Carbomer Gel Research Articles

Efficacy of different dry eye treatments with artificial tears or ocular lubricants: a systematic review

To objectively review the outcome of clinical studies where rose bengal stain (RB) has been used as an outcome measure to assess the efficacy of artificial tears (AT) in patients with dry eye. From peer-reviewed articles published between 1947 and 2008, information was sought on dry eye status, as reported using a grading scheme, after use of RB as a diagnostic test, before and after use of a specific regimen of artificial tears or ocular lubricants for approximately 30 days. Mean baseline scores and post-treatment scores were calculated, along with the net change and the percentage change in the RB scores. From a total of 33 suitable data sets, published between 1985 and 2006, the group mean pre-treatment RB score was 4.25 +/- 1.55 (+/-S.D.), which decreased to 2.84 +/- 1.24 after 30 days of treatment. This represented a net change of -1.43 (95% CI of -1.04 to -1.45). For use of traditional AT (saline, hypromellose, etc), the net change was -0.95, it was -1.33 for use of carbomer (polyacrylic acid) gels and -2.10 for hyaluronic acid (HA) products. These changes represented net improvements of 25.9 +/- 18.4%, 38.0 +/- 20.7% and 41.8 +/- 16.3% respectively. The greater change with HA was not associated with a lower final outcome score, but with higher pre-treatment scores. Based on RB grading schemes used by numerous different clinicians over many years, treatment of dry eye with artificial tears or ocular lubricants can be expected to improve the condition of the exposed ocular surface. Assuming no improvement without treatment, a 30 days treatment period can be projected to produce an overall improvement of around 25%, but with no unambiguous statistical differences between product types.

The traditional Hungarian medicinal plant Centaurea sadleriana Janka accelerates wound healing in rats

Ethnopharmacological relevance The aerial parts of Centaurea sadleriana Janka, a species native to Hungary, have been used for the healing of wounds of livestock in Hungarian folk medicine. This is the first report of the ethnomedicinal use of this plant. Aim of the study This study was aimed at investigating the wound-healing efficiency of different extracts of Centaurea sadleriana. Materials and methods Experimental wounds inflicted on healthy rats by means of a branding iron were treated topically with different extracts and fractions of extracts of the aerial parts of Centaurea sadleriana. To assess the effectiveness of treatment, an absolute control (no treatment), a vehicle control (Carbomer gel) and a positive control group (1% salicylic acid in Carbomer gel) were applied. Results The n-hexane fraction of the methanol extract significantly accelerated the wound-healing process. This effect was rather similar to that of the positive control gel. Other fractions exhibited more moderate activities. Conclusions The apolar fraction of the methanol extract of Centaurea sadleriana facilitated wound healing significantly, corroborating the folk medicinal use of this plant.

Morinda citrifolia Linn. (Rubiaceae) leaf extracts mitigate UVB-induced erythema

Morinda citrifolia Linn. (Rubiaceae) leaves have been used in tropical folk medicine to treat topical inflammation and burns. A carbomer gel base, containing the ethanol extract and juice pressed from the leaves, was evaluated for potential allergenic properties in a repeat-insult patch test in 49 volunteers. To investigate the topical photo-protective properties, the combined ethanol extract and leaf juice were evaluated in a UVB-induced erythema model in 25 volunteers. The crude ethanol extract of M. citrifolia leaves was also evaluated in vitro for potential anti-inflammatory activity in a histamine H-1 receptor antagonism assay. There was no evidence of allergenic potential in the repeat-insult patch test. When the combination of ethanol extract and leaf juice was applied, the UVB dose required to induce erythema was almost 3.5 times greater than with untreated skin (P < 0.001). In the histamine H-1 receptor-binding assay, the crude ethanol extract of M. citrifolia leaves inhibited receptor binding by 57%. These results suggest that M. citrifolia leaves are safe for topical use and may be useful in mitigating UVB-induced injury to the skin.

