Production Of Eye Drops Research Articles

Application of a mixed type of optimization in the implementation of pharmaceutical development of a dosage form of eye drops based on oligohexamethyleneguanidine hydrosuccinate

This study focused on the implementation of the stages of pharmaceutical development of a dosage form of eye drops based on the branched oligohexamethylene guanidine hydrosuccinate according to discrete and continuous optimization, followed by risk assessment and process validation. Experimental samples were developed, critical process and quality parameters were identified, technological characteristics were measured, parameters were normalized, a forecast was made, confirmatory experiments were conducted, the optimal composition was identified, risks in the production of eye drops were assessed, and partial validation was performed. During the implementation of the stages of pharmaceutical development of eye drops based on branched oligohexamethylene guanidine hydrosuccinate, three optimization cycles (discrete and continuous) were carried out, and the optimal ratio of active and auxiliary components was justified based on the results (branched oligohexamethylene guanidine hydrosuccinate 0.05%, polyvinyl alcohol 1%, phosphate-buffered saline 20%, sodium chloride 0.45%, and purified water up to 100%). After reviewing the technological process considering risk analysis, critical points were identified, and partial validation was performed, and the positive results verified and confirmed the optimal choice at this stage of pharmaceutical development. In general, a mixed type of optimization (discrete and continuous) can be used to implement pharmaceutical developments of eye drops based on branched oligohexamethylene guanidine hydrosuccinate, which is confirmed by a series of experiments and risk assessment, and the partial validation verified the data obtained. Thus, pharmaceutical development is a complex and time-consuming process, and limited functionality does not always allow quick identification of the optimal composition of a drug. As an effective solution for implementing the stages of pharmaceutical development, mathematical modeling methods and various types of optimization can be applied.

Phospholipid Free Nano-Vesicles of Brinzolamide Biopolymer Ocular Insert; Design, In vitro and In vivo Evaluation

The aim of this work to study the feasibility of using phospholipid free vesicles with positive charge inducer in a slowly dissolving polymer ocular insert to successfully control intraocular pressure (IOP) for an extended period. Brinzolamide (BRNZ) was chosen as a model drug and a full factorial design was assembled to investigate the drug loading effect, ratio of cholesterol to fatty moiety and the type of the fatty moiety used on the vesicle size and entrapment efficiency. Linear regression models were constructed, and optimization of the formulation compositions yielded two formulae with palmitic acid as a negatively charged vesicles and cetrimide positively charged vesicles. Both formulae were studied in term of permeation efficiency through bovine corneal membranes. Positively charged vesicles although it didn't achieve the highest flux and cumulative amount permeated per unit surface area in the experiment time course, it achieved the highest retention of drug inside the corneal tissue, so it was chosen to be incorporated in a slowly dissolving polymer ocular insert. The insert was evaluated in term content, physical evaluation, and release properties. In vivo evaluation of the casted ocular inserts was conducted in male albino rabbits against market eye drop product and IOP readings were collected for 48 hours. The positively charged sterosomes containing BRNZ and formulated in polymer ocular inserts achieved extended control of IOP of the test animals compared to the market product.

Terahertz Attenuated Total Reflection Spectral Response and Signal Enhancement via Plasmonic Enhanced Sensor for Eye Drop Detection.

With chronic ocular diseases such as glaucoma and dry eye syndrome, patients have to apply eye drops over the long term. The therapeutic effects of eye drops depend on the amount of drug contained and the stability of the solution. In addition, contamination during usage and transport can also negatively affect the quality and efficacy of eye drops. The current techniques for the characterization of eye drops are often complicated and time-consuming. Developing a fast and non-invasive way of accurately measuring eye drop quality remains an ongoing challenge. The biggest challenge and primary prerequisite for the application of this new detection technique for eye drops is the obtention of a sufficient spectral response and resolvable signal, considering the large background signal contributed by water. In this work, we use terahertz (THz) attenuated total reflection (ATR) spectroscopy combined with a sensitive hybrid graphene oxide (GO) and carbon nanotube (CNT) thin-film sensors to obtain distinct THz spectral signals in commercial eye drops. Various commercial eye drop products have been tested, and we show that they can be differentiated via their spectral signals. Our results provide a solid foundation for the future fine analysis of eye drops and the detection of their quality. Furthermore, THz spectroscopy combined with GO/CNT films has significant potential and advantages for the non-destructive characterization of aqueous pharmaceutical products.

