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Increasing the number of elderly causes an increase in health problems one of which is associated with hypertension which can cause complications and death. The purpose of this study was to determine the description and accuracy of the use of antihypertensive drugs in geriatric patients who were diagnosed with hypertension at the Tajinan Primary Health in Malang in the period January-December 2019. This study was an observational or non-experimental study conducted using retrospective medical record data. The measuring instrument used was the data collection sheet from the medical record, the Consensus for Hypertension Management 2019 to see the accuracy of indications, patient accuracy, drug accuracy, and dose accuracy. Data analysis using Correlation Test. The results of the correlation analysis showed that the resulting Standardize estimates were 0.002 (p

Pneumonia was pulmonary lung disease called parenchyma caused by microorganism, Pneumonia can be cured byantibiotic to prevent the resistantof bacteria and to improve the effective of the treatment, the right antibiotic must be determining. This research purpose is to determine the accuracy of using antibiotic in toddler patients suffering pneumonia who hospitalized in RSUD “Y” “X” City, in 2016. This is nonexperimental research. Data collected retrospectively and was analized descriptively. Samplestaken by purposive sampling method which searched the medical report of toddler patient suffer pneumonia hospitalized in RSUD “Y”X City, in 2016 which met the inclusion criteria. Reseach accuracy was analized used “Pedoman Pelayanan Medis Ikatan Dokter Anak Indonesia year 2009” and “British National Formularium for Children 2011-2012”, Such as indication accuracy, precision medicine accuracy, patient accuracy and drug dose accuracy. The result of the research was found that in 49 toddler patient suffering pneumonia, the kind of antibiotic used was cefotaxime (89,80%), Ampicillin (4,08%), combination of cefotaxime + gentamicin (4,08%) and ampicillin + gentamicin (2,04%). Evaluation of accuracy of the use antibiotic 100% right in indication, precision medicine by 93,87%,100% patient accuracy, and 10,20% drug dose accuracy.

Background: High Dose Rate (HDR) brachytherapy sources with high photon energy have been widely used in treating tumors. Dosimetric parameter of these brachytherapy sources should be determined according to the AAPM TG-43 recommendation. Gafchoromic films are reliable tools for this evaluation. Objective: The aim of this study is to evaluate and compare dose accuracy of the two-brachytherapy sources in a dedicated phantom.Material and Methods: In this analytical study, two common sources, including Cobalt and Iridium, were loaded into the dedicated phantom. The two-dimensional dose distribution around the source was calculated by TPS system for certain activities and geometries around the sources. Then, the experimental dose measured by Gafchromic film dosimetry was reported for different angles ranging from 0 to 180 degrees. Results: The difference between calculated and measured doses was less than 6 percent (-5 to +6 percent) for all of the channels and angles. These errors are smaller and mainly more than zero (Dfilm>DTPS) for angles less than 20 and larger than 110 degrees. There is no statistically significant discrepancy in dose calculation by treatment planning system. Conclusion: Although the estimated error in dose calculation is not significant, there is still an opportunity to increase the treatment precision. The correlation between the error and the angle should be considered in further plans of brachytherapy. The present study showed comparable errors compared to results of other research studies.

Aim Tablets can be manipulated in several ways to obtain a fraction as the dose—a practice frequently seen in paediatric care due to lack of suitable formulations. Splitting tablets prior to fragment dispersion in a small volume of liquid is one such method. The objective of this study was to investigate the accuracy and precision of this method. Methods Four different types of aspirin tablets (two dispersible, one conventional and one chewing) were split with a tablet splitter into half and quarter fragments. The fragments were dispersed in a medicine measure or an oral syringe. The amount recovered was determined by UHPLC analysis. Results The largest quarter fragments ranged from 26.7% to 31.5% of the full tablet weight. Dispersing the fragment in an oral syringe, the amount recovered was greater than 90.8% of the fragment manipulated for all four tablet types, when rinsing was performed. Dispersing the fragment in a medicine measure, the amounts recovered spanned from 32.9% for the conventional tablets to 98.7% for one of the dispersible tablets. Conclusion Dispersion of half or quarter tablets directly in an oral syringe, but not a medicine measure, could give satisfactory recovery from fragments of all the investigated aspirin tablets.

Tablet splitting is a common practice in clinical settings to lower doses, facilitate swallowing or save costs. Splitting devices can be used when hand splitting is difficult or painful. However, data on the accuracy of tablet splitting are limited and it presents a number of patient or formulation-related problems. Thirty nebivolol IR tablets on the Turkish market were split by hand, a tablet cutter (Rabir (R)) or a knife, and tested for weight variation, loss of mass, disintegration, and friability. The accuracy of split tablets was in the range of 75.4-121, 82.4-115, and 86.9-115% when split by hand, the cutter, and knife, respectively. No significant difference in accuracy was determined between the left and right sides split by the cutter (p = 0.222). The differences were significant for hand and knife splittings (p < 0.005). The precision was 9.02, 7.87, and 6.11% (CV%) for hand, tablet cutter, and knife, respectively. Only hand splitting failed to comply with the subdivision test of European Pharmacopoeia. The split portions met USP standards for friability (

Objectives When caring for children in a hospital setting, tablets are often manipulated at the ward to obtain the right dose. One example is manipulation of tablets containing the slightly water-soluble substance aspirin, used in paediatric care as an antiplatelet agent. The evidence base, however, for choosing certain tablet formulations and manipulation methods over others for extraction of proportions is lacking. The aim of this study was to investigate the effect of tablet formulation and manipulation technique on the dose accuracy and precision attained when dispersing different commercially available aspirin tablets and extracting a small proportion suitable for children. Methods The manipulation methods investigated simulated those observed in the paediatric clinic. Four tablet formulations—one chewable, one conventional and two dispersible—were dispersed in 10 mL water in a medicine measure. On (1) passive dispersion, (2) mixing by stirring with the syringe, or (3) stirring and pumping the dispersion in and out of the syringe, respectively, proportions (1 mL or 2 mL) were extracted and the doses recovered were determined using a validated UHPLC (ultra high-pressure liquid chromatography) method. Results Fractions from the four different dispersed aspirin tablet formulations varied from 99% to 3% of that intended with the lowest degree of mixing, and from 96% to 34% of that intended with the highest degree of mixing. Only the dispersible tablets gave average doses within 20% of the intended dose. Conclusions Fraction extraction from dispersed aspirin tablets only gave doses within 20% of intended for the dispersible tablets, and then only for some of the manipulation methods: ‘passive dispersion’ for the 75 mg dispersible tablet and ‘stirring and pumping’ for the 300 mg dispersible tablet. The tablets not intended for dispersion gave unsatisfactory results, outside 20%, regardless of manipulation method. The findings underline the importance of considering both tablet formulation and dose extraction technique when manipulations are required.

