Formulation and Physical Characterization of Bio-Degradable Chitosan-Poloxamer Gel Base for Local Drug Delivery
Abstract
Objective: Thermo-modulated in-situ hydrogel (TSHG) are formulated routinely utilizing poloxamer for extended drug release. However physical properties of such formulations may have some flaws, which can be rectified using a combination of polymers with better physical properties such as chitosan. The purpose of the present study was to fabricate biodegradable chitosan-poloxamer-based in-situ drug delivery systems and assessment of their physical properties.
Methods: The present chitosan-poloxamer gel base was formulated using a two-stage method. Initially, chitosan gel was prepared by dissolving 1% w/w chitosan in glacial acetic acid. The poloxamer gel was prepared using “cold method”. The final chitosan-poloxamer gel base was prepared by mixing equal amounts of both solutions and evaluated for physical and mechanical properties.
Result and Discussion: The DSC thermogram demonstrated no obvious interactions among ingredients or micellization temperature. The gelation temperature of the gel was between 27 and 330C. The pH was 7 with slight clarity. The viscosity of the gel ranged from 15.14 to 41.19 pa.s. The gel was syringable between 4-300C and biodegradable under physiological conditions. The mean particle size of the gel under SEM was found in the range of 300-554 nm.
Conclusion: After the evaluation of the formulation, it can be concluded that all the ingredients in the gel showed good compatibility with each other, which could form a stable and homogeneous gel with favorable mechanical and physical properties.
Keywords: chitosan, drug delivery system, hydrogels, poloxamer
Keywords:
chitosan, drug delivery system, hydrogels, poloxamer
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References
1. Van de Velde K, Kiekens P. Biopolymers: overview of several properties and consequences on their applications. Polym Test 2002;21(4):433–442.
2. Shive MS, Anderson JM. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 1997;28(1):5-24.
3. Zargar V, Asghari M, Dashti A. A Review on Chitin and Chitosan Polymers: Structure, Chemistry, Solubility, Derivatives, and Applications. ChemBioEng Rev 2015;2(3):204–226.
4. Rinaudo M. Chitin and chitosan: Properties and applications. Prog Polym Sci 2006;31(7):603–632.
5. Murakami K, Aoki H, Nakamura S, Nakamura S, Takikawa M, Hanzawa M, et al. Hydrogel blends of chitin/chitosan, fucoidan and alginate as healing-impaired wound dressings. Biomaterials 2010;31(1):83–90.
6. Tamer TM, Hassan MA, Omer AM, Baset WMA, Hassan ME, El-Shafeey MEA, et al. Synthesis, characterization and antimicrobial evaluation of two aromatic chitosan Schiff base derivatives. Process Biochem 2016;51(10):1721–1730.
7. Tamura H, Furuike T, Nair SV, Jayakumar R. Biomedical applications of chitin hydrogel membranes and scaffolds. Carbohydr Polym 2011;84(2):820–824.
8. Zhang K, Shi X, Lin X, Yao C, Shen L, Feng Y. Poloxamer-based in situ hydrogels for controlled delivery of hydrophilic macromolecules after intramuscular injection in rats. Drug Deliv 2015;22(3):375–382.
9. Liu Y, Lu W-L, Wang J-C, Zhang X, Zhang H, Wang X-Q, et al. Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic® F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization. J Controlled Release 2007;117(3):387–395.
10. Klouda L, Mikos AG. Thermoresponsive hydrogels in biomedical applications. Eur J Pharm Biopharm 2008;68(1):34–45.
11. Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RFV. A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur J Pharm Biopharm 2010;75(2):186–193.
12. Varshosaz J, Tabbakhian M, Salmani Z. Designing of a Thermosensitive Chitosan/Poloxamer In Situ Gel for Ocular Delivery of Ciprofloxacin. Open Drug Deliv J 2008;2(1):61–70.
13. Matthew JE, Nazario YL, Roberts SC, Bhatia SR. Effect of mammalian cell culture medium on the gelation properties of Pluronic® F127. Biomaterials 2002;23(23):4615–4619.
14. Mora PC, Cirri M, Mura P. Differential scanning calorimetry as a screening technique in compatibility studies of DHEA extended-release formulations. J Pharm Biomed Anal 2006;42(1):3–10.
15. Mura P, Faucci MT, Manderioli A, Bramanti G, Ceccarelli L. Compatibility study between ibuproxam and pharmaceutical excipients using differential scanning calorimetry, hot-stage microscopy and scanning electron microscopy. J Pharm Biomed Anal 1998;18(1–2):151–163.
16. Lakshmi P, Harini K. Design and Optimization of Thermo-reversible Nasal in situ Gel of Atomoxetine Hydrochloride Using Taguchi Orthogonal Array Design. Dhaka Univ J Pharm Sci 201922;18(2):183–193.
17. Pandit AP, Pol VV, Kulkarni VS. Xyloglucan Based In Situ Gel of Lidocaine HCl for the Treatment of Periodontosis. J Pharm 2016;2016:1–9.