Dextran: A Multifunctional and Universal Electrolyte Additive for Aqueous Zn Ion Batteries

AbstractThe aqueous Zn ion battery (ZIB) is a potentially sustainable energy storage device. However, its performance is still far from satisfactory. Herein, it is demonstrated that a branched sugar, dextran, widely used in eyedrop products to relieve irritated eyes, is a multifunctional and universal electrolyte additive to enable high‐performance ZIBs. Experimental and theoretical results reveal that dextran has four functions: forming a surface protective layer to minimize side reactions, facilitating stepwise [Zn(H2O)6]2+ desolvation, preferably adsorbing on Zn(0002) planes to supply desolvated Zn2+ and homogenizing electric field. These functions are universally observed in Zn(CF3SO3)2, ZnSO4, Zn(ClO4)2, and ZnCl2 aqueous electrolytes. As demonstrations for practical applications, Zn anodes deliver Coulombic efficiency of 99.97% after 3400 cycles in an electrolyte with 50 mg mL‒1 of dextran and cumulative plating capacity of 3400 mAh cm‒2 at 5 mA cm‒2. Zn//V2O5 full cells with a low negative/positive electrode capacity ratio of 2.18 can be stably cycled over 138 cycles at 1 A g‒1. Pouch full cells can work under mechanical bending conditions. Zn//polyaniline full cells can cycle steadily for 3000 cycles at 0.5 A g‒1 at −10 °C. Dextran shows excellent potential as a low‐cost and non‐toxic electrolyte additive to enable safe and reliable ZIBs.

Peculiarities of the filtration process of liposomal emulsion for the production of eye drops based on a peptide complex

Liposomes are increasingly being studied and implemented as drug delivery systems in the form of eye drops. An important stage in the production of a liposomal preparation in the form of eye drops is the stage of sterilization filtration before filling the medicinal product into a container for final dosage. It is assumed that liposome components interact with the membrane and clog it due to their unique physicochemical properties. Therefore, a deeper understanding of the sterilization filtration of liposomes is needed to make appropriate decisions regarding the choice of filters for sterilization.Resistance and permeability values calculated from the Darcy equation are well suited for comparing different filter membranes or process parameters. Aim. To substantiate the choice of optimal brands of filter membranes and parameters of the liposomal emulsion filtration process for the production of eye drops based on a peptide complex. Materials and methods. The study object was a liposomal emulsion for the production of eye drops based on a peptide complex. A prepared liposomal emulsion of eye drops based on a peptide complex and membrane filters of various brands were used for filtration. Filtration tests were performed on a Zero-T scaling unit manufactured by Sartorius, Germany. For all measurements, the filtrate weight was controlled using a balance. Filtration experiments were evaluated using Zero-T 2.0 software from Sartorius Stedim Biotech, Germany. At the first stage, the recorded data of the results was saved to a file. Based on the data obtained using the Excel table processor, the filtration flow J°, the initial resistance of the membrane R°zag and the throughput Ṽ were calculated according to the calculated measurement time: the beginning of T10 % and the end of T80 %. Results and discussion. According to the results obtained, the optimal brands of sterilizing membranes were determined; it was shown that by increasing the pressure drop, the volumetric throughput was significantly improved by more than 18 times (from 0.7 to 4.1 bar), and in another experiment – by more than 10 times (from 0.3 to 2.1 bar). In addition, the benefit of using a higher pressure drop to filter liposomes through various sterilizing membranes was shown. Conclusions. The obtained values of the initial resistance of the membrane showed that the geometrical aspects and properties of the material of the Supor® (Pall) and Sartopore 2® (Sartorius) membrane brands have a lower ability to block the membrane during filtration and provide the filtration resource due to greater throughput. It has been also shown that the use of a higher pressure drop increases the productivity of the process.