Marilyn S Kwolek,1 Jon E Block2 1Private Practice, Danville, CA 94526, USA; 2Independent Clinical Consultant, San Francisco, CA 94115, USA Background: Although freehand injection of botulinum toxin remains the status quo, it is an inaccurate technique for delivering precise amounts of neurotoxin at multiple injection sites with expediency. We developed an inexpensive, ergonomic, single-use, disposable exostructure device that rapidly converts a standard syringe into a highly accurate injection instrument. Materials and methods: Based on the results of two independent injectors, we determined the comparative delivery dose accuracy, precision, and amount of product waste associated with a standard syringe using the freehand injection technique vs a prototype injection assist device. Fifteen experienced injectors were also surveyed regarding their satisfaction using the device in a controlled research setting. Results: The average percentage difference from the expected dose value was 10% or 0.0025 mL). Accuracy estimates were also superior with the device over freehand for 2- and 4-unit doses. Precision estimates favored the device for all comparisons and all dosing regimens. The magnitude of variability around the average difference ranged from 2.2 to 5.4 times worse for the freehand method compared to the device. The overall percentage of product waste was substantial with the freehand method (>10%) compared to the device (4.3%) (P=0.04) for 1-unit injections. The percentage of injections showing measurable product waste was also significantly lower with the device (78% vs 25%, P=0.01). Fourteen of 15 (93%) injectors surveyed would use the device in daily practice if it were included complimentary with the neurotoxin. Conclusion: The injection assist device offered superior accuracy and precision compared to the freehand method across the entire injection regimen. The ancillary finding of a significant reduction in product waste with the device was particularly notable. Keywords: neurotoxin, injection, syringe, accuracy

Background: The main goal of radiation therapy is to deliver the highest dose to the tumor and at the same time the lowest dose to the surrounding normal tissue. In vivo dosimetry is a quality control procedure that, instead of controlling the components separately, directly examines the dose reached to the tumor area. Objectives: In this study, the entrance, exit, and middle dose of the breast and supraclavicular area of patients with breast cancer under radiation therapy were measured and compared with calculations. Methods: In this experimental study, the entrance and exit doses of 33 patients with breast tumors treated with 6 MV and 18MV photons were measured simultaneously. The measurement was done, using p-type diodes after calibration and, then, the midpoint dose was calculated, using the transfer method and arithmetic mean method. Also, the entrance dose, exit dose, and midline dose measured with dosimeter were compared with the calculated values in the treatment planning system. Results: There was no significant difference between calculated and measured doses in the entrance, exit, and midline point in breast regions (P > 0.05), but in the supraclavicular region, a challenge was observed. The difference in entrance and midline point between calculation and measurement is not significant based on the transfer method, but there is a significant error based on the arithmetic mean method (P < 0.05). Conclusions: In vivo dosimetry by measured real given dose to the patient can perform a basic role in the quality control of the radiotherapy department. It seems in the entrance dose, the relative error is smaller but due to the smaller value of exit dose, the relative error in small values is more apparent.

Background and importance Manipulation of tablets is often necessary to achieve an appropriate dose in the paediatric ward.1 However, previous studies have shown a difference in dose accuracy obtained on manipulation for different tablets, in particular for the slightly soluble drug substance aspirin.2 Prednisolone is a very slightly soluble drug substance, and prednisolone tablets are frequently manipulated in paediatric care. Aim and objectives To investigate the dose accuracy and dose precision attained after manipulation of a commercially available prednisolone tablet, and to compare the results with those previously found for aspirin, a drug substance where solubility may similarly be challenging. Material and methods Prednisolone tablets: Prednisolon Alternova 5 mg, Alternova A/S. Instrument: UHPLC-system from Shimadzu Corp (Nexera, with prominence DAD detector). Analytical column: ACE Excel 2 μm C18-AR, 2.1 × 100 mm (Advanced Chromatography Technologies Ltd). The analytical method was validated for linearity, precision and specificity. Dosing accuracy study: six tablets were dissolved in 10 mL water. After 4 min of intermittent stirring, samples of 1 mL, a 10th of the tablet, were withdrawn. Dosing accuracy was recorded and compared with previous findings for aspirin. Results After manipulation of Prednisolon Alternova 5 mg tablets, 92.2% (85.3–95.1%) of the intended dose was retrieved. Conclusion and relevance After manipulation by dispersion and dose extraction, the prednisolone tablets were found to give doses within the limits of tablet fractions according to the European Pharmacopeia (85–115%). In contrast, conventional tablets containing aspirin (Aspirin ‘Bayer’ 500 mg), a slightly soluble drug substance, has previously been shown to have never exceeded 55% of the intended dose when a 10th of the tablet was extracted.2 This shows that knowledge about solubility is not always sufficient for estimating the suitability for manipulation of tablets. References and/or acknowledgements Bjerknes K, Boyum S, Kristensen S, et al. Manipulating tablets and capsules given to hospitalised children in Norway is common practice. Acta Paediatr 2017;106:503–8. Brustugun J, Notaker N, Paetz LH, et al. Adjusting the dose in paediatric care: Dispersing four different aspirin tablets and taking a proportion. Eur J Hosp Pharm 2019. https://doi.org/10.1136/ejhpharm-2019-001903 Conflict of interest No conflict of interest

