Accelerated Wound Healing with a Diminutive Scar through Cocrystal Engineered Curcumin.

Pharmaceutical cocrystals ( Regulatory Classification of Pharmaceutical Co-Crystals Guidance for Industry; Food and Drug Administration, 2018) are crystalline solids produced through supramolecular chemistry to modulate the physicochemical properties of active pharmaceutical ingredients (APIs). Despite their extensive development in interdisciplinary sciences, this is a pioneering study on the efficacy of pharmaceutical cocrystals in wound healing and scar reducing. Curcumin-pyrogallol cocrystal (CUR-PYR) was accordingly cherry-picked since its superior physicochemical properties adequately compensate for limitative drawbacks of curcumin (CUR). CUR-PYR has been synthesized by a liquid-assisted grinding (LAG) method and characterized via FT-IR, DSC, and PXRD analyses. In vitro antibacterial study indicated that CUR-PYR cocrystal, CUR+PYR physical mixture (PM), and PYR are more effective against both Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) bacteria in comparison with CUR. In vitro results also demonstrated that the viability of HDF and NIH-3T3 cells treated with CUR-PYR were improved more than those received CUR which is attributed to the effect of PYR in the form of cocrystal. The wound healing process has been monitored through a 15 day in vivo experiment on 75 male rats stratified into six groups: five groups treated by CUR-PYR+Vaseline (CUR-PYR.ung), CUR+PYR+Vaseline (CUR+PYR.ung), CUR+Vaseline (CUR.ung), PYR+Vaseline (PYR.ung), and Vaseline (VAS) ointments and a negative control group of 0.9% sodium chloride solution (NS). It was revealed that the wounds under CUR-PYR.ung treatment closed by day 12 postsurgery, while the wounds in other groups failed to reach the complete closure end point until the end of the experiment. Surprisingly, a diminutive scar (3.89 ± 0.97% of initial wound size) was observed in the CUR-PYR.ung treated wounds by day 15 after injury, followed by corresponding values for PYR.ung (12.08 ± 2.75%), CUR+PYR.ung (13.89 ± 5.02%), CUR.ung (16.24 ± 6.39%), VAS (18.97 ± 6.89%), and NS (20.33 ± 5.77%). Besides, investigating histopathological parameters including inflammation, granulation tissue, re-epithelialization, and collagen deposition signified outstandingly higher ability of CUR-PYR cocrystal in wound healing than either of its two constituents separately or their simple PM. It was concluded that desired solubility of the prepared cocrystal was essentially responsible for accelerating wound closure and promoting tissue regeneration which yielded minimal scarring. This prototype research suggests a promising application of pharmaceutical cocrystals for the purpose of wound healing.

A Method for Measuring the Surface Free Energy of Topical Semi-solid Dosage Forms.

Our aim was to determine the surface free energy (SFE) of semi-solid dosage forms (SSDFs) by establishing a reproducible method for measuring the contact angle of liquids to SSDFs. Four SSDFs were used: petrolatum, an oil/water (O/W) and a water/oil (W/O) cream, and an alcohol-based gel. The SSDFs were evenly spread on a glass slide, and the change in contact angle over time was measured by dropping water, glycerol, diiodomethane and n-hexadecane as the test liquids. Depending on the combination of test liquid and SSDF, the contact angle was either constant or decreased in an exponential manner. Contact angles may have decreased in an exponential manner because the reaction between the test liquid and the SSDF altered the interfacial tension between the two phases and changed the surface tension of the test liquid and the SFE of the SSDF. The contact angle of the test liquid to the SSDF could be determined reproducibly using the initial contact angle immediately after dropping the liquid on the SSDF as the contact angle before reaction. Using the obtained contact angles and the Owens-Wendt-Rabel-Kaelble equation, we calculated the SFE and its component for the SSDFs tested and found that the results reflect the physicochemical properties of SSDFs. Furthermore, the work of adhesion (WA) of the SSDF to Yucatan micropig skin was calculated using the SFE for the SSDFs. Interestingly, the WA values for all SSDFs tested were comparable.

Effect of Topical Garlic on Wound Healing and Scarring: A Clinical Trial.