Effect of storage temperature on the dispersibility of commercially available 0.1% fluorometholone ophthalmic suspension.

In this study, we focused on the storage conditions and investigated the effects of low-temperature storage (10°C) on the dispersibility of active components in three formulations of fluorometholone (FLU) suspension eye-drops (one original drug and two generic drugs, P1-P3). For all three eye-drop products, before shaking by hand, white sediment anticipated to be the principal active component was seen at the vial base. In the ordinary-temperature storage group, the FLU contents per drop after shaking by hand were 0.076% in P1, 0.023% in P2, and 0.100% in P3, and the content in P2 was significantly lower than that in P1 and P3. In contrast, almost no dispersion was observed in the low-temperature group. The results after sufficient shaking of these samples with a vortex, in contrast, were such that the FLU contents per drop were 0.063% in P1, 0.086% in P2, and 0.088% in P3; the content in P1 was significantly lower than that in P2 and P3, and there was no difference between P2 and P3. Moreover, we evaluated the dispersibility according to the evaluation "Vs / (ρg - ρf) g." In both the low- and ordinary-temperature storage groups, the value of Vs / (ρg - ρf) g, proportional to the terminal velocity, decreased in the following order: P3 > P1 ≫ P2, and each value in the ordinary-temperature was higher than that in low temperature. The zeta potential decreased in the following order: P2 > P3 ≫ P1. In conclusion, when FLU suspension eye drops are stored at low temperatures until use, such as in a refrigerator, ordinary shaking does not help achieve dispersion to the specified concentration, and even with vigorous shaking with some formulations, the specified concentration cannot be achieved.

Validation of Stability-Indicating RP-HPLC Method and Determination of Impurities by LC-QTOF-MS for Adenosine in Eye Drops

Presently, there is no validated method for stability-indicating related substances of adenosine used in the treatment of cataracts and found in different combined eye drop products. A stability-indicating related substances analytical method for adenosine used in the treatment of cataracts and found in different combined eye drop products should be developed and validated. A new reverse phase-HPLC method of determination for adenosine-related compounds has been developed and validated according to the International Council for Harmonisation. In this method, all impurities were easily detected for adenosine, which is found in combination with different active ingredients such as nicotinic acid and nicotinamide. The impurities obtained by a stress test were purified and their structures were characterized by mass spectroscopy (LC-QTOF-MS). The concentration range for linearity was evaluated as 0.06-4.27 µg/mL for adenosine, 0.15-4.27 µg/mL for uridine, 0.15-4.17 µg/mL for inosine, 0.13-4.35 µg/mL for guanosine, and 0.12-4.26 µg/mL for adenine. Good linearity was achieved for each component, and it was determined that the correlation coefficient (r) met the acceptance criterion r ≥ 0.99. The accuracy of the method was good-to-excellent recoveries at each concentration level (from LOQ to 120% of the specification limit) were achieved within the limit range of 80.0-120.0%, and RSD of recoveries was found below 10.0% for both formulations. With this economical and simple method validated in accordance with the ICH Q2 (R1) guideline, a new method has been created for adenosine, which is suitable for routine analysis. The validated method is a very simple and suitable method for green chemistry without any pre-processing, and the structure of the impurities obtained as a result of stress studies was confirmed by LC-QTOF-MS.

The Effect of Antimicrobial Peptides on the Viability of Human Corneal Epithelial Cells.

