Physicochemical Stability of a Novel Tacrolimus Ophthalmic Formulation for the Treatment of Ophthalmic Inflammatory Diseases

Tacrolimus is an immunosuppressant used to treat a large variety of inflammatory or immunity-mediated ophthalmic diseases. However, there are currently no commercial industrial forms available that can provide relief to patients. Various ophthalmic formulations have been reported in the literature, but their stability has only been tested over short periods. The objective of this study was to evaluate the physicochemical stability of a preservative-free tacrolimus formulation (0.2 and 1 mg/mL) at three storage temperatures (5 °C, 25 °C and 35 °C) for up to nine months in a multidose eyedropper. Analyses performed were the following: visual inspection and chromaticity, turbidity, viscosity, size of micelles, osmolality and pH measurements, tacrolimus quantification by a stability-indicating liquid chromatography method, breakdown product research, and sterility assay. In an in-use study, tacrolimus quantification was also performed on the drops emitted from the eyedroppers. All tested parameters remained stable during the nine month period when the eyedrops were stored at 5 °C. However, during storage at 25 °C and 35 °C, several signs of chemical instability were detected. Furthermore, a leachable compound originating from a silicone part of the eyedropper was detected during the in-use assay. Overall, the 0.2 mg/mL and 1 mg/mL tacrolimus ophthalmic solutions were physicochemically stable for up to nine months when stored at 5 °C.

Preservative free travoprost and timolol fixed combination in the initial treatment of primary glaucoma: an assessment of hypotensive efficiency and safety

Purpose. To evaluate the efficacy and safety of Travapress Duo with respect to hypotensive results, changes in functional parameters, and adverse reactions. Material and methods. 30 patients aged 65–75 (averagely 71.3 ± 3.2 years) with a newly diagnosed primary open-angle glaucoma (POAG) received Travapress Duo in the evening, once a day. Goldman tonometry was performed during the screening, then 1 week, 1 month and 3 months from the treatment start. Static perimetry and optical coherence tomography (OCT) were performed before treatment and at the end of the 3rd month since the treatment start. Adverse events were recorded at each stage of the study.Results. As a result of a 3 month long therapy with Travapress Duo, a significant decrease in IOP was noted starting from the 1st week of instillations (by 34 %), after 1 month, by 35 % and after 3 months of observation by 36 %. By the end of the 3rd month of treatment, we noted an insignificant increase in visual acuity, a positive dynamic of the standard deviation and the standard deviation pattern, as well as OCT indicators, such as average thickness of the layer of retinal nerve fibers and the layer of retinal ganglion cells in the macula, stabilization of the thickness of the retinal ganglion cell complex layer and the size of the inner plexiform layer. One patient complained of discomfort and hyperemia by the end of the 1st week of drug instillation. No systemic side effects were noted during the follow-up, and in no case drug withdrawal was require. Conclusion. The preservative-free Travapress Duo drug displayed a high hypotensive efficacy, reducing the IOP to 36% of the initial value. The hypotensive effect was accompanied by indirect neuroprotection, which manifested itself in the positive changes observable in the results of functional studies with varying degrees of reliability. Travapress Duo is characterized by a low level of local side effects and can be recommended for both for the initial and long-term therapy of primary glaucoma of developed and advanced stages.

Peculiarities of the Anterior Surface of the Eye in Patients with Newly Diagnosed Primary Open-Angle Glaucoma

The aim. To conduct an analysis of the anterior surface of the eye in patients with the newly diagnosed primary open-angle glaucoma in order to choose treatment with or without preservative. Materials and methods. We evaluated the front surface of the eye in 46 patients (92 eyes) diagnosed with primary open-angle glaucoma: 20 men and 26 women aged from 58 to 80 years. The anterior surface of the eye was examined using an analyzer of the anterior eye. Results. The signs of previously diagnosed dry eye syndrome (DES) with various manifestations of dysfunction of meibomian glands and complaints about dry eyes, foreign body sensation, lacrimation and blurred vision were reported in 39 patients (85%). Based on the examination results, preservative-free topical hypotensive medications were recommended for these 39 patients. Conclusion. In order to preserve visual functions and quality of life in patients with newly diagnosed POAG, it is advisable to conduct a preliminary assessment of the condition of the anterior surface of the eye when prescribing drug therapy in order to rationalize the choice of first-line drugs with or without preservative in accordance with the European recommendations of Diagnosis and Treatment for glaucoma. Keywords: preservative-free medications, dry eye syndrome, primary open-angle glaucoma.

