Microbial contamination of multiple-dose preservative-free hospital ophthalmic preparations in a tertiary care hospital.

Background: It is possible that preservative-free eye drops can be contaminated. The aim of this study was to assess the incidence of microbial contamination of preservative-free hospital-prepared anti-infective eye drops and investigate factors that contribute to contamination. This finding may help to raise awareness of this problem to medical healthcare staff and patients in order to prevent the transmission of microorganisms from eye drops to the patients through treatment of pre-existing eye diseases. Methods: Two hundred and ninety-five eye drop bottles were collected from patients attending Rajavithi Hospital Ophthalmologic outpatient and inpatient department, including both those used by patients at home and those administered in the hospital by medical staff. Samples were taken from the tips of droppers and bottles, and the residual fluid inside the bottles was then cultivated onto different culture plates. The culture results were identified and analyzed according to various factors related to both individual users and the bottles. Results: Seven different types of eye drops were collected and 71 (24.06%) of the 295 bottles were contaminated. Vancomycin eye drops were the most contaminated. Twenty-six different types of pathogens were identified, most frequently mold (42.98%), and the amount of contamination was higher in tips than in residual fluid inside the bottle. There was no statistically significant difference in contamination between patients used eye drops collected in outpatient units (32.14%) and medical staff used eye drops collected in inpatient settings (23.22%). The only factor that was statistically significant was the number of eye drops used per person. We found that samples from patients who used only up to 2 eye drops suffered contamination (42.8%) more than those from their counterparts who used at least 3 (22.18%), P â€‹= â€‹0.02. Conclusions: Of these preservative-free hospital preparations anti-infective eye drops, 24.06% were contaminated. The number of eye drops used per person was statistically significant in triggering contamination. There is a possibility of number of eyedrops use person may trigger contamination.

Physical study of Chloramphenicol In Situ Gel with Base Hydroxypropyl Methylcellulose and Poloxamer 188.

OBJECTIVE: The aim of this study was to determine the best formulation of ophthalmic in situ gel preparation by two different bases, Poloxamer 188 and HPMC (hydroxypropyl methylcellulose), with physical evaluation, such as organoleptic, pH, viscosity, and gel capacity during 28 days of storage time. MATERIALS AND METHODS: The two different concentrations of the gel made by using Poloxamer 188 were F1 (5%) and F2 (10%), and those made by using HPMC were F3 (0.45%) and F4 (1%). RESULTS: The results of this study showed that formulation 1 (F1) was the optimum formulation, having pH 6.45, viscosity of 5.47 cP, and a better gel capacity than other formulas. CONCLUSION: In situ gel for ophthalmic preparations is developed to mask the limitation of conventional forms of ophthalmic preparation. In situ gel technology significantly increase the effectivity of drugs in the raw material and drug bioavailability in new drug delivery systems based on in situ gel concept.

Formulation of in-situ ophthalmic microemulsion gel loaded with tacrolimus / 中国药学杂志

OBJECTIVE: To develop the formulation of in-situ ophthalmic microemulsion gel loaded with tacrolimus and evaluate its quality and safety. METHODS: The formulation to make tacrolimus microemulsion into thermosensitive in-situ ophthalmic gel was optimized by orthogonal experiment design using poloxamer 407(F127)and poloxamer 188(F68)as the thermosensitive gel matrix and the gelatinization temperature(Tg) of in-situ gel before and after diluting in simulated tear fluid as compounding effect indicator. The appearance, particle size, gelation temperature, morphological characteristics, rheological properties and dissolution behavior of the optimal in situ microemulsion gel were determined. Simultaneously, the residence time of tacrolimus microemulsion and its in-situ gel were examined using tacrolimus suspension eye drops as control. Irritation of these ophthalmic preparations after single and multiple dose administrations were evaluated against normal saline as control by intra-individual self-control method with Draize test criteria. RESULTS: The gel matrix of the optimal in-situ microemulsion gel containing 1 mg•mL-1 tacrolimus was composed of 140 mg•mL-1 F127 and 20 mg•mL-1 F68. The oval-shaped emulsion droplets homogenously dispersed in the in-situ emulsion gel with average particle size of 18.70 nm. Its gelation temperatures inside and outside eyes were 27.1 and 33.9 ℃, respectively. In vitro dissolution and release tests showed that its releasing characteristics followed zero-order kinetics. The average residence time of tacrolimus in-situ microemulsion gel in rabbit eyes was 22.67 min,significantly longer than those of the suspension and microemulsion of tacrolimus. No irritation was observed for tacrolimus suspension drops, microemulsion and its in-situ gel. CONCLUSION: It would be feasible to prepare tacrolimus temperature-sensitive in-situ gel from microemulsion with a simple preparation process. The gel was of controllable quality, good stability,good temperature sensitivity,and good spreadability, with low eye irritation. Compared with suspension eye drops, in-situ microemulsion gel can be expected to be a superior ophthalmic drug delivery system for hydrophobic drugs due to its steady and sustained release characteristics.

