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Electrochemical behavior of naphazoline hydrochloride on a carbon paste electrode that was modified with aluminium oxide nanoparticles (Al2O3NPs) was investigated in a Britton-Robinson (BR) buffer (pH 7.0) using various voltammetric techniques. The results support the presence of an irreversible and diffusion-controlled electrochemical oxidation signal of naphazoline hydrochloride which is approximately at 0.9 V vs. Ag/AgCl. A selective, accurate, and simple square-wave anodic adsorptive stripping voltammetric method was proposed for naphazoline hydrochloride detection. The linear response was within the range of 5.0 × 10-8-3.0 × 10-5 mol L-1 with a detection limit of 2.6 × 10-9 mol L-1 (0.642 ?g L-1). In addition, the proposed method was also utilized for naphazoline hydrochloride determination in human serum sample. © 2019, Turkish Chemical Society. All rights reserved. 00.10, YL.14.03 This work was funded by Nam?k Kemal University Research Fund. Project No. NKU BAP. 00.10.YL.14.03. The authors would like to thank to Prof. Esma K?l?? at Ankara University for helpful discussions. This work was funded by Namık Kemal University Research Fund. Project No. NKU BAP. 00.10.YL.14.03. The authors would like to thank to Prof. Esma Kılıç at Ankara University for helpful discussions.

A nafazolina tem sua eficácia comprovada na redução das manifestações da obstrução nasal que tanto prejudica a qualidade de vida das pessoas, porém seus benefícios têm tido caminhos distorcidos, colocando em risco a saúde humana, principalmente quando existe o uso descontrolado e prevalente. Alguns excipientes utilizados no cloridrato de nafazolina podem causar a diminuição significativa da função pulmonar e reações de hipersensibilidade em pacientes asmáticos, além de poder agravar o quadro de rinite medicamentosa induzida por descongestionantes nasais. A facilidade em obter a nafazolina contribui para o agravamento de algumas patologias já pré-existentes e o aparecimento de efeitos adversos pelo uso incorreto, a dependência à substância, e em alguns casos pode ocasionar algumas outras patologias como a rinite medicamentosa, e a potencialização dos efeitos em contato com outros medicamentos. A falta de conhecimento, os riscos da automedicação, a venda sem prescrição médica, o baixo custo e a oferta destes descongestionantes são fatores que influenciam o consumo desordenado do medicamento, um grave problema de saúde pública. O atual estudo tem o objetivo de analisar os riscos na automedicação, e o uso incorreto de descongestionantes nasais que possuam Cloridrato de Nafazolina na sua composição e o farmacêutico como protagonista para o uso racional de medicamentos. Foram utilizados base de dados online aplicando coo descritores: cloridrato de nafazolina, nafazolina, derivados imidazolínicos, intoxicações por nafazolina, dependência à nafazolina, descongestionantes nasais, rinite medicamentosa. A orientação farmacêutica torna-se imprescindível para orientar o uso correto do medicamento, visto que este profissional possui o conhecimento específico sobre os medicamentos em geral independentemente de sua classe e quais benefícios e riscos ele pode oferecer a saúde afim de evitar futuras patologias além de contribuir com a política nacional do uso correto de medicamentos. O farmacêutico tem uma função importante em ajudar a sociedade, promovendo a educação em saúde quanto ao uso de medicamentos e seus principais efeitos adversos, intervindo na automedicação e minimizando a mesma.