Safety of a preservative system containing 1,2-hexanediol and caprylyl glycol

To study the potential for delayed Type IV dermal sensitivity of a new preservative system containing 1,2-hexanediol and caprylyl glycol, 200-subject repeat insult patch tests were performed with a 15% mixture of 1,2-hexanediol and caprylyl glycol (equal parts of the 2 ingredients) in carbomer gel and a cosmetic formulation at an actual use concentration. No delayed Type IV hypersensitivity reactions were observed.

A comparative assessment of the efficacy of carbomer gel and carboxymethyl cellulose containing artificial tears in dry eyes

The present study aimed to compare the clinical efficacy of a 0.4% carbomer gel and 1% carboxymethyl cellulose (CMC) containing artificial tears in treatment of dry eye patients. Sixty subjects with mean age of 45.89 years who had symptoms and signs of dry eye were enrolled in this prospective, investigator-masked and stratified random sampling study. The subjects were divided into two parallel groups with 30 subjects (60 eyes) in each group. One group received carbomer gel, and the other group received 1% CMC containing artificial tears. Subjects received the drops 3 to 4 times or more per day for 3 months. At the first visit time, the precorneal residence time of these two drops was measured. The efficacy was assessed by comparing the subjective symptoms (ocular dryness, foreign body sensation, burning sensation and pain), and the objective test results of tears breakup time, Schirmer's test and corneal fluorescein staining prior to the study and after the treatment. As a result, the ocular residence time of carbomer gel was significantly longer than that of 1% CMC (P<0.001). Most of the primary subjective symptoms and objective test results were improved after treatment in both carbomer gel group and 1% CMC group. As to the improvement of each symptom and objective test result, carbomer gel was more effective than 1% CMC group (P<0.01). In conclusion, carbomer gel had longer precorneal residence time and was more effective than 1% CMC in the treatment of patients with dry eyes.

Contamination of semi-solid dosage forms by leachables from aluminium tubes

The objective of this study was to determine to what extent bisphenol A (BPA), bisphenol A diglycidyl ether (BADGE) and its derivatives are extractable from epoxy-based coatings of aluminium tubes for pharmaceutical use and to monitor their leaching into different kinds of semi-solid dosage forms. Migration increasing factors should be evaluated. Extraction tests using acetonitrile for 10 days at 40 °C turned out to be suitable to estimate the maximum amount of extractables. A plain variability in the nature and amount of extractables among tubes of different vendors ( n = 7) could be demonstrated. Leaching of the remnants into various semi-solid drug products (ointment, cream, gel) during storage (30 °C/40 °C) was verifiable. Leachable profiles were, apart from storage time and temperature, decisively influenced by the matrix. In particular, matrix polarity seemed to play a crucial role. Thus, the highest amount of leachables was found in isopropanol-based carbomer gel. Furthermore, in-use conditions (mechanical stress) enhanced migration significantly. In order to ensure quality and safety of semi-solid formulae, interactions between the coating material and the drug product should be thoroughly evaluated.

Factors affecting the diffusion of meloxicam from different bases

The value of meloxicam as a non-steroidal anti-inflammatory drug is well established. This study was carried out to formulate a stable and effective meloxicam topical preparation. The in vitro release of meloxicam from different semisolid bases, which are: o/w, w/o emulsions, sodium carboxy methylcellulose gel and carbomer gel base was established. The study also involved the diffusion of meloxicam through excised mouse skin with different concentrations using carbomer gel in addition to the effect of different enhancing agents such as PG (Propylene Glycol), methyl salicylate, urea, oleic acid, DMSO (Dimethyl Sulfoxide), xanthan gum and PEG1000 (Poly Ethylene Glycol) and the last one gave the highest diffusion. The results showed that the selected formula of meloxicam was not irritant and this result was supported by histological examination. In addition, the results showed that the use of disodium EDTA (stabilizer) gave more stable formula where the expiration date was 2 years compared to 0.8 year when using both dl- α tocopherol and blank formula. The results showed that the temperature and the storage period led to decrease both the diffusion rate and viscosity of meloxicam 1% gel but with little change in pH. On the other hand preliminary clinical study was carried out for 26 patients and the results indicated that 84.6% of patients got positive responses.