BACKGROUND: Historically, garlic containing compounds have been used on wounds to improve healing and ward off infection. Researchers have tested many of these ancient ointments, discovering that garlic is a common ingredient in those that are effective. OBJECTIVE: To determine the efficacy of topical garlic on surgical wounds compared with Vaseline by analysis of visual analog scales and digital photograph analysis. MATERIALS AND METHODS: Seventeen patients with 2 skin excisions applied a 30% garlic ointment to one surgical wound and Vaseline to the other surgical wound twice daily. They were followed up at 2 weeks and 4 weeks post-op. Digital photographs were taken of the sites, and wound visual analog scales were filled out by the patient and the physician. RESULTS: Patients and the onsite physician stated the garlic site healed better in 59% and 65% of the wounds, respectively, at 2 weeks. At 4 weeks, the patients and the onsite physician stated the garlic site healed better in 76% and 88% of wounds, respectively. Digital photograph analysis revealed less erythema at the garlic sites (p-value = .02). CONCLUSION: Surgical wounds treated with 30% garlic ointment healed with more cosmetically appealing scars than the Vaseline-treated sites.

Use of autologous platelet-rich plasma in healing skin graft donor sites.

OBJECTIVE: To demonstrate that the use of platelet-rich plasma (PRP) enhances both the quality of healing and the time required for wound healing at a skin graft donor site. METHODS: Patients who had dermo-epidermal skin grafts taken from the thigh area were included in a prospective, randomised clinical study. PRP was applied to one donor site and then covered with Vaseline-impregnated, open-weave gauze and gauze, while the contralateral donor site on the other thigh served as a control and was covered with the open-weave gauze and gauze without PRP. RESULTS: A total of 24 patients took part in the study, of which three developed infections and were thus removed from the study. Use of PRP reduced the wound healing time of the dermo-epidermal graft donor sites by a mean 17.8% and median 18 days. On average, the treated donor sites healed in 14.9 days compared with 18.4 days for the control group. The median was 14 days compared with 18 days in the control group (p=0.026). In one patient, healing was slower on the side where PRP was applied. In 20 patients, healing of the donor site was accelerated where PRP was applied. CONCLUSION: The study demonstrated a beneficial effect of PRP, as healing time was shortened. Using PRP to heal wounds could be beneficial for patients for whom commonly available wound healing therapies have failed, as well as for high-risk patient groups for whom problematic wound healing may be expected.

Patients use more topical medication when the medications come in a larger container.

INTRODUCTION: Research shows that individuals consume more calories when provided with a larger portion size. It is unclear if similar behavior translates to topical medication use. The impact of container size and provider instructions on patient usage of topical medications has yet to be assessed. METHODS: Data was collected from 128 participants in an IRB randomized, controlled trial. To a marked 3cmx8cm rectangle on the forearm, patients applied petroleum jelly from either a large container or a small tube. Pre and post application container weights were measured. RESULTS: Patients applied more topical medication from the large container compared to the small tube. CONCLUSION: Topical medication usage is influenced by the size of the container provided. It is beneficial to consider container size when prescribing topical medications and greater application is desired.

The Low Prevalence of Allergic Contact Dermatitis Using a Petrolatum Ointment Containing Lanolin Alcohol

Lanolin alcohol is a high cholesterol containing naturally derived material used as a skin protectant in wound healing petrolatum-based ointments. It is a highly purified fraction of lanolin wool wax that has been identified as a possible cause of allergic contact dermatitis. This 3-center study enrolled 499 subjects who underwent a variety of in-office surgical procedures followed by application of a wound healing ointment containing lanolin alcohol without antibiotics. No allergic contact dermatitis was identified in the 499 subjects who completed the study. The lack of allergic contact dermatitis observed may be due to the proprietary highly purified lanolin alcohol utilized in the study formulation. This is not the lanolin alcohol preparation found on the standard dermatology patch test tray. Not all lanolin alcohols are equal. This is an important consideration when examining the reported incidence of allergic contact dermatitis to lanolin alcohol and the absence of allergic contact dermatitis demonstrated in this research. J Drugs Dermatol. 2019;18(10):1002-1004.

Impregnated acetate gauze compared with lipido-colloid contact layer at dressing removal pain: a single-blind cross-over randomised control trial.

