Drop Bottles Research Articles

Optical design and study of a wireless IV drip detection device

During the treatment process, intravenous infusion therapy is a common medical treatment for many inpatients. However, patients may experience side effects that increase the hours of care and interfere with their families' work and sleep. During the infusion, the nursing staff have to control the flow rate, monitor the emptying of the drop bottle (drip bag) and pay attention to the possibility of an obstruction which are activities that increase their workload. In this study, the wireless intravenous (IV) drip injection detection device is equipped with an infrared induction magnetic buckle group on the sleeve of the intravenous infusion in order to monitor the infusion flow rate and reduce the risk of a complication. The device has many features such as light weight, high portability, simple operation, and reusability.This study involved the design of a photovoltaic system that automatically detects the level of an IV drop bottle or drip bag. The system mainly includes an LED light source, a sensing module for detecting light passing through the drop bottle, and a biconvex focusing lens (BFL) for concentrating light to enhance the intravenous drip injection detection device's signal. Therefore, in this study, wireless IV drip injection detection device was designed, evaluated and analyzed. The system also uses a built-in database to analyze the difference between coloured drops and blood to improve the reliability of the IV drip detection assembly. When the light sensing module detects the liquid in the drop bottle (drip bag), the receiver sends a signal; if the bottle (bag) is empty, the light sensing module activates the wireless transmitter and the wireless transmitter warns the caregiver via the wireless transmission mode. In the future, cooperation between manufacturers and clinical trials will help to stabilize the cost, thereby improving the quality of intravenous infusion care and reducing the workload on nursing staff.

Serum growth factor stability in different eye drop packaging systems during storage

Serum eye drops (SED) have shown beneficial effects in patients suffering from dry eye syndrome and are manufactured for an increasing number of patients in Australia every year. Previous studies have examined the stability of serum growth factors during storage in either experimental vessels not used as the final packaging system or in eye drop bottles. To ensure the quality and safety of SED product manufactured in Australia, the stability of growth factors in serum packaged into two different systems during storage at different temperatures was examined. Healthy blood donors provided a whole blood donation, from which serum was prepared, diluted to 20% and dispensed into either a tube or a vial packaging system. The stability of growth factors, fibronectin and total protein in tube segments was comparable to matched vials samples during storage at −30 °C, 4 °C, 22 °C and 37 °C, with the exception of EGF and fibronectin in 20% SED stored in tube segments, which were more sensitive to storage conditions at 4 °C and 22 °C when compared to vials. Additionally, the growth factor, fibronectin and total protein concentration in both tube segments and vials was stable during storage at −30 °C for at least 9 months. This study highlights the impact of different manufacturing procedures on serum growth factor stability during storage.

Reduction of Contamination Rate by Reducing the Volume of Preservative-free 20% Autologous Serum Eye Drops

This study investigated whether contamination can be mitigated by halving the filling volume of autologous serum eye drops from 5.0 to 2.5 mL eye drop bottles. Twelve 5.0 mL and eleven 2.5 mL ophthalmic solution bottles were prepared. The ophthalmic solution was all used after opening, leaving one to two drops of the remaining liquid. Immediately after preparation, the remaining liquid was cultured, and, after use, the nozzle and residual liquid were cultured. As a result, twelve 5.0 mL and nine 2.5 mL ophthalmic solution bottles were collected. The average use days of the 5.0 mL ophthalmic solution were 9.6 days and those of the 2.5 mL eye drops were 4.7 days. Bacteria and fungi were not detected from the residual liquid immediately after preparation. However, after use, bacteria were detected in at least one of the nozzles or residual liquid of all eye drops, and fungi were detected in one. Contamination could not be reduced by shortening the period of use of eye drops. Therefore, 20％ autologous serum eye drops need to be handled more appropriately.

Cap-puncturing mechanism for ophthalmic postoperative antibiotic eye drops: friend or foe?