The objective of this study is to evaluate the dosimetric precision of the Monte Carlo (MC) algorithm to validate the Monaco® (Elekta) treatment planning system for the two radiotherapy techniques IMRT and VMAT® on the Infinity™ Elekta linear accelerator. Several irradiation plans were created on the Monaco® treatment planning system (TPS) and calculated by the integrated MC algorithm for its validation. The same plans were applied experimentally using the Matrixx Evolution 2D array with its appropriate phantom. All measurements were performed by superimposition with those calculated on the Infinity™ linear accelerator (ELEKTA). The calculated and measured dosimetric data were overlaid to make the comparison of what is realistic and what was simulated using the MyQA (IBA) software associated with the Matrixx. Good agreement was observed between calculated and measured data using 3%, 3mm distance to agreement (DTA) and low dose threshold 5% criteria. Global gamma analysis passing rates for all tests are greater than 95%. An agreement less than 2 mm is shown for open fields and homogenous dose test. However, there was increase in the agreement criteria above 3 mm for chair and pyramid test as a result of high gradient dose regions especially at the edge of target volumes. Results obtained from this study allowed, in one hand to confirm the accuracy of our MC model dose calculation with Monaco® TPS, and in the other hand, the use of the matrix detector as a standard tool for IMRT/VMAT® patient quality control.

Background: The diagnostic reference level (DRL) is measured with different methods in the common Computed tomography (CT) exams, but it has not been measured through the size-specific dose estimate (SSDE) method in Iran, yet. Objective: This study aimed to calculate the local DRL (LDRL) using the new quality control-based dose survey method (QC) and patients’ effective diameter (MQC) and compare them with a data collection method (DC) as well as local national DRLs (NDRL). Material and Methods: In this cross-sectional study, LDRL, based on the third quartile of volumetric computed tomography dose index (CTDIvol) and dose length product (DLP) values, was calculated for the four common CT examinations in four CT scan centers affiliated with Shiraz University of Medical Sciences by DC, QC and MQC methods. The CTDIvol of each patient for each CT exam calculated with three methods was compared with paired t-test. Also, the LDRL using MQC method was compared with other national DRL studies. Results: There was a significant difference between the CTDIvol values calculated with MQC and QC in all four examinations (P

Background The purpose of this study was to assess dose accuracy improvement and dosimetric impact of switching from the anisotropic analytical algorithm (AA) to the Acuros XB algorithm (AXB) when performing an accurate beam calibration in head and neck (H&N) FFF-VMAT treatments. Materials and methods Twenty H&N cancer patients treated with FFF-VMAT techniques were included. Calculations were performed with the AA and AXB algorithm (dose-to-water — AXBw– and dose-to-medium — AXBm–). An accurate beam calibration was used for AXB calculations. Dose prescription to the tumour (PTV70) and at-risk-nodal region (PTV58.1) were 70 Gy and 58.1 Gy, respectively. A PTV70_bone including bony structures in PTV70 was contoured. Dose-volume parameters were compared between the algorithms. Statistical tests were used to analyze the differences in mean values and the correlation between compliance with the D95 > 95% requirement and occurrence of local recurrence. Results AA systematically overestimated the dose compared to AXB algorithm with mean dose differences within 1.3 Gy/2%, except for the PTV70_bone (2.2 Gy/3.2%). Dose differences were significantly higher for AXBm calculations when including accurate beam calibration (maximum dose differences up to 2.8 Gy/4.1% and 4.2 Gy/6.3% for PTV70 and PTV70_bone, respectively). 80% of AA-calculated plans did not meet the D95 > 95% requirement after recalculation with AXBm and accurate beam calibration. The reduction in D95 coverage in the tumour was not clinically relevant. Conclusions Using the AXBm algorithm and carefully reviewing the beam calibration procedure in H&N FFF-VMAT treatments ensures (1) dose accuracy increase by approximately 3%; (2) a consequent dose increase in targets; and (3) a dose reporting mode that is consistent with the trend of current algorithms.

Obtention of customized dosage forms is one of the main attractions of 3D printing in pharmaceuticals. In this sense, children are one of the groups within the population with a greater need for drug doses adapted to their requirements (age, weight, pathological state…), but most 3D printed oral dosages are solid forms and, therefore, not suitable for them. This work developed patient-tailored medicinal gummies, an alternative oral dosage form with eye-catching appearance and appropriate organoleptic characteristics. Four inks were formulated, characterised and 3D printed by means of syringe-based extrusion mechanism. Different tests were performed to ensure reproducibility of the process and validate work methodology for dosage unit fabrication applying basic manufacturing standards. Rheological test helped in evaluating inks printability. Visual characterization concluded that drugmies, apart from a high fidelity in the 3D model shape reproduction, had a bright and uniformly coloured appearance and a pleasant aroma, which made them highly appetising and attractive. The printed gummy oral dosages complied comfortably with the mass uniformity assay regardless of the formulated ink used or the 3D model selected for printing. Ranitidine hydrochloride individual contents were determined using uv-vis spectrophotometry, showing successful results both in dose accuracy, uniformity of drug content and dissolution.

Background: A basal bolus insulin regimen requires multiple daily insulin injections, which might discourage patient adherence. As a potential solution, a mealtime insulin-delivery system—a 3-day wearable bolus-only patch—was designed to manually administer mealtime insulin discreetly by actuating buttons through clothing, without the need for multiple needle sticks. Method: Extensive functional testing of the patch included dose accuracy (from initial fill of the device to empty), pressure-vacuum leak testing, last-dose lockout and occlusion detection (safety alert features that lock the dosing buttons when no insulin is delivered), assessments of insulin drug stability, toxicological risk (including chemical testing), and system biocompatibility. Results: Dosing accuracy was 2 units ±10% (with U-100 insulin) over a range of environmental conditions, with ≥95% reliability and confidence. The fluid seal performance and the safety alert features performed with ≥95% reliability and ≥95% confidence. The system met acceptable standards for insulin (U-100 lispro and aspart) stability for its intended 3-day use, in addition to the operational requirements. The toxicological risk assessment and demonstrated biocompatibility suggested that the patch is safe for human use. Conclusions: Benchtop performance showed that the bolus-only patch is a safe, accurate, and reliable device for mealtime insulin delivery.

