Ophthalmic Gels Research Articles

Drainage pattern of commercial ophthalmic gels: an innovative method of evaluation

The feasibility of an innovative in vitro technique for providing information about the drainage pattern of certain commercially available ophthalmic gels has been investigated. The samples showed qualitatively and/or quantitatively different formulations in terms of either the gelforming agents or the other auxiliary substances. Both torsional oscillation and sine-wave vibro viscometers have been employed during the experiments. The drainage behavior of the gels in systems that essentially differ in both probe adhesiveness and tonicity level of the dispersing media have been estimated. The results obtained revealed different patterns of drainage over time among the various samples. In conclusion, the technique developed offers a viable means of characterizing gels in terms of consistency, adhesion and clearance and it appears to be a useful tool for estimating the surface residence times of gels.

Influence of various concentrations of terpene-4-ol enhancer and carbopol-934 mucoadhesive upon the in vitro ocular transport and the in vivo intraocular pressure lowering effects of dorzolamide ophthalmic formulations using albino rabbits

The objectives of the current study are (i) to maximize the ocular bioavailability of dorzolamide hydrochloride (DZD) through; (a) enhancement of the DZD corneal transport using various concentrations of selected natural terpene-4-ol enhancers, (b) increasing the contact time of the drug with the absorbing tissues of the eye using selected carbopol-934 (C-934) as mucoadhesive to reduce the extensive pre-corneal loss of the installed dose due to the physiologically normal fast tear-washout, and (ii) to assess the in vivo intraocular pressure (IOP) lowering effects of the gel test formulations using normotensive New Zealand albino rabbits. In this study, DZD was formulated as 2% formulations ophthalmic gels containing different concentrations of C-934 as mucoadhesive, as well as, with various concentrations of terpene-4-ol as a natural corneal penetration enhancers. The transport of DZD from the gel formulations was quantitatively determined using in vitro diffusion experiments. The permeability parameters of DZD were calculated employing the most appropriate mathematical equations. Further, the in vivo IOP lowering effects of the test formulations were also assessed using the TONO-PEN®XL applanation tonometer in normotensive New Zealand albino rabbits. The overall results revealed that there is a direct correlation between both the in vitro permeability parameters and the contact period with the ocular tissues and the in vivo ΔIOP. In such case, the in vitro permeability parameters of DZD could be used as a determinant for the in vivo IOP measurements. The magnitude of the DZD-IOP lowering effects as well as the durations of actions for the test formulations has been found to be greatly dependent upon (a) the concentration of the terpene-4-ol corneal penetration enhancer and (b) the duration of contact period with the ocular tissues, which was found to be a single-valued function of the C-943 mucoadhesive concentration. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:119–127, 2010

OCULAR BOAVAILABILIIY OF TRIAMICINOLONE ACETONIDE COMPLEX FROM DIFFERENT OPHIHALMIC PREPARATIONS IN RABBITS’ EYES

The effect of beta-cyclodextrin (β-CyD) on the solubility , release characteristics and ocular bioavailability of triamcinolone acetonide (TA) from ophthalmic gels and ocuserts were investigated. Triamcinolone acetonide- β-CyD complex was prepared by kneading method in a molar ratio of 1:1. The ophthalmic gels [carbopol 934. hydroxy propy] methyl cellulose (HPMC). sodium alginate| and ocuserts (HPMC and carbopol 934 combination. sodium alginate and carbopol 934 combination) were prepared using 0.1% of the drug or its equivalent amount of complex with β-CyD. The in vivo study was performed on male albino rabbits. The drug concentrations were determined in different eye tissues and aqueous humor of the rabbits after 1. 2.4. and 6 hr of the application by HPLC method. The obtained results revealed that. the solubility of TA was increased linearly as a function of β-CyD concentration following AL type phase solubility diagram. The percent released of the drug from the prepared formulations containing free TA could be arranged in the following order: HPMC and carbopol 934 combination ocuserts > sod. alginate and the percent released of the drug from ophthalmic gels and ocuserts containing the drug complex with β-CyD was significantly higher than that of the free drug. Concerning the ocular bioavailability, all tested formulations provided the highest Cmax Of the drug in conjunctiva folloWed by cornea, i is-ciliary bod!. then the aqueous humor. except that after 6 hr. it was high in cornea followed by iris-ciliary body. conjunctiva and then the aqueous humor. The peak time of maximum drug concentration (Tmax) in rabbits eye tissues and aqueous humor was 4 hr for all ophthalmic gels and ocuserts. The total ocular bioavailability of triamcinolone acetonide was improved when the drug was complexed with β-CyD.

