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Aim: To develop new selective and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) approach for the quantification of antifungal drug Luliconazole integrate with corticosteroid drug Clobetasol Propionate in a synthetic mixture. Methods: The method was validated to achieve International Conference Harmonization (ICH) requirements. Chromatographic separation was carried out by isocratic technique on a reversed-phase Inertsil C18 column (5 µm, 250mm x 4.6mm i.d with the mixture of Acetonitrile: Water pH adjusted with H3PO4 (60: 40) and UV detection at 264 nm. The compounds were eluted at a flow rate of 1.0 mL/min with an injection volume of 20μL. Results: The calibration curves were linear (r2 > 0.999) over the concentration range 10-200 μg/mLfor Luliconazole and 5-100 μg/mL for Clobetasol Propionate. The average retention times for Luliconazole and Clobetasol Propionate were 3.16 and 6.94 min, respectively. The % RSD for the proposed method was found to be less than %2. The % recovery was found to between 99.22-99.48% for the developed method. Conclusion: The developed method is simple, rapid, precise, and accurate and hence was successfully applied for the determination of Luliconazole and Clobetasol Propionate in a synthetic mixture.

With the increased presence of novel psychoactive substances (NPSs) in casework, drug analysis has become more challenging. To address these challenges, new screening technologies with improved specificity are being implemented, allowing for the creation and adoption of targeted confirmatory analyses that produce more conclusive results. This paper outlines a six-step, data-driven, framework to develop and evaluate gas chromatography mass spectrometry (GC-MS) methods for targeted classes of drugs. The process emphasizes maximizing retention time differences (to minimize the potential for retention time acceptance windows to overlap) and understanding the tradeoffs between sensitivity and reproducibility using a test solution containing pairs of compounds that are difficult to distinguish. The method is then evaluated by expanding the panel of compounds analyzed, identifying limitations in compound discrimination, comparing to current methods, and analyzing representative casework to establish usability. To demonstrate this framework, a method for synthetic cannabinoids was created. The developed method utilizes a DB-200 column and an isothermal temperature program. It was found that sensitivity could be adjusted, without compromising reproducibility, by altering the split ratio and injection volume. The targeted method successfully differentiated 50 cannabinoids based on either retention time differences or mass spectral dissimilarity – determined using a newly developed spectral comparison test. Compared to the general method investigated for comparison, the targeted method was an order of magnitude more sensitive and a minute shorter while providing major increases in retention time differences. This framework can be implemented and adapted to develop targeted methods for other applications or compound classes.

Background During diagnostic cerebral angiography, the contrast bolus injected into a vessel can cause substantial changes in baseline pressures and flows. One potential, and serious complication is the re-rupture of aneurysms due to these injections. The goals of this in vitro study were to evaluate the effect of injection conditions on intraneurysmal pressure changes during angiography. Methods A silicone replica of a complete circle of Willis model with ophthalmic, anterior communicating, and basilar tip aneurysms was connected to a physiologically accurate flow pump. Contrast injections were performed under different conditions (carotid or vertebral vessel imaging, catheter diameter, injection rate, injection time, and arterial blood flow rate) and the pressure in each aneurysm was recorded before and during each injection. The effect of injection conditions on percentage increase in aneurysm pressures was statistically assessed. Additionally, the effect of the distance between the aneurysm and the catheter-tip on aneurysmal pressures was assessed. Results Mean intraneurysmal pressures during injection (84.5 ± 10.8 mmHg) were significantly higher than pre-injection pressures (80.4 ± 10.6 mmHg, p Conclusions Increasing contrast injection rates and decreasing catheter diameters are correlated to intraneurysmal pressure increases during angiography irrespective of the distance to the catheter tip. Future in vivo studies are required to confirm these findings and determine whether the amplitude of pressure increases with commonly used injection rates can be clinically detrimental.

The therapeutic regimen for the treatment of AIDS using efavirenz, lamivudine and tenofovir disoproxil fumarate has demonstrated efficacy and safety. In this work, an analytical method was developed and validated for simultaneous quantitation of efavirenz (EFV), lamivudine (3TC) and tenofovir disoproxil fumarate (TDF) in fixed-dose combination tablet. Analysis by high performance liquid chromatography was performed using a reversed phase column Sun Fire® C18 (250 mm x 4,6 mm; 5 μm) at 30 °C, 20 μL injection volume and detection at 260 nm. The mobile phase, composed of acetate buffer pH 5.4 and methanol, was employed at 1.0 mL/min flow rate and gradient elution. Adequate linearity was obtained in the range from 66 to 198 μg/mL for EFV, 66 to 198 μg/mL from 3TC and 33 to 99 μg/mL for TDF. Relative standard deviation values were lower than 5% and mean recoveries were within 98% to 102%, confirming the precision and accuracy of the method, respectively. In addition, the developed method showed to be selective and robust and can be successfully applied for routine quality control analysis.

Background Increasing the reconstitution and injection volumes of abobotulinumtoxinA (aboBoNT-A) could provide more options for aesthetic healthcare professionals. Objective To evaluate efficacy and safety of aboBoNT-A treatment of moderate-to-severe glabellar lines (GL) versus placebo, using a new reconstitution and injection volume. Methods a Materials: In this 6-month, Phase III, randomized, double-blind study, subjects 18-64 years were administered aboBoNT-A 50 U (N=224) or placebo (N=77), as five 0.1-mL-injections (10 U) in the glabellar region following reconstitution of a 300-U-vial in 3 mL. Assessments included time to onset of effect, investigator- (ILA) and subject- (SSA) assessed GL severity, subject satisfaction, aesthetic improvement and safety. The primary endpoint was composite 2-grade response at month 1 (a GL severity of none-or-mild at maximum frown and g2-grade improvement from baseline concurrently on both ILA and SSA). Results Median time to onset was 2 days, 34% of subjects reporting effect on day 1. At month 1, the composite 2-grade responder rate was 65.8% for aboBoNT-A versus 0% for placebo, Pl0.001, 91n92% had none-or-mild GL severity, and 95n100% had a g1-grade GL severity improvement. A g1-grade improvement was sustained in 46-56% of aboBoNT-A-treated subjects up to 6 months (Pl0.001 vs placebo). Aesthetic improvement and subject satisfaction were high throughout 6 months and aboBoNT-A treatment was well tolerated. Conclusion Safety and efficacy of GL treatment using 0.1 mL (10 U) aboBoNT-A per injection site were demonstrated, with rapid onset and up to 6 monthsr duration of effect. Severity improvement was accompanied by sustained aesthetic improvement and subject satisfaction. J Drugs Dermatol. 2021;20(9):988-995. doi:10.36849/JDD.6130.

Purpose To determine the relationship between stopper position and injection volume in aflibercept and ranibizumab prefilled syringes (PFS). Methods Empty aflibercept 2.0 mg PFS and ranibizumab 0.3 mg and 0.5 mg PFS were collected and refilled with saline. The stopper was positioned relative to the preprinted mark and resulting injection volumes were recorded. The position for double the on-label volume was confirmed with repeated testing. The quantitative relationship between position and volume was calculated. Results In ranibizumab PFS, doubling the distance increased the volume injected by 2.6 times. Positioning the stopper 4.0, 3.0, 2.0, and 0 mm proximal to and 1.0 mm distal to the mark injected volumes of 0.13, 0.1, 0.08, 0.05 and 0.03 mL, respectively. The relationship between position (x) and volume (y) was y = 0.019x + 0.048.In aflibercept PFS, doubling the distance increased the volume injected by 3.2 times. Positioning the stopper 2.5, 2.0, 1.0, and 0 mm proximal to and 1.0 mm distal to the mark injected volumes of 0.16, 0.14, 0.11, 0.05 and 0.02 mL, respectively. The relationship between position (x) and volume (y) was y = 0.041x - 0.059. Conclusions Proper positioning of the stopper at the preprinted mark accurately delivers the on-label volume with both the ranibizumab and aflibercept PFS. However, small variations in stopper position appear to have substantial impacts on the volume of drug injected, particularly with the aflibercept PFS.

