Differences in Viscoelasticity of Ophthalmic Polymer Solution after Sterilization

  • Yotsanan WEERAPOL Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand
  • Pornsak SRIAMORNSAK Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand
Keywords: Viscosity, Viscoelastic, Ophthalmic drug, Polymer, Sterilization


Polymer solution has been used for increasing viscosity of ophthalmic solution in order to prolong the retention of active drug in the eye. The ophthalmic solution must be sterilized, which may affect the rheology properties of viscosity-inducing polymers. The aim of this study was to investigate the effect of sterilization treatment on viscosity-inducing agents (i.e., poloxamer, polyvinyl alcohol; (PVA), methyl cellulose (MC), polyvinylpyrrolidone (PVP) and carbomer). The effect of membrane filtration and steam sterilization or autoclaving (121 °C, 15 Ib/inch2, 15 min) were determined. A rheometer was used to investigate the viscosity and viscoelastic properties between treated and untreated polymer solutions. The power law model, consistency index (k), and power law index (n) of polymer solution viscosity were compared. For viscoelastic properties, storage modulus and loss modulus were examined. The results demonstrated that, viscosity of carbomer and MC solution (1 and 2 %) were changed after steam sterilization. No difference in viscosity was observed for PVP, PVA and poloxamer solution, between untreated and treated samples. The storage and loss moduli of PVA solution after autoclaving were not different when comparing with the untreated polymer solution. From this study, it could be concluded that the sterilization treatment influenced the viscosity behavior and viscoelastic properties of polymer solution used as viscosity-inducing agent in ophthalmic solution. Therefore, the selection of polymer and sterilization method should be carefully considered.


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Author Biographies

Yotsanan WEERAPOL, Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand

Faculty of Pharmaceutical Sciences

Pornsak SRIAMORNSAK, Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand

Department of Pharmaceutical Technology


SB Makwana, VA Patel and SJ Parmar. Development and characterization of in-situ gel for ophthalmic formulation containing ciprofloxacin hydrochloride. Res. Pharm. Sci. 2016; 6, 1-6.

KA Khateb, EK Ozhmukhametova, MN Mussin, SK Seilkhanov, TK Rakhypbekov, WM Lau and VV Khutoryanskiy. In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery. Int. J. Pharm. 2016; 502, 70-9.

H Almeida, MH Amaral, P Lobão and JM Lobo. In situ gelling systems: A strategy to improve the bioavailability of ophthalmic pharmaceutical formulations. Drug. Discov. Today 2014; 19, 400-12.

WD Ma, H Xu, C Wang, SF Nie and WS Pan. Pluronic F127-g-poly (acrylic acid) copolymers as in situ gelling vehicle for ophthalmic drug delivery system. Int. J. Pharm. 2008; 350, 247-56.

S Yu, X Zhang, G Tan, L Tian, D Liu, Y Liu, X Yang and W Pan. A novel pH-induced thermosensitive hydrogel composed of carboxymethyl chitosan and poloxamer cross-linked by glutaraldehyde for ophthalmic drug delivery. Carbohydr. Polym. 2017; 155, 208-17.

Sterility Test. US Pharmacopoeia. United States Pharmacopeial, Rockville, 1955, p. 841-6.

AS Mundada. Update on Polymers for Ocular Drug Delivery. iSmithers, Shropshire, 2011, p. 23-43

A Bindal, G Narsimhan, SL Hem and A Kulshreshtha. Effect of steam sterilization on the rheology of polymer solutions. Pharm. Dev. Tech. 2003; 8, 219-28.

RG Fiscella. Ophthalmic Drug Formulations. In: JD Bartlett (Ed.). Clinical Ocular Pharmacology. 5th ed. Butterworth-Heinemann, Saint Louis, 2008, p. 17-37.

NM Davies, SJ Farr, J Hadgraft and IW Kellaway. Evaluation of mucoadhesive polymers in ocular drug delivery. I. Viscous solutions. Pharm. Res. 1991; 8, 1039-43.

G Bonacucina, S Martelli and GF Palmieri. Rheological, mucoadhesive and release properties of carbopol gels in hydrophilic cosolvents. Int. J. Pharm. 2004; 282, 115-30.

B Abu-Jdayil and M Ghannam. The modification of rheological properties of sodium bentonite-water dispersions with low viscosity CMC polymer effect. Energ. Source A 2014; 36, 1037-48.

S Li, Y Ma, T Fu, Z Chunying and L Huaizhi. The viscosity distribution around a rising bubble in shear-thinning non-newtonian fluids. Braz. J. Chem. Eng. 2012; 29, 265-74.