More than 50% of patients with type 2 diabetes mellitus are associated with hypertension. Uncontrolled blood pressure in patients with type 2 diabetes mellitus correlated with the onset of cardiovascular and cerebrovascular complications. Therefore, proper blood pressure management is needed to delay and prevent complications. Selection of appropriate antihypertensive drugs along with appropriate doses is one way to inhibit the possibility of complications. The purpose of this study is to know about the accuracy of the use of antihypertensive drugs and doses used. This research is a descriptive and observational retrospective research. The subjects of the study were 88 patients with diabetes mellitus with accompanying hypertension. Data taken include antihypertensive, antidiabetes mellitus, laboratory data. The data obtained are then analyzed descriptively using JNC edition 8 and DIH 2015. The results showed that there were 88 samples meeting the inclusion and exclusion criteria. The commonly used single antihypertensive group is Angiotensin Receptor Blocker (ARB) of 56.09%, and antihypertensive combination is Angiotensin Receptor Blocker (ARB) - Calsium Chanel Blocker (CCB) of 65.95%. Based on the results of analysis, the results obtained for the right drug and the patient is 98.86% and for the accuracy of the dose obtained 97.72%.

To date, self administrations of recombinant human follicle-stimulating hormone (rhFSH) are carried out using pen injectors with minimal dose increments of 8.33 IU or 12.5 IU (IU – international units of activity). To ensure the accuracy of dose titration and to minimize the dose adjustments during the treatment, new pen injectors are needed. Those would provide for the self administration of rhFSH in a wide range of doses and with a dose increment less than the existing fractional values. Aim: to develop a pre-filled, multi-dose pen injector for rhFSH solution with a 5 IU dose increment and a dose setting from 0 to 300 IU. Materials and methods. Dispensed volumes containing the minimal dose of 5 IU were measured gravimetrically. Results. After testing 48 pen injectors the estimated minimal dose of 5 IU (0.0083 ml of the solution) produced the following results: the mean value of the dispensed volume was 0.0081 ml, the mean deviation was ± 0.0006 ml (or ± 0.36 IU). The results are in consistence with the ISO 11608-1:2014(E) requirements of dose accuracy for the minimal dose setting in commercial injectors. Conclusion. We have developed a pen injector for rhFSH administration with a dose setting from 0 to 300 IU and with a minimal increment of dose adjustment of 5 IU. The individual approach to the dose selection/adjustment with a minimal increment of 5 IU may help achieving a highly accurate administration of rhFSH for the controlled ovarian hyperstimulation and for the induced-ovulation protocols with growth activation of 1-2 follicles.

Polymer gels are three-dimensional dosimetric tools. The purpose of the present study was to investigate the temperature dependence of polymer gels during scanning Magnetic Resonance Imaging. Prepared gels were irradiated with a 6MV X-ray beam at intensities ranging from 0 to 20 Gy in order to investigate their dose-R2 and dose-R1 responses. Irradiated gels were evaluated from 1.5-T magnetic resonance R2 and R1 images for each 5°C change in temperature from 5°C to 41°C, and then the four-field box technique irradiation plan was used to deliver a total dose of 4 Gy using the same beam weight in each direction to the prepared gels. The profile of the dose map generated from the four-field irradiated gel data at 20°C was then compared with the planned data. The dose-R2 response curve was linear up to 20 Gy at 20°C, with a slope of 1.17 Gy-1˙s-1. The slopes of the fitted curves of the dose-R2 decreased as gel temperature increased. The slopes of the dose-R1 curves were more parallel than the slopes of the dose-R2 curves between 5 and 41°C. The difference in the full width of half maximum of the gel profile data obtained using the four-field box technique at 20°C and the planned data were below 5% on average. The dose map from the irradiated gels obtained using the dose-R2 curve was the same as that from the planned data under the same temperature conditions. Measurement of difference between various temperatures is significant with dose accuracy. It is suitable to evaluate the gel dosimeter under the thermal equilibrium condition, MRI room temperature from the point of view of the stability of the irradiated gels.

Purpose/Objective(s) MR-guided radiotherapy relies on the daily assignment of a relative electron density (rED) map to acquire the fraction specific dose calculation. The approach to acquire the rED map is used bulk rED assignment based on the rED values of the delineated region of interests (ROIs) to generate a synthetic CT (sCT). This study aims to evaluate the dose accuracy of this approach for application in 1.5 T MR-Linac, to assess the reliability of this approach in the case of online adaptive MR-guided radiotherapy for Nasopharyngeal Carcinoma (NPC) patients. Materials/Methods The original CT and MRI T2 were acquired for 10 NPC patients and targets, organs at risk (OARs), bone and air regions were delineated on original CT in a treatment planning software. Each patient's MRI/CT image pair was aligned using a rigid registration algorithm, and the contours were copied to MRI from original CT. The sCT was then generated in MRI using bulk rED assignment approach, based on the rED values of the delineated region of interests (ROIs). Three different types of sCT images were generated: The sCTICRU uses the rED values recommended by ICRU46, the sCTtailor uses the patient-specific mean rED values, and the sCTHomogeneity was created using water equivalent value of 1 g/cm3 for entire patient data set. The same treatment plan was calculated on three sCTs and original CT. The dose calculation accuracy was investigated in terms of gamma analysis, point dose comparison and dose volume histogram (DVH) parameters. Results For both criteria, 1%/1mm and 2%/2mm gamma passing rate results of plans on sCTtailor were always higher than plans on sCTICRU and sCTHomogeneity when compared with original CT based plans (P = 0.005). The difference on point dose in high dose planning target volume for each case calculated on sCTtailor (-0.14% ± 1.44%) was smaller if compared to those calculated on sCTICRU (-8.77% ± 2.33%) and sCTHomogeneity (1.65% ± 2.57%). The DVH differences for plan based on sCTtailor were much smaller than sCTICRU and sCTHomogeneity. Conclusion The sCT generated with bulk rED assignment approach guarantees an acceptable level of dose accuracy for NPC patients with 1.5 T MR-Linac, making this approach suitable to online adaptive MR-guided radiotherapy. The accuracy can be improved by using patient-specific rED values.

