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Anesthesiology May 2014
Topics: Amber; Anesthesiology; Chloroform; Drug Storage; Equipment Design; History, 20th Century; Humans
PubMed: 24755787
DOI: 10.1097/01.anes.0000446485.73012.ec -
Clinical Ophthalmology (Auckland, N.Z.) 2014Loteprednol etabonate (LE) ophthalmic gel 0.5% (Lotemax®) is a new polycarbophil-based, nonsettling topical ophthalmic formulation. The formulation is a semisolid gel...
INTRODUCTION
Loteprednol etabonate (LE) ophthalmic gel 0.5% (Lotemax®) is a new polycarbophil-based, nonsettling topical ophthalmic formulation. The formulation is a semisolid gel at rest and a shear thinning fluid when expressed through a dropper tip. The present study was undertaken to determine how the nonsettling character of LE ophthalmic gel affects dose uniformity. Prednisolone acetate ophthalmic suspension 1% (Pred Forte®) and a generic prednisolone acetate suspension 1% were used as comparators.
METHODS
Drug concentrations of LE ophthalmic gel, Pred Forte, and a generic prednisolone acetate suspension were determined following simulated dosing - consisting of 2 drops, expressed four times daily for 2 weeks, with bottles that were shaken or not shaken immediately prior to expressing the drops. Drug concentrations were determined using a reverse-phase high-performance liquid chromatography (HPLC) method and reported as a percentage of the declared (labeled) concentration. Comparative kinetics of drug particle sedimentation were also determined for each formulation, using dispersion analysis under gravity.
RESULTS
Mean drug concentrations in drops of all three formulations were within a few percentage points of the declared concentration when the bottles were shaken for 5 seconds prior to dispensing. Only LE ophthalmic gel showed consistent and on-target concentrations when the bottles were unshaken prior to dispensing, with a mean (standard deviation [SD]) percent declared concentration of 102% (1.92%) over the 2-week dosing regimen. Drug concentrations for the branded and generic prednisolone acetate suspensions following expression from unshaken bottles were highly variable (overall relative SDs of 16.8% and 20.3%, respectively), with mean concentrations for both falling significantly below the declared concentration for drops expressed at the beginning of the 2-week dosing regimen and significantly above the declared concentration for drops expressed near the end of the dosing regimen. Dispersion analysis at 120× g showed no drug particle sedimentation for LE ophthalmic gel over the 24-hour testing period, whereas the prednisolone acetate suspensions settled in less than 6 hours.
CONCLUSION
LE ophthalmic gel 0.5% provided consistent dose uniformity at the declared concentration whether or not the bottle was shaken prior to dispensing, whereas Pred Forte® and the generic prednisolone acetate required shaking to provide consistent drug concentrations. LE ophthalmic gel may be beneficial to patients because it eliminates the potential impact on the clinical response of both under- and overdosing.
PubMed: 24357925
DOI: 10.2147/OPTH.S55004 -
Journal of Advanced Pharmaceutical... Jul 2011In this work we devised a method to create smaller eye drops of the glaucoma medication timolol maleate by altering the dropper tip design and changing the physical...
In this work we devised a method to create smaller eye drops of the glaucoma medication timolol maleate by altering the dropper tip design and changing the physical properties of the formulation. Most ocular diseases are treated with topical application of eye drops. After instillation of an eye drop, typically, less than 5% of the applied drug penetrates the cornea and reaches the intraocular tissues; the major fraction of the instilled drug is absorbed and enters the systemic circulation. Ophthalmic solutions are available in multidose or single-dose glass/plastic dropper bottles that deliver drops with a volume that ranges from 25 μL to 70 μL (average 40 μL). Because of the low capacity of the precorneal area, the optimal drop volume is about 20 μL; with larger volumes there is the risk of adverse systemic effects due to absorption of the drug via the nasal mucosa. Thus, both from the biopharmaceutical and economic point of view, drops of only 5-15 mL volume should be instilled into the eye. In this present work we devised a method to reduce the size of the drop by inserting a glass capillary tube into the dropper tip and by changing the physical properties of the formulation (by altering the concentration of Tween 80™, i.e., 0.05% and 0.1% of Tween 80™). We measured the drop sizes of the different timolol eye drop formulations available in the market and estimated the yearly cost of the medications. Our timolol maleate formulation with 0.1% concentration of Tween 80™ delivered through the dropper tip with the inserted glass capillary was shown to be better than the other formulations available in the market in terms of ability to deliver smaller drops, meaning that each bottle would last longer and that the yearly cost of treatment would be lower.
PubMed: 22171317
DOI: 10.4103/2231-4040.85540 -
Clinical Ophthalmology (Auckland, N.Z.) May 2010To investigate the influence of container structures and content solutions on the time of dispensing from eye dropper bottles.
PURPOSE
To investigate the influence of container structures and content solutions on the time of dispensing from eye dropper bottles.
METHODS
Eye dropper bottle models, solution models (filtrate water/surfactant solution) and a dispensing time measuring apparatus were prepared to measure the dispensing time.
RESULTS
With filtrate water and pressure thrust load of 0.3 MPa, the dispensing time significantly increased from 1.1 +/- 0.5 seconds to 4.6 +/- 1.1 seconds depending on the decrease of inner aperture diameters from 0.4 mm to 0.2 mm (P < 0.0001). When using the bottle models with inner aperture diameters of 0.4 mm or larger, the dispensing time became constant. The dispensing time using surfactant solution showed the same tendency as above. When pressure thrust load was large (0.07 MPa), the solution flew out continuously with inner aperture diameters of 0.4 mm or larger and the dispensing time could not be measured. The inner aperture diameter most strongly explained the variation of the dispensing time in both the content solutions in the multiple linear regression analysis (filtrate water: 46%, R(2) = 0.462, surfactant solution: 56%, R(2) = 0.563).
CONCLUSIONS
Among content solutions and container structures, the dispensing time was mostly influenced by the diameter of the inner aperture of bottles.
PubMed: 20535225
DOI: 10.2147/opth.s10804 -
BMJ Case Reports 2010A 64-year-old man presented to casualty with blurred vision and pain in his left eye, 2 h after inadvertently instilling clear nail glue into his eye instead of...
A 64-year-old man presented to casualty with blurred vision and pain in his left eye, 2 h after inadvertently instilling clear nail glue into his eye instead of postoperative Timolol eye drops. The glue was removed at the slit lamp revealing a corneal abrasion, which was managed with topical antibiotics. Inadvertent ocular cyanoacrylate, or 'superglue', instillation has been reported frequently since 1982 when superglue was repackaged into ophthalmic style dropper bottles. This case report highlights the continuing problem of cyanoacrylate eye injuries and serves as a reminder to healthcare professionals to report such incidents to manufacturers and regulatory bodies, on behalf of their patients, to promote the introduction of universal safety mechanisms on all household chemical containers. Failure of glue manufacturers to introduce safety cap mechanisms has resulted in significant ocular morbidity over the last 27 years, and such incidents are expected to occur until superglue bottles are redesigned.
PubMed: 22442649
DOI: 10.1136/bcr.11.2009.2435 -
British Medical Journal (Clinical... Jun 1987
Topics: Equipment Contamination; Humans; Ophthalmic Solutions; Ophthalmology; Outpatient Clinics, Hospital
PubMed: 3113539
DOI: 10.1136/bmj.294.6587.1587 -
The British Journal of Ophthalmology Oct 1939
PubMed: 18169660
DOI: 10.1136/bjo.23.10.679