In the present study, a newly developed method based on ultrahigh performance liquid chromatography (UHPLC) was optimized for the simultaneous determination of antazoline hydrochloride (ANZ) and naphazoline hydrochloride (NFZ) in ophthalmic formulations. Isocratic separation of ANZ and NFZ was performed at 40 °C with an ACE Excel 2 C18-PFP column (2 μm, 2.1 × 100 mm) at a flow rate of 0.6 mL min-1 whereas the mobile phase consisted of acetonitrile/phosphate buffer (60:40, v/v, pH 3.0) containing 0.5% triethylamine. Both analytes were detected at a wavelength of 285 nm and the injection volume was 1.0 μL. The overall run time per sample was 4.5 min with retention time of 0.92 and 1.86 min for NFZ and ANZ, respectively. The calibration curve was linear from 0.500-100 μg mL-1 for ANZ and NFZ with a correlation coefficient ≥ 0.9981 while repeatability and reproducibility (expressed as relative standard deviation) were lower than 1.28 and 2.14%, respectively. In comparison with high-performance liquid chromatography (HPLC), the developed UHPLC method had remarkable advantages over HPLC as the run time was significantly reduced by 3.4-fold with a 5-fold decreased solvent consumption. Forced degradation studies indicated a complete separation of the analytes in the presence of their degradation products providing high degree of method specificity. The proposed UHPLC method was demonstrated to be simple and rapid for the determination of ANZ and NFZ in commercially available ophthalmic formulations providing recoveries between 99.6 and 100.4%.

Three smart spectrophotometric methods were developed for the simultaneous estimation of chlorpheniramine maleate and naphazoline hydrochloride, a binary mixture with overlapping spectra, without preliminary separation. These methods include area under the curve (AUC), graphical absorbance ratio (Q-analysis) and isosbestic point spectrophotometry. A comparative study among the methods was done showing the advantages and the disadvantages of each method. Beer’s law is obeyed over the concentration range of 5- 35 and 5-40 μg/ml for chlorpheniramine maleate and naphazoline hydrochloride,respectively (for area under the curve), and 5-40 μg/ml for each drug (for Q-analysis and isosbestic point). All the proposed methods were extensively validated according to the ICH guidelines and the obtained accuracy, precision and repeatability were found to be within the acceptable limits. The selectivity of the proposed methods was tested using laboratory prepared mixtures and assessed by applying the standard ad...

A novel method is developed for the direct determination of naphazoline hydrochloride (NAP) and pyridoxine hydrochloride (VB6) in commercial eye drops. By using excitation–emission matrix (EEM) fluorescence coupled with second-order calibration method based on the alternating trilinear decomposition (ATLD) algorithm, the proposed approach can achieve quantitative analysis successfully even in the presence of unknown and uncalibrated interferences. The method shows good linearity for NAP and VB6 with correlation coefficients greater than 0.99. The results were in good agreement with the labeled contents. To further confirm the feasibility and reliability of the proposed method, the same batch samples were analyzed by multiple reaction monitoring (MRM) based on LC–MS/MS method. T -test demonstrated that there are no significant differences between the prediction results of the two methods. The satisfactory results obtained in this work indicate that the use of the second-order calibration method coupled with the EEM is a promising tool for industrial quality control and pharmaceutical analysis due to its advantages of high sensitivity, low-cost and simple implementation.

A series of eleven drugs, namely, atorvastatin calcium, diclofenac sodium, fluoxetine, ketoconazole, ibuprofen, dexamethasone, tioconazole, naphazoline hydrochloride, valsartan, guaifenesin and paracetamol, were comparatively degraded under UV and visible radiation in the presence of a supported photocatalyst generated from the catalyst residue from a Ziegler–Natta catalyst petrochemical plant. The presence of Mg (4.4%) and Ti (2.5%) afforded a catalyst that was active over the UV and visible spectral regions. For comparative reasons, commercial P25 (titania) was also evaluated. Among the tested systems, the highest drug degradation was observed under UV (48.6%) and visible (45.2%) radiation with the synthesized photocatalyst, whereas under the same conditions, the commercial P25 catalyst achieved 66.3% and 50.2% degradation, for UV and visible radiation, respectively. Despite the comparable degradation capability, the proposed photocatalyst could be reused five times without losing catalyst activity.

