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Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties

Yıl 2017, Cilt: 21 Sayı: 4, 762 - 770, 01.12.2017

Öz

The use of in situ hydrogel systems for vaginal drug delivery
is an important strategy in the treatment of vaginitis. The
aim of this study was to develop in situ vaginal hyrogels for
benzydamine hydrochloride (BNZ) which were composed of
poloxamer and chitosan. The reason for development of these
hydrogels was to obtain a vaginal delivery system with improved
mechanical and mucoadhesive properties that could provide
prolonged retention time for the treatment of vaginits. The
hydrogels were also designed for once a day dosage of the drug
and to obtain a controlled release of the BNZ. For this purpose
BNZ containing hydrogel formulations using thermosensitive
polymer (Poloxamer 407) and mucoadhesive polymer
(Chitosan H, Chitosan M and Chitosan L) were developed. The
hydrogels are composed of polymers which have promising
potential for vaginal delivery systems. These formulations were
evaluated by rheology, texture, mucoadhesive profiles and drug
diffusion with a Franz diffusion cell. It was observed that the
diffusion of BNZ from the in situ poloxamer-chitosan hydrogel
was more sustained and controlled than with the poloxamer gel.
The hydrogel formulations diffused about 65.3±5.1, 80.6±3.8,
88.1±7.3 and 100.4±4.8% of BNZ at 6h. The formulation
containing Poloxamer 407 and Chitosan H has the best
controlled release profile and mucoadhesive properties, results
which indicate that it could suitable for use once a day on the
vaginal route. Moreover, the hydrogels higher mucoadhesion
exhibited by this formulation prolongs the drug residence
time compared with the poloxamer gel and may increase the
BNZ efficacy. These BNZ mucoadhesive vaginal hydrogel
formulations may be a promising alternative to conventional
dosage forms for vaginal topical therapy.