Antimicrobial peptides are polypeptides composed of less than 100 amino acids and are a class of antibiotics with strong activity against some infectious bacteria. This study examined the safety of four chosen antimicrobial peptides using primary human corneal epithelial cells (HCEC) and explored their potential therapeutic use. The efficacy of the peptides was also studied by evaluating the minimum inhibitory concentrations (MIC) against Gram-negative and Gram-positive bacteria. One of the peptides (polymyxin E) was found to have antibacterial efficacy against a common Gram-negative bacterium (MIC 1.56μg/mL for Pseudomonas aeruginosa), and another one (nisin) was found to have antibacterial efficacy against a common Gram-positive bacterium (MIC 125μg/mL for Staphylococcus aureus). Metabolic activity and live/dead/apoptotic effects were measured with fluorescent dyes after HCEC were exposed to the peptides for 30min. Three of the peptides exhibited lower toxicity against HCEC than a currently marketed eye drop product. Regarding both efficacy and safety, two of the peptides (polymyxin E and nisin) were found to have potential use for treating ocular infections.

Clinical translation of eye drops and complex drug products

AbstractEye drops constitute majority of ophthalmic drug products, with solutions, suspensions, ointments, and emulsions being the top formulations. While solutions are considered simple formulations, with biowaiver granted for qualitatively and quantitatively similar generic formulations, others are complex formulations, whose generic products are difficult to develop and translate. In particular, manufacturing processes as well as the grades of inactive ingredients used can affect drug product attributes and bioavailability. Thus, bioequivalence of complex generics is less certain. The US FDA issued some draft guidance documents to ease approval of complex generic drug products. One purpose of this presentation is to discuss the difficulties in clinical translation of complex generic eye drop products. In recent years, there has been significant effort in developing eye drops for back of the eye drug delivery, using either pure drug formulations or carrier‐drug composite formulations (e.g., polymeric nanoparticles), with little or no success to date. The second purpose of this presentation is to discuss translational gaps in advancing eye drops for back of the eye drug delivery and to further discuss the difficulties in manufacturing and stabilizing composite nanoparticle formulations for eye drop applications.

Cardiac safety of ophthalmic timolol

ABSTRACTIntroduction: It is generally believed that topical administration of eye drops safeguards against harmful systemic effects. However, about 80% of the drug in the ophthalmic products is systemically absorbed and the first-pass metabolism is avoided. Ophthalmic timolol is widely prescribed in the treatment of glaucoma either alone or in the combination eye drop products, many of which have been launched fairly recently. Ophthalmic timolol may cause serious adverse effects such as symptomatic bradycardia, various conduction disorders in the heart, orthostatic hypotension, syncope and falls.Areas covered: In this review we document a number of factors associated with the properties of ophthalmic timolol and specific features of a patient, which may jeopardize patient’s cardiac safety even after topical treatment.Expert opinion: Plasma timolol levels are correlated with cardiovascular adverse effects in patients, since timolol is mainly metabolized by cytochrome P450 2D6 (CYP2D6) enzyme in the liver. Patients who are lacking the functional CYP2D6 or who are concomitantly using potent CYP2D6 inhibitor drugs (e.g. paroxetine or fluoxetine) or verapamil or other beta-blockers are at risk of getting serious cardiac adverse effects. Prior to treatment initiation, ECG should be always performed and CYP2D6 genotyping should be considered, if routinely available.

Bacterial spectrum and resistance patterns in corneal infections at a Tertiary Eye Care Center in South China.