Many over-the-counter drug products lack official compendial analytical methods. As a result, the United States Pharmacopeia and the United States Food and Drug Administration are seeking to develop and validate new methods to establish analysis standards for the assessment of the pharmaceutical quality of over-the-counter drug products. Diphenhydramine and phenylephrine hydrochloride oral solution, a combination drug product, was identified as needing a compendial standard. Therefore, an ultra-high-performance liquid chromatography method was developed to separate and quantify the two drug compounds and eleven related organic impurities. As part of a robustness study, the separation was demonstrated using different high-performance liquid chromatography systems and columns from different manufacturers, and showed little dependence with changes in flow rate, column temperature, detection wavelength, injection volume and mobile phase gradient. The method was then validated conformant with the International Council for Harmonisation guidelines. For impurities, adequate specificity, linearity, accuracy and precision were demonstrated. For assay, a slight modification to the injection volume was necessary to achieve adequate analytical performance. With successful development and validation, these methods were shown to be suitable for their intended purpose and may be considered for adoption as compendial procedures.

Introdução: O p-fenilenodiamina (PPD), amina aromática sensibilizante, vem sendo adicionado ao pó de hena para modificar sua cor natural para preta, aumentando seu tempo de fixação, prática proibida em tinturas para cílios e sobrancelhas. Objetivo: O objetivo deste estudo foi otimizar e validar, em níveis intralaboratoriais, um método analítico por CLAE/UV para identificação e quantificação de PPD em tinturas de hena para cabelos e sobrancelhas. Método: Foi utilizada coluna em fase reversa C8, fase móvel trietanolamina 1% (pH 8,4) e acetonitrila (99:1, v/v), detecção a 280 nm, volume de injeção de 10 μL, fluxo 1,0 mL/min, temperatura da coluna 32°C, tempo de corrida 10 min, linearidade 5-45 μg/mL (n = 5) com coeficiente de correlação de 0,9982. Para o teste de Cochran (homocedasticidade), 0,3350 e o Ccrítico (0,3934), com 99% de confiança. Limites de detecção, 1,17 μg/mL e quantificação, 3,54 μg/mL. O coeficiente de variação da repetibilidade 0,12% e na precisão intermediária pelo teste F obteve-se p-valor de 0,283 com 95% de confiança. Resultados: Os resultados da exatidão compreenderam os critérios de aceitação (90%-107%). Das 19 amostras analisadas, 14 apresentaram teor de PPD entre 1,74% a 3,65% p/p, em desacordo com a Legislação. Conclusões: O método proposto poderá contribuir com o monitoramento da qualidade e segurança de uso destes produtos.

The objective of the method was to develop a simple, rapid, sensitive, precise, accurate and validated Ultra Performance Liquid Chromatographic (UPLC) method for the estimation of Ticagrelor in tablet dosage form. Chromatographic separation was achieved on an acquity UPLC BDS C8 (150 x 4.6 mm, 5m) column with a mobile phase composed of Buffer 0.1% OPA (2.2 pH) and Acetonitrile in the ratio of 60:40 at a flow rate of 1.0 ml/min and 1 μl injection volume. The effluents were detected at a wavelength of 240 nm using TUV detector. The retention time of Ticagrelor was found to be at 0.942 min. %RSD of the Ticagrelor was found to be 0.7 The method was validated with respect to specificity, accuracy, linearity, precision, robustness. The correlation coefficient for Ticagrelor was found to be 0.999. Recovery of Ticagrelor in formulation was found to be 99.51% . LOD, LOQ values obtained from regression equations of Ticagrelor were 0.45, 1.35 respectively. Due to simplicity, high precision and rapidness the method can be successfully applied for estimation of Ticagrelor in tablet dosage form. Keywords: Ultra Performance Liquid Chromatographic, Ticagrelor, Tablet dosage form.

A new simple, rapid and sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method was developed by employing Quality by Design (QbD) approach for determination of levetiracetam and pyridoxine HCl in prepared tablets. Levetiracetam and pyridoxine HCl are co-administered because treatment with the antiepileptic levetiracetam leads to a deficiency in pyridoxine HCl. Fractional factorial design (FFD) was applied for screening of the four independent factors: pH of the aqueous part of the mobile phase, flow rate, injection volume and % of the organic modifier. Analysis of variance (ANOVA) confirmed that the four factors were significant. Optimization of the chromatographic conditions was performed using central composite design (CCD). The Analysis was achieved on BDS Hypersil C8 (250 × 4.6 mm, 5 μm) column applying an isocratic mobile phase containing MeOH and 25 mM KH2PO4 buffer pH 3 (38.4:61.6, v/v) at 0.8 mL/min flow rate with UV detection at 214 nm and 5 μL injection volume. The proposed method was validated according to ICH guidelines. Under optimized conditions, linear ranges of 1.56–100 μg/mL and 0.39–100 μg/mL were obtained for levetiracetam and pyridoxine HCl, respectively, with correlation coefficients (R2) of 0.999. The average recoveries ranged from 95.46 to 101.14%. The inter- and intra-day precisions were lower than 1%. The proposed method showed good predictability and robustness.

Cervical dystonia (CD) is primarily treated with botulinum toxin, at intervals of ≥ 12 weeks. We present efficacy, patient-reported outcomes (PROs), and safety in adults with CD at the last available visit after a single set of abobotulinumtoxinA (aboBoNT-A) injections versus placebo using 500 U in a 2-mL injection volume. In this 12-week, randomized, double-blind trial, patients were ≥ 18 years of age with primary idiopathic CD, had a Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score ≥ 20, and TWSTRS-Severity subscale score > 10 at baseline. Patients (N = 134) were randomized (2:1) to aboBoNT-A (n = 89) or placebo (n = 45), with aboBoNT-A patients treated with 500 units (U) if toxin-naïve, and 250 to 500 U based on previous onabotulinumtoxinA dose if non-naïve. Endpoints included total TWSTRS, Pain Numeric Rating Scale (NRS-Pain; 24-hour), Treatment Satisfaction Questionnaire for Medication, and other PROs for pain, depression, and global health. Results are for the intent-to-treat population, with “Week 12” (Wk12) comprising the last available post-baseline assessment (end-of-study or early withdrawal). Mean TWSTRS total scores improved from 42.5 at baseline to 35.4 at Wk12 with aboBoNT-A and 42.4 to 40.4 with placebo (treatment difference: –4.8; 95% confidence interval [CI]: –8.5, –1.1; p = 0.011). At Wk12, mean (95% CI) change from baseline in NRS-Pain was –1.0 (–1.59, –0.45) for aboBoNT-A and –0.2 (–0.96, 0.65) for placebo. AboBoNT-A demonstrated numeric improvements in other PROs. More aboBoNT-A–treated patients than patients receiving placebo reported being at least “somewhat satisfied” with treatment (60.4% vs 42.2%, respectively), symptom relief (57.0% vs 40.0%), and time for treatment to work (55.8% vs 33.3%). No new adverse events were reported. Results indicate that in patients with CD, treatment with aboBoNT-A using a 2-mL injection provided sustained improvement in the TWSTRS total score and patient-perceived benefits up to 12 weeks. Trial registration: Clinicaltrials.gov Identified: NCT01753310.

In Japan, two 0.4% sodium hyaluronate (HA)-based submucosal injection materials (SIMs) are currently used in endoscopic submucosal dissection (ESD): MucoUp (HA-Mc) and Ksmart (HA-Ks). HA-Mc and HA-Ks have the same concentration and are, thus, construed by most endoscopists to have no difference. Nevertheless, visual observation conveys the impression that HA-Ks have a higher viscosity than HA-Mc, suggesting that HA-Ks performs better than HA-Mc. This study aimed to examine the differences between HA-Mc and HA-Ks. HA-Ks exhibited higher viscosity due to greater weight-average molecular weight compared with HA-Mc. HA-Ks had significantly greater submucosal elevation height (SEH) than HA-Mc; the SEH of HA-Ks-80% (80% dilution of HA-Ks) was the same as that of HA-Mc. The ESD procedure time was significantly shorter with HA-Ks than with HA-Mc (15.2 ± 4.1 vs. 19.5 ± 5.9; P = 0.049). The total injection volume for HA-Ks was significantly lower than that for HA-Mc (10.8 ± 3.6 vs. 14.4 ± 4.6; P = 0.045). However, no significant difference in these items was observed between HA-Mc and HA-Ks-80%. HA-Mc and HA-Ks were considered to be almost the same. Nonetheless, HA-Ks exhibited higher viscosity and SIM performance than HA-Mc. HA-Ks-80% had almost the same performance as HA-Mc. Thus, understanding SIM performance and characteristics requires a focus on the viscosity of SIMs.