Kaynakça

  • 1. Sandri G, Rossi S, Ferrari F, Bonferoni MC, Caramella C. Strategies to improve systemic and local availability of drugs administered via vaginal route. In: Enhancement in Drug Delivery. Editors: E. Touitou, B.W. Barry, Taylor and Francis CRC Press, Boca Raton FL. 2007, pp. 441–470
  • 2. Machado R, Palmeira-De-Oliveira A, Martinez-De-Oliveira J, Palmeira-De-Oliveira R. Vaginal films for drug delivery. J Pharm Sci 2013;102: 2069-81.
  • 3. Mehta S, Verstraelen H, Vandaele L, Mehuys E, Remon JP, Vervaet C. Vaginal distribution and retention of tablets comprising starch-based multiparticulates: Evaluation by colposcopy. Drug Dev Ind Pharm 2013;39: 1944-50.
  • 4. Neves J, Bahia MF. Gels as vaginal drug delivery. Int J Pharm 2006;318: 1–14.
  • 5. Acartürk F. Mucoadhesive vaginal drug delivery systems. Recent Pat Drug Deliv Formul 2009;3: 193–205.
  • 6. Valenta C. The use of muchoadhesive polymers in vaginal drug delivery. Adv Drug Deliv Rev 2005;57: 1692–1712.
  • 7. Baloglu E, Karavana, SY, Senyigit ZA, Guneri T. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm Dev Technol 2011;16: 627–36.
  • 8. Caramella CM, Rossi S, Ferrari F, Bonferoni MC, Sandri G. Mucoadhesive and thermogelling systems for vaginal drug delivery. Adv Drug Deliv Rev 2015;15: 39-52.
  • 9. Miyazaki M, Maeda T, Hirashima K, Kurokawa N, Nagahama K, Hotta A. PEG-based nanocomposite hydrogel: Thermoresponsive sol-gel transition controlled by PLGAPEG- PLGA molecular weight and solute concentration. Polymer In Pres, 2017.
  • 10. Thompson DO. Cyclodextrins enabling excipients: Their present and future use in pharmaceuticals. Crit Rev Ther Drug Carrier Syst 1997;14:1–104.
  • 11. Aka-Any-Grah A, Bouchemal K, Koffi A, Agnely F, Zhang M, Djabourov M, Ponchel G. Formulation of mucoadhesive vaginal hydrogels insensitive to dilution with vaginal fluids. Eur J Pharm Biopharm 2010;76:296–303.
  • 12. Chang JY, Oh YK, Choi H, Kim YB, Kim CK. Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. Int J Pharm 2002;241:155–63.
  • 13. Lin HR, Sung KC, Vong WJ. In situ gelling of alginate/ pluronic solutions for ophthalmic delivery of pilocarpine. Biomacromolecules 2004;6: 2358–65
  • 14. Bilensoy E, Rouf MA, Vural I, Şen M, Hıncal AA. Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole:β-cyclodextrin complex. AAPS PharmSciTech 2006;7: E1-E8.
  • 15. Mayol L, Quaglia F, Borzacchiello A, Ambrosio L, La Rotonda MI, A novel poloxamers/hyaluronic acid in situ forming hydrogel for drug delivery: Rheological, mucoadhesive and in vitro release properties. Eur J Pharm Biopharm 2008;70: 199– 206.
  • 16. Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RF, A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur J Pharm Biopharm 2010;75:186-93.
  • 17. Perioli L, Ambrogi V, Venezia L, Giovagnoli S, Pagano C, Rossi C. Formulation studies of benzydamine mucoadhesive formulations for vaginal administration. Drug Dev Ind Pharm 2009;31: 1–11.
  • 18. Mekhemar NA, El-Agwany A.S, Radi WK, El-Hady SM. Comparative study between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on endotracheal tube cuff as regards postoperative sore throat. Braz J Anesthesiol 2016;66: 242-8.
  • 19. Perioli L, Ambrogi V, Pagano C, Massetti E, Rossi C. New solid mucoadhesive systems for benzydamine vaginal administration. Colloids Surf B Biointerfaces 2011;84:413-20.
  • 20. Schmolka IR. Artificial skin. I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res 1972;6: 571–82.
  • 21. Tuğcu-Demiröz F, Acartürk F, Erdoğan D. Development of long-acting bioadhesive vaginal gels of oxybutynin: Formulation, in vitro and in vivo evaluations. Int J Pharm 2013;457: 25-39.
  • 22. Jones DS, Woolfson AD, Brown AF. Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers. Int J Pharm 1997;151:223–33.
  • 23. Tuğcu-Demiröz F, Acartürk F, Özkul A. Preparation and characterization of bioadhesive controlled-release gels of cidofovir for vaginal delivery. J Biomater Sci Polym Ed 2015;26:1237-55.
  • 24. Patel P, Patel P. Formulation and evaluation of clindamycin HCL in situ gel for vaginal application. Int J Pharm Investig 2015;5: 50–6.
  • 25. Owen DH, Katz DF, A vaginal fluid simulant. Contraception 1999;59: 91–5.
  • 26. Ibrahim el-SA, Ismail S, Fetih G, Shaaban O, Hassanein K, Abdellah NH. Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application. Acta Pharm 2012;62: 59– 70.
  • 27. Machado RM, Palmeira-de-Oliveira A, Gaspar C, Martinezde- Oliveira J, Palmeira-de-Oliveira R. Studies and methodologies on vaginal drug permeation. Adv Drug Deliv Rev 2015;15:14-26.
  • 28. Ur-Rehman T, Tavelin S, Gröbner G. Chitosan in situ gelation for improved drug loading and retention in poloxamer 407 gels. Int J Pharm 2011;409:19-29.
  • 29. Jones DS, Lawlor MS, Woolfson AD. Rheological and muchoadhesive characterisation of polymeric systems composed of poly(methylvinylether-co-maleic acid) and poly (vinylpyrrolidone), designed as platforms for topical drug delivery. J Pharm Sci 2003;92: 995–1007.
  • 30. Jones DS, Lawlor MS, Woolfson AD. Examination of the flow rheological and textural properties of polymer gels composed of poly(methylvinylether-co- maleic anhydride) and poly(vinylpyrrolidone): rheological and mathematical interpretation of textural parameters. J Pharm Sci 2002;91: 2090–2101.
  • 31. Cevher E, Sensoy D, Taha MA, Araman A. Effect of thiolated polymers to textural and mucoadhesive properties of vaginal gel formulations prepared with polycarbophil and chitosan. AAPS PharmSciTech 2008;9: 953–65.
  • 32. Jones DS, Woolfson AD, Brown AF, O’Neill MJ. Mucoadhesive, syringe- able drug delivery systems for controlled application of metronidazole to the periodontal pocket: in vitro release kinetics, syringeability, mechanical and mucoadhesive properties. J Control Release 1997;49: 71–9.
  • 33. El Kamel A, Sokar M, Naggar V, Al Gamal S. Chitosan and sodium alginate- based bioadhesive vaginal tablets. AAPS Pharm Sci 2002;4: E44.
  • 34. Deacon MP, McGurk S, Roberts CJ, Williams PM, Tendler SJB, Davies MC, Davis SS, Harding SE. Atomic force microscopy of gastric mucin and chitosan mucoadhesive systems. Biochem J 2000;348: 557–63.
Yıl 2017, Cilt: 21 Sayı: 4, 762 - 770, 01.12.2017

