Autoinjector Research Articles

The report of a new Teriparatide auto injector

The report of a new Teriparatide auto injector

Tezepelumab Pharmacokinetics, Safety, and Tolerability After Administration via Vial-and-syringe, Accessorized Prefilled Syringe, or Autoinjector: A Randomized Trial in Healthy Volunteers

PurposeTezepelumab is an anti–thymic stromal lymphopoietin monoclonal antibody therapeutic in development for patients with severe, uncontrolled asthma. In ongoing Phase III studies, tezepelumab is administered via subcutaneous (SC) injections using a vial-and-syringe (V–S). This study compared the pharmacokinetic (PK) parameters, safety, and tolerability of tezepelumab administered subcutaneously via V–S versus via an accessorized prefilled syringe (APFS) or autoinjector (AI). MethodsThis single-center, randomized, open-label, parallel-group study was conducted in healthy volunteers aged 18–65 years. Participants, stratified according to weight (50 to <70 kg, 70 to <80 kg, or 80–90 kg), were randomized evenly to 9 groups representing injections to the abdomen, thigh, or upper arm via V–S, APFS, or AI. Tezepelumab PK parameters over 113 days were evaluated after a single 210-mg SC dose. The primary end points were comparison of Cmax and AUC0–∞ between device groups. Further PK parameters, immunogenicity, safety (including injection site reactions [ISRs] and injection site pain [visual analog scale]) were also assessed. FindingsA total of 315 adults were randomized to treatment. Geometric mean ratios for comparisons between device groups of Cmax, AUC0–∞, and AUC0–last were close to 1, with 90% CIs all within the range of 0.8–1.25, meeting bioequivalence criteria. PK variables were also similar between devices across injection sites and weight categories. Across devices, thigh injection resulted in slightly higher exposure than upper arm injection, and abdomen injection resulted in exposure similar to or slightly lower than thigh injection; however, these differences were not clinically meaningful. Treatment-emergent anti-tezepelumab antibodies were present in 3 (2.9%), 1 (1.0%), and 0 participants in the V–S, APFS, and AI groups, respectively. Treatment-related adverse events were reported in 15.0% of participants overall (V–S, 10.7%; APFS, 18.1%; AI, 16.0%), including ISRs in 1 (1.0%), 3 (2.9%), and 3 (2.8%) participants in the V–S, APFS, and AI groups. Median visual analog scale pain score (0–100 mm scale) was 2 mm immediately after injection and was 0 mm at 30 min for all groups. ImplicationsTezepelumab PK parameters after a single 210-mg SC dose were comparable when administered via V–S, APFS, or AI. In all groups, immunogenicity rate and injection site pain were low, and ISRs were uncommon. These findings support administration of tezepelumab via APFS or AI, in addition to V–S, providing patients and physicians with greater choice and the potential convenience of at-home use. ClinicalTrials.gov identifier: NCT03989544.

Estimation of measurement uncertainty for the quantitative analysis of pharmaceutical residues in river water using solid-phase extraction coupled with injector port silylation-gas chromatography-tandem mass spectrometry

Measurement uncertainty (MU) is associated with analytical methods; it enhances the confidence of the method and helps in improving the quality of the analytical results. The present study aims to estimate MU of an analytical method used for analyzing the pharmaceutical residues in river water by using solid-phase extraction (SPE) followed by auto injector port silylation coupled with gas chromatography-tandem mass spectrometry (IPS-GC-MS/MS) system. The SPE conditions were optimized by using design of experiments approach (Plackett-Burman Design and Central Composite Design); top-down and bottom-up approaches were used for the estimation of MU. The calibration curves of all pharmaceutical residues showed dynamic linearity in the concentration range of 10–2000 ng/L with coefficient of determination (R2) ranging between 0.985 and 0.999. The limit of detection, limit of quantification, and recovery were found to be in the range of 2.52–7.31 ng/L, 8.33–24.12 ng/L and 81.82–114.14%, respectively. The method robustness was found within acceptation limit (<15% RSD) for system suitability. The expanded uncertainty was estimated in the range of 1.28–32.96% for the SPE method. Precision and recovery were identified as major uncertainty sources of SPE-IPS-GC-MS/MS method for the analysis of pharmaceutical residues in river water.

Mistaking an Auto-injector for a Ballpoint Pen.

Mistaking an Auto-injector for a Ballpoint Pen.

SAT0634-HPR PATIENT-REPORTED OUTCOMES REGARDING TWO FORMS OF METHOTREXATE AUTOINJECTORS IN RHEUMATOID ARTHRITIS: AN INTERNATIONAL CROSS-OVER SURVEY.