To the Editor We read with great interest the brief technical report ‘Opening injection pressure monitoring using an in-line device does not prevent intraneural injection in an isolate nerve model’ by Mejia et al .[1][1] We do concur with their findings but believe that a clarification should

Injection of biological molecules into the intravitreous humor is of increasing interest for the treatment of posterior segment eye diseases such as age-related degenerative macular degeneration. The injection volume is limited by an increase in intraocular pressure (IOP) and 50–100 µL are typically used for most intravitreally (IVT) applied commercial products. Direct measurement of IOP is difficult and has not been studied dependent on solution properties and injection rates. We used an instrumental set-up to study IOP ex vivo using healthy enucleated porcine eyes. IOP was determined as a function of injection volume for viscosities between 1 and 100 mPas, injection rates of 0.1, 1, and 1.5 mL/min, and needle length and diameter (27/30G and 0.5/0.75″) using Dextran solutions. IOP increased exponentially for injection volumes larger than 100 µL. We did not observe differences in IOP dependent on viscosity, injection rate, and needle diameter. However, variability increased significantly for injection volumes larger than 100 µL and, unexpectedly, declined with higher viscosities. We demonstrate that the exponential increase in IOP is not reflected by injection force measurements for typical configurations that are used for IVT application. The present findings may guide injection volumes for intravitreal injection and inform injection force considerations during technical drug product development.

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%, all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 &mu, L, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

Summary Objectives The main objective of the present study was to develop and validate simple, precise, sensitive and accurate RP-HPLC method for the simultaneous estimation of docetaxel (DTX) and ritonavir (RTV) in PLGA nanoparticles (PLGA-NPs). Methods The DTX and RTV co-loaded PLGA-NPs were developed by the nanoprecipitation technique. The RP-HPLC method was developed by using (Agilent Compact LC-1220) and Zorbax Eclipse plus C18 column (150 × 4.6 mm, 3.5 μm, Agilent). Finally, the developed method was validated according to the international conference on harmonization (ICH) guidelines. Results The chromatographic separations of DTX and RTV with good resolutions have been achieved by using the mobile phase Acetonitrile: Water (60:40 v/v) containing 0.1% v/v of orthophosphoric acid at a flow rate of 1.0 mL/min, injection volume of 25 μL, and at 239 nm wavelengths. The validated method found to be linear in the range of 0.001–100 μg/mL for DTX and RTV. Detection and quantification limits for DTX were found to be 0.7 and 2.31 μg/mL respectively and for RTV it is 0.3 and 2.87 μg/mL respectively. The % RSD was found to be less than 2% revealing the precision of the developed method. Besides, the recovery rate was observed close to 100% for both the drugs confirming the accuracy of the method. Minor alterations in the chromatographic conditions have revealed robustness and ruggedness of the developed method. Conclusion The developed analytical method is simple, precise, sensitive, and reproducible which can be used for the simultaneous estimation of DTX and RTV in the PLGA-NPs.

Background and importance Different factors can influence the compatibility and stability of the mixture: drug type, concentration, solvent, container, temperature and light. There are some mixtures of drugs with proven stability, but there is a lack of evidence about the stability and compatibility of the combination of ondansetron and midazolam. The objective of this investigation was to study the compatibility and stability of a binary mixture of these drugs in solution for subcutaneous infusion in palliative care Aim and objectives To evaluate the compatibility and stability of two admixtures of ondansetron and midazolam at two different temperatures (25°C and 37°C). The concentrations of the admixtures were 0.1 g/L–0.1 g/L and 0.5 g/L–1.0 g/L in NaCl 0.9% stored in elastomeric infusors protected from light Material and methods Samples were prepared and diluted in NaCl 0.9% in elastomeric infusors in triplicate to obtain four different conditions of concentration and/or storage temperature (0.1 g/L–0.1 g/L; 0.5 g/L–1.0 g/L for ondansetron and midazolam, respectively, stored at temperatures of 25°C and 37°C). The concentration of each drug was periodically determined using HPLC-UV and UV-Vis spectrophotometry methods in the analytical chemistry laboratory between February and June 2019. Conditions: C18 column, mobile phase methanol:KH2PO40.05 M, adjusted to pH 3 with H3PO3 (60:40, v/v) delivered at a flow rate of 1.0 mL/min. The sample injection volume was 20 μL, and triplicate injections were performed for every sample. The signal was recorded over 14 min and the retention times were 4.1 min for ondansetron and 7.8 min for midazolam. Ondansetron and midazolam concentrations were determined at 254 nm. Results HPLC-UV and UV-Vis spectrophotometric methods gave the same results. The stability of the admixtures diluted in NaCl 0.9% were as follow: ondansetron–midazolam (0.1 mg/mL–0.1 mg/mL and 0.5 mg/mL –1.0 mg/mL) were stable (retained >90% of their initial concentrations) for only 1 day at 25°C and 37°C, respectively Conclusion and relevance Recommended use is for a maximum of 1 day, at the concentrations evaluated; over time it tends to precipitate. Infuser conditioning decreases stability with respect to other conditioning materials, so other stability studies may not be extrapolated if stored under different conditions. References and/or acknowledgements No conflict of interest.

Kyphoplasty is performed to treat symptomatic osteoporotic or pathologic acute or subacute vertebral body compression fractures of the thoracic or lumbar spine. A unilateral or bilateral transpedicular approach may be safely utilized for up to three fractures at one time. The ability to treat potential complications is mandatory if performing the procedure. Awareness of cement viscosity and injection volume is important with regard to timing of injecting cement during a kyphoplasty procedure to minimize cement-related complications.

The earliest marketed insulins were crude acidic formulations with concentrations of ≤10 units/mL. Since the early 1920s, insulins have improved continually, via bioengineering, process, and chemical modifications. Today, most insulin formulations have a concentration of 100 units/mL (U100). However, more concentrated insulin formulations (200, 300, and 500 units/mL; U200, U300, and U500, respectively) are also available. There is a tendency to assume that concentrated insulins are similar, both to each other and to their U100 counterparts, but this is not always the case: two concentrated insulins, namely insulin degludec U200 and insulin lispro U200, are bioequivalent to their U100 counterparts, whereas regular human insulin U500 and insulin glargine U300 are not. The advent of these concentrated insulins offers greater opportunities to provide tailored therapy for patients; it also introduces potential confusion, and highlights the need for prescriber and patient education. Precise and accurate dedicated insulin delivery devices are also necessary for the safe use of these concentrated insulins. Although some clinicians only use concentrated insulin with obese and severely insulin-resistant patients, other patients would also benefit from the reduced injection volume associated with concentrated insulins, or the modified time-action profile of some concentrated insulins. The aim of this review is to enhance understanding of the historic development and the safe and effective use of concentrated insulins in clinical practice.

The United States Pharmacopeia 39 uses an HPLC–UV method for the assay of acarbose and its impurities in bulk form. However, there is no information about the stability-indicating nature of the proposed method for the assay of acarbose in tablets. Therefore, in this study, stress tests were firstly applied on the bulk and drug product based on International Conference on Harmonization. Then, verification and revalidation of the proposed method were performed using stressed and untreated samples. Separation was achieved on a Lichrospher®‒100–NH2, 5 µm, 250 × 4.6 mm i.d. column using a mobile phase consisting of acetonitrile–0.007 M phosphate buffer (pH 6.7) (750 : 250, v/v) at a flow rate of 2 mL/min and UV detection at 210 nm. The column was maintained at 35°C and an injection volume of 10 µL was used. The linearity of the developed method was investigated in the range of 2.5–20 mg/mL (R2 = 0.9995). Peak purity results using a diode array detector have shown that degradation products did not interfere with the detection of acarbose and the assay can thus be considered stability-indicating.