Öz

Kaynakça

  • 1. Sandri G, Rossi S, Ferrari F, Bonferoni MC, Caramella C. Strategies to improve systemic and local availability of drugs administered via vaginal route. In: Enhancement in Drug Delivery. Editors: E. Touitou, B.W. Barry, Taylor and Francis CRC Press, Boca Raton FL. 2007, pp. 441–470
  • 2. Machado R, Palmeira-De-Oliveira A, Martinez-De-Oliveira J, Palmeira-De-Oliveira R. Vaginal films for drug delivery. J Pharm Sci 2013;102: 2069-81.
  • 3. Mehta S, Verstraelen H, Vandaele L, Mehuys E, Remon JP, Vervaet C. Vaginal distribution and retention of tablets comprising starch-based multiparticulates: Evaluation by colposcopy. Drug Dev Ind Pharm 2013;39: 1944-50.
  • 4. Neves J, Bahia MF. Gels as vaginal drug delivery. Int J Pharm 2006;318: 1–14.
  • 5. Acartürk F. Mucoadhesive vaginal drug delivery systems. Recent Pat Drug Deliv Formul 2009;3: 193–205.
  • 6. Valenta C. The use of muchoadhesive polymers in vaginal drug delivery. Adv Drug Deliv Rev 2005;57: 1692–1712.
  • 7. Baloglu E, Karavana, SY, Senyigit ZA, Guneri T. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm Dev Technol 2011;16: 627–36.
  • 8. Caramella CM, Rossi S, Ferrari F, Bonferoni MC, Sandri G. Mucoadhesive and thermogelling systems for vaginal drug delivery. Adv Drug Deliv Rev 2015;15: 39-52.
  • 9. Miyazaki M, Maeda T, Hirashima K, Kurokawa N, Nagahama K, Hotta A. PEG-based nanocomposite hydrogel: Thermoresponsive sol-gel transition controlled by PLGAPEG- PLGA molecular weight and solute concentration. Polymer In Pres, 2017.
  • 10. Thompson DO. Cyclodextrins enabling excipients: Their present and future use in pharmaceuticals. Crit Rev Ther Drug Carrier Syst 1997;14:1–104.
  • 11. Aka-Any-Grah A, Bouchemal K, Koffi A, Agnely F, Zhang M, Djabourov M, Ponchel G. Formulation of mucoadhesive vaginal hydrogels insensitive to dilution with vaginal fluids. Eur J Pharm Biopharm 2010;76:296–303.
  • 12. Chang JY, Oh YK, Choi H, Kim YB, Kim CK. Rheological evaluation of thermosensitive and mucoadhesive vaginal gels in physiological conditions. Int J Pharm 2002;241:155–63.
  • 13. Lin HR, Sung KC, Vong WJ. In situ gelling of alginate/ pluronic solutions for ophthalmic delivery of pilocarpine. Biomacromolecules 2004;6: 2358–65
  • 14. Bilensoy E, Rouf MA, Vural I, Şen M, Hıncal AA. Mucoadhesive, thermosensitive, prolonged-release vaginal gel for clotrimazole:β-cyclodextrin complex. AAPS PharmSciTech 2006;7: E1-E8.
  • 15. Mayol L, Quaglia F, Borzacchiello A, Ambrosio L, La Rotonda MI, A novel poloxamers/hyaluronic acid in situ forming hydrogel for drug delivery: Rheological, mucoadhesive and in vitro release properties. Eur J Pharm Biopharm 2008;70: 199– 206.
  • 16. Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RF, A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur J Pharm Biopharm 2010;75:186-93.
  • 17. Perioli L, Ambrogi V, Venezia L, Giovagnoli S, Pagano C, Rossi C. Formulation studies of benzydamine mucoadhesive formulations for vaginal administration. Drug Dev Ind Pharm 2009;31: 1–11.
  • 18. Mekhemar NA, El-Agwany A.S, Radi WK, El-Hady SM. Comparative study between benzydamine hydrochloride gel, lidocaine 5% gel and lidocaine 10% spray on endotracheal tube cuff as regards postoperative sore throat. Braz J Anesthesiol 2016;66: 242-8.