Preparation and In Vitro and In Vivo Evaluation of Sirolimus Ophthalmic Micelles / 中国药学杂志

OBJECTIVE: To prepare sirolimus micelles for the purpose of improving the solubility and applicability in the eye. METHODS: Sirolimus micelles were prepared by thin-film dispersion with Tween-80 and polyoxyethylene stearate (P40S) as carriers. Size distribution, X-ray diffraction spectra, IR spectra and encapsulation efficiency were used to evaluated the character of micelles. The in vitro release and scleral permeability were investigated, and the pharmacokinetics of micelles formulation in rabbit aqueous humor was preliminarily studied. RESULTS: The average particle size was (12.36±0.21) nm, the mean potential was (-6.08±0.98) mV, and the entrapment efficiency was (99.6±0.20)%. Both X-ray diffraction and IR spectra showed that there was almost no free drug. The in vitro release and scleral permeation profiles were in accordance with Higuchi equation. The pharmacokinetic RESULTS: of aqueous humor showed that sirolimus micelles could reach and maintain the therapeutic concentration in the eye for a long time. CONCLUSION: The prepared sirolimus ophthalmic micelles is suitable for ocular administration and is expected to become a promising formulation in the treatment of immune rejection for corneal transplantation.

Effect of Storage Conditions on Stability of Ophthalmological Compounded Cysteamine Eye Drops.

Cystinosis is a hereditary genetic disease that results in the accumulation of cystine crystals in the lysosomes, leading to many clinical manifestations. One of these manifestations is the formation of corneal cystine crystals, which can cause serious ocular complications. The only available drug to treat cystinosis is cysteamine, which breaks cystine and depletes its accumulation in the lysosomes. However, the oral form of cysteamine is not effective in treating corneal manifestations. Thus, ophthalmic solutions of cysteamine are applied. Because the commercial cysteamine eye drops are not available in most countries, hospital pharmacies are responsible for preparing "homemade" drops usually without a control of stability of cysteamine in different storage conditions. Hence, we aimed in this study to investigate the effect of different storage conditions on the stability of a cysteamine ophthalmic compounded solution. Cysteamine ophthalmic solution was prepared in the hospital pharmacy and sterilized using a candle filter. The preparations are then stored either in the freezer at -20°C or in the refrigerator at +4°C for up to 52 weeks. The amount of cysteamine hydrochloride in the preparation at different time points was determined using capillary electrophoresis (CE). Storage of the cysteamine ophthalmic preparations at +4° resulted in significant loss of free cysteamine at all time points, from 1 to 52 weeks of storage, when compared with storage in the freezer (-20°C). We demonstrate that cysteamine 0.5% compounded eye drops are easily oxidized within the first week after storage at +4°C, rendering the preparation less effective. Storage at -20°C is recommended to prevent this process.

Research in rheological properties of four types of ophthalmic preparations / 药学学报

This study is prepared to provide the basis of rheological parameters for the additional quality standard of ophthalmic gels, the rheological properties of the ophthalmic gels and the other three types of ophthalmic preparations. The medicines were compared through the study of the rheological properties for four types of ophthalmic preparations. The cone-plate rheometer was used to determine the dynamic and steady rheological parameters of four types of ophthalmic preparations. The similarities and differences of the measured results were analyzed to summarize the rheological indexes and parameters which are applied to distinguish the ophthalmic gels and the other types of ophthalmic preparations. ① The elastic modulus should be greater than the viscous modulus for the ophthalmic gels in the range of the linear viscoelastic region. ② The ophthalmic gels should be shear thinning non-Newtonian fluid with a certain yield stress and thixotropy. ③ The dynamic viscosity of the ophthalmic gels should be greater than 0.5 Pa·S at the temperature of 25℃ with the 50 s-1 shear rate. The typical rheological indexes and parameters of the ophthalmic gels were proposed in this article. The determination methods are simple and feasible. The rheological indexes and parameters have an important significance in the prescription design, production technology and quality control of the ophthalmic gels.