A retrospective case series highlights two cases of postoperative endophthalmitis, in which similar improper technique of puncturing the antibiotic bottle with a nonsterile needle was noted.
 Patient A, a 65-year-old man with three weeks’ history of uneventful combined cataract and pars plana vitrectomy (PPV) presented with acute painful right eye and vision blurring from 6/12 to 1/60 for two days. Examination showed severe anterior chamber activity and hazy fundal view. B-scan showed dense vitritis. Vitreous sampling revealed gram positive cocci, but no culture growth. Patient B, a 69-year-old man presented with three days’ history of right painful red eye and vision dropped to light perception following an uneventful cataract surgery. Examination showed severe anterior chamber activity with hypopyon, raised intraocular pressure, and no fundal view. B-scan detected dense vitritis with loculation. Vitreous sampling cultured Pseudomonas aeruginosa in Patient B. In both cases, the patients reported piercing the generic topical ciprofloxacin 0.3% bottle tip with a nonsterile needle instead of the prescribed method of using the sterile, inner aspect of the bottle cap. However, the cultures of the bottle contents were negative in both cases. Both patients received intravitreal, topical, and systemic antibiotics and subsequently underwent PPV. Patient A recovered vision to baseline, while Patient B recovered to counting finger vision.
 The cap-puncturing mechanism for eye drop bottles is designed to maintain the sterility of the contents. However, this may backfire when patients do not understand the prescribed technique. We postulate that this improper technique predisposed the two cases to endophthalmitis.

Spectroscopy of Oxygen-Sensitive Material for Measuring Contact Lens Oxygen Transmissibility

ABSTRACTPurpose: Oxygen permeability or transmissibility is a crucial parameter for contact lenses to ensure that extended wear will not induce corneal hypoxia. This work tests a new method of using the oxidation of cysteamine, an oxygen-sensitive chemical, to quantify the oxygen transmissibility of current commercial contact lenses and contact lenses loaded with vitamin E.Methods: 3D printing was used to modify eye drop bottles and quartz cuvettes to create systems that allowed insertion of a contact lens in between the cysteamine solution and air. Both systems were exposed to atmospheric conditions where the only path of entry for oxygen was through the contact lens. The entering oxygen reacted with cysteamine, and the rate of cysteamine oxidation was measured using UV-vis spectrophotometry. The rate was then stoichiometrically related to oxygen transmissibility.Results: The eye drop method predicted transmissibility values within 9% of established, commercial values. The cuvette method predicted values within 10% of established values for silicone hydrogel lenses without any correction factor and within 11% for poly-hydroxyethyl-methacrylate lenses after correcting for oxygen entering the system. Incorporation of 20% (w/w) vitamin E into Acuvue® Oasys® lenses did not have a significant impact on the oxygen transmissibility.Conclusions: Both methods presented in this work can reliably measure oxygen transmissibility of contacts lenses or other materials. Further improvements in manufacturing could lead to improved accuracy and reliability, allowing wider use of this method for quantifying the oxygen transport in contact lenses.

A Novel Method to Eliminate Preservatives in Eye Drops.

Multiuse eye drops must maintain sterility and typically accomplish this by added preservatives. However, preservatives often cause harmful side effects. A gauze barrier dressing ("BIOGUARD®") recently cleared by the FDA has an immobilized poly diallyldimethylammonium chloride (p-DADMAC) coating and is an effective antimicrobial with minimal compound release into solution. To implement use of this dressing as a replacement for preservatives in multidose eye drop bottles, its ability to maintain sterility without interacting with the active ingredient (AI) of the ophthalmic medication was tested. To determine immobilized p-DADMAC's microbicidal efficacy, it was added to eye drop bottles, then contaminated with Staphylococcus aureus (SA113) bacteria. To assess interference with AI in eye drops, high performance liquid chromatography was used to determine whether the AIs timolol and dorzolamide were affected after exposure to p-DADMAC. To further investigate effects on AI, the microbicidal activity of Vigamox® (moxifoxacin) was assessed after p-DADMAC gauze exposure. S. aureus bacteria were eliminated by p-DADMAC-treated gauze for all samples. The concentrations of both timolol and dorzolamide increased after exposure to p-DADMAC-treated gauze, but spectrometric analysis showed that this did not occur when the p-DADMAC-coated material was presoaked in deionized water. The microbicidial activity of moxifloxacin was unaffected by exposure to p-DADMAC-treated gauze. Due to its lack of effect on eye drop AI and its microbicidal efficacy, p-DADMAC treatment would make an excellent candidate for replacing preservatives in eye drops.