A simple and highly sensitive chemiluminescence (CL) method is reported for the determination of naphazoline hydrochloride (NH). It was found that the weak CL from the reaction of luminol and KIO4 in an alkaline medium could be highly amplified by cysteine-capped cadmium telluride quantum dots (QDs) and the enhanced CL was effectively quenched by NH and this finding was utilized as a basis for the determination of NH. The QDs were synthesized in aqueous medium and characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), and UV-vis and photoluminescence spectroscopy. A possible mechanism was proposed for the CL system based on radical identification experiments, along with CL spectrum of the system. The experimental parameters were optimized by the reliable response surface methodology (RSM). Under the optimized experimental conditions, the proposed method allowed the determination of NH over the range of 5.0 × 10(-10) -2.0 × 10(-7) mol/L (r(2) = 0.9993, n = 10). The precision (RSD%) of the method, obtained from five replicate determinations of 2.0 and 150 nmol/L NH, was found to be 1.0% and 1.3%, respectively. The method was successfully applied to the determination of NH in pharmaceutical formulations and human urine and serum samples with results corroborated with the aid of those obtained from a standard method.

The construction and performance characteristics of new sensitive and selective in situ modified screen printed (ISPE) and carbon paste (ICPE) electrodes for determination of naphazoline hydrochloride (NPZ-HCl) have been developed. The electrodes under investigation show potentiometric response for NPZ-HCl in the concentration range from 7.0Ã10â7 to 1.0Ã10â2 M at 25 °C and the electrode response is independent of pH in the range of 3.1â7.9. These sensors have slope values of 59.7±0.6 and 59.2±0.2 mV decadeâ1 with detection limit values of 5.6Ã10â7 and 5.9Ã10â7 M NPZ-HCl using ISPE and ICPE, respectively. These electrodes show fast response time of 4â7 s and 5â8 s and exhibits lifetimes of 28 and 30 days for ISPE and ICPE, respectively. Selectivity for NPZ-HCl with respect to a number of interfering materials was also investigated. It was found that there is no interference from the investigated inorganic cations, anions, sugars and other pharmaceutical excipients. The proposed sensors were applied for the determination of NPZ-HCl in pharmaceutical formulation using the direct potentiometric method. It showed a mean average recovery of 100.2% and 102.6% for ISPE and ICPE, respectively. The obtained results using the proposed sensors were in good agreement with those obtained using the official method. The proposed sensors show significantly high selectivity, response time, accuracy, precision, limit of detection (LOD) and limit of quantification (LOQ) compared with other proposed methods. Keywords: ISPE and ICPE, Potentiometry, Naphazoline hydrochloride, Eye drops

A simple and sensitive flow injection chemiluminescence (FI-CL) method was developed for the determination of naphazoline hydrochloride (NPZ). The method is based on the enhancing effect of NPZ on the weak CL signal from the reaction of KIO4 with H2 O2 . Experimental parameters that affected the CL signal, including the pH of the KIO4 solution, concentrations of KIO4 , H2 O2 and disodium-EDTA and flow rate were optimized. Under the optimum conditions, the increment of CL intensity was linearly proportional to the concentration of NPZ in the range 5.0 × 10(-6) to 70 × 10(-6) mol/L. The detection limit was 1.0 × 10(-6) mol/L and the relative standard deviation for 50 × 10(-6) mol/L NPZ solution was 2.8% (n = 11). In addition, a high throughput of 120 samples/h was achieved. The utility of this method was demonstrated by determining NPZ in pharmaceuticals.

The influence of the ageing process on the low frequency behavior of some electrical parameters of naphazoline hydrochloride solutions at 0.5% and 1% in concentration and of 2% paracetamol syrup, is studied. The impedance measurements were performed, in the range between 200 Hz and 1 MHz, using an impedance analyzer and a cell for liquids with plane parallel electrodes whose separation can be changed by using a set of spacers, provided by the manufacturer, in order to get better control of the influence of electrodes polarization effect. The ageing state was artificially generated by dilution and/or heating separated procedures. The results show that this dielectric technique can be used as a good quality complementary control technique.

A zero-crossing first-derivative spectrophotometric method is applied for the simultaneous determination of naphazoline hydrochloride and antazoline phosphate in eye drops. The measurements were carried out at wavelengths of 225 and 252 nm for naphazoline hydrochloride and antazoline phosphate, respectively. The method was found to be linear (r2>0.999) in the range of 0.2-1 microg/ml for naphazoline hydrochloride in the presence of 5 microg/ml antazoline phosphate at 225 nm. The same linear correlation (r2>0.999) was obtained in the range of 1-10 microg/ml of antazoline phosphate in the presence of 0.5 microg/ml of naphazoline hydrochloride at 252 nm. The limit of determination was 0.2 microg/ml and 1 microg/ml for naphazoline hydrochloride and antazoline phosphate, respectively. The method was successfully used for simultaneous analysis of naphazoline hydrochloride and antazoline phosphate in eye drops without any interference from excipients and prior separation before analysis.