To investigate the spectrum and antibiotic susceptibility of bacteria isolated from patients with suspected corneal infections in Zhongshan Ophthalmic Center in South China over the past four years retrospectively. Totally 1943 corneal scrapes from patients with corneal infections from 2010 to 2013 were cultured and processed using standard microbiological procedures to identify bacterial isolates. Simultaneously, the bacterial isolates were tested for antibiotic susceptibility to 8 antibiotics (ceftazidime, cefuroxim, cefazolin, levofloxacin, ofloxacin, neomycin, tobramycin, chloramphenicol) using the Kirby-Bauer disc diffusion technique. Of the total 1943 scrapes, 397 (20.43%) were culture-positive, of which 294 (74.06%) were gram-positive (GP) and 103 (25.94%) were gram-negative (GN) bacteria. Of the GP organisms, the most prevalent genera were Staphylococcus spp. (56.17%, n=223), Kocuria spp. (5.29%, n=21) and Micrococcus spp. (1.26%, n=5). On the other hand, the most prevalent genera were Pseudomonas spp. (12.85%, n=51), Burkholderia spp. (2.02%, n=8) and Acinetobacter spp. (1.51%, n=6) for the GN organisms. Among five antibiotics that have eye drop products, the resistant to neomycin of GP (7.82%, 95% CI: 4.72%-10.92%) and GN isolates (9.71%, 95% CI: 4.01%-15.41%) was lowest, while the resistant to chloramphenicol was highest (GP: 34.35%, 95% CI: 28.92%-39.78%; GN: 60.19%, 95% CI: 50.74%-69.64%). Staphylococcus spp. was the most common bacterial pathogens isolated from patients with corneal infections in this setting. High percentages of GP and GN bacteria were mostly susceptible to neomycin and highly resistant to chloramphenicol.

Avaliação histomorfométrica e da proliferação celular em úlceras de córnea superficiais, induzidas em coelhos, após o uso de colírio de Citrus lemon

O objetivo do presente estudo foi avaliar e comparar, por meio de histomorfometria e imuno-histoquímica para PCNA (Antígeno Nuclear de Proliferação Celular), o processo de reparação corneal de úlceras superficiais induzidas em coelhos e tratadas com colírios de óleo essencial de Citrus lemon (CL). Foram utilizadas 40 fêmeas da espécie leporina, constituindo-se quatro grupos experimentais de 10 animais cada. Todos os animais foram submetidos à indução da úlcera superficial experimental por meio da aplicação tópica de n-heptanol. Em dois grupos foram instilados colírios à base de óleo essencial de Citrus lemon, em diferentes concentrações, sendo 3% (GL3) e 5% (GL5). Outro grupo foi tratado com Tween 80 8% (GT), que é o diluente utilizado na produção dos colírios de CL; o grupo controle (GC) recebeu apenas substituto da lágrima. Todos os colírios foram aplicados quatro vezes ao dia. Os grupos experimentais foram distribuídos em dois subgrupos, com cinco animais cada, de acordo com os períodos finais de avaliação. O primeiro subgrupo (M1) foi avaliado após 24 horas e o segundo (M2), após cinco dias. Nas comparações entre os momentos iniciais e finais, os grupos tratados com substituto da lágrima, Tween 80 8% e colírio à base de óleo essencial deCitrus lemon 5% promoveram aumento na espessura epitelial na periferia da córnea e maior percentual de proliferação celular. Não houve diferença de celularidade entre os tratamentos. Os colírios à base de óleo essencial de Citrus lemon, nas diferentes concentrações, promoveram a reepitelização corneal, sem causar lesões adicionais ao epitélio ou estroma corneal, podendo ser utilizado na superfície ocular.

Ripasudil: first global approval.

Ripasudil hydrochloride hydrate (Glanatec® ophthalmic solution 0.4 %; hereafter referred to as ripasudil) is a small-molecule, Rho-associated kinase inhibitor developed by Kowa Company, Ltd. for the treatment of glaucoma and ocular hypertension. This compound, which was originally discovered by D. Western Therapeutics Institute, Inc., reduces intraocular pressure (IOP) by directly acting on the trabecular meshwork, thereby increasing conventional outflow through the Schlemm's canal. As a result of this mechanism of action, ripasudil may offer additive effects in the treatment of glaucoma and ocular hypertension when used in combination with agents such as prostaglandin analogues (which increase uveoscleral outflow) and β blockers (which reduce aqueous production). The eye drop product has been approved in Japan for the twice-daily treatment of glaucoma and ocular hypertension, when other therapeutic agents are not effective or cannot be administered. Phase II study is underway for the treatment of diabetic retinopathy. This article summarises the milestones in the development of ripasudil leading to the first approval for glaucoma and ocular hypertension.