Cubosome Dispersions as Delivery Systems for Percutaneous Administration of Indomethacin

The present study concerns the production and characterization of monooleine (MO) dispersions as drug delivery systems for indomethacin, taken as model anti-inflammatory drug. Dispersions were produced by emulsification and homogenization of MO and poloxamer in water. Morphology and dimensional distribution of the disperse phase have been characterized by cryo-transmission electron microscopy and photon correlation spectroscopy, respectively. X-ray diffraction has been performed to determine the structural organization of the disperse phase. Sedimentation field flow fractionation (SdFFF) has been performed to investigate drug distribution in the dispersion. An in vitro diffusion study was conducted by Franz cell associated to stratum corneum epidermis membrane on cubosome dispersions viscosized by carbomer. In vivo studies based on skin reflectance spectrophotometry and tape stripping were performed to better investigate the performance of cubosome as indomethacin delivery system. Microscopy studies showed the coexistence of vesicles and cubosomes. X-ray diffraction revealed the presence of a bicontinuous cubic phase of spatial symmetry Im3m (Q229). SdFFF demonstrated that no free drug was present in the dispersion. Indomethacin incorporated in viscosized MO dispersions exhibited a lower flux with respect to the analogous formulation containing the free drug in the aqueous phase and to the control formulation based on carbomer gel. Reflectance spectroscopy demonstrated that indomethacin incorporated into MO dispersions can be released in a prolonged fashion. Tape-stripping experiments corroborated this finding. MO dispersions can be proposed as nanoparticulate systems able to control the percutaneous absorption of indomethacin.

Efficacité et tolérance d’un gel de carbomère fluide versus un gel de carbomère classique lors du traitement du syndrome sec

To compare the risk/benefit for C974P (a 0.25% fluid carbomer gel in a vial allowing dropwise instillation) versus a conventional carbomer gel. During this multicenter, randomized, investigator-masked trial, patients with dry eye syndrome were treated with C974P or C940. Control visits were planned on day 7, day 28 (efficacy evaluation) and day 56 (tolerance evaluation). The main criterion was dry eye symptoms globally assessed by a visual analog scale (VAS). The non-inferiority limit for the between-group difference of VAS changes was 10 mm. In the population of 169 patients (87 patients for C974P, 82 for C940), C974P was at least as effective as C940 on symptoms (non-inferiority hypothesis confirmed). The mean VAS value fell by one third in the two groups. The objective signs improved identically in the two groups: corneal staining by fluorescein (p=0.96), rose Bengal score (p=0.73), and lacrimal break-up time (p=0.73). The dosage adaptation was slightly lower than three instillations per day (p=0.16). The adverse events were mild or moderate. C974P galenic changes are able to reach the same level of efficacy on dry eye symptoms and ocular surface damages as the conventional tube carbomer gels.

In Vitro and Ex Vivo Permeation Studies of Chlorpheniramine Maleate Gels Prepared by Carbomer Derivatives