Background:This study examines the utility of the first prefilled, rapid-acting insulin pen that can be dialed in half-unit increments. Dose accuracy and injection force were examined through a series of design-verification tests, and usability was established by human factors validation testing.Methods:Devices were tested for dose accuracy at 3 different doses and temperatures and under free fall, vibration, and cold storage conditioning. Injection force was measured at the maximum dose (30 units). Both experiments used the same semiautomated testing system. Usability was validated in a human factors simulated-use study that included 60 participants (patients with type 1 or type 2 diabetes [aged 10-79 years], adult caregivers, and health care providers).Results:The pen met the International Organization for Standardization (ISO) 11608-1:2014 requirements for dose accuracy at all settings and conditions tested. Furthermore, all individual results were within the ISO specification limits. Mean injection force across temperature settings ranged from 9.25 to 10.85 N at the highest dose. The usability validation study confirmed that use-related risks were reduced to the extent possible and that additional modifications were not likely to afford further reductions.Conclusions:The results from these studies demonstrated accurate dosing over the dose range (0.5-30 units) at different temperatures and conditions with an injection force that should accommodate the intended users. Use safety and usability in patients with diabetes, caregivers, and health care professionals were validated. The added convenience of this new half-unit, prefilled pen may ease the burden of diabetes management for patients who require smaller incremental dosing.

Background: Physical manipulation of the manufactured dose form is a common practice, with almost a quarter of all drugs administered in primary care having their dose altered. Splitting a tablet can be advantageous as it facilitates swallowing, allows for dose flexibility and provides cost reductions. However, there are concerns these physical changes can lead to inaccurate portions resulting in significant variations from the prescribed dose. Thus, the review described in this protocol aims to summarise the literature assessing the effect of tablet splitting on dose accuracy. Methods: Relevant studies will be identified through electronic searches in databases including EMBASE, MEDLINE, CINAHL, and the Cochrane Library, from the beginning of databases until January 2020. Studies investigating any drug, where the tablet was split, will be potentially eligible. Two reviewers will independently screen studies and extract data using standardised forms. Data extracted will include general study information, characteristics of the study, intervention characteristics and outcomes. Primary outcome is to assess dose accuracy of a split tablet measured by drug content or weight variability. Assessment of risk of bias will be dependent upon study design. If deemed feasible, meta-analysis will be performed. Results: The study described within this protocol will provide a synthesis of current evidence assessing the effect of tablet splitting on dose accuracy. Conclusion: The conclusion of our study will provide evidence to judge whether splitting a tablet results in an accurate half dose. Ethics and dissemination: Ethics approval was not required for this study. The results of the systematic review described will be published in a peer-reviewed journal. Registration details: PROSPERO CRD42018106252

Objective. To demonstrate the impact of an extended intervention on the dose accuracy and consistency of a compounded zonisamide suspension. Methods. A laboratory exercise was initially conducted by pharmacy students to determine the beyond-use date (BUD) of a compounded zonisamide suspension. The student results were inconsistent with data in a published reference study. The exercise was repeated several times testing various hypotheses to explain the inconsistency. The final hypothesis was the student techniques of shaking and sampling their suspensions resulted in inaccurate samples. Therefore, a final hypothesis study was designed to include an extended intervention (weeks 5-7) that would demonstrate the impact of explicit verbal and visual instructions on the proper shaking and sampling of suspensions on dose accuracy and consistency. Results. The initial study found that students’ weekly average zonisamide potencies ranged from 71%-122% of label, with a relative standard deviation (RSD) of 17%-53%; weekly potencies in the reference study had ranged from 92%-105%. In the final hypothesis study before the extended intervention, dosing accuracy ranged from 64%-111% (RSD 17%-76%). During the 3 week long intervention, dosing accuracy became 91%-118% with a RSD of 5%-29% which were consistent with the reference study. Conclusion. Providing more explicit auditory and visual instructions to pharmacy students regarding the proper shaking and sampling techniques of their compounded suspensions resulted in more consistent and accurate dosing of a zonisamide suspension. By implication, pharmacists providing specific and personalized instructions to patients should reduce their self-dosing inconsistencies at home.

Concerns about uniformityand the accuracy of the doses resulting from tablet manipulation havepreviously been reported. When aspirinis required to treat children, an oral liquid is not readily available,therefore health care providers or parents are required to manipulate aspirintablets to produce the appropriate dose. In this work, aspirin 75mg dispersible tablets were dispersed in a rangeof waters (room temperature and warm deionized and tap water and sparklingwater) and the dose accuracy was measured. The impact of temperature on the dose accuracy for the tap water wasless pronounced yet there was overall lower accuracy compared to the deionisedwater. Dispersion of the tablet in sparkling water does not give an accuratedose. Heatingfluid used in dispersion is practically achievable yet deionized water in thehome or a ward is impractical. Sparklingwater should be avoided when dispersing aspirin tablet. Thereis a need to evaluate the apparatus and methods used to manipulate medicinesfor children as both the water used and the tools to undertake the manipulationhave significant effects on the accuracy of the dose obtained.

Background Manipulation of drug formulations to achieve an appropriate dose is often necessary in the paediatric ward (e.g crushing and dispersion of tablets, followed by extraction of a fraction). However, such manipulation has previously been shown to result in inaccurate dosing for some tablet formulations of the poorly soluble anticoagulant aspirin. Using the same manipulation procedure, a dispersible tablet formulation of aspirin yielded 99% of the intended dose while a chewable tablet yielded only 9%.1 Warfarin is another anticoagulant used in paediatric care. Despite having good solubility, ensuring a reliable dose of this substance is important, considering the narrow therapeutic index of the drug. Purpose To investigate the dose accuracy and dose precision attained after manipulation of two different warfarin tablets, using validated ultra high-performance liquid chromatography (UHPLC-analysis). Material and methods Warfarin tablets: Marevan (2.5 mg; Takeda AS, Norway) and Warfarin Orion (2.5 mg; Orion Pharma, Finland). Instrument: UHPLC-system from Shimadzu Corp (Nexera, with Prominence DAD-detector). Analytical column: Inertsil 2 µm C8–3, 2.1 × 100 mm, (GL Sciences Inc., Tokyo, Japan). The analytical method was validated for linearity, precision and specificity. Dosing accuracy study: six tablets from each of the two formulations were individually dissolved in 10 ml water. After 8 min, a sample (1 ml) was withdrawn. Dosing accuracy and precision was recorded and compared between formulations. Results For Warfarin Orion (2.5 mg) 96.5% (SD 4.8; range 89.8%–101.4%) of the intended dose was found. For Marevan (2.5 mg) 101.4% (SD 4.2; range 96.3%–107.2%) of the intended dose was found. Conclusion Using a validated UHPLC-method, the dosing accuracy upon dispersion and dose extraction from two warfarin tablets (Marevan and Warfarin Orion) was found to be both accurate and precise – unlike that which had previously been published for different aspirin tablets. These results underline the importance of considering both formulation and drug characteristics when manipulating tablets. References and/or acknowledgements 1. Notaker N, Brustugun J, Tho I, Bjerknes K. Manipulation and formulation – the tale of two aspirin tablets. Poster abstract. EAHP 2016. No conflict of interest.