To determine the triamcinolone concentration in the aqueous humor after anterior sub-Tenon injection versus posterior sub-Tenon injection and the possible association between the levels of triamcinolone in the aqueous and the elevation in intraocular pressure (IOP).University teaching hospitals at Wenzhou and Shanghai, China.Prospective case series.The aqueous humor was sampled and triamcinolone quantitated after anterior sub-Tenon injection or posterior sub-Tenon injection in a cohort of patients and in experimental rabbits. Patients' IOPs were measured before and up to 3 months after triamcinolone acetonide injection.The study comprised 46 patients and 18 rabbits. The mean aqueous humor triamcinolone concentration in rabbit eyes and human eyes was significantly higher after an anterior sub-Tenon injection than that after a posterior sub-Tenon injection (rabbit eye: anterior sub-Tenon injection, 2.67 ng/mL ± 0.78 [SD] and posterior sub-Tenon injection 1.38 ± 0.48 ng/mL; human eye: 133.8 ± 149.2 ng/mL and 10.2 ± 10.9 ng/mL, respectively) (both P .0001). After anterior sub-Tenon injection, the mean triamcinolone concentration in the aqueous humor was significantly higher in human eyes than in rabbit eyes (133.8 ± 149.2 ng/mL versus 11.0 ± 8.1 ng/mL) (P = .0003). The levels of triamcinolone in the human aqueous humor had a significant positive association with the elevation in IOP (β = 0.12, P = .026).The triamcinolone level in aqueous humor was associated with IOP elevation after sub-Tenon application. Posterior sub-Tenon injection with a small injection volume of concentrated suspension offered a better targeted delivery and might significantly reduce steroid-associated IOP elevation.

In order to increase the economic efficiency of conformance control in the time of low oil price, a gelant should be injected into the specified location (positioning conformance control) to improve the swept volume in the maximum extent in the heterogeneous oil reservoir. For this purpose, an in-situ cross-linking polymer gelant (it is consisting of modified starch, acrylamide, N, N'- methylene diacrylamide, and potassium persulfate) is taken as the object of study by CT scan. Based on the dynamic and visible images of fluids distribution in the porous media, the gelant can be used to achieve the positioning conformance control because it can almost maintain a whole slug during transportation in porous media. According to the relationship of transportation distance and injection volume of the gelant in porous media, the gelant can be displaced to the specified location in porous media. In addition, the characteristics of water flooding of heterogeneous porous media before and after positioning conformance control are studied by CT scan, which can investigate the function of positioning conformance control and the extent of improving the swept volume in the heterogeneous reservoirs. The experimental results in this paper can provide theoretical guidance for the practical application of positioning conformance control in the heterogeneous oil reservoirs.

Intrathecal drug delivery is an attractive option to circumvent the blood-brain barrier for pain management through its increased efficacy of pain relief, reduction in adverse side effects, and cost-effectiveness. Unfortunately, there are limited guidelines for physicians to choose infusion or drug pump settings to administer therapeutic doses to specific regions of the spine or the brain. Although empiric trialing of intrathecal drugs is critical to determine the sustained side effects, currently there is no inexpensive in vitro method to guide the selection of spinal drug delivery parameters. The goal of this study is to demonstrate current computational capabilities to predict drug biodistribution while varying 3 parameters: (1) infusion settings, (2) drug chemistry, and (3) subject-specific anatomy and cerebrospinal fluid dynamics. We will discuss strategies to systematically optimize these 3 parameters to administer drug molecules to targeted tissue locations in the central nervous system.We acquired anatomical data from magnetic resonance imaging (MRI) and velocity measurements in the spinal cerebrospinal fluid with CINE-MRI for 2 subjects. A bench-top surrogate of the subject-specific central nervous system was constructed to match measured anatomical dimensions and volumes. We generated a computational mesh for the bench-top model. Idealized simulations of tracer distribution were compared with bench-top measurements for validation. Using reconstructions from MRI data, we also introduced a subject-specific computer model for predicting drug spread for the human volunteer.MRI velocity measurements at 3 spinal regions of interest reasonably matched the simulated flow fields in a subject-specific computer mesh. Comparison between the idealized spine computations and bench-top tracer distribution experiments demonstrate agreement of our drug transport predictions to this physical model. Simulated multibolus drug infusion theoretically localizes drug to the cervical and thoracic region. Continuous drug pump and single bolus injection were successful to target the lumbar spine in the simulations. The parenchyma might be targeted suitably by multiple boluses followed by a flush infusion. We present potential guidelines that take into account drug specific kinetics for tissue uptake, which influence the speed of drug dispersion in the model and potentially influence tissue targeting.We present potential guidelines considering drug-specific kinetics of tissue uptake, which determine the speed of drug dispersion and influence tissue targeting. However, there are limitations to this analysis in that the parameters were obtained from an idealized healthy patient in a supine position. The proposed methodology could assist physicians to select clinical infusion parameters for their patients and provide guidance to optimize treatment algorithms. In silico optimization of intrathecal drug delivery therapies presents the first steps toward a possible care paradigm in the future that is specific to personalized patient anatomy and diseases.

The pivotal approval trial for a smooth, highly cohesive, viscous, 20-mg/mL hyaluronic acid filler demonstrated sustained aesthetic improvement, with a mean injection volume of 6.65 mL. In daily practice, however, it is not often practical or necessary to use large injection volumes to achieve the desired cosmetic outcome.To assess the efficacy, longevity, and patient satisfaction associated with correction of age-related midface volume loss using the low volumes of hyaluronic acid filler more commonly used in day-to-day practice.A 2-center, retrospective cohort study examined medical records of 61 healthy patients who underwent treatment for facial volume loss with hyaluronic acid filler from November 1, 2013, through April 31, 2014. Follow-up visits were conducted at 1, 3, 6, and 12 months after the procedure. Data were pooled from a private facial plastic surgery practice in Weston, Florida, and a private cosmetic dermatology practice in San Diego, California.Patients were treated with hyaluronic acid filler according to the investigator's usual practices.The main outcome measure was patient-graded Global Aesthetic Improvement Scale scores at 1, 3, 6, and 12 months after treatment. Scores range from 1 to 5; 1 indicates very much improved and 5, worse.A total of 61 consecutive, healthy adult patients (mean [SD] age, 57.4 [12.8] years) with mild to severe facial volume loss were enrolled in the study. A total of 46 patients (75%) were white, 3 (5%) were black/African American, 9 (15%) were Hispanic/Latino, 1 (2%) was Asian/Pacific Islander, and 2 (3%) were other. Three patients (5%) were male, and 58 (95%) were female. Mean initial treatment volume was 1.6 mL. At follow-up, 29 patients (48%) elected to have a touch-up treatment; mean total touch-up volume was 1.4 mL. The patient-graded Global Aesthetic Improvement Scale scores at 1, 3, 6, and 12 months after treatment demonstrated that 73% (41 of 56) to 89% (24 of 27) of the study patients reported being very much or moderately improved. Most patients were rated by investigators on the Global Aesthetic Improvement Scale as very much or moderately improved at the 12-month follow-up. At 12 months after the procedure, 43 of 51 patients (84%) reported satisfaction with their outcome. At all time points, most patients would elect to undergo the procedure again (range, 17 [68%] to 61 [100%]). Adverse events were mild, and all resolved spontaneously within 14 days. At the 2-year follow-up, there were no reports of delayed adverse events.Midface volumization using the low volumes of hyaluronic acid filler more commonly used in daily clinical practice is effective and well tolerated.3.