  • 19. Perioli L, Ambrogi V, Pagano C, Massetti E, Rossi C. New solid mucoadhesive systems for benzydamine vaginal administration. Colloids Surf B Biointerfaces 2011;84:413-20.
  • 20. Schmolka IR. Artificial skin. I. Preparation and properties of pluronic F-127 gels for treatment of burns. J Biomed Mater Res 1972;6: 571–82.
  • 21. Tuğcu-Demiröz F, Acartürk F, Erdoğan D. Development of long-acting bioadhesive vaginal gels of oxybutynin: Formulation, in vitro and in vivo evaluations. Int J Pharm 2013;457: 25-39.
  • 22. Jones DS, Woolfson AD, Brown AF. Textural, viscoelastic and mucoadhesive properties of pharmaceutical gels composed of cellulose polymers. Int J Pharm 1997;151:223–33.
  • 23. Tuğcu-Demiröz F, Acartürk F, Özkul A. Preparation and characterization of bioadhesive controlled-release gels of cidofovir for vaginal delivery. J Biomater Sci Polym Ed 2015;26:1237-55.
  • 24. Patel P, Patel P. Formulation and evaluation of clindamycin HCL in situ gel for vaginal application. Int J Pharm Investig 2015;5: 50–6.
  • 25. Owen DH, Katz DF, A vaginal fluid simulant. Contraception 1999;59: 91–5.
  • 26. Ibrahim el-SA, Ismail S, Fetih G, Shaaban O, Hassanein K, Abdellah NH. Development and characterization of thermosensitive pluronic-based metronidazole in situ gelling formulations for vaginal application. Acta Pharm 2012;62: 59– 70.
  • 27. Machado RM, Palmeira-de-Oliveira A, Gaspar C, Martinezde- Oliveira J, Palmeira-de-Oliveira R. Studies and methodologies on vaginal drug permeation. Adv Drug Deliv Rev 2015;15:14-26.
  • 28. Ur-Rehman T, Tavelin S, Gröbner G. Chitosan in situ gelation for improved drug loading and retention in poloxamer 407 gels. Int J Pharm 2011;409:19-29.
  • 29. Jones DS, Lawlor MS, Woolfson AD. Rheological and muchoadhesive characterisation of polymeric systems composed of poly(methylvinylether-co-maleic acid) and poly (vinylpyrrolidone), designed as platforms for topical drug delivery. J Pharm Sci 2003;92: 995–1007.
  • 30. Jones DS, Lawlor MS, Woolfson AD. Examination of the flow rheological and textural properties of polymer gels composed of poly(methylvinylether-co- maleic anhydride) and poly(vinylpyrrolidone): rheological and mathematical interpretation of textural parameters. J Pharm Sci 2002;91: 2090–2101.
  • 31. Cevher E, Sensoy D, Taha MA, Araman A. Effect of thiolated polymers to textural and mucoadhesive properties of vaginal gel formulations prepared with polycarbophil and chitosan. AAPS PharmSciTech 2008;9: 953–65.
  • 32. Jones DS, Woolfson AD, Brown AF, O’Neill MJ. Mucoadhesive, syringe- able drug delivery systems for controlled application of metronidazole to the periodontal pocket: in vitro release kinetics, syringeability, mechanical and mucoadhesive properties. J Control Release 1997;49: 71–9.
  • 33. El Kamel A, Sokar M, Naggar V, Al Gamal S. Chitosan and sodium alginate- based bioadhesive vaginal tablets. AAPS Pharm Sci 2002;4: E44.
  • 34. Deacon MP, McGurk S, Roberts CJ, Williams PM, Tendler SJB, Davies MC, Davis SS, Harding SE. Atomic force microscopy of gastric mucin and chitosan mucoadhesive systems. Biochem J 2000;348: 557–63.
Toplam 34 adet kaynakça vardır.