OBJECTIVE: To evaluate the performance of Jelonet Plus (JP) and UrgoTul (UT), assessing pain at dressing removal when managing acute or chronic wounds at granulation and epithelialisation stages. METHODS: This was a randomised, multicentre, controlled single-blinded study using a cross-over design. Hospitalised and ambulatory patients presenting with non-infected acute or chronic wounds (at least 40% of wound area of ≤100cm2 covered with granulation tissue) were randomly allocated to be treated with either JP or UT dressings applied according to a standardised local care procedure for two days. At the following visit, patients received the other dressing for a second 2-day period. Pain was evaluated after two days of dressing application and immediately after its removal using a 100mm Visual Analog Scale (VAS). A pain level >30mm was considered as clinically relevant. A lower limit of -12% was determined as the threshold necessary to demonstrate the non-inferiority of JP compared to UT. RESULTS: For the 99 patients completing the study, a difference of 7.9% was observed in favour of JP (83.8% JP versus 75.9% UT) for pain immediately after dressing removal (VAS score < 30mm) with a confidence interval (CI) lower limit of -2.6%, demonstrating non-inferiority (pre-defined limit of -12%). Concerning pain at dressing removal, a difference of 19.6% was observed in favour of JP (81.6% versus 62.0%; p=0.029 for superiority analysis), with a CI lower limit ranging from 2.4% to 38.9%. Therefore, superiority could be concluded. A statistically significant period effect was detected (p=0.003) with fewer patients experiencing pain after the second period day 2 (D2) to day 4 (D4) than the first day 0 (D0) to D2. A statistically significant cross-over effect was also detected (p=0.047), with fewer patients experiencing pain when JP was applied first followed by UT. This suggests a carry-over effect thus preventing a full cross-over design analysis. Adherence of the dressing was less frequent with the JP than the UT dressing (2.0% JP versus 6.9% with UT). CONCLUSION: Non-inferiority of pain at dressing removal was demonstrated with JP. Superiority on this criteria was non-significant but we found adherence of the dressing to the wound bed to be more rare.

[Injected non-absorbable fillers in large volumes]. / In''ektsionnye nerassasyvaemye fillery miagkikh tkanei v bol'shikh ob''emakh.

AIM: To present treatment strategy for large volumes of injectable non-absorbable 'shell-less' soft tissue fillers (vaseline, synthol, silicone etc.). MATERIAL AND METHODS: The authors present an experience of surgical treatment of 8 patients who underwent injections of medical vaseline (breast augmentation, n=5) and synthol (muscles enlargement, n=3) and review of the current literature devoted to this problem. RESULTS: Injection of large amounts (over 50 ml) of non-absorbable fillers into soft tissues is unacceptable and leads to numerous complications. Oil-based 'shell-less' fillers cannot be removed by minimally invasive techniques (puncture, mini-incisions, etc.) due to multiple diffuse lesions in the form of oleogranulomas (cysts of different size) and surrounding widespread inflammation and fibrosis of tissues. Surgery is the only adequate method. However, this approach is followed by scars and often tissue contour deformation. Migration of these fillers to other anatomical areas (from the neck to the lower extremities) significantly complicates the situation, treatment and results. In case of categorical refusal of patients from surgical treatment and no complaints, they should be properly informed about possible consequences and complications and dynamic medical supervision is necessary. Intraoperative ultrasound examination is useful for the control of radical removal of pathological areas. Timely removal of non-absorbable fillers allows to avoid serious complications and to achieve good aesthetic results.

Perspectives on Physicochemical and In Vitro Profiling of Ophthalmic Ointments.

Ophthalmic ointments are unique in that they combine features of topical drug delivery, the ophthalmic route and ointment (semisolid) formulations. Accordingly, these complex formulations are challenging to develop and evaluate and therefore it is critically important to understand their physicochemical properties as well as their in vitro drug release characteristics. Previous reports on the characterization of ophthalmic ointments are very limited. Although there are FDA guidance documents and USP monographs covering some aspects of semisolid formulations, there are no FDA guidance documents nor any USP monographs for ophthalmic ointments. This review summarizes the physicochemical and in vitro profiling methods that have been previously reported for ophthalmic ointments. Specifically, insight is provided into physicochemical characterization (rheological parameters, drug content and content uniformity, and particle size of the API in the finished ointments) as well as important considerations (membranes, release media, method comparison, release kinetics and discriminatory ability) in in vitro release testing (IVRT) method development for ophthalmic ointments. Graphical Abstract Summary of the physicochemcial profiling and in vitro drug release testing (IVRT) for ophthalmic ointments.