Neuraxial administration of morphine combined with lidocaine induces regional antinociception in inland bearded dragons (Pogona vitticeps)

OBJECTIVE To assess the antinociceptive efficacy and safety of neuraxial morphine in inland bearded dragons (Pogona vitticeps). ANIMALS 10 healthy adult bearded dragons. PROCEDURES Animals were sedated with alfaxalone (15 mg/kg) SC prior to neuraxial injections. In a randomized, blinded, placebo-controlled, crossover design, animals received preservative-free morphine (0.5 mg/kg) combined with lidocaine (2 mg/kg) or lidocaine (2 mg/kg) only (control treatment). For both treatments, saline (0.9% NaCl) solution was used for dilution to a total volume of 0.3 mL/kg. If the initial injection did not result in motor block of the pelvic limbs or cloaca relaxation within 10 minutes, a second injection was performed. Measurements consisted of bilateral mechanical stimulation of the limbs and at 25%, 50%, and 75% of the trunk’s length as well as cloacal tone to assess spread and duration of motor block. Pelvic limb withdrawal latencies in response to a thermal noxious stimulus were measured over a 48-hour period to assess antinociception. RESULTS Success rate following the first injection was 90% (18/20 injections) and increased to 100% following a second injection. Motor block occurred within 5 minutes with both treatments. Pelvic limb withdrawal latencies were significantly prolonged following neuraxial morphine versus control treatment for at least 12 hours after injection. By 24 hours, no effect of morphine on pelvic limb latencies was detectable. CLINICAL RELEVANCE These results demonstrated that neuraxial administration of morphine results in regional antinociceptive effects for at least 12 hours and has no clinically relevant adverse effects in healthy bearded dragons. This technique has potential for providing regional analgesia in this species.

In vivo antimicrobial activity of 0.6% povidone-iodine eye drops in patients undergoing intravitreal injections: a prospective study

To investigate the antimicrobial activity of a preservative-free 0.6% povidone-iodine eye drop as an antiseptic procedure in decreasing the conjunctival bacterial load in eyes scheduled for intravitreal treatment and to compare its efficacy to the untreated fellow eye used as the control group. Prospective cohort analysis in which 208 patients received preservative-free 0.6% povidone-iodine eye drops three times a day for three days before intravitreal injection. Before and after the prophylactic treatment, a conjunctival swab was collected from both the study eye and the untreated contralateral eye, used as control. The swab was inoculated on different culture media and the colony-forming units were counted. Bacteria and fungi were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Treatment with 0.6% povidone-iodine eye drops significantly reduced the conjunctival bacterial load from baseline (p < 0.001 for blood agar and p < 0.001 for chocolate agar) with an eradication rate of 80%. The most commonly isolated pathogen at each time-point and in both groups was coagulase-negative Staphylococci, isolated in 84% of the positive cultures. The study provides evidence about the effectiveness of 0.6% povidone-iodine eye drops treatment in reducing the conjunctival bacterial load in eyes scheduled for intravitreal treatment.

Comparison of Ketamine Nebulisation with Ketamine Gargle in Attenuating Post Operative Sore Throat Following General Anaesthesia with Endotracheal Intubation

Background & Objective: In the post operative period, Sore throat is a common morbidity following tracheal intubation. The aim was to compare ketamine nebulisation with ketamine gargle to see the effectiveness of nebulisation over gargle in reducing the incidence and severity of post operative sore throat (POST). Methods: In this prospective, randomized study 80 patients between 18-64 year, of either sex belonging to ASA I/II, scheduled for elective surgery under general anaesthesia, were assigned into two groups of 40 patients each. Group GK received preservative free ketamine 50mg in 29 ml of saline, gargled for 30 seconds and Group NK received ketamine 50 mg in 4ml of normal saline via nebulisation for 15 min. General anaesthesia was induced 5 min later in both the groups. Postoperatively sore throat was assessed at 0, 2, 4, 24 hrs using four point scale (0-3). Results: The incidence of POST at 0, 2, 4, 24 hrs was 27%, 25%, 20% and 17% respectively in GK group and 20%, 17.5%, 12.5% and 7.5% in NK group respectively with no statistical difference between the two.. None of the patients in either group experienced severe sore throat. Conclusion: Ketamine nebulisation seemed to represent an effective alternative to ketamine gargle for reliving Post Operative sore throat.