society, 1991, pp. 11-23.
[16] N. A. Peppas, P. Bures, W. Leobandung and H. Ichikawa, "Hydrogels in
pharmaceutical formulations," Eur. J. Pharm. Biopharm., vol. 50, pp. 27-
46, July 2000.
[17] J. Y. Fang, Y. L. Leu, Y. Y. Wang, and Y. H. Tsai, "In vitro topical
application and in vivo pharmacodynamic evaluation of nonivamide
hydrogels using Wistar rat as an animal model," Eur. J. Pharm. Sci., vol.
15, pp. 417-423, June 2002.
[18] L. Shoufeng, L. Senshang, P.D. Bruce, L.M. Haresh, and W.C. Yie,
"Effect of HPMC and carbopol on the release and floating properties of
gastric floating drug delivery system using factorial design," Int. J.
Pharm., vol. 253, pp. 13-22, Mar. 2003.
[19] A. A. Koffi, F. Agnely, G. Ponchel, and J.L. Grossiord, "Modulation of
the rheological and mucoadhesive properties of thermosensitive
poloxamer-based hydrogels intended for the rectal administration of
quinine," Eur. J. Pharm. Sci., vol. 27, pp. 328-335, Mar. 2006.
[20] F. Nakamura, R. Ohta, Y. Machida, and T. Nagai, "In vitro and in vivo
nasal mucoadhesion of some water-soluble polymers," Int. J. Pharm.,
vol. 134, pp. 173-181, May 1996.
[21] C. M. Klech, "Gels and Jellies," in Encyclopedia of Pharmaceutical
Technology, vol. 6, J. Swarbrick, and J. C. Boylan, Eds. New York:
Marcel Dekker, Inc., 1992, pp. 415-439
[22] S. Ungphaiboon and Y. Maitani, "In vitro permeation studies of
triamcinolone acetonide mouthwashes," Int. J. Pharm., vol. 220, pp. 111-
117, June 2001.
[23] W. I. Higuchi, "Diffusional models useful in biopharmaceutics: drug
release rate processes," J. Pharm. Sci., vol. 56, pp. 315-324, 1967.
[24] D. J. Aframian, T. Davidowitz, and R. Benoliel, "The distribution of oral
mucosal pH values in healthy saliva secretors," Oral Dis., vol 12, pp.
420-423, July 2006.
[25] C. Tas, C. K. Ozkan, A. Savaser, Y. Ozkan, U. Tasdemir, and H.
Altunay, "Nasal absorption of metoclopramide from different
Carbopol® 981 based formulations: In vitro, ex vivo and in vivo
evaluation," Eur. J. Pharm. Biopharm., vol. 64, pp.246-254, Oct. 2006.
[26] C. Tas, Y. Ozkan, A. Savaser, and T. Baykara, "In vitro release studies
of chlorpheniramine maleate from gels prepared by different cellulose
derivatives," IL Farmaco., vol. 58, pp. 605-611, Aug. 2003.
[1] A. H. Shojaei, "Buccal mucosa as a route for systemic drug delivery: a
review," J. Pharm. Pharm. Sci., vol. 1, pp 15-30, Jan. 1998.
[2] D. N. Thorburn and M. M. Ferguson, "Topical corticosteroids and
lesions of the oral mucosa," Adv. Drug Deliv. Rev., vol. 13, pp. 135-
149, Jan. 1994.
[3] C. S. Sweetman, Martindale: The Complete Drug Reference. 34 th ed.
London: The Pharmaceutical Press, 2005, pp. 1441-1442.
[4] U. R. Hengge, T. Ruzicka, R. A. Schwartz, and M. J. Cork, "Adverse
effects of topical glucocorticosteroids," J. Am. Acad. Dermatol., vol. 4,
pp. 1-15, Jan. 2006.
[5] S. J. Sveinsson and W. P. Holbrook, "Oral mucosal adhesive ointment
containing liposomal corticosteroid," Int. J. Pharm., vol. 95, pp.105-109,
June 1993.
[6] N. Otte, C. Borelli, and H. C. Korting, "Nicotinamide-biologic actions of
an emerging cosmetic ingredient." Int. J. Cos. Sci., vol. 27, pp. 255-261,
Oct. 2005.
[7] N. M. Niren, "Pharmacologic doses of nicotinamide in the treatment of
inflammatory skin conditions: a review," Cutis, vol. 77 (1 Suppl.),
pp.11-16, Jan. 2006.
[8] Expert Group on Vitamins and Minerals. Safe Upper Levels for
Vitamins and Minerals. United Kingdom: Food Standards Agency, 2003,
pp. 52-61.
[9] J. I. Rader, R. J. Calvert, and J.N. Hathcock, "Hepatic toxicity of
unmodified and time -release preparations of niacin," Am J. Med., vol.
92, pp. 77-81, Jan. 1992.
[10] A. R. Shalita, J. G. Smith, L. C. Parish, M. S. Sofman, and D. K.
Chalker, "Topical nicotinamide compared with clindamycin gel in the
treatment of inflammatory acne vulgaris," Int. J. Dermatol., vol. 34, pp.
434-437, June 1995.
[11] D. L. Bissett and J. E. Oblong, "Cosmeceutical vitamins: Vitamin B,".
in Procedures in Cosmetic Dermatology Series: Cosmeceuticals, Z. D.
Draelos, Ed. Philadelphia: Elsevir Saunders, 2005, pp. 57-62.
[12] T. Hakozaki, L. Minwalla, J. Zhuang, M. Chhoa, A. Matsubara, K.
Miyamoto, A. Greatens, G. G. Hillebrand, D. L. Bissett, and R. E.
Biossy., "The effect of nicotinamide on reducing cutaneous
hyperpigmentation and suppression of melanosome transfer," Br. J.