A capillary zone electrophoresis (CZE) method with ultraviolet-visible detection has been established and validated for the determination of five phenothiazines: thiazinamium methylsulfate, promazine hydrochloride, chlorpromazine hydrochloride, thioridazine hydrochloride, and promethazine hydrochloride in human urine. Optimum separation was obtained on a 64.5 cm x 75 microm bubble cell capillary using a buffer containing 150 mM tris(hydroxymethyl)aminomethane and 25% acetonitrile at pH 8.2, with temperature and voltage of 25 degrees C and 20 kV, respectively. Naphazoline hydrochloride was used as an internal standard. Field-amplified sample injection (FASI) has been applied to improve the sensitivity of the detection. Considering the influence of parameters affecting the on-line preconcentration (nature of preinjection plug, sample solvent composition, injection times, and injection voltage) and due to the significant interactions among them, in this paper we propose for the first time the application of a multivariate approach to carry out the study. The optimized conditions were as follows: preinjection plug of water for 7 s at 50 mbar, electrokinetic injection for 40 s at 6.2 kV, and 32 microm of H3PO4 in the sample solvent. Also, a solid-phase extraction (SPE) procedure is developed to obtain low detection limits and an adequate selectivity for urine samples. The combination of SPE and FASI-CZE-UV allows adequate linearities and recoveries, low detection limits (from 2 to 5 ng/mL), and satisfactory precisions (3.0-7.2% for an intermediate RSD %).

Senepul™ solution is frequently used as a topical antiseptic solution in Korea in cases with abrasion, laceration and impetigo. 100 ml of this solution contains a mixture of 100 mg naphazoline hydrochloride, 100 mg dibucaine hydrochloride, 200 mg chlorpheniramine maleate, and 100 mg benzethonium chloride. Naphazoline is an alpha sympathomimetic and an imidazoline derivative. In excessive dosage or ingested by accident, naphazoline may cause not only local but also systemic side effects like hypertension, bradycardia with arrhythmia, hypotension, respiratory depression, excitation or severe central nervous system depression. We report a case of a patient with prolonged bradycardia, hypotension, central nervous system depression that occurred after ingestion of a small amount of this topical antiseptic solution.

Two methods were developed for simultaneous determination of naphazoline hydrochloride and chlorpheniramine maleate in bulk drug and dosage forms (eye and nose drops). Derivative spectrophotometry was used to eliminate band overlapping during analysis of such 2-component mixtures. Naphazoline hydrochloride was determined by recording first-derivative (D 1 ) absorbance curves: at 295.5 nm, naphazoline hydrochloride exhibits a maximum D 1 absorption whereas chlorpheniramine maleate has zero D 1 absorption. Chlorpheniramine maleate was determined by scanning the second-derivative (D 2 ) absorption spectra: at 261.7 nm chlorpheniramine maleate exhibits a D 2 maximum absorption whereas naphazoline hydrochloride has negligible D 2 absorption. Linear relations between concentration and absorbance were obtained for the concentration range 20-100 g/mL for both bulk drugs. Mean recoveries were 99.96 ± 0.97 and 99.92 ± 0.62%, for naphazoline hydrochloride and chlorpheniramine maleate, respectively. The second method Involves quantitative densitometric evaluation of thin-layer chromatograms of ethanolic solutions of the drug mixtures. Separation was performed on silica gel plates (20 x 20 cm) with acetone-25% ammonium hydroxide (90 + 10, v/v) as mobile phase. R f values were 0.68 and 0.86 for naphazoline hydrochloride and chlorpheniramine maleate, respectively. Densitometric evaluation was done by recording peak areas at 280 nm for naphazoline hydrochloride and at 262 nm for chlorpheniramine maleate. Linear relationships between concentration and peak area were obtained for the concentration ranges 2-10 g/spot and 4-10 g/spot for bulk naphazoline hydrochloride and chlorpheniramine maleate, respectively. Mean recoveries were 99.99 ± 0.75 and 99.67 ± 0.73%, respectively. The presence of the preservative cetrimide did not interfere with determination of the 2 drugs or with accuracy and precision of the 2 proposed methods.