Ayrıntılar

Konular Sağlık Kurumları Yönetimi
Bölüm Makaleler
Yazarlar

Fatmanur Tuğcu-demiröz Bu kişi benim

Yayımlanma Tarihi 1 Aralık 2017
Yayımlandığı Sayı Yıl 2017 Cilt: 21 Sayı: 4

Kaynak Göster

APA Tuğcu-demiröz, F. (2017). Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties. Marmara Pharmaceutical Journal, 21(4), 762-770.
AMA Tuğcu-demiröz F. Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties. mpj. Aralık 2017;21(4):762-770.
Chicago Tuğcu-demiröz, Fatmanur. “Development of in Situ Poloxamer-Chitosan Hydrogels for Vaginal Drug Delivery of Benzydamine Hydrochloride: Textural, Mucoadhesive and in Vitro Release Properties”. Marmara Pharmaceutical Journal 21, sy. 4 (Aralık 2017): 762-70.
EndNote Tuğcu-demiröz F (01 Aralık 2017) Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties. Marmara Pharmaceutical Journal 21 4 762–770.
IEEE F. Tuğcu-demiröz, “Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties”, mpj, c. 21, sy. 4, ss. 762–770, 2017.
ISNAD Tuğcu-demiröz, Fatmanur. “Development of in Situ Poloxamer-Chitosan Hydrogels for Vaginal Drug Delivery of Benzydamine Hydrochloride: Textural, Mucoadhesive and in Vitro Release Properties”. Marmara Pharmaceutical Journal 21/4 (Aralık 2017), 762-770.
JAMA Tuğcu-demiröz F. Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties. mpj. 2017;21:762–770.
MLA Tuğcu-demiröz, Fatmanur. “Development of in Situ Poloxamer-Chitosan Hydrogels for Vaginal Drug Delivery of Benzydamine Hydrochloride: Textural, Mucoadhesive and in Vitro Release Properties”. Marmara Pharmaceutical Journal, c. 21, sy. 4, 2017, ss. 762-70.
Vancouver Tuğcu-demiröz F. Development of in situ poloxamer-chitosan hydrogels for vaginal drug delivery of benzydamine hydrochloride: Textural, mucoadhesive and in vitro release properties. mpj. 2017;21(4):762-70.