Paraffinoma, siliconoma and Co: Disastrous consequences of failed penile augmentation-A single-centre successful surgical management of a challenging entity.

The purpose of this study was to present our series of patients with disastrous consequences of failed penile self-augmentation and suggested surgical reconstruction. Ten patients with median age of 23 years and a variety of penile and scrotal deformities due to injections of several substances had undergone successful surgical reconstruction of external genitalia. The injections were self-performed in nine cases and the patients reported from 4 to 20 substance injections throughout the penile shaft. Three patients presented with fibrotic scirrhous masses in their scrotum, although they did not report any injections in scrotal area. All patients underwent extended penile-shaft skin excision, while all palpable scrotal lesions were removed in one-by-one fashion, as an attempt to destroy the less possible scrotal tissue. All patients were discharged on first post-operative day and reassessed at 2 months post-operatively. As a result, penile self-augmentation with injected substances may cause severe complications. Our proposed single-staged procedure seems safe and effective.

Superiority of a vitamin B12-barrier cream compared with standard glycerol-petrolatum-based emollient cream in the treatment of atopic dermatitis: A randomized, left-to-right comparative trial.

Atopic dermatitis (AD) is a result of complex genetic, epigenetic, environmental, and immunological interactions with an overlapping epidermal barrier defect. The study evaluates the efficacy and tolerability of topical Vitamin B12-barrier cream (MB12) compared with standard glycerol-petrolatum-based emollient cream (GPC) used three times a day for mild AD. The study was conducted as a on one hemi-body randomized, controlled, single-blind, intra-patient left-to-right comparative trial by patients with clinical diagnosis of mild AD measured with total SCORAD index over 4 months. MB12 was compared on one hemi-body treated (GPC). The comparisons of score values were performed primarily by using non-parametric procedures: Mann-Whitney-U test (for independent samples) and Wilcoxon test (for dependent samples). All 22 patients were randomized (left or right side treated with MB12 or GPC). At week 12 a reduction from baseline in SCORAD index was assessed in both body sites with 77.6% SCORAD index reduction in the MB12 treated body sites versus 33.5% in the GPC treated body sites. These results suggest that MB12 could represent a new option in the treatment of mild AD.

Interventions for preventing and treating incontinence-associated dermatitis in adults.

BACKGROUND: Incontinence-associated dermatitis (IAD) is one of the most common skin problems in adults who are incontinent for urine, stool, or both. In practice, products and procedures are the same for both prevention and treatment of IAD. OBJECTIVES: The objective of this review was to assess the effectiveness of various products and procedures to preventand treat incontinence-associated dermatitis in adults. SEARCH METHODS: We searched the Cochrane Incontinence Group Specialised Trials Register, which contains trials identified from the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE In-Process, MEDLINE Epub Ahead of Print, CINAHL, ClinicalTrials.gov, WHO ICTRP and handsearching of journals and conference proceedings (searched 28 September 2016). Additionally we searched other electronic databases: CENTRAL(2015, Issue 4), MEDLINE (January 1946 to May Week 3 2015), MEDLINE In-Process (inception to 26 May 2015), CINAHL(December 1981 to 28 May 2015), Web of Science (WoS; inception to 28 May 2015) and handsearched conference proceedings (to June 2015) and the reference lists of relevant articles, and contacted authors and experts in the field. SELECTION CRITERIA: We selected randomised controlled trials (RCTs) and quasi-RCTs, performed in any healthcare setting, with included participants over 18 years of age, with or without IAD. We included trials comparing the (cost) effectiveness of topical skin care products such as skin cleansers, moisturisers, and skin protectants of different compositions and skin care procedures aiming to prevent and treat IAD. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles, abstracts and full-texts, extracted data, and assessed the risk of bias of the included trials. MAIN RESULTS: We included 13 trials with 1295 participants in a qualitative synthesis. Participants were incontinent for urine, stool, or both, and were residents in a nursing home or were hospitalised.Eleven trials had a small sample size and short follow-up periods. .The overall risk of bias in the included studies was high. The data were not suitable for meta-analysis due to heterogeneity in participant population, skin care products, skin care procedures, outcomes, and measurement tools.Nine trials compared different topical skin care products, including a combination of products. Two trials tested a structured skin care procedure. One trial compared topical skin care products alongside frequencies of application. One trial compared frequencies of application of topical skin care products.We found evidence in two trials, being of low and moderate quality, that soap and water performed poorly in the prevention and treatment of IAD (primary outcomes of this review). The first trial indicated that the use of a skin cleanser might be more effective than the use of soap and water (risk ratio (RR) 0.39, 95% confidence interval (CI) 0.17 to 0.87; low quality evidence). The second trial indicated that a structured skin care procedure, being a washcloth with cleansing, moisturising, and protecting properties, might be more effective than soap and water (RR 0.31, 95% CI 0.12 to 0.79; moderate quality evidence). Findings from the other trials, all being of low to very low quality, suggest that applying a leave-on product (moisturiser, skin protectant, or a combination) might be more effective than not applying a leave-on product. No trial reported on the third primary outcome 'number of participants not satisfied with treatment' or on adverse effects. AUTHORS' CONCLUSIONS: Little evidence, of very low to moderate quality, exists on the effects of interventions for preventing and treating IAD in adults. Soap and water performed poorly in the prevention and treatment of IAD. Application of leave-on products (moisturisers, skin protectants, or a combination) and avoiding soap seems to be more effective than withholding these products. The performance of leave-on products depends on the combination of ingredients, the overall formulation and the usage (e.g. amount applied). High quality confirmatory trials using standardised, and comparable prevention and treatment regimens in different settings/regions are required. Furthermore, to increase the comparability of trial results, we recommend the development of a core outcome set, including validated measurement tools. The evidence in this review is current up to 28 September 2016.