Novel approaches for improving stability of cysteamine formulations

Cystinosis is a genetic disorder that leads to the formation of cystine crystals in many organs in the body including cornea. Ocular manifestation of this disease is treated by eye drops of cysteamine which can easily oxidize into its disulfide cystamine. The rapid oxidation limits the shelf life as well the duration during which the drug can be used after opening the eye drop bottle. We evaluate two approaches of preventing the oxidation of cysteamine with the goal of increasing the time of use after opening the bottle to one month. The first approach integrates antioxidants such as catalase enzyme and vitamins C and E into the aqueous solution. Results show that catalase is the most effective additive as it decreases the oxidation rate by 58%, which on its own is not sufficient to reach targeted one month stability. The second approach focuses on incorporating diffusion barriers to prevent oxygen from reaching the cysteamine solution. This was accomplished by two methods: formulation of a hydrophobic layer which floats on the surface of the aqueous solution and integration of OMAC® oxygen-resistant material into the eye drop bottle. Both methods delay the onset of cysteamine degradation and decrease the rate of degradation. In particular, an eye drop bottle with three layers of OMAC® has less than 10% degradation after one month of opening the bottle and withdrawing a drop each day. By integrating all three methods, we designed a system where >90% of cysteamine remains in the active form for 70 days after opening the bottle. In addition, we examine the use of OMAC® as heat-sealed pouches for storage of cysteamine eye drop bottles during packaging to eliminate the need for the current approach of freezing the formulation during shipping. The results show that such heat-sealed pouches would keep cysteamine stable for over one year at ambient conditions.

Drop instillation and glaucoma.

To describe the current state of knowledge regarding glaucoma patients' eye drop technique, interventions attempting to improve eye drop technique, and methods for assessing eye drop technique. In observational studies, between 18.2 and 80% of patients contaminate their eye drop bottle by touching their eye or face, 11.3-60.6% do not instill exactly one drop, and 6.8-37.3% miss the eye with the drop. Factors significantly associated with poorer technique include older age, lack of instruction on eye drop technique, female sex, arthritis, more severe visual field defect, lack of positive reinforcement to take eye drops, lower educational level, low self-efficacy, and being seen at a clinic rather than a private practice. Among intervention studies, four of five studies using a mechanical device and three of four studies using educational interventions to improve technique showed positive results, but none of the studies were randomized controlled trials. Poor eye drop technique is a significant impediment to achieving good control of intraocular pressure in glaucoma. Both mechanical device interventions and educational interventions offer promise to improve patients' technique, but studies with stronger designs need to be done followed by introduction into clinical practice.

Multidose Preservative Free Eyedrops by Selective Removal of Benzalkonium Chloride from Ocular Formulations.