The antihistaminic chlorpheniramine maleate (CPM) is used for symptomatic relief of hypersensitivity reactions and in pruritic skin disorders. At present, the drug is marketed in tablet, capsule, syrup, cream, and injectable dosage forms. Chlorpheniramine maleate has some side effects when taken orally. Due to its first pass effect, only 25%–45% of the orally administered dose reaches the blood circulation. To bypass these disadvantages, we aimed to investigate percutaneous absorption of CPM from gel formulations prepared with different carbomer derivatives (Carbopol 934, 940, 941, 2984, 980, and 981; main differences are related to presence of a comonomer and cross‐link density). Cellulose membrane was used as the diffusion barrier for all the formulations' drug‐release studies. The release of active substance from carbopol derivatives, which have the least cross‐linking density (Carbopol 941 and 981) was found to be numerically higher than the others. The formulation (F8; 1% Carbopol 941) that exhibited the maximum drug release through the cellulose membrane was further studied for drug release by using polyurethane membrane, excised rat skin, and human skin. The penetration of the active substance through different diffusion barriers was found to be statistically different (p < 0.05) when compared. Of all the different diffusion barriers, rat skin gave the closest results to human skin. Thus topical application of CPM in the carbomer gel may be of potential use for local activity. The type and concentration of carbomers can affect drug release. The synthetic membranes are useful in assessments of formulations in quality assurance but they do not give definite indication of how a formulation will behave when it is used on skin.#Presented at The Second Int. Postgraduate Research Symposium on Pharmaceutics (IPORSHIP‐2000), September 6–8, 2000, Istanbul, Turkey.

Effect of Buffers on the Properties of Microbicidal Hydrogels Containing Monoglyceride as the Active Ingredient

Hydrogel formulations containing the monoglyceride monocaprin have shown potent microbicidal activity against several sexually transmitted viruses and bacteria. It is recommended that formulations for preventing infection in the vagina have a low pH as the HIV virus is inactivated at low pH. The object of the work was to investigate how incorporation of buffers into the hydrogel formulations affects physicochemical properties and microbicidal activity of the active substance. Two series of gels were formulated using carbomer (Carbopol 934) and sodium carboxymethylcellulose (NaCMC) as gel-forming agents. The presence of buffers in the gels caused a lowering in gel viscosity, with carbomer gels being more sensitive to buffer presence than NaCMC gels. To obtain viscosity similar to that of a gel without buffer, the amount of polymer needs to be increased. An increase in the amount of NaCMC by 60–70% is needed to obtain the same viscosity as in gel without buffers; but for carbomer, the amount of polymer needs to be doubled. It appears that the effect of maleate buffer on NaCMC gel formation is greater than that of the citrate/lactate buffer; but for carbopol gels, the effects of the buffer systems tested on gel viscosity were equal. The virucidal activity of NaCMC gel buffered with citrate/lactate buffer against herpes simplex virus type 1 and HIV was not reduced by the presence of buffer. The results show that the presence of buffers in the hydrogel formulations affects gel viscosity, but the virucidal effect of the active compound, monocaprin, is not diminished.

Effect of Dispersion Stirring Speed on the Particle Size Distribution and Rheological Properties of Carbomer Dispersions and Gels

ABSTRACT Studies on the influence of the stirring speed during the dispersion stage of Carbopol 5984 on the particle size distributions and rheological characteristics of the gel showed that increasing the stirring speed leads to a decrease in the particle size and in the polydispersity of the dispersion. These two characteristics have antagonist effects on the viscosity: a decrease of particle size leads to a decrease in viscosity while a decrease of polydispersity leads to an increase in viscosity. In this study, for low stirring speed, even if the particle size decreased, the viscosity remained constant because the polydispersity decreased also. For high stirring speed during the dispersion stage, the polydispersity remained constant and the particle size continued to decrease therefore the viscosity decreased. Therefore it is important to monitor the particle size and polydispersity of Carbopol 5984 dispersion during manufacturing to be able to ensure the rheological properties of the gels produced.

Coefficient of Friction of Ocular Surface Lubricants for Laser in situ Keratomileusis

The coefficient of friction was empirically derived for a series of commercially available ophthalmic lubricants having potential use during laser in situ keratomileusis (LASIK). Measurements were obtained using a modified tensile testing machine. Solutions tested included the artificial tear supplements Polytears-free, Bion Tears, Genteal, Refresh, Cellufresh, Celluvisc, Theratears, and Viscotears gel; and balanced salt solution (BSS). Viscotears carbomer gel had a significantly lower mean coefficient of friction compared to other ophthalmic lubricants tested (P=.002) and the dry plate (P=.005). Addition of 0.1 ml of BSS to 0.025 ml of Celluvisc significantly reduced the coefficent of friction of Celluvisc (P=.01). Polytears, Bion Tears, Genteal, Refresh, Celluvisc, Theratears, and BSS had coefficients of friction significantly higher than that of the dry plate. A range of values were obtained for the coefficient of the ophthalmic lubricants tested. Viscotears gel (0.1 ml), and Celluvisc (0.025 ml) + BSS (0.1 ml) had coefficients of friction significantly lower than that of the dry plate.