Background:Several types of methotrexate (MTX) autoinjectors (AI) are currently marketed in rheumatoid arthritis (RA), yet comparative data are scarce.Objectives:Investigate respective perceptions of patients regarding two marketed forms of MTX AIviaa survey conducted by a global market research company.Methods:Patients with moderate to severe RA treated by one of the two forms of MTX AI were recruited. In each participating country (France, Ireland, United-Kingdom, Spain), the respective proportions of recruited patients were approximately aligned on local market shares. The two investigated devices were: A-AI/ The first MTX AI marketed in Europe: bigger size, with an activation button, without double injection sound-control, with a larger window; B-AI/ The second MTX AI commercialized in Europe: smaller and thinner size, without activation button, with double injection sound-control and a smaller window. Each patient was interviewed during 30 minutes on his or her satisfaction level with the currently used device. Then, they were presented the alternative AI and they could test it on skin-mimicking pads. After this step, the patients were interviewed on the alternative device.Results:100 patients were enrolled over one-month period (A-AI users, n=65; B-AI users, n=35). Overall, 61% of A-AI users reported that B-AI was “better” or “much better” whereas 43% of B-AI users judged A-AI as “better” or “much better”. When B-AI users were asked to evaluate convenience elements of A-AI, recognition of injection ending, general design and ease of use were the indicators that were the most poorly judged (60%, 54%, and 46% respectively). When A-AI users were cross-tested for B-AI, injection mode, general feeling, and ease of use were the three items providing the greatest satisfaction (80%, 77%, and 75%, respectively). When they were asked about the characteristics of their usual device, the button, the design of the device and discomfort associated with the injection were the most dissatisfactory elements (30%, 31%, 34% respectively). Also, 73% of A-AI users reported being interested in trying B-AI while 26% of B-AI users replied being so.Last, 95% of B-AI users declared being “very satisfied” or “totally satisfied”, with ease of use and recognition of injection ending being the most attractive items (94% and 95% of high or full satisfaction respectively).Conclusion:In this international cross-over survey, the newest autoinjector on the market, B-AI has shown to exhibit better reported outcomes with respect to ease of use and recognition of the end of the injection and other tested indicators.Treatment of patients with RA should aim at the best care and must be based on a shared decision between the patient and the rheumatologist.1In this scope, the shared decision making is permitted when the patient agrees with the choice of treatment (medication, administration route, device, etc.). Patient’s involvement in decision making is assumed to lead to improvement in health outcomes such as a better adherence to the treatment.2

Why Do the Majority of Submissions for Bridging from a Prefilled Syringe to an Autoinjector Include Bioequivalence Studies in Order to Demonstrate Comparability?

A recent paper reviewed clinical studies intending to bridge a prefilled syringe (PFS) to an autoinjector (AI) based on regulatory submission packages sent to the FDA. An AI generally uses the identical PFS within the AI and the AI typically results in a more consistent injection than can be achieved with a PFS. It is noted that several studies submitted to the FDA did not demonstrate bioequivalence (BE) between the PFS and AI, yet the products were approved anyway. The author of this Commentary believes that formal BE studies should not be required for such bridging studies.

Epinephrine pens (Emerade) recalled in UK due to autoinjector fault

Epinephrine pens (Emerade) recalled in UK due to autoinjector fault

An open-label, randomized, single-dose, two-period, two-treatment crossover bioavailability study comparing 5 mg/0.5 mL of intramuscular naloxone hydrochloride to 2 mg/0.4 mL intramuscular naloxone hydrochloride autoinjector in healthy subjects.

Naloxone is an opioid antagonist used for the acute treatment of opioid overdoses. There has been a dramatic increase of deaths due to synthetic opioids such as fentanyl, some requiring multiple doses of naloxone for reversal of opioid tox-icity. Fentanyl appears to differ from other opiates as having a very rapid onset and transport in and out of the central nervous system (CNS). Fentanyl is therefore widely distributed in the CNS. Furthermore, a high range of systemic levels of fentanyl have been observed in overdose victims. Taken together, we believe it is very likely that higher doses of naloxone are needed to combat this new era of overdoses. We examined the bioavailability of an investigational 5 mg intramuscular naloxone in a prefilled syringe (PFS) compared to 2 mg intramuscular naloxone in an autoinjector (AI) at the current approved dose in a crossover design which included 14 healthy subjects. Overall, both doses were well tol-erated with no adverse events noted during the trial. The pharmacokinetic results showed that a higher dose of intra-muscular naloxone hydrochloride increases Cmax, AUC, and t1/2; however, Tmax was similar for both treatments. Statistical analysis indicated that there were statistical differences between the test and reference treatments for Cmax, AUCs, and t1/2 with ratios of test to reference for Cmax of 337.1 percent (CI: 263.3 percent, 431.5 percent), AUC0-t of 277.5 percent (CI: 260.4 percent, 295.7 percent), AUC0-inf of 273.4 percent (CI: 255.6 percent, 292.4 percent), and t1/2 of 110.5 percent (CI: 95.5, 127.9). These results are consistent with the study rationale that indicated higher doses of intramuscular naloxone hy-drochloride would result in higher Cmax and AUCs. These PK characteristics may be desirable for reversing opioid toxicity caused by the higher, more potent synthetic opioids.

Systematic Review of Device Parameters and Design of Studies Bridging Biologic-Device Combination Products Using Prefilled Syringes and Autoinjectors.