Objective Several laryngeal injection techniques are technically difficult and have limitations. In this study, we modified a transcricothyroid approach for injections to enhance needle visualization during procedures. The objective of this study was to investigate the efficacy of this alternative injection technique. Methods We performed a retrospective analysis of 51 patients who had undergone injection laryngoplasty for unilateral vocal paralysis between March 2014 and February 2015. In total, 17 patients underwent a transcricothyroid injection laryngoplasty via the contralateral paramedian approach (ILC) and 34 patients underwent transcricothyroid injection laryngoplasty via the conventional approach (ipsilateral approach, ILI). Acoustic analyses, aerodynamic analyses, voice handicap index (VHI), and GRBAS scale were assessed pre-operatively and at 2 weeks and 3 months postoperatively. Results From our acoustic and aerodynamic analyses, jitter, shimmer, noise-to-harmonic ratio (NHR), maximum phonation time (MPT), and mean flow rate (MFR) were all significantly improved in both groups after injection. VHI and GRBAS scales also improved postoperation. There were no significant differences between the pre-operative and postoperative subjective and objective parameters between both groups. The total injection volume used on the ILI group was larger than the volume given to the ILC group. Conclusion The transcricothyroid injection laryngoplasty via the contralateral paramedian approach is potentially more beneficial to performing injection laryngoplasty under local anesthesia. One important advantage of this approach to conventional approaches is its enhanced visualization of the needle during procedures.

Purpose To test the effect of injection volume and concentration on dosing and residence time of moxifloxacin in the anterior chamber (AC). Setting Kaiser Permanente, Walnut Creek, California, USA. Design Experimental study. Methods Moxifloxacin 0.5%/0.05 mL, moxifloxacin 0.5%/0.10 mL, and moxifloxacin 0.15%/0.50 mL were drawn into 5 1.0 mL syringes each, injected into tared vials, and weighed. The doses delivered were calculated. The AC concentrations and elimination rates of the drug for two AC volumes were modeled for each dosing method. Results The 0.05 mL injection volume resulted in the greatest range (35 μg) of delivered dose compared with larger injection volumes (≤25 μg). The mathematical model predicted that variation in dosing in each group would result in differences of 12 minutes or less for the presence of the drug in the AC. Injection of 0.5%/0.1 mL produced AC concentrations above 500 μg/mL for 1.9 to 3.0 hours and above 64 μg/mL for 5.5 to 6.5 hours, depending on the AC volume; however, flushing with a 0.15% concentration sustained AC levels for 1.9 hours and 5.5 hours, respectively, for the two AC volumes. Conclusions Smaller injection volumes of a higher concentration moxifloxacin resulted in less accuracy and less precision in the delivered dose (0.05 mL, P = .005; 0.10 mL, P = .03); however, the clinical significance of this might vary. Injection of 0.5%/0.1 mL and flushing with 0.15%/0.5 mL of moxifloxacin would provide similar drug AC residence times according to the model. Flushing provided more consistent AC concentrations with differing AC volumes.

Botulinum neurotoxin (BoNT) effectively downregulates the secretion of eccrine sweat glands in patients with axillary and palmoplantar primary hyperhidrosis (PH).To demonstrate the efficacy and safety of pressure- and dose-controlled, needle-free, transcutaneous pneumatic injection (TPI) of BoNT-A for treating axillary and palmoplantar PH.Needleless TPI-BoNT-A treatments were delivered on the axillary or palmoplantar skin at a pneumatic pressure of 2.05 bars and an injection volume of 0.08 mL/shot. The efficacy thereof was assessed by evaluating starch-iodine test results and Hyperhidrosis Disease Severity Scale (HDSS) scores.At baseline, median HDSS scores were 3 (IQR, 3-4) for axillary lesions and 4 (IQR, 3.5-4) for palmoplantar lesions. Median HDSS scores at 1 month after TPI-BoNT-A treatment significantly decreased to 1 (IQR, 1-1.75) for axillary lesions (P .001) and 1 (IQR, 1-2) for palmoplantar lesions (P .001). Median global improvement scale scores were 4 (IQR, 3.25-4) for axillary PH and 3 (IQR, 2.5-4) for palmoplantar PH (P .05). In all patients, pain was tolerable during treatments for both axillary and palmoplantar PH after the application of topical anesthetic cream.Pressure- and dose-controlled, needle-free, BoNT delivery effectively and safely decreased sweating in axillary and palmoplantar skin.

Background and objectivesWe hypothesized that different injection techniques and volumes in thoracic-paravertebral blocks (TPVB) lead to different patterns of dye spread. In particular, we investigated whether an alternating injection technique leads to complete staining of all adjacent intercostal nerves.MethodsThis comparative anatomical investigation was performed using 10 or 20 mL of dye (Alcian Blue) in 10 unfixed donor cadavers (54 injections) that were designated for education or research purposes.ResultsIn landmark-guided TPVB, the thoracic-paravertebral space (TPVS) was either not stained at all (spread of dye in the paraspinal muscles, n=3) or the dye was predominantly found in the epidural space (n=3). In ultrasound-guided TPVB, the TPVS was correctly identified in all cases (n=48). The sympathetic trunk was stained in 84.6% of injections (multi-injection technique: 100%), independent of injection technique and volume. The epidural space was stained more frequently (p≤0.001) if both the puncture site (sagittal transducer position) and guidance of the needle were more medial (77.8%). Finally, a higher injection volume (20 vs 10 mL) resulted in a higher number of stained intercostal nerves (p=0.04).ConclusionFor ultrasound-guided techniques, a higher injection volume resulted in a larger number of stained intercostal nerves. Staining of the sympathetic trunk was independent of the injection technique. Epidural spread was observed significantly less frequently if the injection was lateral (transducer transversal) or with a strictly cranial injection direction (transducer sagittal). Landmark-guided injections reliably achieved the TPVS (and the epidural space) only after a needle advance of 2.5 cm after initial contact with the transverse process.

Azithromycin (Azr) is a member of the macrolide antibiotic and it used on a wide scale in prescribed antibiotic drugs as anti-gram-positive and anti-gram-negative microorganisms. The present study aimed to develop an HPLC method of Azr analysis enjoyed highly linearity, repeatability, robust, rugged, selective and rapid to use. The chromatographic method uses a reversed phase column ODS-3 (250 mm × 4.6 mm x 5 μm). The mobile phase was prepared by mixing Methanol: Phosphate buffer (9:1, v/v) at flow rate 1.2 ml/min with PDA detector 210 nm, column oven adjusted to 40° C with injection volume 50 μL. The method revealed satisfied linearity regression R2 (0.9996) with repeatability (0.66%), LOD and LOQ 28.7 µg/ml and 86.9 µg/ml respectively. The method showed a successful application for Azr determination in bulk and pharmaceutical formulations.