Proposal of standardized guidelines for the production and quality control of autologous serum eye drops in Korea: based on a nationwide survey

Autologous serum eye drops (ASEDs) have been used to treat many eye diseases. However, there are no standardized guidelines for the production and quality control (QC) of ASEDs in Korea. Our aim was to propose standardized guidelines for the production and QC of ASEDs. We conducted a nationwide survey consisting of questions regarding the methods used in each hospital for the production and QC of ASEDs. The survey was sent by e-mail to 89 doctors responsible for the blood banks at different hospitals. Thirty-two hospitals replied, and 13 hospitals reported using the ASEDs in the treatment of patients with eye diseases. The screening test for patients, amount of blood sampling, type of bottle used for blood collection, details about the production of the eye drops, and storage methods and shelf life of unopened and opened bottles of eye drops varied between hospitals. Based on an analysis of the survey results and a review of the standard operating procedures and protocols for ASEDs used in Japan, Germany, England and Wales, and the United States, we proposed standardized guidelines for the production and QC of ASEDs in Korea. ASEDs are not cell therapy products in the strictest sense. However, because eye drops are composed of serum isolated from blood and are used in patients, we consider ASEDs to be the basis for cell therapy products. Therefore, ASEDs should be produced and stored according to standardized guidelines based on the Good Manufacturing Practice guidelines.

An evaluation of the pharmaceutical quality and antimicrobial effectiveness of some frequently used eye drop products available for sale in Nigeria

Aim: Eye drop products must be properly packaged and must be sterile throughout the period of use. For this reason, we evaluated eye drops offered for sale and used for the treatment of eye diseases in Nigeria for their pharmaceutical quality and antimicrobial effectiveness. Materials and Methods: Eleven different sterile eye-drop product samples containing gentamicin, chloramphenicol, timolol, tropicamide, tetrahydrozoline, pilocarpine, antazoline-tetryzoline, diclofenac, dexamethasone, and flubiprofen were opened and tested for bacterial contamination after exposure to air over 56 days. To assess the possibility of contaminations by pathogens due to repeated handling during use about 10 7 -10 8 cells of Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans were added to other newly opened eye drops and incubated at room temperature. Samples were collected and the number of viable organisms was estimated. Eye-drop product samples were also investigated for packaging, pH, and clarity. Results: No viable microorganisms were detected in the eye drops during and at the end of the 56 days exposure to air. All the samples exhibited rapid bactericidal and fungicidal activities at a rate which depended on the species of pathogens and the content of the sample. The anti-infective samples demonstrated the highest rapidity in microbicidal activities. There were no microbial survivors in any of the samples after 4 h of inoculation by pathogens. Conclusions: The study concluded that generally multi-dose eye drop products offered for sale in Nigeria were of acceptable microbial quality and possessed good antimicrobial effectiveness.

Topical drug delivery to the eye: dorzolamide

Topically applied carbonic anhydrase inhibitors (CAIs) in eye drop solutions are commonly used to treat glaucoma. However, local eye irritation and multiple daily administrations may hamper their clinical usefulness. Aqueous eye drop formulations that improve their topical bioavailability and reduce their eye irritation can improve their clinical efficacy. Earlier studies showed that dorzolamide and closely related CAIs are more effectively delivered into the eye from acidic eye drop solutions than from comparable neutral solutions. Consequently, dorzolamide was marketed as an aqueous pH 5.6 eye drop solution (Trusopt(®) , Merck). Later, it was shown that increasing the pH of the eye drops from pH 5.6 to physiologic pH significantly reduced their local irritation. Earlier attempts to use cyclodextrins (CDs) as ocular penetration enhancers in dorzolamide eye drop solutions failed since; although the CDs were able to enhance the aqueous solubility of dorzolamide, increasing the pH from 5.6 to physiologic pH reduced the ability of the drug to permeate into the eye. Later, it was discovered that formulating the drug as aqueous dorzolamide/γCD eye drop microparticle suspension resulted in significant bioavailability enhancement. The solid dorzolamide/γCD microparticles are mucoadhesive and release dorzolamide into the aqueous tear fluid for extended time period. Consequently, sustained high dorzolamide concentrations in aqueous humour and various eye tissues were observed after single administration of the aqueous dorzolamide/γCD eye drop microsuspension. The microsuspension has a potential of being developed into a once-a-day eye drop product. This article reviews the physicochemical properties of dorzolamide, its permeation characteristics and topical bioavailability.

