Tear Film Stabilization and Symptom Improvement in Dry Eye Disease: The Role of Hyaluronic Acid and Trehalose Eyedrops versus Carmellose Sodium.

This study evaluated the effectiveness of hyaluronic acid and trehalose (HA/trehalose) eyedrops in managing dry eye disease (DED) symptoms by measuring tear stability and administering a DED questionnaire. Sixty patients were treated with either HA/trehalose eyedrops (Tear A) or carmellose sodium eyedrops (Tear B) as controls. The tear breakup time (TBUT) and non-invasive breakup time (NIBUT) were monitored, and patients completed the standard patient evaluation of eye dryness (SPEED) questionnaire. After two months of twice-daily applications, patients treated with the HA/trehalose eyedrops demonstrated significant improvements in the NIBUT (12.98 ± 3.22 s) and TBUT (12.95 ± 2.98 s), indicating increased tear stability. Moreover, they reported lower dry eye sensation (6.70 ± 4.94 SPEED score points), suggesting a reduction in DED symptoms. These findings underscore the efficacy of HA/trehalose eyedrops in improving both the objective and subjective signs of DED, with twice-daily application enhancing ocular surface conditions and reducing patient-reported symptoms.

A biocompatible and easy-to-make polyelectrolyte dressing with tunable drug delivery properties for wound care.

Chitosan (CS) is a biodegradable and biocompatible polysaccharide which displays immune-stimulatory effects and anti-bacterial properties to facilitate wound closure. Over the years, different CS-based dressings have been developed; however, most of them are not fully biodegradable due to the involvement of synthetic polymers during dressing fabrication. In addition, preparation of many of these dressings is laborious, and may impose damaging effects on fragile therapeutic molecules. The objective of this study is to address these problems by developing a tunable, biocompatible, and biodegradable CS-based dressing for wound treatment. The dressing is fabricated via electrostatic interactions between CS and carmellose (CM). Its swelling properties, erosion behavior, loading efficiency and drug release sustainability can be tuned by simply changing the CS/CM mass-to-mass ratio. Upon loaded with minocycline hydrochloride, the dressing effectively protects the wound in mice from infection and enhances wound closure. Regarding its high tunability and promising in vivo performance, our dressing warrants further development as a user-friendly dressing for use in wound care.

A randomized multicenter study comparing seawater washes and carmellose artificial tears eyedrops in the treatment of dry eye syndrome.

PURPOSE: To investigate the safety and efficacy of sterile isotonic seawater washes vs standard treatment with carmellose artificial tears in dry eye syndrome (DES). PATIENTS AND METHODS: This is a randomized multicenter prospective study with 12 weeks of follow-up. A group of patients with DES (N=60) were treated with seawater spray (Quinton®) five times daily, and another similar group (N=60) were treated with carmellose artificial tears eyedrops (Viscofresh® 0.5%) five times a day. The parameters studied and measured were as follows: Ocular Surface Disease Index questionnaire score, Schirmer I test (without anesthesia) score, tear osmolarity (TearLab®), tear breakup time, tear meniscus height (meniscography OCT), fluorescein corneal staining score (National Eye Institute scale), lissamine green conjunctival staining score, and levels of IL-1 beta and IL-6 in tears (Luminex® 200). RESULTS: In the group treated with seawater, symptoms decreased by 68%, and the decrease was 26% statistically superior to the group treated with carmellose artificial tears eyedrops (P<.001). Levels of IL-1 beta and IL-6 in tears significantly decreased in the seawater group compared to the carmellose artificial tears group (19%/17% vs 52%/51%) (P<0.001). There were no statistically significant differences in the other measured parameters. There were no cases of poor tolerance or side effects. CONCLUSION: Administration of seawater is more effective than treatment with carmellose artificial tears in reducing symptoms and pro-inflammatory molecules (IL-1 beta and IL-6) in tears of patients with DES.

Combination of hyaluronic acid, carmellose, and osmoprotectants for the treatment of dry eye disease.