Subcutaneous immunoglobulin (SCIg) treatment has been shown to control symptoms and improve overall satisfaction in patients with neurological disorders. However, a large injection volume can be overwhelming and a barrier to successful SCIg treatment. We established a nurse-led individualized approach program to facilitate a smooth and successful treatment transition from intravenous immunoglobulin (IVIg) to SCIg. The program involved a lead nurse to provide two or more individual educational sessions on SCIg administration, establish a written transition plan, and liaise care with physicians.We aimed to evaluate the impact of our program to a successful transition defined as SCIg retention or adherence without a need to restart IVIg by six or twelve months.We reviewed medical charts of all patients with immune-mediated neuromuscular disorders who were in our program during January 2010 to Dec 2016.Nineteen patients were identified. Mean IVIg treatment duration was 31.5 months (range 4-98) before the transition. Mean steady state SCIg dosage was 26.2 g/week (SD 10.3). All patients were initially able to switch to SCIg, with a retention rate of 17/19 (89.5%) at six months and 15/19 (78.9%) at twelve months. Two patients reverted back to IVIg treatment due to worsening of their symptoms at two and three months, while two required supplemental IVIg infusions. There were no major adverse events reported during the twelve-month period, but one minor cutaneous adverse event (redness around the injection site).Successful treatment transition may be achieved with the nurse led individualized approach program.Il a été prouvé que les traitements à l’immunoglobuline par voie sous-cutanée (IgSC) permettent de contrôler les symptômes qui affectent des patients atteints de troubles neurologiques et d’améliorer leur satisfaction générale. Toutefois, de grands volumes injectés peuvent devenir accablants et représenter un obstacle à un traitement par IgSC qui soit efficace. Nous avons ainsi mis sur pied un programme reposant sur une approche individuelle et dirigé par du personnel infirmier afin de favoriser une transition en douceur efficace entre les traitements d’immunoglobuline par voie intraveineuse (IgIV) et ceux par IgSC. Un tel programme impliquait la présence d’une infirmière en chef chargée d’offrir deux séances de formation ou plus en ce qui concerne l’administration d’un traitement par IgSC mais aussi d’établir un plan écrit de transition entre les deux traitements et d’assurer une liaison avec les médecins traitants.Nous avons cherché à évaluer l’impact de notre programme en matière de transition. C’est ainsi que nous avons voulu savoir dans quelle mesure un traitement par IgSC entraînait une forme d’adhésion thérapeutique en vertu de laquelle un traitement par IgIV n’était plus nécessaire au bout de six ou de 12 mois.Nous avons passé en revue les dossiers médicaux de tous les patients atteints de troubles neuromusculaires d’origine auto-immune ayant fait partie de notre programme de janvier 2010 à décembre 2016.Au total, dix-neuf patients ont été sélectionnés. Avant d’amorcer notre transition, la durée moyenne d’un traitement par IgIV était de 31,5 mois (étendue : 4-98). La posologie moyenne à l’équilibre d’un traitement par IgSC était de 26,2 g/semaine (écart-type : 10,3). Au début, tous les patients ont été en mesure de passer à un traitement par IgSC, le taux d’adhésion étant de 89,5 % (17/19) au bout de six mois et de 78,9 % (15/19) au bout de douze mois. Deux patients ont recommencé à suivre un traitement par IgIV en raison d’une détérioration de leurs symptômes au bout de deux et de trois mois tandis que deux autres ont eu besoin d’injections à l’immunoglobuline additionnelles. Outre un seul événement indésirable mineur de nature cutanée, à savoir de la rougeur autour de la zone d’injection, aucun événement indésirable majeur n’a été signalé au cours de la période de transition de douze mois.Il est possible, au moyen d’un programme dirigé par une infirmière chef dont l’approche est individuelle, d’effectuer une transition efficace entre les deux traitements évoqués ci-dessus.

To develop and validate a novel reverse-phase high-performance liquid chromatography determination of Tinidazole and Roxithromycin in its Bulk and Pharmaceutical Dosage Forms. Examination of simultaneous determination is centered around the advancement of novel RP-HPLC systematic technique for the assurance of medication substance in strong oral dose shapes and their approval. The optimized chromatographic condition was established for the estimation of Tinidazole and Roxithromycin by using Agilent C18 (4.6 X 250mm, 5μm) column, sodium acetate buffer (pH 3) and Methanol (30:70% v/v) as mobile phase at a flow rate of 1.0ml/min sustain an ambient temperature. The total analysis time was 10 minutes and the retention of Tinidazole and Roxithromycin was found to be 2.352 and 5.941min with an injection volume of 20μl. The system suitability parameters proved for optimized chromatographic conditions for Tinidazole and Roxithromycin were within limits. The developed method was showing good resolution and separation factors. © 2020 Author(s).

An HPLC-PDA method was developed and validated for the determination of hydrochlorothiazide in bulk and pharmaceutical formulation. The method was optimized selecting chromatographic conditions of 50 : 50 acetonitrile : water, Inertsil® column (ODS-3 250 mm × 4.6 mm 5 μm), 20 μL injection volume, flow rate of 1 mL/min at ambient temperature (30°C), and 272 nm. Another column of C18Zorbax® (Eclipse Plus, 4.6 × 250 mm, 5 μm) was tested showing no big difference in the method results. The method was validated giving good precision (RSD% < 1), acceptable linearity (R2 ≥ 0.9978), and low LOD and LOQ (0.5 and 1.7 μg/mL, resp.) on both columns. Successful application on pharmaceutical dosage tablet form gave high recovery of 99.93%. The method was compared with official BP and other reported methods. The proposed method is economic, simple, and rapid and hence can be employed for routine analysis in quality control laboratories.

Administration into the subcutaneous (SC) tissue is a typical route of delivery for therapeutic proteins, especially for frequent treatments, long-term regimens, or self-administration. It is currently believed that the maximum volume for SC injections is approximately 1.5 mL. Larger SC injection volumes are considered to be associated with injection pain and adverse events at the injection site. However, no controlled clinical studies and actual evidence exist to support this assumption. In this review, we discuss current and publically available data related to SC administration volumes. We conclude that injection volumes higher than 3.5 mL are worth exploring if required for the development of efficacious drug treatments. Studying tissue back pressure, injection site leakage, local tolerability, and injection-related adverse events, such as injection pain, should be considered for the development of higher SC injection volumes.

In this work, a batch-injection analysis system with square-wave voltammetric (BIA-SWV) detection was applied for the first time to the simultaneous determination of inorganic (zinc) and organic (naphazoline) species. Both compounds were detected in a single run (70 injections h(-1)) with a small injection volume (∼100 µL). The calibration curves exhibited linear response range between 3.0 and 21.0 μmol L(-1) (r=0.999) for naphazoline and between 10.0 and 60.0 μmol L(-1) (r=0.992) for zinc. The detection limits were 0.13 and 0.04 μmol L(-1) for zinc and naphazoline, respectively. Good reproducibility was achieved for multiple measurements of a solution containing both species (RSD

Background Poly-L-lactic acid (PLLA) filler is known to have continuous volume effect. Objective The objective of this study is to analyze objective volume effect of PLLA in different settings of injection schedule on the cheek. Methods A split-face, evaluator-blind randomized study in 24 volunteers was conducted. One side was injected 3 times with 4 cc dose and the other side was injected 2 times with 6 cc dose per visit. Facial volume loss scale (FVLS) and Vectra were evaluated. Results Measured average FVLS showed statistically significant improvement both in 3 and 2 times injection sides and maintained efficacy until 12 months. Vectra showed volume difference (cc) between before and after injection. In 3 times injection side, it was increased 2.12 (after 1 month) to 3.17 (after 12 months). In 2 times injection side, it was increased 2.26 (after 1 month) to 3.19 (after 12 months). Gradual volume improvement over 12 months was statistically significant in both sides. There was no statistically significant difference between 3 and 2 times injection in FVLS and Vectra. There was no severe adverse event. Conclusion Poly-L-lactic acid has continuous volume effect and there was no significant difference by injection times at the same total injection volume.

Limited data exist on the efficacy of high- compared to low-volume US-guided corticosteroid injections (CI) in the subacromial-subdeltoid (SA-SD) bursa. Our purpose was to compare the short- and long-term efficacy of low- and high-volume injections, by using a capacity reference of SA-SD bursa volume, as assessed on cadaveric specimens.Within two years, 136 patients (63 males, 73 females; mean age: 46.11 ± 10.28 years) who underwent SA-SD bursa US-guided CI for subacromial impingement, rotator cuff tendinopathy or shoulder overuse were prospectively included. Patients were randomly assigned to low-volume (1 mL triamcinolone acetonide/40 mg) or high-volume (1 mL triamcinolone acetonide/40 mg, 9 mL anaesthetic agents) groups (67 and 69 patients, respectively). Visual Analogue Scores (VAS) were recorded at baseline, 30 min, 3 weeks, 3 months, 6 months and 1 year post-treatment. Predictors of complete recovery (VAS ≤ 2) at 1 year were analysed with multivariate Cox regression analysis. SA-SD bursa cadaveric dissection in 10 specimens was performed for volume assessment.Injection volume was the only predictor of complete pain resolution at 1 year. High-volume CI yielded higher chances of early pain recovery (2.837 HR, 95% CI 1.737-4.633, P .001). Mean VAS scores at baseline and subsequent time-points were 6, 2.6, 2.2, 2, 1.6 and 1 for the high-volume and 7.8, 7.3, 4.7, 3.2, 2.5 and 1.8 for the low-volume group, respectively (P .001, at all time-points). Cadaveric measurements showed a minimum SA-SD bursa volume of approximately 6.9 mL.High-compared to low-volume US-guided CI are superior for achieving early pain recovery.