Dermatol., vol. 147, pp. 20-31, July 2002.
[13] F. C. Kull, Jr., and F. A. Voelker, "Method of promoting healing," U.S.
Patent 4725609, Feb. 16, 1988.
[14] R. B. Gandhi and J. R. Robinson, "Oral cavity as a site for bioadhesive
drug delivery," Adv. Drug Deliv. Rev., vol. 13, pp. 43-74, Jan. 1994.
[15] R. L. Dunn, "Polymeric matrices," in Polymeric Drugs and Drug
Delivery Systems, R. L. Dunn, and R. M. Ottenbrite, Eds. Washington,
DC: American Chemical Society, 1991, pp. 11-23.
[16] N. A. Peppas, P. Bures, W. Leobandung and H. Ichikawa, "Hydrogels in
pharmaceutical formulations," Eur. J. Pharm. Biopharm., vol. 50, pp. 27-
46, July 2000.
[17] J. Y. Fang, Y. L. Leu, Y. Y. Wang, and Y. H. Tsai, "In vitro topical
application and in vivo pharmacodynamic evaluation of nonivamide
hydrogels using Wistar rat as an animal model," Eur. J. Pharm. Sci., vol.
15, pp. 417-423, June 2002.
[18] L. Shoufeng, L. Senshang, P.D. Bruce, L.M. Haresh, and W.C. Yie,
"Effect of HPMC and carbopol on the release and floating properties of
gastric floating drug delivery system using factorial design," Int. J.
Pharm., vol. 253, pp. 13-22, Mar. 2003.
[19] A. A. Koffi, F. Agnely, G. Ponchel, and J.L. Grossiord, "Modulation of
the rheological and mucoadhesive properties of thermosensitive
poloxamer-based hydrogels intended for the rectal administration of
quinine," Eur. J. Pharm. Sci., vol. 27, pp. 328-335, Mar. 2006.
[20] F. Nakamura, R. Ohta, Y. Machida, and T. Nagai, "In vitro and in vivo
nasal mucoadhesion of some water-soluble polymers," Int. J. Pharm.,
vol. 134, pp. 173-181, May 1996.
[21] C. M. Klech, "Gels and Jellies," in Encyclopedia of Pharmaceutical
Technology, vol. 6, J. Swarbrick, and J. C. Boylan, Eds. New York:
Marcel Dekker, Inc., 1992, pp. 415-439
[22] S. Ungphaiboon and Y. Maitani, "In vitro permeation studies of
triamcinolone acetonide mouthwashes," Int. J. Pharm., vol. 220, pp. 111-
117, June 2001.
[23] W. I. Higuchi, "Diffusional models useful in biopharmaceutics: drug
release rate processes," J. Pharm. Sci., vol. 56, pp. 315-324, 1967.
[24] D. J. Aframian, T. Davidowitz, and R. Benoliel, "The distribution of oral
mucosal pH values in healthy saliva secretors," Oral Dis., vol 12, pp.
420-423, July 2006.
[25] C. Tas, C. K. Ozkan, A. Savaser, Y. Ozkan, U. Tasdemir, and H.
Altunay, "Nasal absorption of metoclopramide from different
Carbopol® 981 based formulations: In vitro, ex vivo and in vivo
evaluation," Eur. J. Pharm. Biopharm., vol. 64, pp.246-254, Oct. 2006.
[26] C. Tas, Y. Ozkan, A. Savaser, and T. Baykara, "In vitro release studies
of chlorpheniramine maleate from gels prepared by different cellulose
derivatives," IL Farmaco., vol. 58, pp. 605-611, Aug. 2003.
@article{"International Journal of Medical, Medicine and Health Sciences:60361", author = "Sarunyoo Songkro and Naranut Rajatasereekul and Nipapat Cheewasrirungrueng", title = "In vitro Studies of Mucoadhesiveness and Release of Nicotinamide Oral Gels Prepared from Bioadhesive Polymers", abstract = "The aim of the present study was to evaluate the
mucoadhesion and the release of nicotinamide gel formulations using
in vitro methods. An agar plate technique was used to investigate the
adhesiveness of the gels whereas a diffusion apparatus was employed
to determine the release of nicotinamide from the gels. In this
respect, 10% w/w nicotinamide gels containing bioadhesive
polymers: Carbopol 934P (0.5-2% w/w), hydroxypropylmethyl
cellulose (HPMC) (4-10% w/w), sodium carboxymethyl cellulose
(SCMC) (4-6% w/w) and methylcellulose 4000 (MC) (3-5% w/w)
were prepared. The gel formulations had pH values in the range of
7.14 - 8.17, which were considered appropriate to oral mucosa
application. In general, the rank order of pH values appeared to be
SCMC > MC4000 > HPMC > Carbopol 934P. Types and
concentrations of polymers used somewhat affected the
adhesiveness. It was found that anionic polymers (Carbopol 934 and
SCMC) adhered more firmly to the agar plate than the neutral
polymers (HPMC and MC 4000). The formulation containing 0.5%
Carbopol 934P (F1) showed the highest release rate. With the
exception of the formulation F1, the neutral polymers tended to give
higher relate rates than the anionic polymers. For oral tissue
treatment, the optimum has to be balanced between the residence
time (adhesiveness) of the formulations and the release rate of the
drug. The formulations containing the anionic polymers: Carbopol
934P or SCMC possessed suitable physical properties (appearance,
pH and viscosity). In addition, for anionic polymer formulations,
justifiable mucoadhesive properties and reasonable release rates of
nicotinamide were achieved. Accordingly, these gel formulations
may be applied for the treatment of oral mucosal lesions.", keywords = "Nicotinamide, bioadhesive polymer,
mucoadhesiveness, release rate, gel.", volume = "3", number = "7", pages = "151-8", }
