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Literature Review: Gel Ocular Drug Delivery Systems

Info: 2383 words (10 pages) Nursing Literature Review
Published: 24th Mar 2021

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Smadar et al, developed a new in situ gel forming ocular delivery system of drug from alginate undergoing gelation in the eye. They established that an aqueous solution of sodium alginate might gel in the eye, without adding together of external calcium ions or additional bivalent/polyvalent cations. Alginate with guluronic acid filling of more than 65% such as Manugel DMB, at once produced gels leading their accumulation to simulated tear fluid, while those having low glucoronic acid contents, such as Ketton LV, formed weak gels at a relatively slow rate and hence it was indicated that the in situ gelling alginate systems, based on polymers with high guluronic acid contents was superior drug carrier for the sustained delivery of pilocarpine41.

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Ashish et al, in situ gels of optimized Levobunolol Hydrochloride for the therapy of glaucoma. Levobunolol HCl in situ gel was formulated using different proportions of polymers such as Carbopol 940, HPMC E4M and HPMC E50LV by pH induced gelling system with the aim of to enhance the time of contact, to achieve the control release, to decrease the rate of administration better therapeutic efficacy of drug. The formulated in situ gels were subsequently assessed for their visual appearance, pH, clarity, drug content analysis, in vitro gelation (Gelling strength), rheological studies, in-vitro drug release studies and sterility testing. The formed polymeric in situ gels were transparent, clear, possessing acceptable gelling strength42.

Srividya et al, developed and characterized an ophthalmic drug delivery system of Ofloxacin, based on the idea of pH triggered in situ gelation. Polyacrylic acid (Carbopol 940) was utilized as the gel forming agent in a combination with HPMC E50LV which behaved as a viscosity increasing agent. The developed formulations was found to be therapeutically efficient, non-irritant, stabilize and provided steady release of the drug over a 8 h period. The formulated system was thus a realistic substitute to conventional eye drops43.

Balasubramaniam et al, studied an ophthalmic delivery system of indomethacin, based on the assumption of ion activated in situ gelation. Gelrite (gellan gum), a novel ocular medium, which gels in the existence of mono or divalent cations there in the tear fluid, was utilized as the gelling agent. Gellan gum was investigated as a medium for the preparation of eye drops of indomethacin (1% m/V), which experience gelation when instilled into the cul-de-sac of the eye and offer constant release of the drug throughout the treatment of uveitis. The prepared formulations were therapeutically effective (in a uveitis induced rabbit eye model) and rendered constant release of the drug over an 8 hour period in vitro and the prepared formulations were devoid of any harmful consequence on the ocular tissues44.

Wu et al, formulated a pH triggered in situ gelling medium for ocular release of puerarin. The importance of hydroxy propyl-beta-cyclodextrin (HP-beta-CD) on the aqueous solubility and in vitro corneal penetration of puerarin was furthermore inquired. The puerarin solubility raised linearly and proportionately to the HP-beta-CD concentrations and 5% (w/v) HP-beta-CD improved its ocular permeableness drastically. Carbopol 980NF was utilized as the gelling agent in mixture with HPMC (Methocel E4M) which behaved as a viscosity increasing agent. The most selected concentrations of Carbopol 980NF and HPMC E4M for the in situ gel forming delivery systems were 0.1% (w/v) and 0.4% (w/v) respectively. As these two vehicles were compounded, an in situ gel which is having the suitable gel strength and gelling ability under physiological condition might be obtained. This compounded solution might flow freely under non- physiological condition and depicted the quality of pseudoplastic fluid in both situation. Both in vivo pharmacokinetics studies and in vitro release studies suggested that the combined polymer systems executed better in sustaining puerarin than puerarin eye drops did45.

Shivanand et al, developed a novel in situ gum based ocular drug delivery system of linezolid. Hydroxypropyl guar (HPG) and xanthum (XG) were utilized as gum with the mixture of HEC, carbopol, and sodium alginate as viscosity increasing agents. The prepared formulations showed constant release of drug from formulation over a period of 6 h, thus enhancing residence time of the drug. The formulations were recognized to be non-irritating with no ocular damage46.

Harish et al, formulated in situ oral topical gels of clotrimazole established on the theory of pH triggered and ion activated systems. A pH triggered system comprising of Carbopol 934P (0.2-1.4% w/v) and ion triggered system comprising gellan gum (0.1-0.75% w/v) with HPMC E50LV which was utilized to extend the release of clotrimazole (0.1% w/v). Formulations were assessed for gelling capability, gel strength, viscosity, bioadhesive force, spreadability, anti microbiological efficacy studies and in vitro drug release. The role of Carbopol as in situ gel forming system was confirmed by the characteristic to change into powerful gels when the pH was increased while in gellan gum this alteration occurred in the existence of monovalent /divalent cations. Result of calcium carbonate along with further process parameters modified and established that addition of calcium ions developed stiffer gels. The clarity, drug content, and pH of the prepared gel were detected to be acceptable. The viscosity was detected to be in the range 5 to 85 cPs for the sol, while for the gels it was up to 16000 cPs. The formulation showed pseudo plastic flow with thixotrophy. The highest gel strength (using texture analyzer) in addition to bioadhesion was determined to be up to 6.5 g and 4 g correspondingly. The optimized preparations were capable to release the drug up to 6 h47.