About 70% of eye drops contain benzalkonium chloride (BAK) to maintain sterility. BAK is an effective preservative but it can cause irritation and toxicity. We propose to mitigate ocular toxicity without compromising sterility by incorporating a filter into an eye drop bottle to selectively remove BAK during the process of drop instillation. The filter is a packed bed of particles made from poly(2-hydroxyethyl methacrylate) (pHEMA), which is a common ophthalmic material. We showed that pHEMA particle prepared by using ethoxylated trimethylolpropane triacrylate as crosslinker can be incorporated into a modified eyedrop bottle tip to selectively remove the preservative as the formulation is squeezed out of the bottle. Hydraulic permeability of the plug is measured to determine the resistance to eye drop squeezing, and % removal of BAK and drugs are determined. The modified tip has a hydraulic permeability of about 2 Darcy, which allows eyedrops formulations to flow through without excessive resistance. The tip is designed such that the patients can create an eyedrop of solution of 1-10cP viscosity in 4s with a nominal pressure. During this short contact time, the packed particles removed nearly 100% of benzalkonium chloride (BAK) from a 15mL, 0.012% BAK solution but have only minimal impact on the concentration of contained active components. Our novel design can eliminate the preservative induced toxicity from eye drops thereby impacting hundreds of millions of patients with chronic ophthalmic diseases like glaucoma and dry eyes.

Profiling extractable and leachable inorganic impurities in ophthalmic drug containers by ICP-MS

In this study, we investigated the elemental impurities present in the plastic material of ophthalmic eye drop bottles using inductively coupled plasma-mass spectrometry (ICP-MS). Metallic contaminations, especially localized within the small cavity of the eye, can significantly perturb the ocular metallome. The concern is two-fold: first certain elements, for example heavy metals, can be toxic to humans at even trace levels, and second, these contaminations can have adverse reactions with other medicines or enzymatic processes in the eye. The implication of redox-active metals in cataract formation is one such biological consequence. The analysis demonstrated the effect of aggressive storage and transportation conditions on elemental extractable and leachable contamination, and posits that release of these elemental impurities can disrupt metallome equilibrium in the ocular compartment, leading to toxicity and disease.

Intrarectal Anesthesia in Neurosurgery.

In the early days of modern neurologic surgery, the inconveniences and potential dangers of general anesthesia by chloroform and ether using the so-called "open-drop technique" led to the quest for alternative methods of anesthesia. This became all the more necessary, since patient positioning and the surgical arrangements often hindered the use of a drop bottle. One approach to solve this problem was intrarectal ether application. The present article aims to shed light on this original, less well-known anesthesia technique in the neurosurgical field.

Comparison of Eye Drop Instillation Before and After Use of Drop Application Strips in Glaucoma Patients on Chronic Topical Therapy

To evaluate the impact of using drop application strips on eye drop instillation in glaucoma patients on chronic topical ocular hypotensive therapy. A total of 72 patients with primary open-angle glaucoma with an uncorrected visual acuity of 3/60 or more, self-administering topical antiglaucoma medication for >1 year were evaluated. One eye of each patient was included in the study. Patients were instructed to instill 0.5% carboxymethyl cellulose drop in 1 eye. They were then instructed to instill the same drop using the drop application strips. Mean age of the patients included in the study was 50.39 ± 12.04 years. Before assistance of drop application strips, 35 (48.61%) patients placed the drop into the eye without any contact of the dropper nozzle, and, after application of the drop application strips, 66 (91.67%) patients placed the drop in the eye without any contact (P=0.025). The number of patients putting the first drop of drug into the eye without spilling over the adenexae increased from 30 (41.67%) to 45 (62.5%) after application of the strip (P<0.001). The mean number of drops instilled to get 1 drop into the eye decreased from 2 ± 0.95 to 1.56 ± 0.78 when the drop application strip was used (P<0.001). Use of a drop application strip causes a significant decrease in contact of the eye drop bottle nozzle with the eyeball and eyelid, decreases the number of drops instilled to get 1 drop into the eye, and is associated with an overall improvement in eye drop instillation.

Microbiological Safety of Using Eye Drops After One Month: Contamination is A Rule or Mere Regulation ?

Objective: The study was aimed to assess microbial contamination of the eye drop solution after using for one month. Design: A prospective study of the sterility of sixty multi-drop residual eye drops was done. Eye drops were collected from the rural based patients, after at least one month of use. All the eye drop bottles were de-labeled and coded and sent for microbiological evaluation. Only eye drop solution was examined for contamination. Results: None of the eye drop had any qualitative or quantitative evidence of growth after 14 days of incubation on various culture media. Conclusion: The eye drops can be used without fear of microbiological contamination for at least six weeks after opening the vial irrespective of its contents and presence of preservatives .