BACKGROUND: Dry Eye Disease (DED) is a multifactorial disease, with a high prevalence, that can have a great impact on the quality of life of patients. The first step of treatment includes the use of lacrimal substitutes composed of polymers, possible to associate osmoprotectant agents to the lacrimal substitutes. The aim of this article is to analyze the properties of the combination of hyaluronic acid (HA), carmellose, and osmoprotectors (Optava Fusion®; Allergan, Inc., Irvine, CA, USA) on DED. General considerations on the use of artificial tears are also proposed. METHODS: A group of ophthalmologists, experts in the management of the ocular surface, analyzed different aspects related to DED; among them, the use of artificial tears in general and the properties of the combination of HA, carmellose, and osmoprotectors, in particular, were discussed. A review of the literature was carried out, which included different articles published in Spanish, English, and French until April 2017. CONCLUSIONS: DED is a common chronic pathology that usually requires sustained treatment. In addition, the combination of HA, carmellose, and osmoprotectors has proven to be effective in the treatment of symptoms and signs of dry eye by the synergistic action of all its components. This review provides key elements to help ophthalmologists who begin in the management of DED.

Design and evaluation of mucoadhesive oral films containing sodium hyaluronate using multivariate data analysis.

CONTEXT: Mucoadhesive oral films, with their prolonged residence time at the site of application, offer a promising approach for protection of the oral lesion surface. The addition of sodium hyaluronate of different molecular weights as a second mucoadhesive polymer into the film matrix could positively influence the physico-mechanical and mucoadhesive properties of films. OBJECTIVE: The aim of this study was to investigate the formulation of a monolayered film matrix containing varying amounts of sodium hyaluronate and to test the properties of such matrices by applying different characterization methods. MATERIALS AND METHODS: Film matrix was composed of two mucoadhesive polymers, carmellose sodium and sodium hyaluronate, plasticized with glycerol. Resulting films were characterized with regard to their viscosity and physico-mechanical properties. RESULTS AND DISCUSSION: Multivariate data analysis was employed to evaluate the influence of varying amounts of mucoadhesive polymers on the main mucoadhesive oral films' properties. The lower content of sodium hyaluronate caused improvements in mechanical properties and residence time on the artificial oral mucosa, both of which are the main characteristics that determine the quality of the final product. CONCLUSIONS: The best results were obtained by samples containing carmellose sodium with a small amount of sodium hyaluronate (about 0.5% in casting dispersion).

Efficacy and safety of two new formulations of artificial tears in subjects with dry eye disease: a 3-month, multicenter, active-controlled, randomized trial.

PURPOSE: To evaluate and compare the efficacy and safety of two investigational artificial tear formulations (CHO-1 and CHO-2) containing carmellose sodium, hyaluronic acid at different concentrations, and osmoprotectants, with a standard carmellose sodium-containing formulation (Refresh Tears [RT]) in the treatment of dry eye disease. SUBJECTS AND METHODS: In this 3-month, double-masked, multicenter study, subjects (n=305) were randomized 1:1:1 to receive CHO-1, CHO-2, or RT, used as needed but at least twice daily. The primary endpoint was change in ocular surface disease index (OSDI) score from baseline to day 90. Other key outcomes included symptoms evaluated on a visual analog scale, corneal and conjunctival staining, and adverse events. RESULTS: OSDI scores and dry eye symptoms showed a rapid and sustained reduction from baseline in each group. Both CHO-1 and CHO-2 met the primary efficacy endpoint of noninferiority to RT in day 90 OSDI score change from baseline. OSDI ocular symptoms subscale improved more with CHO-1 than CHO-2 (P=0.048). In subjects with clinically relevant baseline ocular surface staining (>14 total score of a maximum of 55), day 90 improvements were greater with CHO-1 and CHO-2 than RT (P≤0.044). Day 90 improvements in OSDI ocular symptoms subscale scores were also greater with CHO-1 than RT (P<0.007) in subjects with clinically relevant ocular staining. All treatments were well tolerated. CONCLUSION: Both combination artificial tear formulations were efficacious and well tolerated in subjects with dry eye. CHO-1 demonstrated the best performance in improving ocular symptoms and reducing ocular staining in this heterogeneous study population.

Determination of dependencies among in vitro and in vivo properties of prepared mucoadhesive buccal films using multivariate data analysis.