Background Cytostatic drugs are increasingly being prepared with a cytostatic robot, though it is not known whether the dose of the final product is more accurate after automated or manual preparation. This study is the first to compare accuracy and precision of automated preparations with manual preparations by measuring volumes and drug concentrations. Methods The accuracy and precision of automated and manual preparations were compared by gravimetric and concentration measurements. During ten days 80 solutions were prepared; 40 robot preparations and 40 manual preparations. With both preparation methods, 20 methotrexate (MTX) and 20 cyclophosphamide (CP) bags were compounded. We simulated normal working conditions by performing the preparations on Monday till Friday. The MTX and CP concentrations were measured with validated ultra high performance liquid chromatography (UHPLC) methods on the last preparation day. Results With UHPLC analysis, dose accuracy (mean dose error) of robotic or manual preparation of MTX were 1.70% and 0,96% respectively. With gravimetric analysis, these values were 0.50% and 1.96%. Precision (standard error) of the robotic preparation for MTX was significantly smaller than that of manual preparation (p Dose accuracy (mean dose error) of robotic or manual preparation of CP, with UHPLC analysis, were 6.10% and 5.20% respectively. With gravimetric analysis, these values were 0,67% and 0,18%. Conclusion We conclude that both robotic and manual compounding produce accurate cytostatic products in which the mean percentage of active substance differs by less than 10% from the prescribed amount. Both preparation methods are compliant with the Dutch Medicines Act and the European Pharmacopoeia.

This study explores the methodology advised by healthcare professionals and the methods used by parents/carers to identify whether there is a best practice method for manipulation of 10 mg hydrocortisone tablets to provide an accurate dose to children. Bespoke surveys were used to identify methods recommended and used in manipulation of tablets. Hydrocortisone tablets were manipulated to provide a specified dose by both naïve participants and parents/carers. The accuracy of manipulation was assessed using HPLC analysis. Competed surveys were received from 159 parent/carers reporting doses that ranged from 0.25 to 15 mg. Parents/carers most commonly reported splitting the tablet and administering the solid fraction; however more than 30% of those reporting physically splitting tablets were preparing doses that were not simply halving or quartering tablets. In a naïve population the dose accuracy, defined as percent of doses within 20% of the theoretical dose ranged from 57 to 58% depending on the tablet brand and the method of manipulation used. Almost three-quarters (74.1%) of parent/carers (n = 27) were able to produce a dose within 20% of the theoretical value and the most accurate method was to split tablets and administer the solid fraction. This study shows that a lack of age-appropriate medicines results in children being at risk of sub-optimal dosing.

Evaluation of drug use is a quality assurance process that is carried out continuously, organizational structured and recognized to ensure that the drug is used appropriately and effectively. Until recently, Jayapura city is still as a malarial endemic area. In 2012, the number of malaria cases are malarial tertiana 8.535 (39%) cases, malarial tropical 12.256 (57%), malarial mix (tertiana+tropical) 612 (2,84%) and malarial quartana 73 (0,33%). The highest percentage of malarial cases in the Jayapura city is caused by Plasmodium falciparum. The aims of this study are to evaluate the drug use and the dose accuracy of antimalarial drugs in the General Hospital of Abepura from July to December 2014. This is a descriptive study conducted by a retrospective review of medical records of patients. The results of the study concluded that the highest incidence rates occurred in the male (59.04%) and lowest in women (40.96%), 15-25 years of age (57.8%), 26-35 years of age (27.7%) and 36-45 years of age (14.5%). The dose accuracy for antimalarial drugs (100%) indicated that antimalarial drugs used are Primaquine, Artesunate injection and Dihydroartemisin + piperaquine (DHP) or Darplex. Key words: Abepura hospital, antimalarial drug, Jayapura, malaria

A basal bolus insulin regimen requires multiple daily insulin injections, which might discourage patient adherence. As a potential solution, a mealtime insulin-delivery system-a 3-day wearable bolus-only patch-was designed to manually administer mealtime insulin discreetly by actuating buttons through clothing, without the need for multiple needle sticks.Extensive functional testing of the patch included dose accuracy (from initial fill of the device to empty), pressure-vacuum leak testing, last-dose lockout and occlusion detection (safety alert features that lock the dosing buttons when no insulin is delivered), assessments of insulin drug stability, toxicological risk (including chemical testing), and system biocompatibility.Dosing accuracy was 2 units ±10% (with U-100 insulin) over a range of environmental conditions, with ≥95% reliability and confidence. The fluid seal performance and the safety alert features performed with ≥95% reliability and ≥95% confidence. The system met acceptable standards for insulin (U-100 lispro and aspart) stability for its intended 3-day use, in addition to the operational requirements. The toxicological risk assessment and demonstrated biocompatibility suggested that the patch is safe for human use.Benchtop performance showed that the bolus-only patch is a safe, accurate, and reliable device for mealtime insulin delivery.