Preparation and Stability of Voriconazole Eye Drop Solution

The combined systemic and topical administration of voriconazole has successfully been used to treat keratomycosis. Because no voriconazole eye drop product is commercially available, we prepared a sterile eye drop solution (10 mg/ml). Voriconazole remains stable over 30 days, providing an eye drop solution suitable for use for the topical treatment of fungal keratitis.

Determination of tropicamide and its major impurity in raw material by the HPLC-DAD analysis and identification of this impurity using the off-line HPLC–FT-IR coupling

This study presents TLC, HPLC-DAD and HPLC–FT-IR analyses concerning the detection, identification and determination of organic impurities of commercial tropicamide (( R, S)- N-ethyl-3-hydroxy-2-phenyl- N-(4-pyridylmethyl)propanamide) as a medical substance designed for the production of eye drops. In the examined samples from several random production batches, only one impurity (defined by Ph. Eur. 6th Ed.) was discovered in the amount sufficient for the quantitative analysis. On the basis of comparison of retention times, UV and IR spectra of the impurity and its synthesized standard, this impurity was identified as apotropicamide ( N-ethyl-2-phenyl- N-(4-pyridylmethyl)prop-2-enamide). For the chemical identification of organic compounds occurring in the tropicamide samples, an off-line coupling of HPLC with FT-IR was used. The structure of a standard of apotropicamide was confirmed by 1H NMR and 13C NMR analysis. Validation of the HPLC-DAD method of determination both tropicamide and apotropicamide in the tropicamide medical substance was performed. This method is suitable for use in the quality control of tropicamide during its production.

Erfahrungen mit einem national zentralisierten Herstellungsverfahren für Eigenserum-Augentropfen in England

The majority of patients with dry eye syndromes respond to conventional treatment aimed at optimising the ocular surface environment. There are some, however, who do not respond adequately to conventional lubricants. The first description of the use of autologous serum as a nutrient tears substitute was published more than 20 years ago. In 1997, NHS Blood and Transplant (NHSBT) developed a reliable and reproducible method for the production of eyedrops derived from autologous serum according to GMP Guidelines. The current cost of a batch of eyedrops (i. e. the product from one donation episode) is approximately 1300 GBP - this covers costs of collection, processing, testing and distribution. One "batch" of eyedrops will last for approximately 5 months if a bottle a day is used. A 6 month shelf life is put on the product and patients keep them in their domestic freezer.

点眼薬の分注に関するアンケート調査―流行性角結膜炎の集団発生を経験して―

To investigate the cause of an outbreak of epidemic keratoconjunctivitis (EKC) that occurred in the Department of Ophthalmology of our hospital,we conducted an environmental PCR test which produced adenovirus-positive reactions.The positive environmental factors included eye drops for treatment purposes that were shared by some patients,suggesting that eye drop contamination was a possible cause of the outbreak of EKC.Following this,our Department of Pharmacy started distributing small volumes of eye drops all of which were used by individual patients (none left to share with other patients).In view of this,we conducted a questionnaire survey regarding the present status of the small-volume transfer of eye drops at 45 health care institutions.Replies were obtained from 37 institutions (78%).The methods of usage of eye drops for treatment purposes and those administered after surgery varied among institutions and there was also a difference in the way that they were used between inpatients and outpatients.Seven institutions distributed small volumes of eye drops for the treatment of individual patients.As for the desires of institutions concerning eye drops for treatment purposes and those for use after surgery,25 said that eye drop products should be standardized to contain a small volume just sufficient for administration to 1 patient.In conclusion,to prevent nosocomial infections,pharmaceutical companies should supply eye drops in small-volumes to prevent cross-contamination.