Differences in Cutaneous Irritation of Five Commonly Used Topical Products.

INTRODUCTION: Irritation, such as burning and stinging, on the site of application, is a common side effect of topical dermatologic products including creams, lotions, sprays, and foams. This effect may be more pronounced when applying products to atopic or psoriatic skin. The composition of the vehicle may affect the extent of the irritation. This study compared the irritation and erythema potential of 7 different topical dermatologic products to determine the products with the least likelihood of causing discomfort when applied.
METHODS: Seven sites on the anterior leg of 30 subjects were dry shaven with 10 upward strokes. Subjects rated the stinging of petrolatum (negative control), isopropyl alcohol (positive control), Cetaphil Lotion, triamcinolone 0.1% cream, triamcinolone 0.2% spray, betamethasone foam, and clobetasol 0.05% spray, 1 minute after product application, using a scale of 0 (no symptoms) to 10 (intolerable stinging/burning). The investigator assessed erythema at the sites 30 minutes after application of the products using a scale of 0 (none) to 4 (severe).
RESULTS: Stinging rating score of each product was statistically significant from one another. Petrolatum produced the least stinging (0) and isopropyl alcohol the most (10). Stinging with triamcinolone spray, Cetaphil Lotion, and triamcinolone cream ranked in the lower half of the rating scale (all below 5). Betamethasone foam and clobetal spray ranked the highest at >7. When corrected for the erythema caused by shaving, triamcinolone spray and Cetaphil Lotion produced the least amount of erythema of all the products tested.
DISCUSSION: Rapid evaporation of the volatile vehicle of triamcinolone spray and the non-irriating nature of the medication left behind may contribute to its low erythema and stinging. This product may be an appropriate choice for patients with compromised skin but who require the advantages and conveniences of a spray vehicle.

J Drugs Dermatol. 2016;15(7):870-873.

ICHTHYOSIS LINEARIS CIRCUMFLEXA: NOT ALWAYS A PART OF NETHERTON SYNDROME.

Ichthyosis Linearis Circumfiexa (ILC) is a rarely seen autosomal recessive keratinization disorder and is characterized by erythematous, polycystic, plaques with 'double-edged' scales. Its histological features resemble psoriasis. A triad of ichthyosis (usually Ichthyosis Linearis Circumfiexa), trichorrhexis invaginata (a distinctive hair shaft disorder) and atopy is named as Netherton syndrome. Herein, we report a 12 year-old girl presenting with ILC not accompanied with typical atopy findings and hair shaft disorder.

Adverse reactions to injectable soft tissue fillers: memorable cases and their clinico-pathological overview.