The interaction of sodium salicylate and naphazoline hydrochloride with polyvinylpyrrolidones having four different molecular weights (10, 25, 40, and 360kDa), and with the micelles of non-ionic surfactant polyoxyethylene n-dodecylethers having various numbers of oxyethylene units (5, 6, 7, and 8) were investigated using the freezing point depression method. The advantages of this method are that the binding parameters can be rapidly obtained by a simple procedure using a commercially available osmometer. Based on the colligative properties, the binding parameters were calculated. The data were expressed in the form of nonlinear Scatchard plots. The results suggested that salicylate and naphazoline were bound to two kinds of binding sites on a molecule of polyvinylpyrrolidone or to a micelle of polyoxyethylene n-dodecylether; the primary binding site exhibited a high affinity but a low capacity for the drug, while the second binding site has a lower affinity and a high capacity; that is, the interaction on the second binding site could be described as non-specific binding. For the interactions of drugs with polyvinylpyrrolidone, the number of N-vinyl-2-pyrrolidone units (monomer) that interacted with one molecule of salicylate and naphazoline were fairly constant, and from 10 to 14 and from 21 to 30, respectively. For the interactions of drugs with a micelle of polyoxyethylene n-dodecylether, the number of polyoxyethylene n-dodecylether molecules which interacted was also nearly constant at 3 to 4 and 5 to 6, respectively.

This paper describes the development of screen-printed (SPE) and carbon paste (CPE) sensors for the rapid and sensitive quantification of naphazoline hydrochloride (NPZ) in pharmaceutical formulations. This work compares the electroactivity of conventional carbon paste and screen-printed carbon paste electrodes towards potentiometric titration of NPZ. The repeatability and accuracy of measurements performed in the analysis of these pharmaceutical matrices using new screen printed sensors were evaluated. The influence of the electrode composition, conditioning time of the electrode and pH of the test solution, on the electrode performance were investigated. The drug electrode showed Nernstain responses in the concentration range from 1 × 10(-6) to 1 × 10(-2) mol L(-1) with slopes of 57.5 ± 1.3 and 55.9 ± 1.6 mV per decade for SPE and CPE, respectively, and was found to be very precise and usable within the pH range 3-8. These sensors exhibited a fast response time (about 3 s for both SPE and CPE, respectively), a low detection limit (3.5 × 10(-6) and 1.5 × 10(-6) M for SPE and CPE, respectively), a long lifetime (3 and 2 months for SPE and CPE, respectively) and good stability. The selectivity of the electrode toward a large number of inorganic cations, sugars and amino acids was tested. It was applied to potentiometric determination of NPZ in pure state and pharmaceutical preparation under batch conditions. The percentage recovery values for the assay of NPZ in tablets (relative standard deviations ≤0.3% for n = 4) were compared well with those obtained by the official method.

A sensitive and simple flow-injection chemiluminescence (FI-CL) method, which was based on the CL intensity generated from the redoxreaction of potassium permanganate (KMnO4)–formaldehyde in vitriol (H2SO4) medium, has been developed, validated and applied for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride. Besides oxidants and sensitizers, the effect of the concentration of H2SO4, KMnO4 and formaldehyde was investigated. Under the optimum conditions, the linear range was 1.0 × 10−2–7.0 mg/L for naphazoline hydrochloride and 5.0 × 10−2–10.0 mg/L for oxymetazoline hydrochloride. During seven repeated inter-day and intra-day precision tests of 0.1, 1.0 and 10.0 mg/L samples, the relative standard deviations all corresponded to reference values. The detection limit was 8.69 × 10−3 mg/L for naphazoline hydrochloride and 3.47 × 10−2 mg/L for oxymetazoline hydrochloride (signal-to-noise ratio ≤3). This method has been successfully implemented for the determination of naphazoline hydrochloride and oxymetazoline hydrochloride in pharmaceuticals. Copyright © 2009 John Wiley & Sons, Ltd.

