Development of an In situ Gel Polymer Composite for Local and Sustained Delivery of Drugs in Vaginal Cavity

Author(s): Sateesha S. Boregowda* , Sadanand R. Maggidi , Rajamma A. Jayaramu , Nethravathi Puttegowda , Nikhat Parbin .

Journal Name: Drug Delivery Letters

Volume 9 , Issue 3 , 2019

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Graphical Abstract:


Abstract:

Objective: The present research work is aimed at the development of an in situ gel polymer composite to provide local and sustained delivery of therapeutic agents in the vaginal cavity. Administration of medicated gel into a vaginal cavity is very complicated, inconvenient and needs expert assistance. There is a chance of expulsion of liquid formulation from site of application, leads to poor therapeutic efficacy. The effective drug delivery system for the vaginal cavity should be of liquid for application and gel to reside in the cavity.

Methods: In situ gel composed of chitosan (0.8%) cross-linked with β-glycerol phosphate (15%) and glutaraldehyde treated guar gum (0.2%) was developed. Gel was characterized for in situ gelling properties. In vitro drug release pattern of the gel was tested on a nutrient agar medium containing attenuated E. coli and B. Subtilis. In vitro diffusion pattern of gel was tested using KC-diffusion cell with Simulated Vaginal Fluid (SVF) (pH 4.2) as the diffusion medium.

Results: In situ gel exhibited sharpest sol-gel transition at 35±2°C, at pH 5.4 in 62±1.31sec. The viscosity of polymer composite is 51.25±3.68 CPs at 20±2°C and 328.56±4.16 CPs at 35±2°C. The gelation time of gel was found to be decreasing as the concentration of cross-linking agent β-GP increased. Formulations exhibited a shear thinning property. Drug release from this polymeric composite was found to be highly linear and follows non-fickian diffusion mechanism.

Conclusion: This advanced thermosensitive in situ gel is convenient to apply and reside in the vaginal cavity for a prolonged period of time. The gel is mucoadhesive, biodegradable and suitable for controlled drug delivery in the cavity.

Keywords: In situ gel, vaginal cavity, chitosan, β-glycerol phosphate, guar gum, mucoadhesive.