Development of a membrane-controlled transdermal therapeutic system containing isosorbide dinitrate

The formulation of a transdermal delivery system for isosorbide dinitrate (ISDN) was examined. It was found that the target release rate should be 4.01 mg/h per 20 cm 2 for optimal dosing. In order to reach such this zero order release rate, a membrane permeation controlled transdermal therapeutic system (TTS) formulation was developed, with ethylene vinyl acetate copolymer (EVAC) and polyethylene (PE) membranes as rate controlling membranes; a carbomer gel was used as the drug reservoir. The release of ISDN from this drug delivery device was studied in vitro using FDA recommended method. PIB adhesive on the EVAC or PE membrane caused a decreased flux of ISDN; the release kinetics fitted Higuchi matrix kinetics. TTS with EVAC membrane release ISDN at a rate much lower than the calculated target release rate, but with PE membranes, the release rate was very close to the target. Release rate studies have revealed that, as the VA content in EVAC membrane increased, the flux of ISDN increased. All these results were compared with the commercial product Frandol ® Tape S from Japan. It was found that the release rate of Frandol was close to target release rate and fitted matrix kinetics. These results suggested that TTS that contain PE membrane as rate controlling membrane, polyisobutylene (PIB) adhesive and carbomer gel as a reservoir can be applicable as a TTS for ISDN.

Ocular contact time of a carbomer gel (GelTears) in humans

BACKGROUND/AIMSCarbomers are widely used in products for the treatment of dry eye; however, the polymer gel thins on addition of probes (for example, fluorescein salt) confounding the comparison of products...

Efficacy and Safety of 0.3% Carbomer Gel Compared to Placebo in Patients with Moderate-to-Severe Dry Eye Syndrome

Carbomer gel is a water-soluble polymeric resin that has been reported to maintain the tear film in contact with the eye for an extended period. The efficacy and safety of this new artificial tear were assessed. A multicenter, single-masked, randomized, placebo-controlled study was carried out on 123 patients with moderate-to-severe dry eyes. The placebo was a mannitol solution with benzalkonium chloride 0.008% as preservative. Patients were observed over an 8-week period, and subjective and objective changes analyzed, compared to a baseline of no therapy, after 1 to 7 days washout period from previous medication. All primary subjective symptoms decreased significantly in the carbomer gel-treated group compared to the placebo group (i.e., dryness, discomfort, and foreign body sensation). The carbomer gel also significantly improved the rose bengal staining score relative to placebo. When data for the primary subjective efficacy variables were stratified for disease severity, there was a statistically significant improvement from baseline by day 10 for severely affected patients and from day 42 for patients with moderate disease. Secondary subjective symptoms that improved significantly in the tear gel group compared to placebo were photophobia, erythema, tear breakup time, blurry-filmy, dry-sandy sensation, and physician impression. However, no significant improvements in the secondary subjective symptoms of tearing, itching, scaling, conjuctival discharge, palpebral conjunctival redness, bulbar conjuctival redness, conjunctival luster, relief of discomfort, ease of use, and overall acceptability were found in either group over the baseline score. In addition, neither carbomer gel nor placebo improved the baseline fluorescein staining score or the Schirmer test score. Two patients suffered local allergic reactions to the carbomer gel or its preservative, which settled on withdrawal of the medication. Carbomer gel was more efficacious than was placebo in improving a number of subjective and objective symptoms of moderate-to-severe dry eye syndrome. The results of this study indicate that carbomer gel was a safe as was the placebo.