OCULAR BIOAVAILABILITY OF ENROFLOXACIN-CYCLODEXTRIN COMPLEXES FROM CERTAIN OPHTHALMIC PREPARATIONS IN RABBITS EYES

The effect of inclusion complexes of enrofloxacin (Enr) with cyclodextrins (CyDs): hydroxypropyl beta-cyclodextrin (HP-β -CYD) and beta-cyclodextrin (β -CyD) was studied. These complexes were prepared in a molar ratio (1:2). The ophthalmic gels [sodium carboxymethyl cellulose (sod CMC), sodium alginate] and ointments (emulsion, absorption and water soluble bases) were prepared using 0. 5% of the drug or equivalent amounts of its complexes with HP- β -CyD or β -CyD. The ocular disposition of the drug in rabbit's eyes has been studied. The obtained results revealed that, all tested formulations provided the highest Cmax of the drug in conjunctiva followed by Cornea, iris-ciliary body, and then aqueous humor .The peak time of maximum drug concentration in rabbit's eye tissues and aqueous humor was two hours for various ophthalmic ointments and gels The total availability of enrofloxacin was improved when the drug was complexed with HP-β –CYD.

Ion-Activated, Gelrite®-Based in Situ Ophthalmic Gels of Pefloxacin Mesylate: Comparison with Conventional Eye Drops

The purpose of our work was to develop an ophthalmic delivery system of a flouroquinolone antibiotic, pefloxacin mesylate, based on the concept of ion-activated in situ gelation. Gelrite® gellan gum, a novel ophthalmic vehicle, that gels in the presence of mono- or divalent-cations present in the lacrimal fluid, was used as the gelling agent. The developed formulation was compared with marketed eye drops in efficacy of treatment of bacterial conjunctivitis that was induced artificially in rabbits. The formulations were evaluated for rheological characteristics, in vitro release behavior, antimicrobial efficacy, and efficacy against bacterial conjunctivitis.We found that in situ gelling formulations passed the test for sterility. The formulations exhibited a first-order release pattern over 12 hr in in vitro release studies. The developed formulation was effective against selected micro-organisms in antimicrobial efficacy studies. The shelf lives of formulation was >2 years. The formulation demonstrated better therapeutic efficacy compared with standard eye drops because it improved the clinical parameters monitored for prolonged periods. The developed formulations can be considered as a viable alternative to conventional eye drops.

Preparation of In Situ-Forming Ophthalmic Gels of Ciprofloxacin Hydrochloride for the Treatment of Bacterial Conjunctivitis: In Vitro and In Vivo Studies

Sol-to-gel systems of ciprofloxacin hydrochloride were prepared utilizing the phase transition properties of hydroxy propyl methyl cellulose K 15 M grade (HPMC) and carbopol 934. The sol-to-gel systems were sterilized by gamma radiation and/or filtration. The sol-to-gel systems were evaluated for rheological characteristics, in vitro release behavior, microbial efficacy, in vivo release behavior, and efficacy against induced bacterial conjunctivitis in rabbits' eyes. Concentration in aqueous humor was determined and stability studies were carried out as per the ICH guidelines. The system passed the test for sterility. The sol-to-gel system exhibited a zero-order drug release pattern over 24 h in in vitro release studies. The drug was active against selected microorganisms in microbial efficacy studies. Better improvement in artificially induced bacterial conjunctivitis in rabbits' eyes was observed in animals treated with the sol-to-gel system compared with marketed eye drops. Drug concentration in aqueous humor was greater than the minimum inhibitory concentration (MIC 90) against selected microorganisms. The shelf-life of the product was >2 years.

Topical use of chitosan in ophthalmology: tolerance assessment and evaluation of precorneal retention

The mucoadhesive polysaccharide chitosan was evaluated as a potential component in ophthalmic gels for enabling increased precorneal drug residence times. This cationic vehicle was expected to slow down drug elimination by the lacrymal flow both by increasing solution viscosity and by interacting with the negative charges of the mucus. The molecular weight ( M w) and concentration of polysaccharide were studied in four types of chitosan as parameters that might influence ocular tolerability and precorneal residence time of formulations containing tobramycin as therapeutic agent. An ocular irritation test, using confocal laser scanning ophthalmoscopy (CLSO) combined with corneal fluorescein staining, clearly demonstrated the excellent tolerance of chitosan after topical administration onto the corneal surface. Gamma scintigraphic data showed that the clearance of the formulations labelled with 99mTc-DTPA was significantly delayed in the presence of chitosan with respect to the commercial collyrium (Tobrex ®), regardless of the concentration and of the molecular weight of chitosan in solution. At least a 3-fold increase of the corneal residence time was achieved in the presence of chitosan when compared to Tobrex ®.