18. Garala K, Joshi P, Patel J, Ramkishan A, Shah M. Formulation and evaluation of periodontal in situ gel. Int J Pharm Investig 2013;3(1):29.
19. Choi H-G, Jung J-H, Ryu J-M, Yoon S-J, Oh Y-K, Kim C-K. Development of in situ-gelling and mucoadhesive acetaminophen liquid suppository. Int J Pharm 1998;165(1):33–44.
20. Bruschi ML, Jones DS, Panzeri H, Gremião MPD, de Freitas O, Lara EHG. Semisolid Systems Containing Propolis for the Treatment of Periodontal Disease: In Vitro Release Kinetics, Syringeability, Rheological, Textural, and Mucoadhesive Properties. J Pharm Sci 2007;96(8):2074–2089.
21. Jones DS, Bruschi ML, de Freitas O, Gremião MPD, Lara EHG, Andrews GP. Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity. Int J Pharm 2009;372(1–2):49–58.
22. Thakur G, Singh A, Singh I. Formulation and evaluation of transdermal composite films of chitosan-montmorillonite for the delivery of curcumin. Int J Pharm Investig 2016;6(1):23.
23. Baumnas V, Remie R, Hackbarth H, Timmerman A. Experimental procedures. In. Principles of Laboratory Animal Science-A contribution to the humane use and care of animals and to the quality of experimental results. 1st ed. Netherlands: Elsevier Science B.V., Amsterdam,; 2001. 313–333 p.
24. 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(1–2):19–29.
25. Kenawy E, Omer AM, Tamer TM, Elmeligy MA, Eldin MSM. Fabrication of biodegradable gelatin/chitosan/cinnamaldehyde crosslinked membranes for antibacterial wound dressing applications. Int J Biol Macromol 2019;139:440–448.
26. Kumar P, Dehiya BS, Sindhu A. Comparative study of chitosan and chitosan–gelatin scaffold for tissue engineering. Int Nano Lett 2017;7(4):285–290.
27. Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics. Pharm Res 2006;23(12):2709–2728.
28. Packhaeuser CB, Schnieders J, Oster CG, Kissel T. In situ forming parenteral drug delivery systems: an overview. Eur J Pharm Biopharm 2004;58(2):445–455.
29. Su Y, Wang J, Liu H. Melt, Hydration, and Micellization of the PEO–PPO–PEO Block Copolymer Studied by FTIR Spectroscopy. J Colloid Interface Sci 2002;251(2):417–423.
30. Alexandridis P, Holzwarth JF, Alan Hatton T. A correlation for the estimation of critical micellization concentrations and temperatures of polyols in aqueous solutions. J Am Oil Chem Soc 1995;72(7):823–826.
31. Mahnama H, Dadbin S, Frounchi M, Rajabi S. Preparation of biodegradable gelatin/PVA porous scaffolds for skin regeneration. Artif Cells Nanomedicine Biotechnol 2017; 45(5):928–935.
2. Shive MS, Anderson JM. Biodegradation and biocompatibility of PLA and PLGA microspheres. Adv Drug Deliv Rev 1997;28(1):5-24.
3. Zargar V, Asghari M, Dashti A. A Review on Chitin and Chitosan Polymers: Structure, Chemistry, Solubility, Derivatives, and Applications. ChemBioEng Rev 2015;2(3):204–226.
4. Rinaudo M. Chitin and chitosan: Properties and applications. Prog Polym Sci 2006;31(7):603–632.
5. Murakami K, Aoki H, Nakamura S, Nakamura S, Takikawa M, Hanzawa M, et al. Hydrogel blends of chitin/chitosan, fucoidan and alginate as healing-impaired wound dressings. Biomaterials 2010;31(1):83–90.
6. Tamer TM, Hassan MA, Omer AM, Baset WMA, Hassan ME, El-Shafeey MEA, et al. Synthesis, characterization and antimicrobial evaluation of two aromatic chitosan Schiff base derivatives. Process Biochem 2016;51(10):1721–1730.
7. Tamura H, Furuike T, Nair SV, Jayakumar R. Biomedical applications of chitin hydrogel membranes and scaffolds. Carbohydr Polym 2011;84(2):820–824.
8. Zhang K, Shi X, Lin X, Yao C, Shen L, Feng Y. Poloxamer-based in situ hydrogels for controlled delivery of hydrophilic macromolecules after intramuscular injection in rats. Drug Deliv 2015;22(3):375–382.
9. Liu Y, Lu W-L, Wang J-C, Zhang X, Zhang H, Wang X-Q, et al. Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic® F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization. J Controlled Release 2007;117(3):387–395.
10. Klouda L, Mikos AG. Thermoresponsive hydrogels in biomedical applications. Eur J Pharm Biopharm 2008;68(1):34–45.
11. Gratieri T, Gelfuso GM, Rocha EM, Sarmento VH, de Freitas O, Lopez RFV. A poloxamer/chitosan in situ forming gel with prolonged retention time for ocular delivery. Eur J Pharm Biopharm 2010;75(2):186–193.