Background: The functional performance of the JuniorSTAR® (Sanofi, Paris, France) half-unit insulin pen was evaluated through a series of specific objective tests to assess the dose accuracy, pen weight, injection force, and dialing torque. Method: Pens (n = 60) were tested under standard atmospheric conditions with 3 different types of insulins manufactured by Sanofi (insulin glargine, insulin glulisine, and biphasic insulin isophane). The dose accuracy was tested according to the ISO 11608-1:2012 standards. Injection doses of 0.010, 0.155, and 0.300 ml were evaluated. For mean weight evaluation, the pens without the cartridge were weighed on precision balances. The injection force was measured using a texture analyzer and the dialing torque was measured using a torque meter. Results: JuniorSTAR met the ISO 11608-1:2012 criteria for dose accuracy as all the delivered doses were within the predefined limits for all types of insulin tested. The mean weight of the JuniorSTAR pen was 33.4 g (SD = 0.075). The mean injection force was 6.0 N (SD = 0.8), 4.3 N (SD = 0.4), and 5.1 N (SD = 0.6) for insulin glargine, insulin glulisine, and biphasic insulin isophane, respectively. The mean dialing torque was 5.09 Ncm (SD = 0.29) and 5.88 Ncm (SD = 0.53) for setting and correcting a dose, respectively. Conclusions: Together with results from a previously reported usability survey, these results show that the JuniorSTAR reusable, half-unit pen is a lightweight and accurate device for insulin delivery with a dialing torque and injection force suitable for young people with type 1 diabetes.

Background Physical manipulation of the manufactured dose form is a common practice, with almost a quarter of all drugs administered in primary care having their dose altered. Splitting a tablet can be advantageous as it facilitates swallowing, allows for dose flexibility and provides cost reductions. However, there are concerns these physical changes can lead to inaccurate portions resulting in significant variations from the prescribed dose. Thus, the review described in this protocol aims to summarise the literature assessing the effect of tablet splitting on dose accuracy. Methods Relevant studies will be identified through electronic searches in databases including EMBASE, MEDLINE, CINAHL, and the Cochrane Library, from the beginning of databases until January 2020. Studies investigating any drug, where the tablet was split, will be potentially eligible. Two reviewers will independently screen studies and extract data using standardised forms. Data extracted will include general study information, characteristics of the study, intervention characteristics and outcomes. Primary outcome is to assess dose accuracy of a split tablet measured by drug content or weight variability. Assessment of risk of bias will be dependent upon study design. If deemed feasible, meta-analysis will be performed. Results The study described within this protocol will provide a synthesis of current evidence assessing the effect of tablet splitting on dose accuracy. Conclusion The conclusion of our study will provide evidence to judge whether splitting a tablet results in an accurate half dose. Ethics and dissemination Ethics approval was not required for this study. The results of the systematic review described will be published in a peer-reviewed journal. Registration details PROSPERO CRD42018106252.

In the study, 10 prostate IMRT plans were prepared to be treated lineer accelerator. These plans were transfered to the water equivalent solid phantom for quality control (QC) plans of each patient. QC plans, gantry, collimator and table angles of original and 0 degrees were created in two different ways. The measurements were performed using film and ion chambers with different volumes at 5 cm depth. Doses obtained with measurement methods, were compared by calculated doses in TPS.

Objectives To assess the pyridoxal 5′-phosphate (PLP) content and stability of extemporaneous PLP liquids prepared from dietary supplements used for the treatment of vitamin B6-dependent epilepsy. Methods Pyridoxal 5′-phosphate liquids were prepared in accordance with the guidelines given to patients from marketed 50 mg PLP dietary capsules and tablets. The PLP content and its stability were evaluated under conditions resembling the clinical setting using reverse phase HPLC and mass spectrometry. Key findings Pyridoxal 5′-phosphate content in most of the extemporaneously prepared liquids from dietary supplements was found to be different from the expected amount (~16–60 mg). Most of these PLP extemporaneous liquids were stable at room temperature (protected from light) after 24 h but unstable after 4 h when exposed to light. A key photodegradation product of PLP in water was confirmed as 4-pyridoxic acid 5′-phosphate (PAP). Conclusion Pyridoxal 5′-phosphate tablets from Solgar® were found to be the most reliable product for the preparation of extemporaneous PLP liquids. This work highlighted the difference between the marketed PLP dietary supplements quality and the importance of proper storage of aqueous PLP. There is a need to develop pharmaceutical forms of PLP that ensure dose accuracy and avoid potentially unsafe impurities with the aim of enhancing safety and compliance.

The HumaPen Luxura HD insulin pen (Eli Lilly and Company, Indianapolis, IN) was originally designed to deliver accurate doses in half-unit increments from 1 to 30 units. Laboratory testing examined the accuracy of the initial 0.5-unit dose within a 95/95% tolerance interval with respect to a specification of +/-0.5 unit (+/-0.005 ml).After priming, operators recorded the first 0.5 unit. Data were analyzed using k-value targets.While examining 577 half-unit doses per device lot, test temperature, operator, or test liquid, at least 95% of the doses were accurate with 95% confidence. All data points were within +/-0.5 unit (+/-0.005 ml).Dose accuracy of the initial half-unit is achieved with the HumaPen Luxura HD insulin pen.

FlexPen® is a widely used, prefilled, insulin-delivery pen for patients with Type 1 or Type 2 diabetes. Well-designed trials suggest that FlexPen is more accurate than other prefilled pens at high, medium and low doses. Furthermore, FlexPen is preferred to the vial-and-syringe method by patients, but comparisons of patient preference for modern pens are currently lacking. Next Generation FlexPen® has similar accuracy to FlexPen but has improved patient perception. FlexPen improves adherence and reduces costs compared with the vial-and-syringe method, but the relative adherence and/or cost benefits of different pens are unknown. Important improvements in Next Generation FlexPen include: a significantly reduced injection force (that is lower than the injection force of other prefilled pens) and clearer labeling for insulin-type differentiation. Current evidence suggests that FlexPen and Next Generation FlexPen are an attractive choice when considering insulin-delivery methods.