Mucoadhesive films represent the most developed medical form of buccal application. Despite the intense focus on buccal film-based systems, there are no standardized methods for their evaluation, which limits the possibility of comparison of obtained data and evaluation of the significance of influence of formulation and process variables on properties of resulting films. The used principal component analysis, together with a partial least squares regression provided a unique insight into the effects of in vitro parameters of mucoadhesive buccal films on their in vivo properties and into interdependencies among the studied variables. In the present study eight various mucoadhesive buccal films based on mucoadhesive polymers (carmellose, polyethylene oxide) were prepared using a solvent casting method or a method of impregnation, respectively. An ethylcellulose or hydrophobic blend of white beeswax and white petrolatum were used as a backing layer. The addition of polyethylene oxide prolonged the in vivo film residence time (from 53.24±5.38-74.18±5.13 min to 71.05±3.15-98.12±1.75 min), and even more when combined with an ethylcellulose backing layer (98.12±1.75 min) and also improved the film's appearance. Tested non-woven textile shortened the in vivo film residence time (from 74.18±5.13-98.12±1.75 min to 53.24±5.38-81.00±8.47 min) and generally worsened the film's appearance. Mucoadhesive buccal films with a hydrophobic backing layer were associated with increased frequency of adverse effects.

Application properties of oral gels as media for administration of minitablets and pellets to paediatric patients.

Modern solid multiparticulate drug forms (minitablets, pellets, granules) can provide the possibility of precise dosing or modified drug release or taste masking for medicines used in children. However, these solid particles require an adequate medium to ease swallowing. The aim of the research was to design a universal semisolid dispersing medium for administration of minitablets and pellets. High viscosity sodium carmellose and carbomer were considered as gelling agents. The hydrogels were prepared with sucrose, glycerol, and potassium sorbate or parabens. Preliminary studies were undertaken to estimate the application properties of the gels under conditions where a medicine is administered to a child. Besides standard tests (viscosity, sedimentation) the following measurements were conducted: gel ductility, mass of the gel removed from a spoon under shaking, ability of the gels to disperse solid particles, and disintegration of minitablets in the gels. The oral hydrogels prepared either with 1.0% and 1.5% carmellose or 0.25% and 0.5% (w/w) carbomer were suitable for dispersing and delivery of minitablets or pellets. Not only viscosity but also ductility was an essential criterion in selecting the best vehicle. The in vivo perceptibility test for pellets and minitablets did not confirm that gels are more advantageous than syrups.

Hordeum vulgare hull in the design of fast disintegrating tablets.

In the present study, fast disintegrating tablets were designed with a view to enhance patient compliance. In this method, the hull of Hordeum vulgare, cross carmellose sodium, and sodium starch glycolate were used as superdisintegrants (4 and 6%), along with microcrystalline cellulose and mannitol, to enhance mouth feel. The prepared batches of tablets were evaluated for hardness, friability, drug content uniformity, wetting time, water absorption ratio and in vitro dispersion time. Based on the in vitro dispersion time, the formulations were tested for the in vitro drug release pattern. Tablets having H. vulgare hull showed the release profile comparable to those tablets having sodium starch glycolate and cross carmellose sodium.

Formulation design of fast disintegrating tablets using disintegrant blends.

In the present work, fast disintegrating tablets of prochlorperazine maleate were designed with a view to enhance patient compliance by direct compression method. In this method, crospovidone (up to 3% w/w) and croscarmellose sodium (up to 5% w/w) in combination were used as superdisintegrants. Since disintegrants complement each other, accelerating the disintegration process when used together. Estimation of prochlorperazine maleate in the prepared tablet formulations was carried out by extracting the drug with methanol and measuring the absorbance at 254.5nm. The prepared formulations were further evaluated for hardness, friability, drug content uniformity, in vitro dispersion time, wetting time and water absorption ratio. Based on in vitro dispersion time (approximately 12 s), one promising formulation was tested for in vitro drug release pattern in phosphate buffer pH 6.8 and short-term stability (at 40 degrees /70% RH for 3 mo), drug-excipient interaction (IR spectroscopy) were studied. Among the formulations tested, formulation DCPC(4) containing 5% w/w of croscarmellose sodium and 3% w/w of crospovidone as superdisintegrant emerged as the overall best (t(50%) 7.0 min) based on drug release characteristics in pH 6.8 phosphate buffer compared to commercial conventional tablet formulation (t(50%) 17.4 min). Short-term stability studies on the promising formulation indicated that there were no significant changes in drug content and in vitro dispersion time (p<0.05).