12. Varshosaz J, Tabbakhian M, Salmani Z. Designing of a Thermosensitive Chitosan/Poloxamer In Situ Gel for Ocular Delivery of Ciprofloxacin. Open Drug Deliv J 2008;2(1):61–70.
13. Matthew JE, Nazario YL, Roberts SC, Bhatia SR. Effect of mammalian cell culture medium on the gelation properties of Pluronic® F127. Biomaterials 2002;23(23):4615–4619.
14. Mora PC, Cirri M, Mura P. Differential scanning calorimetry as a screening technique in compatibility studies of DHEA extended-release formulations. J Pharm Biomed Anal 2006;42(1):3–10.
15. Mura P, Faucci MT, Manderioli A, Bramanti G, Ceccarelli L. Compatibility study between ibuproxam and pharmaceutical excipients using differential scanning calorimetry, hot-stage microscopy and scanning electron microscopy. J Pharm Biomed Anal 1998;18(1–2):151–163.
16. Lakshmi P, Harini K. Design and Optimization of Thermo-reversible Nasal in situ Gel of Atomoxetine Hydrochloride Using Taguchi Orthogonal Array Design. Dhaka Univ J Pharm Sci 201922;18(2):183–193.
17. Pandit AP, Pol VV, Kulkarni VS. Xyloglucan Based In Situ Gel of Lidocaine HCl for the Treatment of Periodontosis. J Pharm 2016;2016:1–9.
18. Garala K, Joshi P, Patel J, Ramkishan A, Shah M. Formulation and evaluation of periodontal in situ gel. Int J Pharm Investig 2013;3(1):29.
19. Choi H-G, Jung J-H, Ryu J-M, Yoon S-J, Oh Y-K, Kim C-K. Development of in situ-gelling and mucoadhesive acetaminophen liquid suppository. Int J Pharm 1998;165(1):33–44.
20. Bruschi ML, Jones DS, Panzeri H, Gremião MPD, de Freitas O, Lara EHG. Semisolid Systems Containing Propolis for the Treatment of Periodontal Disease: In Vitro Release Kinetics, Syringeability, Rheological, Textural, and Mucoadhesive Properties. J Pharm Sci 2007;96(8):2074–2089.
21. Jones DS, Bruschi ML, de Freitas O, Gremião MPD, Lara EHG, Andrews GP. Rheological, mechanical and mucoadhesive properties of thermoresponsive, bioadhesive binary mixtures composed of poloxamer 407 and carbopol 974P designed as platforms for implantable drug delivery systems for use in the oral cavity. Int J Pharm 2009;372(1–2):49–58.
22. Thakur G, Singh A, Singh I. Formulation and evaluation of transdermal composite films of chitosan-montmorillonite for the delivery of curcumin. Int J Pharm Investig 2016;6(1):23.
23. Baumnas V, Remie R, Hackbarth H, Timmerman A. Experimental procedures. In. Principles of Laboratory Animal Science-A contribution to the humane use and care of animals and to the quality of experimental results. 1st ed. Netherlands: Elsevier Science B.V., Amsterdam,; 2001. 313–333 p.
24. 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(1–2):19–29.
25. Kenawy E, Omer AM, Tamer TM, Elmeligy MA, Eldin MSM. Fabrication of biodegradable gelatin/chitosan/cinnamaldehyde crosslinked membranes for antibacterial wound dressing applications. Int J Biol Macromol 2019;139:440–448.
26. Kumar P, Dehiya BS, Sindhu A. Comparative study of chitosan and chitosan–gelatin scaffold for tissue engineering. Int Nano Lett 2017;7(4):285–290.
27. Dumortier G, Grossiord JL, Agnely F, Chaumeil JC. A Review of Poloxamer 407 Pharmaceutical and Pharmacological Characteristics. Pharm Res 2006;23(12):2709–2728.
28. Packhaeuser CB, Schnieders J, Oster CG, Kissel T. In situ forming parenteral drug delivery systems: an overview. Eur J Pharm Biopharm 2004;58(2):445–455.
29. Su Y, Wang J, Liu H. Melt, Hydration, and Micellization of the PEO–PPO–PEO Block Copolymer Studied by FTIR Spectroscopy. J Colloid Interface Sci 2002;251(2):417–423.
30. Alexandridis P, Holzwarth JF, Alan Hatton T. A correlation for the estimation of critical micellization concentrations and temperatures of polyols in aqueous solutions. J Am Oil Chem Soc 1995;72(7):823–826.
31. Mahnama H, Dadbin S, Frounchi M, Rajabi S. Preparation of biodegradable gelatin/PVA porous scaffolds for skin regeneration. Artif Cells Nanomedicine Biotechnol 2017; 45(5):928–935.
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Dahake P, Baliga S, Punse T, Biyani D, Raut N, Umekar M. Formulation and Physical Characterization of Bio-Degradable Chitosan-Poloxamer Gel Base for Local Drug Delivery. JDDT [Internet]. 15Jul.2020 [cited 18Apr.2024];10(4):59-6. Available from: https://jddtonline.info/index.php/jddt/article/view/4216
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