Background: Modern insulin injection pens provide a convenient and accurate way for diabetes patients to inject insulin. They have widespread use among children and adults with type 1 and type 2 diabetes in the U.S. and Europe. This study compared the dosing accuracy of four commonly available insulin pens (OptiClik ® and SoloSTAR ® from sanofi-aventis, FlexPen ® from Novo Nordisk, and HumaPen ® LUXURA™ from Eli Lilly). Methods: The dosing accuracy was tested for all pens with 24 x 10 IU and 9 x 30 IU injection volumes to investigate whether the pens complied with the acceptable International Organization for Standardization (ISO) limits of 10% (± 1 IU) for 10 IU and 5% (± 1.5 IU) for 30 IU. The doses were each applied with a new needle strictly according to the instructions for use by the pen manufacturers. A pharmaceutical balance was used for the assessment of the applied volumes, and the results were corrected for the specific density of the insulin formulations. Four insulin pens (two each from different production lots) were used for each of the two volumes, resulting in a total of 192 doses per pen with 10 IU, and 72 doses per pen with 30 IU. Results: FlexPen (mean absolute percent deviation for 10 IU and 30 IU: 1.64 ± 0.84% and 0.83 ± 0.26%, respectively) and HumaPen LUXURA (1.10 ± 0.20% and 0.62 ± 0.19%; not significant versus FlexPen for both doses) were more accurate than the OptiClik (4.78 ± 3.31% and 2.97 ± 2.48%, p

A new type of rubber plug reduces leakage in the Lantus® OptiClick® 300 insulin pen (Sanofi Aventis K.K. ; n-OPC).In order to evaluate this improvement, using a questionnaire, we asked patients whether they had experienced leakage with the pen having the previous rubber plug (o-OPC) as well as concerning the effect of such leakage. Twenty-seven outpatients with diabetes provided responses.In Japan, the pre-filled insulin pen product NovoRapid FlexPen® (Novo Nordisk Pharma K.K. ; FLX) is widely used. As basic testing, we examined the material and structure of its rubber plug, and conducted an insulin injection accuracy test and a puncture resistance test. We also assessed the n-OPC to see how much it prevented the leakage that frequently occurred with the o-OPC. We compared the elasticity of plugs, conducted a puncture resistance test and an accuracy test, and compared how well they fit in the pens.The responses to the questionnaire indicated that leakage increases patient anxiety and required preventive measures to be taken as early as possible. The results of the basic testing showed that there were no problems with the FLX but the o-OPC had problems with regard to all test parameters. For the n-OPC, while the new plug material helped prevent leakage, there were still various points of the product that required improvement.

To attain effective and safe pharmacotherapy in neonates, caregivers have to consider both the clinical characteristics of the newborn and the pharmacokinetic estimates of a given compound during prescription and administration. Overall, clearance in neonates is low when compared to other pediatric subpopulations. Despite this overall low clearance, there is already extensive between individual variability in clearance in early life. As a consequence, neonates are in urgent need of tailored drug product development that considers the need for both low and flexible dosing to maintain dose accuracy. During the development of such formulations tailored for neonates, there is also a need for guidance on excipient exposure. The available knowledge on the safety or toxicity of excipients is limited and difficult to retrieve, but there are initiatives (e.g. Safety and Toxicity of Excipients for Pediatrics [STEP] database initiative) to improve the present situation. In addition, population focussed studies on aspects of clinical pharmacology of excipients in neonates should be conducted. The propylene glycol research project and the European Study for Neonatal Excipient Exposure (ESNEE) initiative illustrate its feasibility. Finally, until tailored formulations make it to the market, compounding practices for drug formulations in neonates should be evaluated to guarantee correct dosing, product stability, safety and to support pharmacists in their daily practice. ispartof: Current Pharmaceutical Design vol:21 issue:39 pages:5674-5679 ispartof: location:United Arab Emirates status: published

Pen injectors for the administration of insulin have been available since the 1980s. The first insulin pen, NovoPen®, was introduced by Novo in 1985 (http://www.novonordisk.com/about_us/history/step-by-step.asp). In the years since, insulin pens have seen innovation in both features and functionality, and many more manufacturers have entered the market. This analysis discusses several features and design alternatives of insulin pens and comments on a new study by Bohnet and coauthors in this issue of Journal of Diabetes Science and Technology that compared the dosing accuracy of the spring-driven FlexTouch® (FT; Novo Nordisk; insulin aspart) with that of the manually operated SoloSTAR® (Sanofi; insulin glulisine). The volumetric flow rate of insulin delivery with FT was also evaluated.

In radiotherapy gel dosimetry a humanoid phantom is irradiated according to the planned treatment of a patient. This results in a three-dimensional dose distribution. In order to read-out the gel dosimeter phantom, magnetic resonance imaging (MRI) is often used. Due to specific disturbances both the spatial and the dose reliability can be compromised. It is essential that the measurement sequence is optimized and that possible imaging artifacts are compensated in such a way that the proposed spatial and dose accuracy are met. In this review, several sources of disturbances are treated and compensation strategies are proposed. A code of good practice for the read-out technique is proposed. Finally, a tool for quality control of the imaging sequence is presented.

This article reviews the concept of using the proper methods for the proper task, in this case measuring dose-to-dose accuracy of continuous subcutaneous insulin infusion pumps.

Dose accuracy and injection force, representing key parameters of insulin pens, were determined for three pens delivering insulin glargine-based copies, Pen Royale (WR) and DispoPen (WD) for Glaritus® (Wockhardt) and GanLee Pen (GL) for Basalin® (GanLee), compared with pens of the originator, ClikSTAR® (CS) and SoloSTAR® (SS) for Lantus® (Sanofi).Using the weighing procedure recommended by DIN EN ISO 11608-1:2000, dose accuracy was evaluated based on nonrandomized delivery of low (5 U), mid (30 U), and high (60 U) dosage levels. Injection force was measured by dispensing the maximum dose of insulin (60 U for the GL, WR, and WD; 80 U for the SS and CS) at dose speeds of 6 and 10 U/s.All tested pens delivered comparable average doses within the DIN EN ISO 11608-1:2000 limits at all dosage levels. The GL revealed a higher coefficient of variation (CV) at 5 U, and the WR and WD had higher CVs at all dosage levels compared with the CS and SS. Injection force was higher for the WR, WD, and GL compared with the CS and SS at both dose speeds. In contrast to the CS and SS with an end-of-content feature, doses exceeding the remaining insulin could be dialed with the WR, GL, and WD and, apparently, dispensed with the WD.All pens fulfilled the dose accuracy requirements defined by DIN EN ISO 11608-1:2000 standards at all three dosage levels, with the WR, WD, and GL showing higher dosage variability and injection force compared with the SS and CS. Thus, the devices that deliver insulin glargine copies show different performance characteristics compared with the originator.