Eaga et al, developed ophthalmic delivery of Ciprofloxacin, based on the concepts of pH-triggered, ion activated system and thermo reversible gelation. Poly acrylic acid (Carbopol 940) was utilized as the gel forming agent in mixture with HPMC, which behaved as a viscosity increasing agent (pH triggered system). Pluronic F-127 (14 %) was employed as the thermal reversible gelation in mixture of HPMC (1.5 %), integration of HPMC was to decrease the concentration of pluronic needed for in situ gelation. Gelrite (Gellan gum) is an anionic exocellular polysaccharide showed characteristic cation-induced gelation (0.6 %). The developed formulations was found to be therapeutically efficient, non irritant and stable, which offered constant release of the drug over a period of 6 h48.

Hanan et al, formulated ophthalmic delivery systems of moxifloxacin, which is established on the idea of temperature activated in situ gelation with Pluronic (PL) and pH triggered in situ gelation with carbopol 934 were prepared. The produced formulae were assessed considering their gelation temperature (for PL systems), gelling capability (for CL systems), rheological features, in vitro release behavior and mucoadhesion capacity. Among various formulae examined, P6 and C5 depicted best gelation temperature of 33.9°C subsequent to dilution with simulated tear fluid (STF) and instant gelation that remains for few hours correspondingly. Even though the evaluated index of mucoadhesion was more prominent (7.325 Pa) for C5 compared to (1.947 Pa) for P6, more prominent amount of moxifloxacin was sustained in the aqueous humor area of the eye over 8 h subsequent instillation of P6 with considerable 2.8 fold increase in the Cmax and AUC(0-∞) compared to C549.

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Swati et al, studied on pH triggered in situ gelling system of timolol maleate based on the perception of pH activated in situ gelation. Carbopol was utilized as the gelling agent in admixture with chitosan (amine polysaccharide), which acted as a viscosity enhancing agent. Carbopol 0.4% w/v and chitosan 0.5% w/v formulation was in liquid state at room temperature and undergone rapid transition into the viscous gel phase at the pH of the tear fluid (lacrimal fluid, pH 7.4). The results from formulation clearly demonstrated that carbopol-chitosan based formulation was therapeutically efficacious and showed a fickian (diffusion controlled) type of release behavior over a period of 24 hour50.

Padma et al, formulated and evaluated ocular delivery system of an anti-inflammatory drug diclofenac sodium, based on the idea of pH activated in situ gelation by using sodium alginate, In vitro release studies indicated that the formulation showed better drug release when contacted with STF solution at 8 hrs study period. It showed antimicrobial, antibacterial and antifungal efficacy with selected microorganisms. The results demonstrated that the developed system is an alternative to conventional ophthalmic drops, patient compliance, industrially oriented and economical51.

Basavaraj et al, prepared an ophthalmic delivery system of Ketorolac tromethamine, using Polyacrylic acid (Carbopol 934) as gel forming agent in admixture with HPMC K4M which acted as a viscosity increasing agent based on the conception of pH activated in situ gelation. The prepared formulations was found to be therapeutically effective, stable, non-irritant, and rendered constant drug release over an 8 h period. The prepared formulation was thus a viable alternative to conventional eye drops by virtue of its ability to increase bioavailability through its longer precorneal time of residence and ability to develop sustained drug release52.

Kugalur et al, formulated a pH dependent in situ ophthalmic gels of ketorolac tromethamine using Carbopol 940, which is used as gelling agent in combination with hydroxyl propyl methyl cellulose (HPMC K4M) as a viscosity enhancer. Benzalkonium chloride at suitable concentration was used as a preservative. The prepared formulations were evaluated for clarity, pH measurements, gelling capacity, drug content and in vitro diffusion study. Under rheological investigation both solution and gel was found to be having pseudo plastic behavior. The selected formulations showed sustained release of drug over a period of 8 h with increased residence time53.

Jain et al, formulated an ophthalmic delivery system for Ciprofloxacin hydrochloride for once a day, based on the conception of pH activated in situ gelation. The in situ gelling system involved utilization of polyacrylic acid (Carbopol 980NF) as a phase transition polymer, Hydroxypropyl methylcellulose (Methocel K100LV) as a release agent, and ion exchange resin as a complexing agent. The developed formulations were found to be stable, non irritant to rabbit eyes and increased residence time of the gel formed in situ along with its ability to release drugs in a sustained manner with enhanced bioavailability. Hence it was concluded that in situ gels are a practical substitute to conventional eye drops by providing sustained release of medicaments to the eye54.

Gonjari et al, prepared thermoreversible mucoadhesive gel of flucanazole. Gels were developed by means of the cold method along with poloxamer 407 and various mucoadhesive polymers such as HPMC K4M, HEC and PVP K30. A customized device (modified K-C diffusion cell using corneal membrane of sheep's eye as a diffusion membrane) was employed for assessment of permeation of drug through corneal membrane of a sheep. The developed gels were clear, homogenous in consistency, and had spreadability with a pH range of 6.8 to 7.3. Adequate bioadhesion on the corneal surface of sheep and better gel strength were also noticed. Diffusion studies have revealed that a matrix is the best-fit model. As the ratio of mucoadhesive agent is raised, the rate of diffusion decreases. The order of drug diffusion across the membrane was HEC > PVP K30 > HPMC K4M55.

Wu et al, studied the relationship among the stability of baicalin and insitupH-triggered gelling system. In vitro and in vivo evaluations were performed using several methods namely rheometry, Gamma scintigraphic technique and micro dialysis method. The rheological action showed a significant enrichment ingelstrength under physiological conditions, and the formulation rendered constant release of the drug over a period of 8 hour. In elimination studies, the radioactivity of formulation was all the time superior than that of the control solution. In addition, the AUC and Cmax values were 6.1 fold and 3.6 fold higher than those of the control solution respectively. The results demonstrated that an insitu pH triggered gelling system have better capability to maintain baicalin stable and retain drug release than marketed baicalineyedrops to increase the ocular bioavailability56.

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