ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.