Complexities of Medical Glaucoma Therapy--the Elderly Patient in Focus

In order to treat glaucoma with medication successfully, the patient needs to participate actively in the process. "Adherence", formerly "compliance", describes the willingness and capacity to follow the prescribed regimen every day. It is not trivial to measure adherence and persistence, as this quite often relies on self reports by the patient or speculations by the physician. Hence, the overall reported adherence may vary from 5 to 95 %. In general, the following categories have been defined for reduced adherence: medication-related factors, patient-related factors, environmental factors and social factors. Age has been found to intensify or modify many of these factors. Older adults often face various challenges, due to motor disabilities, reduced visual acuity or impaired cognitive capabilities. In patients with movement disorders or tactile limitations, the target area can be reached more successfully with standard eye drop bottles than with single-use dose units. This should be considered if antiglaucoma eye drops are prescribed in the elderly. Frequency of application is a main factor influencing adherence. Monotherapy--as provided with prostaglandins--or drops with a fixed combination have proven to support adherence significantly. A significant boost for self-monitoring activities is initiated by the growing market of electronic devices, like smartphones. For instance, they can provide acoustic alarms as reminders to apply the eye drops. It is evident that any external support or disease-related information by family members, the medical practitioners, support groups or even electronic devices may improve adherence and persistence, even in patients with severe impairments.

Difficulties with self instillation of eye drops and its impact on intraocular pressure in glaucoma patients

Aims: Prevalence of glaucoma increases with age and this potentially blinding condition requires regular instillation of eye drops. But with aging itself and accompanying co-morbidities, self instillation of eye drops gets affected. This study was designed to study the subjective difficulties associated with self instillation of eye drops in glaucoma patients and to quantitatively assess their impact on intraocular pressure (IOP). Settings and Design: Prospective interventional study at primary eye care center. Materials and Methods: A total of 69 persons diagnosed with glaucoma or ocular hypertension (OHT), who were self instilling their eye drops, were included in this study. Patients were interviewed for subjective difficulties being faced during self instillation using a formatted questionnaire. The patients were then subjected to assisted eye drop instillation for 4 weeks. The change IOP and consumption of eye drop bottles were compared between self installation and assisted instillation periods. Statistical Analysis: Paired t-test was applied at 5% significance level to compare pre and post interventional change of parameters. Results: Fifty three percent of patients reported subjective difficulties while self instilling their eye drops. Non-compliance was self-reported in 18% of the patients. The IOP dropped by 10-13% (P-value < 0.0001) and consumption of eye drop bottles was 14% (P-value < 0.0001) higher during self instillation. Conclusion: Assisted eye drop instillation may be beneficial to achieve better IOP control.

Effect of textured eye drop bottles on the photostability of pranoprofen 0.1% ophthalmic solution

Context: Ophthalmic solutions are usually filled in a plastic bottle due to its durability and disposability. In Japan, photostability is one of the concerns for the quality control because an eye drop bottle must be a transparent container.Objective: The present work studied the effect of textured eye drop bottles on its light blocking to improve the photostability of ophthalmic solutions.Materials and methods: We investigated the photostability of Pranoprofen ophthalmic solution filled in a variety of textured eye drop bottles. Pranoprofen content was analyzed by high-performance liquid chromatography and surface structure of textured eye drop bottles was evaluated by transmittance, calculated average roughness (Ra) and haze intensity.Results: We observed that eye drop bottle which had greater than Ra value of 1.0 µm and haze intensity 62% clearly showed photostability improvement.Conclusions: This report is the first one which shows that photostability of ophthalmic solution is improved by using textured eye drop bottle. Moreover, this approach is a simple and effective method to improve the photostability. This method is available for not only various ophthalmic applications but also other liquid pharmaceuticals or food products.