[1]
Kumar, L.; Verma, R. Advantages of intra-vaginal drug delivery system: An overview. Int. J. Pharm. Res. Dev., 2010, 2(6), 1-7.
[2]
Hanan, M.; Laithy, E.I.; Demiana, I. Nesseem; Shoukry, N.M. Evaluation of two in situ gelling systems for ocular delivery of Moxifloxacin: In vitro and in vivo studies. J. Chem. Pharm. Res., 2011, 3(2), 66-79.
[3]
Gariepy, E.R.; Leroux, J.C. In situ-forming hydrogels-review of temperature-sensitive systems. Eur. J. Pharm. Biopharm., 2004, 58(2), 409-426.
[4]
Wu, J.; Su, Z.G.; Ma, G.H. A thermo- and pH-sensitive hydrogel composed of quaternized chitosan/glycerolphosphate. Int. J. Pharm., 2006, 315(1-2), 1-11.
[5]
Wamorker, V.; Varma, M.M.; Manjunath, S.Y. Formulation and evaluation of stomach specific in-situ gel of metoclopramide using natural, bio-degradable polymers. Int. J. Res. Pharm. Biomed. Sci., 2011, 2(1), 193-201.
[6]
Nirmal, H.B.; Bakliwal, S.R.; Pawar, S.P. In-situ gel: New trends in controlled and sustained drug delivery. Int. J. Pharm. Tech. Res., 2010, 2(2), 1398-1408.
[7]
Madan, M.; Bajaj, A.; Lewis, S.; Udupa, N.; Baig, J.A. In situ forming polymeric drug delivery systems. Indian J. Pharm. Sci., 2009, 71(3), 242-251.
[8]
Sobel, J.D. Bacterial vaginosis. Annu. Rev. Med., 2000, 51(1), 349-356.
[9]
Valenta. Theuse of mucoadhesive polymers in vaginal delivery. Adv. Drug Deliv. Rev., 2005, 57(11), 1692-1712.
[10]
Dutta, P.K.; Joydeep, D.J.; Tripathi, V.S. Chitin and chitosan: Chemistry, properties and applications. J. Sci. Ind. Res. , 2004, 63(1), 20-31.
[11]
Faikrua, A.; Jeenapongsa, R.; Asna, M.S.; Viyoch, J. Properties of β-glycerol phosphate/collagen/chitosan blend scaffolds for application in skin tissue engineering. Sci. Asia, 2009, 35(1), 247-254.
[12]
Chenite, A.; Buschmann, M.; Wang, D.; Chaput, C.; Kundani, N. Rheological characterization of thermo-gelling chitosan/glycerol-phosphate solutions. Carbohydr. Polym., 2001, 46(1), 39-47.
[13]
Porazik, C.; Kempe, S.; Mäder, K. Characterization of thermosensitive chitosan-based hydrogels by rheology and electron paramagnetic resonance spectroscopy. Eur. J. Pharm. Biopharm , 2008, 68(1), 26-33.
[14]
Rinaudo, R. Chitin and chitosan: Properties and applications. Prog. Polym. Sci, 2006, 31(1), 603-632.
[15]
Crompton, K.E.; Prankerd, R.J.; Paganin, D.M.; Scott, T.F.; Horne, M.K.; Finkelsten, D.I.; Gross, K.A.; Forsythe, J.S. Morphology and gelation of thermosensitive chitosan hydrogels. Biophys. Chem., 2005, 117(1), 47-53.
[16]
Chudzikowski, R.J. Guar gum and its applications. J. Soc. Cosmet. Chem., 1971, 22(1), 43-60.
[17]
Thakur, S.; Chauhan, G.S.; Ahn, J.H. Synthesis of acryloyl guar gum and its hydrogel materials for use in the slow release of L-DOPA and L-trosine. Carbohydr. Polym., 2009, 76(1), 513-520.
[18]
Dumonceaux, T.J.; Schellenberg, J.; Goleski, V.; Hill, J.E.; Jaoko, W.; Kimani, J.; Money, D.; Ball, T.B.; Plummer, F.A.; Severini, A. Multiplex detection of bacteria associate with normal microbiota and with bacterial vaginosis in vaginal swabs by use of oligonucleotide- coupled fluorescent microspheres J. Clin. Microbiol, 2009, 4.7(12), 4067-4077.
[19]
Wu, W.; Li, X.; Liu, W. Synthesis and properties of thermo-responsive guar gum/poly (N-isopylacrylamide) interpenetrating polymer network hydrogels. Carbohydr. Polym., 2008, 71(1), 394-402.
[20]
Rediguieri, C.F.; Porta, V.; Nunes, D.S.G.; Nunes, T.M.; Hans, E.; Junginger, H.E.; Kopp, S. Biowaiver monographs for immediate release solid oral dosage forms: Metronidazole. J. Pharm. Sci., 2011, 100(5), 1618-1627.
[21]
Korsemeyer, R.; Gurny, R.; Peppas, N. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm., 1983, 15(1), 25-35.
[22]
Monfort, P.; Gal, D.L.; Saux, J.C.L.; Piclet, G.; Raguenes, P.; Boulben, S.; Plusquellec, A. Improved rapid method for isolation and enumeration of salmonella from bivalves using Rambach agar. J. Microbiol. Methods, 1994, 19, 67-79.
[23]
Sateesha, S.B.; Rajamma, A.J.; Narode, M.K.; Vyas, B.D. Influence of organic acids on diltiazem HCl release kinetics from hydroxypropylmethyl cellulose matrix tablets. J. Young Pharm., 2010, 2(3), 229-233.
[24]
Tsai, M.L.; Chang, H.W.; Yu, H.C.; Lin, Y.S.; Tsai, Y.D. Effect of chitosan characteristics and solution conditions on gelation temperature of chitosan/2-glycerolphosphate/nanosilver hydrogels. Carbohydr. Polym., 2011, 84(1), 1337-1343.
[25]
Ngoenkam, J.; Faikrua, A.; Yasothornsrikul, S.; Viyoch, J. Potential of an injectable chitosan/starch/β-glycerol phosphate hydrogel for sustaining normal chondrocyte function. Int. J. Pharm., 2010, 391(1-2), 115-124.
[26]
Schuetz, Y.; Gurny, R.; Jordan, O. A novel thermosensitive hydrogel based on chitosan. Eur. J. Pharm. Biopharm., 2008, 68(1), 19-25.
[27]
Sandolo, C.; Matricardi, P.; Alhaique, F.; Coviello, T. Effect of temperature and cross-linking density on rheology of chemical cross-linked guar gum at the gel point. Food Hydrocoll., 2009, 23(1), 210-220.
[28]
Porazik, C.; Kempe, S.; Madar, K. Chitovation. Thermosensitive Chitosan-based in-situ forming implants for drug delivery , (5th Ed.. ) 2011, , 1-6.
[29]
Higuchi, T. Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J. Pharm. Sci., 1963, 52(1), 1145-1149.
[30]
Chaibva, F.A.; Khamanga, S.M.M.; Walker, R.B. Swelling, erosion and drug release characteristics of salbutamol sulfate from hydroxypropylmethylcellulose-based matrix tablets. Drug Dev. Ind. Pharm., 2010, 36(12), 1497-1510.
[31]
Zare, M.; Mobedi, H.; Barzin, J.; Mivehchi, H.; Jamshidi, A.; Mashayekhi, R. Effect of additives on release profile of leuprolide acetate in an in situ forming controlled-release system: In vitro study. J. Appl. Polym. Sci., 2008, 107, 3781-378.


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Article Details

VOLUME: 9
ISSUE: 3
Year: 2019
Page: [211 - 221]
Pages: 11
DOI: 10.2174/2210303109666190226152857
Price: $58

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