Procedures were developed for the simultaneous determination of pharmaceuticals in two-component commercial formulations by first-order derivative UV spectrophotometry. Phenylephrine hydro chloride and carbinoxamine maleate in capsules and diphenhydramine hydrochloride and naphazolixehydro hydrocloride in nasal gelly were succesfully assayed. A simple sensitive method in the usual range for the binary preparations has been developed. Average recoveries of the four compounds in the formulations under study were 100.04 ± 1.28% 101.50 ± 2.27 %, 101.59 % 1.24 % and 100.49 ± 2.59 %.

Treatment of allergic diseases of eyelids and conjunctiva (conjunctivites and blepharoconjunctivites) often presents difficulties due to peculiarities of their pathogenesis - allergic and vascular reactions, disorder of lacrimal production, meibomian gland dysfunction, and possible bacterial contamination. It has been suggested to use Ocumethyl, which contains zinc sulfate (binding, drying, anti-inflammatory, and antiseptic effect), diphenhydamine hydrochloride (an Н1-antihistamine that decreases capillary permeability and helps resolve conjunctival and eyelid edema), naphazoline hydrochloride (a sympathomimetic notable for its strong, rapid, and long-lasting vasoconstrictive effect), and methylene blue (antiseptic effect, disintoxication, and antioxidant activity). A total of 80 patients with chronic allergic conjunctivitis, blepharoconjuntivitis, or giant papillary conjunctivitis associated with contact lens wearing were treated with Ocumethyl instillations (3 times daily for 15-30 days). A clinically significant effect was obtained in 77-91% of patients depending on the disease entity.Лечение аллергических заболеваний век и конъюнктивы (конъюнктивитов, блефароконъюнктивитов) часто представляет сложности в связи с особенностями патогенеза заболевания - аллергическими и сосудистыми реакциями, нарушением слезопродукции, дисфункцией мейбомиевых желез, возможным бактериальным инфицированием. Предлагается использовать препарат Окуметил, который включает цинка сульфат, оказывающий вяжущее, подсушивающее, противовоспалительное и антисептическое действие; дифенгидрамина гидрохлорид- блокатор Н1-гистаминовых рецепторов, который уменьшает проницаемость капилляров и снимает отечность конъюнктивы и век; нафазолина гидрохлорид - симпатомиметик, оказывающий быстрое, выраженное и продолжительное сосудосуживающее действие; метиленовый синий с антисептическим, дезинтоксикационным и антиоксидантным эффектами. Проведено лечение 80 пациентов с хроническим аллергическим конъюнктивитом, блефароконъюнктивитом, гигантским папиллярным конъюнктивитом, развившимся на фоне ношения контактных линз, препарат инстиллировали 3 раза в день в течение 15-30 дней. Клинический эффект достигался у 77-91% пациентов в зависимости от нозологической формы.Лечение аллергических заболеваний век и конъюнктивы (конъюнктивитов, блефароконъюнктивитов) часто представляет сложности в связи с особенностями патогенеза заболевания - аллергическими и сосудистыми реакциями, нарушением слезопродукции, дисфункцией мейбомиевых желез, возможным бактериальным инфицированием. Предлагается использовать препарат Окуметил, который включает цинка сульфат, оказывающий вяжущее, подсушивающее, противовоспалительное и антисептическое действие; дифенгидрамина гидрохлорид- блокатор Н1-гистаминовых рецепторов, который уменьшает проницаемость капилляров и снимает отечность конъюнктивы и век; нафазолина гидрохлорид - симпатомиметик, оказывающий быстрое, выраженное и продолжительное сосудосуживающее действие; метиленовый синий с антисептическим, дезинтоксикационным и антиоксидантным эффектами. Проведено лечение 80 пациентов с хроническим аллергическим конъюнктивитом, блефароконъюнктивитом, гигантским папиллярным конъюнктивитом, развившимся на фоне ношения контактных линз, препарат инстиллировали 3 раза в день в течение 15-30 дней. Клинический эффект достигался у 77-91% пациентов в зависимости от нозологической формы.