Poisoning of benzodiazepines, particularly triazolam, estazolam and alprazolam usually is caused by consumption of the drug in bigger doses than prescribed. So, for the fast determination of material caused poisoning, selective and effective methods of analysis are requested. Methods. Benzodiazepines triazolam, estazolam and alprazolam, were chosen for investigation. Analysis was performed using chromatograph „Waters 2695” with a photodiode array detector (Waters 996, at wavelength 200-400 nm range), ACE C18 (2,1 mm x 5,0 cm, 5 μm) chromatographic column, gradient eluent flow (sulfuric acid buffer 0,1% and ACN), eluent flow rate 0,1 ml/min and injection volume of 10 µl. Results.Methodics for identification and quantification of triazolam, estazolam, alprazolam and their mixture was developed using reference solutions. Validated methodic was adapted for identification and quantification of triazolam, estazolam, alprazolam in medicinal products. Conclusions.Selected methodic is suitable for qualification and quantification of the medicinal preparations: ACE C18 (2,1 mm x 5,0 cm, 5 μm) chromatographic column, gradient eluent flow (sulfuric acid buffer 0,1% and ACN), eluent flow rate 0,1 ml/min, injection volume of 10 µl and diode array detector. Mixture of components has been examined and retention times have been stated as follows: alprazolam (13,216 min), estazolam (13,407 min) and triazolam (14,340 min). Retention time upon repetition of analysis have not exceeded the relative error of p Limits of detection of alprazolam is 0,01 µg/ml, estazolam 0,012 µg/ml, triazolam 0,020 µg/ml. Limit of quantification of alprazolam is 0, 022 µg/ml, estazolam 0, 025 µg/ml, triazolam 0, 045 µg/ml

Purpose/aim: AbobotulinumtoxinA (Dysport®, Ipsen Biopharmaceuticals, Inc., Basking Ridge, NJ, USA) is an acetylcholine release inhibitor and a neuromuscular blocking agent. The United States prescribing information for abobotulinumtoxinA previously indicated only one dilution for cervical dystonia: 500 U/1 mL. Clinical trial data supporting a larger volume with a 500 U/2 mL dilution would offer clinicians flexibility with injection volume to better meet patient needs.We conducted a 12-week, phase 3b, multicenter, randomized, double-blind, placebo-controlled trial (NCT01753310). Adult subjects with a primary diagnosis of cervical dystonia were randomized (2:1) to receive a single injection of either abobotulinumtoxinA, 500 U/2 mL dilution, or placebo. The primary efficacy endpoint was changed from baseline in Toronto Western Spasmodic Torticollis Rating Scale total score at Week 4.A total of 134 subjects (abobotulinumtoxinA, n = 89; placebo, n = 45) were randomized (intent-to-treat population) and 129 (abobotulinumtoxinA, n = 84; placebo, n = 45) completed the Week 4 primary endpoint evaluation (modified intent-to-treat population). In the modified intent-to-treat population, subjects receiving abobotulinumtoxinA experienced significantly greater changes from baseline versus placebo on the primary endpoint (weighted overall treatment difference -8.3, P0.001). The most common treatment-emergent adverse events (TEAEs) were dysphagia, muscle weakness, neck pain and headache. Overall, TEAEs were consistent with those reported in the abobotulinumtoxinA prescribing information (1 mL dilution) for cervical dystonia patients.This trial provides evidence that a 500 U/2 mL dilution is an effective treatment for cervical dystonia and exhibits a safety profile consistent with the known safety profile of abobotulinumtoxinA.

WOS: 000451852300017, PubMed ID: 30325612, Introduction: Various bulking agents were utilized for endoscopic correction of VUR. A study reviewing multi-institutional data showed that the amount of injection material has increased over time with the purpose of improving success rates, which also resulted in costs. We noticed an opposite trend in our center since we started using a new bulking agent. The aim of this study was to evaluate evolution of our practice with different bulking agents. Patients and Methods: Records of VUR patients who underwent subureteric injection with polyacrylate polyalcohol copolymer (PPC) and dextronomere hyaluronic acide (DxHA) between 2005 and 2014 were reviewed. Variation of different parameters throughout the study period was evaluated along with the success rate. Success was defined as complete resolution of reflux. Results: A total of 260 patients with 384 refluxing units were included. The success rate was higher in PPC group compared to DxHA group. There was no statistically significant difference between years regarding distribution of VUR grade, body weight, patient height, and age in PPC group. Despite significant reduction in injection volume, success rate did not decrease through the years with PPC. Conclusion: Different bulking agents may require different injection volumes to achieve the same success rate in endoscopic treatment of vesicoureteral reflux. Habits gained with previous experience using other materials should be revised while using a new went.

Juvéderm Voluma XC (VYC-20L) is approved in the United States for correction of age-related volume loss in the midface region in adults.To characterize the effects of VYC-20L in 3 midface subregions based on injection volumes.In this single-blind controlled trial, subjects with midface volume deficit received VYC-20L in ≥1 of 3 facial subregions (zygomaticomalar, anteromedial cheek, and submalar), with touch-up treatment available 30 days later. Responders achieved ≥1-point improvement on the Mid-Face Volume Deficit Scale (MFVDS), analyzed by facial subregion and stratified by injection volume quartiles. Subject satisfaction and safety were assessed.The treatment arm comprised 235 subjects aged 35 to 65 years. Month 6 MFVDS responder rates were 75.5% for zygomaticomalar, 83.2% for anteromedial cheek, and 76.9% for submalar subregions. Higher responder rates were observed with increasing injection volume quartiles for each subregion. Similar median injection volumes (≈2.0 mL total) of VYC-20L provided correction durations of 15 to 24 months: 24 months for anteromedial cheek, 19 months for zygomaticomalar, and 15 months for submalar subregions. Subject satisfaction was high across injection volume quartiles. No unanticipated treatment-site adverse reactions occurred.VYC-20L is effective at restoring midface volume, with high subject satisfaction and an acceptable safety profile.

Pain caused by subcutaneous injections is unpleasant, which may limit patient compliance. The objective of this study was to use spinal reflexes to quantify subcutaneous injection pain. Spinal reflexes were measured using an electromyogram (EMG) test. The effects of injection volume, pH and osmotic pressure were investigated. The EMG responses increased with injection volume and the acidity of the solution but did not depend on the osmotic pressure of the solution. The EMG responses differed for subcutaneously injected sodium chloride and glucose over the same range of osmotic pressures. Pain caused by the subcutaneous injections was unrelated to the osmotic ratio up to approximately 5. The injection pain caused by therapeutic protein solutions was also evaluated. We compared the EMG responses of the adalimumab and etanercept, as the injection of adalimumab is more painful than that of etanercept in humans. The EMG magnitude for adalimumab was twice that induced by etanercept as observed for the EMG tests performed in rats. Therapeutic proteins account for an increasingly large proportion of pharmaceutical drugs. When a high dose of therapeutic proteins is required, the protein solution must often be highly concentrated to reduce the injection volume. For patient comfort, it is critical to reduce injection pain. The EMG test reported here allows subcutaneous injection pain to be quantified and may be useful for optimizing drug formulations.

We report two endovascular aneurysm repair procedures achieved under image fusion guidance accomplished with noncontrast injected preoperative computed tomography scans. Such use of this advanced imaging application reduces contrast media injection volume (respectively, 27 and 24 mL throughout the patients' hospital course). No changes in creatinine clearance occurred after the procedures. Contrast-enhanced ultrasound imaging confirmed technical success in both cases.

The purpose of our study was to compare test bolus techniques using undiluted or diluted contrast material for their ability to predict aortic enhancement on coronary computed tomographic angiography (c-CTA) images.We divided 200 consecutive patients who underwent c-CTA on a 64-MDCT scanner into two groups. In group A (n = 100), we used a test bolus of undiluted contrast material and in group B (n = 100), the contrast material was diluted. The injection volume was body weight × 0.2 (contrast material 100%) in group A and body weight × 0.7 (contrast material 30%, saline 70%) in group B. We then compared the CT number in the ascending aorta on c-CTA images obtained with undiluted and diluted contrast media to the CT number on c-CTA images.The mean CT number in the ascending aorta was significantly higher in group B than group A (217.1 vs. 157.4 HU, P .001). There was a significant difference in the correlation between the CT number of the ascending aorta on c-CTA images and on images acquired with the test bolus using undiluted or diluted test bolus (P .001). In group B, the correlation had a strong positive linear relationship (r = 0.72, P .001), whereas in group A the positive linear relationship was weak (r = 0.36).The test bolus with diluted contrast material was useful for predicting aortic enhancement before c-CTA scanning.