Analysis of the Amount of Antibacterial Ophthalmic Preparation and Drug Resistance of Ocular Infection Bacteria in a Hospital during 2013-2016 / 中国药房

OBJECTIVE:To provide reference for suitable selection of antibacterial ophthalmic preparation in the clinic. METHODS:The application of antibacterial ophthalmic preparation in a hospital during Jan. 2013-Dec. 2016 were summarized and analyzed to calculate DDDs. The results of bacterial culture and identification,drug sensitivity test were collected. The correlation of DDDs of antibacterial ophthalmic preparation with resistance rates of bacteria was analyzed by using Pearson test. RESULTS:During 2013-2016,there were 7 categories of antibacterial ophthalmic preparations used in this hospital,involving 10 types. To-tal DDDs showed an upward trend with average annual growth rate of 26.16％. DDDs of Tobramycin (dexamethasone) eye drops were the highest for consecutive 3 years (2013-2015). Gatifloxacin eye drops/eye gel and Ofloxacin eye drops/eye oint-ment ranged 2nd-4th place in the list of DDDs. A total of 26143 ocular specimens were examined,and 21 kinds of bacteria were detected,involving 6221 strains with detection rate of 23.80％. Top 3 bacteria in the list of detection rate were Staphylo-coccus epidermidis (3067 strains),Streptococcus pneumoniae (470 strains) and Staphylococcus aureus (321 strains). Resistance rates of above 3 kinds of bacteria to erythromycin were all higher than 70％,while they were sensitive to rifampicin,chlorampheni-col,gentamicin and levofloxacin,etc. Compared to previous year,the average resistance rates of rifampicin(in 2015),gentamicin (in 2015,2016),tetracycline(in 2015),ofloxacin(in 2014,2015),levofloxacin(in 2016)and gatifloxacin(in 2016)had statisti-cally significant differences(P0.05). CONCLUSIONS:The main ocular infec-tions were S. epidermidis,S. pneumoniae and S. aureus. DDDs of tetracycline is certainly associated with resistant rates. Regulating clinical use of antibacterial ophthalmic preparation is important for delaying the development of bacterial resistance.

Effects of three kinds of cyclodextrin on in vitro corneal penetration of curcumin / 中草药

Objective: To study the effects of β-cyclodextrin (β-CD), hydroxypropyl-β-CD (HP-β-CD), and sulfobutyl-ether-β-CD (SBE-β-CD) on in vitro corneal penetration of curcumin. Methods: Improved Franz-cells were used for the corneal diffusion test and the cumulative permeation quantity of curcumin in the corneal was determined by HPLC. Results: β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved the apparent permeability coefficient as much as 1.06, 1.03, 1.00, and 0.95 times. HP-β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved the apparent permeability coefficient as much as 1.16, 1.19, 1.17, and 1.12 times; HP-β-CD at 0.04% and 0.06% there was a significant deference compared with the control group (P < 0.05). SBE-β-CD at 0.02%, 0.04%, 0.06%, and 0.08% improved apparently the permeability coefficient as much as 1.06, 1.23, 1.08, and 0.90 times. SBE-β-CD at 0.04% there was a significant deference compared with the control group (P < 0.05). SBE-β-CD at 0.06% as penetration enhancer, release curve accorded with zero order release equation (r = 0.9978). The average of the corneal hydration is 81.7%. Conclusion: HP-β-CD at 0.04% and 0.06% could improve the apparent permeability coefficient as much as 1.19 and 1.17 times (P < 0.05). SBE-β-CD at 0.04% could improve the apparent permeability coefficient as much as 1.23 times (P < 0.05). SBE-β-CD as corneal penetration enhancers can release safely and effectively. As corneal penetration enhancers, those three kinds of cyclodextrin are without irritation to corneal.