A second (D2) derivative spectrophotometric technique has been applied for the determination of diphenhydramine hydrochloride in mixture with naphazoline hydrochloride and in presence of Methylene blue. Diphenhydramine hydrochloride has been extracted with chloroform and D2-value was measured at 255 nm. Naphazoline hydrochloride in the mixture has been determined by direct measurement of its D2 at 273 nm. Methylene blue could be determined in the mixture by direct absorbance measurement at 663 nm. As illustrate example, commercial eye drops was analysed for these two drugs in presence of methylene blue in pharmaceutical preparation. The results obtained were of high accuracy and good reproducibility.

The signs and symptoms of allergic conjunctivitis include ocular redness and itching. Two treatment options currently indicated for acute ocular allergic reaction are pheniramine maleate 0.3%/naphazoline hydrochloride 0.025% ophthalmic solution, an over-the-counter antihistamine/vasoconstrictor combination; and olopatadine hydrochloride 0.1% ophthalmic solution, a prescription antihistamine/mast cell stabilizer.This study was designed to compare, at onset of action, the relative effectiveness of pheniramine/naphazoline and olopatadine, when administered before conjunctival allergen challenge (CAC), using the ocular allergy index (OAI) as the primary end point.This was a prospective, randomized, double-masked, contralateral, active- and placebo-controlled, single-center study of the CAC model. The first 2 study visits established and confirmed the subjects' ocular allergic reaction (no medication administered). At visit 3, the subjects were randomly assigned to 1 of 3 contralateral (right eye vs left eye) treatment combinations: pheniramine/naphazoline + olopatadine, pheniramine/naphazoline + placebo, or olopatadine + placebo. Medication was given 10 minutes before CAC. The subjects' erythema in the ciliary, conjunctival, and episcleral vessel beds; eyelid swelling; chemosis; and itching were evaluated at 7, 12, and 20 minutes after CAC. The OAI was calculated as a composite score of 6 signs and symptoms of allergic conjunctivitis to assess global severity. Between-treatment differences in OAI scores were used to evaluate efficacy. Subjects were asked their eye drop preference at the conclusion of visit 3.Subjects (n = 83) ranged in age from 20 to 70 years (mean, 42.5 years), 61.4% (n = 51) were female, and 94.0% (n = 78) were white. Both pheniramine/naphazoline and olopatadine were associated with significantly lower OAI scores than placebo at all 3 time points (all, P0.001). OAI scores were significantly lower with pheniramine/naphazoline than with olopatadine at 12 and 20 minutes (P = 0.005 and P = 0.001, respectively).In this patient sample, studied in a CAC model of onset of action, prophylactic pheniramine/naphazoline was more effective than olopatadine and placebo in alleviating the signs and symptoms of the acute ocular allergic reaction, as measured by the OAI.

Dipotassium beta-glycyrrhizinate (GK2) is a saponin originated from "kanzo" plant. We studied such two functions of GK2 as a drug carrier and a penetration enhancer on the eye mucosa. The interactions of GK2 with various drugs were investigated using the 1-octanol/water partition method. GK2 increased the partition of cationic drugs, i.e., antihistamines (chlorpheniramine maleate (CM), diphenhydramine hydrochloride (DH)), as well as decongestants (naphazoline hydrochloride (NA), tetrahydrozoline hydrochloride (TH)). The carrier effect of GK2 is remarkable at its concentration above critical miceller concentration (CMC) and, especially at its pH value of between 4 to 5, resulting that transfers of drugs increased 2 to 10 times as compared to drugs without GK2. In vivo experiments were carried out using rats and rabbits. The effect of GK2 on the inhibition efficiency by CM was evaluated using experimental conjunctivitis formed by injection of histamine on rat upper eyelid. The Inhibition efficiency of edema by CM with GK2 was 4 times stronger than that without GK2. Cornea permeability of TH increased 1.8 times by the addition of GK2. These results indicated that GK2 is applicable as a carrier of cationic drugs on the eye mucosa and cornea.