Background and aim When carrying out endoscopic submucosal dissection (ESD), procedural safety increases with greater tissue elevation and efficiency increases with longer-lasting submucosal cushion. Fluids specifically developed for ESD in Asia are not commercially available in the West, leaving endoscopists to use a variety of injectable fluids off-label. To determine the optimal fluid available in the West, we compared commonly used fluids for Western ESD. Methods All phases were carried out in an ex vivo porcine stomach model. Phase 1 compared tissue elevation and duration of submucosal cushions produced by various standard volumes of various injectable solutions used for ESD. The two best-performing solutions used off-label were tested head-to-head in ESD in Phase 2. Phase 3 compared the best solution from Phase 2 to Eleview® , currently the only submucosal injection fluid approved in the USA. In Phases 2 and 3, five ESD were carried out with each solution. The solutions were randomized and the endoscopist blinded to the solution. Results The best-performing solutions in Phase 1 were 0.4% hyaluronic acid, 6% hydroxyethyl starch (HES), and Eleview® . Phase 2 compared 6% HES and hydroxypropyl methylcellulose (HPMC), showing that ESD with 6% HES was easier (P = 0.007), faster (P = 0.041) and required less injection volume (P = 0.003). In Phase 3, resection speed, ease of ESD and total volume per area resected were comparable between 6% HES and Eleview® . Conclusions Of the submucosal injection fluids currently available in the West, Eleview® and 6% HES are the best-performing solutions for ESD in a porcine model.

Background: This study compared patient preference for Humalog® KwikPen™ 200 units/mL (insulin lispro; hereafter, IL 200 pen; Eli Lilly and Company, Indianapolis, IN) versus the Humalog KwikPen 100 units/mL (insulin lispro; hereafter, IL 100 pen; Eli Lilly and Company, Indianapolis, IN) in patients with diabetes requiring >20 units of mealtime insulin and diabetes caregivers. This study also determined which attributes had the greatest influence on pen preference selection. Methods: In this 2-period, crossover, simulated-use study, 106 participants were randomized to 1 of 8 sequences that varied the pen order (IL 100 pen or IL 200 pen) and dosing order (15 units = low dose or 50 units = high dose) for a total of 4 simulated injections. Participants then completed a self-administered questionnaire to select their overall preference between the 2 pens and then rated the importance of 11 pen attributes in contributing to their overall preference. Results: Of the 90 participants expressing an overall preference, significantly more preferred the IL 200 pen to the IL 100 pen (IL 200 pen: 80 respondents; IL 100 pen: 10 respondents; 95% confidence interval [0.81, 0.94], P < .0001). The total amount of insulin in the pen, the ease in pressing the injection button, and the amount of fluid injected were key attributes influencing IL 200 pen preference. Conclusions: Based on these key attributes, the IL 200 pen was significantly preferred over the IL 100 pen by patients with diabetes who require >20 daily mealtime insulin units or diabetes caregivers and may improve the injection experience for these patients.

This work proposes an approach to the direct analysis of S-adenosylhomocysteine (SAH) and the methylation index in blood using CE with UV detection (CE-UV). After application of meglumine postinjection, we achieved SAH in-capillary preconcentration in the HClO4 extracts of erythrocytes, which improved the detection limit (S/N = 3) of SAH up to 3 fmol or 180 nmol/L at the injection volume of 50 nL, taking into account the sample dilution rate. CE-UV was carried out in 30 mM glycine and 45 mmol/L HCl (pH ~1.8) at 17 kV in a capillary 48 cm in length and 50 μm id. Accuracy of the technique was 101% and reproducibility was about 12%.

Research into spinal cord injury depends upon animal models of trauma. While investigations using small animals have yielded critical insights into the cellular mechanisms of neurotrauma, no effective therapies have been translated to human clinical treatments. There are considerable differences in pathophysiology, scale, and anatomical organization between rodents and primates. Here, the established method of inflating balloons to compress the cord within the spinal canal was adapted for use in goats. By using surgical techniques to insert a kyphoplasty balloon, spinal cord injury was accomplished with minimal trauma to the surrounding tissues, as is common in other traumatic models. Dye volumes of 0, 1.26 ± 0.18, and 2.82 ± 0.20 mL were injected into the balloon to produce spinal occupancies of 0%, 33 ± 2%, and 89 ± 4%, as evaluated by X-ray and computerized tomography imaging. A significant dose response was observed for the different levels of trauma, with reduced conduction of somatosensory evoked potentials and impaired mobility 7 days after injury. From the strong correlations between injection volume, balloon pressure, spinal occupancy, nerve function, and animal behavior, we conclude that hydraulic compression in goats is a useful model of spinal cord injury.

The aim of this study was to quantitatively define the main measurable technical parameters for the intramuscular transplantation of myogenic cells in primates. Myoblasts transduced with the gene coding for β-galactosidase were injected into the skeletal muscles of 15 monkeys. The following parameters were studied: needle size, number of cells per injection, and volume of cell suspension per injection. Monkeys were immunosuppressed with tacrolimus. The cell-injected sites were biopsied 1 or 2 months later. Biopsies were examined histo logically to assess the myoblast engraftment and the muscle structure. The conclusions were as follows: ( 1 ) Needles should be thin enough to avoid important tissue damage and allow muscle regeneration as satisfactory as possible. Among those tested, 27G should be the choice if the length is consistent with depth of injection. ( 2 ) At least 100,000 cells should be delivered per centimeter of needle trajectory. ( 3 ) The smallest volumes of cell suspension per injection should be used. In this study, 1 μl/cm of injection trajectory was sufficient. In principle, these parameters apply to muscles in which no damage occurred other than the injections.

The first reversed phase high performance liquid chromatographic method for simultaneous determination of, Canagliflozin and Metformin has been developed and validated to be a simple, sensitive, rapid, specific, precise, and accurate method. Chromatographic separation was achieved on C18 column (250×4.6 mm-5μm p.s). Methanol and potassium dihydrogen phosphate buffer in a ratio [90:10 v/v] as a mobile phase at flow rate of 0.9ml/min. UV detection was operated at 222 nm and injection volume was 20 μl. The proposed method showed good linearity, accuracy, precision and was successfully applied for determination of the drugs in laboratory prepared pharmaceutical dosage forms. The current method has been statistically validated according to the ICH guidelines and this method has been subsequently developed and applied successfully to determine the levels of Metformin hydrochloride and Canagliflozin in a combined formulation and in the routine quality control analysis with good accuracy and sensitivity.

Haloperidol is an anti-psychotic drug and Benzhexol (Trihexyphenidyl) is an anticholinergic drug. A newstability indicating UPLC method has been developed for the simultaneous determination of Haloperidol and Benzhexol and the method was validated. Waters UPLC with Empower software, with Acquity UPLC SB C18 x 1.7m. column and PDA detector was used for the simultaneous determination of Haloperidol and Benzhexol. A mixture of phosphate buffer and Acetonitrile taken in the ratio 56:44 v/v was used as mobile phase with a flow rate of 0.2 ml/min (UV detection at 245 nm) (Injection volume 1ml). Haloperidol and Benzhexol have shown linearregression equations, y=13361x+476.2(R² = 0.9998) and y =10609 x + 899.5 (R² = 0.9998). The LOD and LOQ are found to be 0.03 µg/mL and 0.10 µg/mL for Haloperidol and 0.03µg/mL and 0.09 µg/mL for Benzhexolrespectively. The present liquid chromatographic method is precise, accurate and can be used for the simultaneous estimation of Haloperidol and Benzhexol tablets.