On formulating ophthalmic emulsions

The formulation of dilute, transparent ophthalmic emulsions (eye drops) with long shelf lives is a challenge because of the tendency of the emulsion droplets to aggregate, particularly in the presence of the water-soluble polymers typically used in eye drops. While many functions of eye drops, such as lubricity and residence time in the eye, are promoted by high concentrations of high molecular weight water-soluble polymers, emulsified lipids and drugs aggregate in the eye drop bottle if the polymer concentration is above the critical flocculation concentration (CFC). The purpose is to develop a simple approach to predict the CFC for polymers based on information readily available in the literature. High molecular weight guar was hydrolyzed to give a series of guar samples spanning a wide range of average molecular weights. The CFC values and critical viscosity concentrations were measured as functions guar properties, using electrophoresis, dynamic light scattering and rheology measurements. The higher the guar molecular weight, the lower was the CFC, the maximum concentration that can be tolerated in the eye drop formulation. The guar CFC values were approximately equal to the overlap concentrations where guar molecules start to overlap in solution. We propose that the CFC can be estimated for any water-soluble polymer using the polymer molecular weight and the readily available Mark–Houwink parameters, thus providing a design rule for ophthalmic emulsions.

Prevalence of self-reported early glaucoma eye drop bottle exhaustion and associated risk factors: a patient survey.

BackgroundOne barrier to patient adherence with chronic topical glaucoma treatment is an inadequate amount of medication available between prescription refills. We examined the self-reported prevalence of early exhaustion of glaucoma eye drops prior to a scheduled refill, and associated risk factors.MethodsThis cross-sectional survey was performed at a University-based clinical practice. Glaucoma patients at the University of Washington who were experienced with eye drop application and were on a steady regimen of self-administered glaucoma drops in both eyes took a survey at the time of clinic examination. The main outcome measure was self-reported early eye drop bottle exhaustion.Results236 patients were eligible and chose to participate. In general, patients included were relatively healthy (mean 2.3 comorbid medical conditions). Sixty patients (25.4%) reported any problem with early exhaustion of eye drop bottles, and this was associated with visual acuity ≤ 20/70 in the better eye (P = .049). Twelve patients (5.1%) reported that they “often” (5–7 times per year), “usually” (8–11 times per year) or “always” ran out of eye drops prior to a scheduled refill. Patients affected by this higher level (≥5 times yearly) of eye drop bottle exhaustion were more likely to have poor visual acuity in their worse eye ≤ 20/70 (P = .015) and had significantly lower worse-eye logMAR (P = .043).ConclusionsSelf-reported early glaucoma bottle exhaustion regularly affected 5% of patients in our population and 25% reported early exhaustion at least once; the main risk factor was poor vision in at least one eye. These results may not be generalizable to a broad patient population, or to those inexperienced with eye drop self-administration. However, this pilot study compels further evaluation and consideration of early eye drop bottle exhaustion in glaucoma patients.

クロマトグラフィー学習のための携帯用実験教材の試作と実践

A portable kit for performing thin layer chromatography (TLC) was prepared as an experimental tool for learning chromatography in and outside of class. This kit mainly consisted of the following components : (1) two plastic eye drop bottles containing water and ethanol, respectively (for developing or extracting solvents) ; (2) aluminum TLC sheets (15×35mm) precoated with octadecylsilanized silica gel ; (3) a plastic push top vial for development chamber ; (4) a screw top glass vial containing colored bath powder for the extraction of dyes. The better test scores of the students using the experimental kit on the review test for chromatography suggested the kit was effective for better understanding of chromatographic behavior.

GRP-029 Assessment of the Therapeutic Management of Patients on Weekend Leave

BackgroundA patient’s suicide attempt with benzodiazepines was reported to our quality department. The patient ingested a bottle of drops given for his weekend leave. According to French regulations, patients are...