• The ophthalmic combination product of 0.05% naphazoline hydrochloride and 0.5% antazoline phosphate (Vasocon-A) was evaluated as an antiallergic agent in 100 subjects with a known allergic history to cat dander, ragweed, or bluegrass pollen. Three independent study sites were used. The allergen challenge model of acute allergic conjunctivitis was selected to assess the agent as it provided a standardized and precise way to measure drug effectiveness for this indication. In a double-masked randomized fashion, the subjects were assigned to one of three groups that received one drop of Vasocon-A in one eye and one drop of either 0.05% naphazoline (group 1), 0.5% antazoline (group 2), or placebo (group 3) in the contralateral eye. After 10 minutes, the dose of allergen shown to elicit a 2+ redness and itching reaction was instilled bilaterally. Signs and symptoms of allergic conjunctivitis were evaluated after 3, 5, and 10 minutes. Subjects were then rechallenged 2 hours after drug administration to assess the duration of action of the agents. Vasocon-A was found to significantly inhibit all five major signs and symptoms of allergic conjunctivitis: itching, redness, chemosis, lid swelling, and tearing, for more than 85% of the comparisons when compared over time with placebo, naphazoline alone, or antazoline alone. The results of this study indicate that the combination of naphazoline and antazoline was more effective in inhibiting redness than naphazoline and more effective in inhibiting itching than antazoline. These findings support the use of such a combination for the treatment of allergic conjunctivitis.

A second-derivative spectroscopic method for the simultaneous determination of naphazoline hydrochloride and diphenhydramine hydrochloride in nose drops was developed. Solutions of this drug combination in 0.1 M hydrochloric acid were analyzed by measurement of the amplitudes of, respectively, the positive peak at 288 nm with respect to the negative peak at 282 nm, and the negative peak at 249 nm with respect to the base line. The method allows the specific, rapid and accurate determination of the binary mixture in the tested concentration range of 1–5 μg/ml for naphazoline, and 10–50 μg/ml for diphenhydramine.

Using changes in nasal temperature to reflect changes in nasal blood flow, an assessment has been made of the efficacy of various nasal vasoconstrictive drugs. The drugs tested were 10 per cent and 5 per cent cocaine, 1 1,000 epinephrine, and naphazoline hydrochloride 0.05 per cent (Privine), with normal saline solution as a control. The drugs were found to be effective in producing nasal vasoconstriction if applied following induction of anesthesia rather than prior to induction, as usually recommended. Epinephrine 1 1,000 and 10 per cent cocaine were found to be the most efficacious drugs in producing vasoconstriction of nasal mucous membrane. Naphazoline hydrochloride 0.05 per cent was comparable to 5 per cent cocaine in producing vasoconstriction of the nasal mucosa.

A procedure was developed for measuring small amounts of phenylmercuric nitrate in aqueous solutions. The method depends on the formation of insoluble phenylmercuric iodide upon titration of phenylmercuric nitrate with potassium iodide. The end-point can be detected using an iodide-sensitive electrode. The method is able to measure down to 0.000125% aqueous solution of phenylmercuric nitrate with a 1% accuracy. Procedural details and dexcriptions of excipient effects on the assay are presented. Naphazoline hydrochloride, phenylephrine hydrochloride, fluroescein sodium, and antipyrine interfered with the method, while the common buffer systems, polyvinyl alcohol, sodium thiosulfate, edetate sodium, and chloramphenicol had no effect.

• Eight widely used commercially available ocular decongestants were compared on the basis of vasoconstrictive effectiveness. The ability of these preparations to counteract histamine-induced erythema and to block its recurrence when rechallenged after one hour was evaluated in six human subjects in seven sessions. All vasoconstrictors tested were effective. No preparation was statistically different from 0.02% naphazoline hydrochloride in vasoconstrictive effect. In fact, this intermediate concentration of naphazoline (0.02%) was found to be significantly better than the other nonprescription decongestant preparations tested as a group and not significantly different from a group of higher concentrations of naphazoline.