BACKGROUND: Filler injection is a minimally invasive procedure widely used for soft tissue augmentation. Although the safety profile is favorable, adverse events can occur, especially after illegal filler injection. OBJECTIVES: The authors present memorable cases of filler complications and review their clinico-pathological features and treatment strategies. PATIENTS AND METHODS: This is a retrospective, single-center case series. The authors identified eight patients with significant complications following filler injection. A medical record review was performed for clinical history, histopathological studies, and treatment. RESULTS: Six female and two male subjects presented with significant filler complications. The time interval between filler injection and the development of a complication varied greatly among cases (immediately afterwards to 14 years following filler injection). Four of the patients received illegal filler injection where the injected material was either unknown (25%) or was told as paraffin (12.5%) or Vaseline(®) (12.5%). Hyaluronic acid fillers were used in two patients (25%) and the rest were injected with porcine atelocollagen (12.5%) and polyacrylamide hydrogel (12.5%). The complications were classified as an allergic reaction (25%), filler material migration (12.5%), injection necrosis + embolism (25%), and foreign body granuloma (37.5%), based on their clinico-pathological features and were treated accordingly. CONCLUSION: Adverse effects are not uncommon following filler injection. Physicians should be aware of the potential side effects, recognize their presentations, and understand how to manage them.

Efficacy of an emollient dermoprotective cream in the treatment of elderly skin affected by xerosis.

AIM: Xerosis cutis is a frequent condition in the elderly and the topical treatments are aimed to maintain a balance between the physiological components of the epidermis and an optimal moisturization. The aim was to evaluate the efficacy of a dermoprotective cream, glycerol and paraffin-based, in the treatment of individuals affected by senile xerosis. METHODS: The patients were recruited at the Professional Dermatology and Allergology Outpatient Clinic of the San Gallicano Dermatological Institute of Rome, between 1st January 2013 and 30th September 2014. To assess the efficacy of the cream, two different areas of treatment were identified in each patient upper the limbs. All patients were staged at baseline (T0) and evaluated after 14 days (T1) and 28 days (T2) of topical treatment, using five clinical parameters: scaling, sensation of skin tightness, presence of fissuring and excoriations from scratching and erythema. The itching degree was also evaluated using a 10-steps analogical scale. RESULTS: Fifty patients with xerosis, 25 with a severe and 25 with a moderate form, over 60 were recruited and evaluated. Median age was 65 years (IQR=61-70). After 28 day of topical administration of the cream, the 54.0% of patients showed the absence of signs of xerosis, the 44.0% a mild form and the 2.0% (one patient) a moderate form. Consistently, a progressive and significative reduction of itching and transepidermal water loss (TEWL), and an improvement in skin hydration was also measured. A good profile of tolerability and no episodes of undesirable side effects, was also observed. CONCLUSION: The topical daily use of a cream glycerol and paraffin-based, seem to able to control the xerosis in elderly patients, with a significant reduction of all associated signs and symptoms. Further additional data should be collected to better confirm the role of the topical treatment in the control of disease.

A novel nanoscale-dispersed eye ointment for the treatment of dry eye disease.

A novel nanoscale-dispersed eye ointment (NDEO) for the treatment of severe evaporative dry eye has been successfully developed. The excipients used as semisolid lipids were petrolatum and lanolin, as used in conventional eye ointment, which were coupled with medium-chain triglycerides (MCT) as a liquid lipid; both phases were then dispersed in polyvinyl pyrrolidone solution to form a nanodispersion. Single-factor experiments were conducted to optimize the formulations. A transmission electron micrograph showed that the ointment matrix was entrapped in the nanoemulsion of MCT, with a mean particle size of about 100 nm. The optimized formulation of NDEO was stable when stored for six months at 4 °C, and demonstrated no cytotoxicity to human corneal epithelial cells when compared with commercial polymer-based artificial tears (Tears Natural Forte). The therapeutic effects of NDEO were evaluated on a mouse model with 'dry eye'. Both the tear break-up time and fluorescein staining demonstrated therapeutic improvement, displaying a trend of positive correlation with higher concentrations of ointment matrix in the NDEO formulations compared to a marketed product. Histological evaluation demonstrated that the NDEO restored the normal corneal and conjunctival morphology and is safe for ophthalmic application.