In vitro percutaneous absorption of piroxicam through synthetic membranes and abdominal rat skin

The in vitro release of piroxicam from carbomer gels and its penetration through isopropyl myristate impregnated membranes and abdominal rat skin were investigated. Attempts were made to relate the differences in the release rate with physicochemical properties of the drug and the vehicle. The results showed that piroxicam is released from the topical gel formulations and diffuses through skin. It is suggested that although piroxicam flux across abdominal rat skin was lower than through isopropyl myristate membranes, this kind of membranes can be used in preliminary screening among the different piroxicam formulations.

Rheological evaluation and ocular contact time of some carbomer gels for ophthalmic use

The poor uptake of many ophthalmic drugs is mainly due to the rapid elimination process by tear turnover. A prolonged precorneal residence time would result in higher absorption and, for some drugs, a prolonged duration of their therapeutic effect. It is known that gels are retained better in the eye than ordinary solutions but relatively little is known about the importance of the rheological properties of gels for their retention. In this study the ocular residence time of carbomer gels have been monitored in humans and the gels were also rheologically characterised. The contact time of Carbopol 974P and Carbopol 1342NF was concentration dependent and was approximately 2–2.5 h for a 2% gel. There was a good correlation of the human contact time and the elastic properties of the gels. The miotic response from gels with pilocarpine nitrate was monitored in rabbits and the area under the curves (AUCs') were calculated. The relative AUCs were 1.5–2.1 for the gel preparations relative to a solution. No concentration dependence was seen and there was no significant difference in AUC between the different carbomers. The ocular contact time of the gels were much less in rabbits than those obtained in humans.

Release of Tolmetin from Carbomw Gel Systems

AbstractGel-formulations containing a nonsteroidal anti-inflammatory drug, tolmetin, were prepared using three different carbomers namely, Carbopol™ 934, 940 and 941. Effects of cosolvent composition, carbomer type, carbomer concentration and drug concentration on drug release from the gels were analyzed by factorial design. Gels with high aqueous content yielded significantly higher tolmetin release rates than gels with lower aqueous content. Although no significant differences in drug release characteristics were observed between the three carbomer gels, there was a trend in the release profiles; fastest drug release was observed from Carbopol™ 941 gels and the slowest drug release was observed from Carbopol™ 940 gels. Increasing the carbomer concentration from 1% w/w to 2% w/w had no significant effect on drug release from gel formulations prepared with all the three different types of carbomers. However, increasing the tolmetin concentration in the gels from 1% w/w to 4% w/w resulted in a dramatic inc...

The influence of azone on the transdermal penetration of the dopamine D 2 agonist N-0923 in freely moving rats

The transdermal penetration of the dopamine D2 agonist, N-0923, was studied in freely moving male albino Wistar rats, after cutaneous dosing of 2 μmol cm −2 in a carbomer gel. A silicone patch with an effective area of 0.65 or 1.3 cm 2 was filled with 100 or 200 mg gel, respectively. The patch was attached to the rat skin using histoacrylic glue. The drug was tested as N-0923 · HCl. The enhancing effect of azone was studied by adding 5% of the penetration enhancer to the gel. A second enhancement study was performed after pretreatment of shaved rat skin with a solution containing 5% azone at various time points, prior to administrations of drug. The pretreatment solution contained ethanol-propyleneglycol-water-azone (60 : 20 : 15 : 5 v/v). The dermal penetration of N-0923 · HCl from the carbomer gel resulted in plasma levels which were relatively low and often at or just above the limit of quantitation of the assay (10 pmol ml −1). Adding 5% azone to the gel resulted in undetectable plasma levels, indicating the drug not being released from the carrier. Pretreatment of the rat skin with a solution containing 5% azone resulted in a 3-fold increase in the flux vs controls. Plasma levels were detectable up to 10 h after application. All pretreated animals showed stereotypy, indicating that adequate amounts of the drug reached the brain.