R Rezaei, M Khomeiri, M Kashaninejad and A Mehran. Effects of guar gum and arabic gum on the physicochemical, sensory and flow behaviour characteristics of frozen yoghurt. Int. J. Dairy Tech. 2011; 64, 563-8.

M Sengül, MF Ertugay and M Sengül. Rheological, physical and chemical characteristics of mulberry pekmez. Food Control 2005; 16, 73-6.

Lubrizol. Available at: https://www.google.co.th/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1& cad=rja&uact=8&ved=0ahUKEwjk47zz1uDYAhXCRY8KHeLuANwQFggmMAA&url=https%3A%2F%2Fwww.lubrizol.com%2F%2Fmedia%2FLubrizol%2FLifeSciences%2FDocuments%2FLiterature%2FBulletin%2FBulletin-03---Polymer-Handling-and Storage.pdf&usg=AOvVaw0T384GM9 Nq-gxUDcQApvSo, accessed December 2018.

SG Deshpande and S Shirolkar. Sustained release ophthalmic formulations of pilocarpine. J. Pharm. Pharmacol. 1989; 41, 197-200.

S Kirchhof, AM Goepferich and FP Brandl. Hydrogels in ophthalmic applications. Eur. J. Pharm. Biopharm. 2015; 95, 227-38.

Methyl Cellulose. Available at: https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma-Aldrich/Product_Information_Sheet/m0262pis.pdf, accessed December 2018.

MM Knopp, NE Olesen, P Holm, P Langguth, R Holm and T Rades. Influence of polymer molecular weight on drug-polymer solubility: A comparison between experimentally determined solubility in PVP and prediction derived from solubility in monomer. J. Pharm. Sci. 2015; 104, 2905-12.

CL Bourlais, L Acar, H Zia, PA Sado, T Needham and R Leverge. Ophthalmic drug delivery systems: Recent advances. Prog. Retin. Eye Res. 1998; 17, 33-58.

K Hyun, SH Kim, KH Ahn and JL Seung. Large amplitude oscillatory shear as a way to classify the complex fluids. J. Non-newton Fluid Mech. 2002; 107, 51-65.

K Hyun, M Wilhelm, CO Klein, SC Kwang, GN Jung, KA Kyung, JL Seung, HE Randy and HM Gareth. A review of nonlinear oscillatory shear tests: Analysis and application of large amplitude oscillatory shear (LAOS). Prog. Polym. Sci. 2011; 36, 1697-753.

SBDS Ferreira, JBD Silva, MV Junqueira, FB Borghi-Pangoni, RG Gomes and BM Luciano. The importance of the relationship between mechanical analyses and rheometry of mucoadhesive thermoresponsive polymeric materials for biomedical applications. J. Mech. Behav. Biomed. Mater. 2017; 74, 142-53.

E Baloglu, SY Karavana, ZA Senyigit and T Guneri. Rheological and mechanical properties of poloxamer mixtures as a mucoadhesive gel base. Pharm. Dev. Tech. 2011; 16, 627-36.

M Pouzot, T Nicolai, L Benyahia and D Durand. Strain hardening and fracture of heat-set fractal globular protein gels. J. Colloid Interface Sci. 2006; 293, 376-83.

GR Peng, W Li, TF Tian, D Jie and N Masami. Experimental and modeling study of viscoelastic behaviors of magneto-rheological shear thickening fluids. Korea Aust. Rheol. J. 2014; 26, 149-58.

Y Sugino and M Kawaguchi. Fumed and precipitated hydrophilic silica suspension gels in mineral oil: Stability and rheological properties. Gels 2017; 3, 2310-861.

DH Shastri, LD Patel and RK Parikh. Studies on in situ hydrogel: A smart way for safe and sustained ocular drug delivery. J. Young Pharm. 2010; 2, 116-20.

EJ Ricci, LO Lunardi, DM Nanclares and JM Marchetti. Int. J. Pharm. 2005; 288, 235-44.

ML Veyries, G Couarraze, S Geiger, F Agnely, L Massias, B Kunzli, F Faurisson and B Rouveix. Controlled release of vancomycin from Poloxamer 407. gels. Int. J. Pharm. 1999; 192, 183-93.

A Fakhari, M Corcoran and A Schwarz. Thermogelling properties of purified poloxamer 407. Heliyon 2017; 3, e00390.

How to Cite
WEERAPOL, Y., & SRIAMORNSAK, P. (2020). Differences in Viscoelasticity of Ophthalmic Polymer Solution after Sterilization . Walailak Journal of Science and Technology (WJST), 17(7), 686-697. Retrieved from http://wjst.wu.ac.th/index.php/wjst/article/view/6341