Precorneal sampling techniques for ophthalmic gels.

Drug-cornea contact time is a critical issue in ocular drug delivery. Existing methods for its experimental determination are developed mainly for eye drops and ointments, and have not been reported for ophthalmic gels. The present study evaluated two tear film sampling techniques (capillary tubes and Schirmer strips) and one recovery technique (cotton swab) for their suitability for the determination of precorneal drug concentration as a function of time for ophthalmic gels. The study was conducted using the rabbit eye model, and the gel studied was a commercial polyacrylate-based gel containing pilocarpine HCl. The three techniques explored yield similar results with respect to drug-cornea contact time, about one hour for the gel studied. The strip method suffers from a gel-carry-over problem at the early time points; therefore it is not recommended for tear sampling until most of the gel is cleared from the cul-de-sac. Successful tear sampling was accomplished using capillary tubes. Drug concentration in the tear film as a function of time determined using this technique reveals not only the duration of contact between the drug and the cornea, but also demonstrates a nonuniform drug distribution in the tear film at the early time points (10 and 30 minutes). Finally the cotton swab technique is gentle, easy, and nondestructive. It recovers total drug remaining in the cul-de-sac but does not yield information for the tear film.

Effect of Phenylephrine Hydrochloride on Betamethasone Side Effect in Relation to Viscosity of Ophthalmic Preparations II - Gel-State

AbstractCombination preparations of betamethasone and phenylephrine hydrochloride were prepared in the form of ophthalmic gels based on polye thylene glycols, PEG, a carboxyvinyl polymer (carborner 934) or methylcellulose. The intraocular pressure, IOP, was followed after the application of the se gels to the rabbit eye. Three parameters have been utilized to assess the performance of combination preparations of the two drugs. These are the area under the curve, AUC, the maximum response, MR, and the duration of side effect (increased the IOP). It was found that the inclusion of phenyle phrine hydrochloride in the gel reduces, to marked extent, viz. 80-90%, the AUC compared to the corresponding gel devoid of phenylephrine hydrochloride, and that,∼60% reduction in the duration of betamethasone side effect with regard to the IOP. The most effective gel system appeared to be methylcellulose based gel.

Activity of ophthalmic gels of betamethasone and phenylephrine hydrochloride in the rabbit's eye

Four gel systems were considered to represent a differential in viscosity covering the range from ~ 15–200 P (D ∼- 0 s −1). The gel systems were based on methylcellulose (MC), carbomer and polyethylene glycols (PEG) (two gels). The effect of different gel formulations on the activity of betamethasone (increase in the intraocular pressure: IOP) and phenylephrine hydrochloride (decrease in IOP and increase in pupil diameter) was investigated. The parameters that have been utilized to assess the performance of . preparations of the two drugs were the area under (AUC) or above the curve (AAC), the maximum response (MR) time of maximum response (TMR), and duration of activity (DA). In the case of betamethasone, it was found that a 14-fold increase in viscosity (D ∼- 0 s −1) brought about a decrease in the AUC of only 10%. With phenylephrine hydrochloride the AAC (in both drug actions (IOP) or pupil diameter) is independent of the viscosity of the ophthalmic gel over the range of ~ 15–200 P (D ∼- 0 s −2)

In vitro release study of betamethasone and phenylephrine hydrochloride from ophthalmic preparations

The in vitro release of betamethasone and phenylephrine hydrochloride from ophthalmic solutions and gels was investigated. Linearization of release data of either drug or their combination was attempted according to zero-order, first-order and diffusion kinetics. The data obtained are directly in favour of a first-order mechanism both for betamethasone and phenylephrine hydrochloride and they show that the mechanism of drug release from solutions containing viscolizers or from hydrogels is independent of the nature of the drug in terms of its water solubility or ionization. The type of polymer or the increase in viscosity of the ophthalmic preparation do not indicate the release mechanism to any significant extent. The release rate constants of phenylephrine hydrochloride are consistently higher than those of betamethasone. The preparation based on carbomer is the only exception to this. The release rate constant of the drug is highly dependent on the viscosity of the ophthalmic solution. Below the critical viscosity of 5 cp a considerable lowering of the release rate constant takes place. In ophthalmic gel the release rate constant of either drug shows a very low dependency on the basic viscosity of the gel.