Biologic-device combination products using prefilled syringes (PFSs) and autoinjectors (AIs) are popular for biological products administered subcutaneously. Pharmacokinetic (PK) comparability studies commonly provide the scientific data to support introduction of AI presentations via bridging with PFS. A survey of biological products approved by FDA's Center for Drug Evaluation and Research identified 17 biologics license applications (BLAs) with both PFS and AI presentations for subcutaneous (SC) administration, including 16 approved on February 1, 2018, and one with AI presentation under review. A systematic review on the device parameters and the PK comparability studies bridging the two presentations was conducted. Subsequently, whether device parameters or the PK study design may have influenced the PK comparability study results was evaluated. The reported device parameters for AI and PFS are generally consistent across BLAs, whereas the approach to assess PK comparability varied, including the study design. Most PK comparability studies met bioequivalence (BE) criteria. Upon inspection of the studies that did not meet BE criteria, injection depth of AI and the injection site for either AI or PFS were identified as potential influencing factors to the outcome of PK comparability study. This study represents an initial attempt to identify the potential influencing factors on device bridging, including the characteristics of the device and the clinical pharmacology study. These findings may inform the combination product development strategy, specifically design considerations for device and PK comparability studies.

P406 Adherence, acceptability and serum trough concentration of adalimumab autoinjector in quiescent patients with inflammatory bowel diseases

Abstract Background Anti-TNF α antibodies have contributed to the good prognosis in patients with inflammatory bowel diseases (IBDs). Adherence of these drugs affects the treatment effects in patients with IBDs. Recently, the use of an adalimumab (ADA) autoinjector (AI) was approved in Japan. However, the effects of the use of this AI in patients with IBDs are not clear. We elucidated whether the use of an AI for ADA administration improves the adherence to and acceptability of ADA therapy compared with the use of syringe (SYR) type. Methods This was a single-centre prospective observational study approved by the institutional review board of our hospital. Twenty-six quiescent IBD patients, including ulcerative colitis and Crohn’s disease, treated by administration of ADA 40 mg using SYR every other week for &amp;gt;6 months or naive to ADA were enrolled in this study. The patients administered treatment using SYR were switched to an AI. The AI-naive and AI-switched patients were administered ADA treatment using AI for 6 months. The levels of adherence and acceptability, including pain and satisfaction levels, were measured using the visual analogue scale before and after treatment with ADA administered using AI. Serum ADA trough levels were also examined. Results Of the 26 enrolled patients, 1 with selection error, 1 with a rejection of approval and 2 with recurrence were excluded. In total, 24 participants were included in the final analysis. The mean (SD) age of the participants was 12.6 (8.4) years. Of the participants, 54.5% (12/22) were male, 68.2% (15/22) had ulcerative colitis, 27.3% (6/22) used thiopurine and 77.35 (17/22) were administered treatment using SYR. The adherence rate improved after switching to AI. The adherence rate of patients who received maintenance ADA was not significantly different from that of the ADA-naive patients (SYR type: 89.1 ± 12.7 mm, AI-switch: 94.0 ± 8.6 mm, AI-naive: 87.0 ± 21.6 mm, not significant [NS]). According to the acceptability of ADA AI, the pain intensity significantly decreased after switching. It was also significantly lower in the AI-naive group than in the SYR group (SYR: 55.0 ± 24.8 mm, AI-switch*: 87.3 ± 15.4 mm, AI-naive*: 92.2 ± 10.1 mm, *p &amp;lt; 0.01 compared with SYR). The level of satisfaction significantly increased after switching (SYR: 62.6 ± 27.9 mm, AI-switch*: 85.9 ± 12.5 mm, AI-naive: 81.2 ± 20.9 mm; *p &amp;lt; 0.01, compared with SYR). The ADA trough level was not significantly different after switching (SYR: 11.0 ± 9.1 mg/ml, AI-switch: 9.9 ± 5.5 mg/ml, NS). Conclusion ADA administration using AI resulted in significantly improved acceptability without changes in serum ADA trough levels.

STABILITY INDICATING METHOD DEVELOPMENT AND VALIDATION FOR SIMULTANEOUS QUANTIFICATION OF SORAFENIB AND REGORAFENIB DRUG SUBTANCES BY USING RP-UPLC

Objective: The aim of the research work is to develop and validate a novel, sensitive, specific, rapid, accurate, precise and stability indicating gradient reverse phase ultra-performance liquid chromatography (RP-UPLC) method for the quantitative determination of sorafenib and regorafenib drug substances.&#x0D; Methods: Liquid chromatographic method used for the analysis of the anti-cancer drug substances like sorafenib and regorafenib and method was developed and validated by using efficient chromatographic separation method and was achieved with the use of acquity UPLC system was used consisting of quaternary pump, photodiode array detector an auto injector and on line degasser.&#x0D; Results: The separation was achieved using acquity UPLC BEH C18, 1.7 µm.2.1×50 mm analytical column at 30 °C employing a gradient elution. Empower software was used for data acquisition. During method validation all the parameters were evaluated as per ICH guidelines, which remained well within acceptable limits. Degradation of the drug substances was found to be stable to acidic, aqueous, basic hydrolysis, thermal hydrolysis and photolytic stress condition and the tests solution of the drug substance was found to be stable up to 24 h.&#x0D; Conclusion: The results of linearity, precision accuracy and specificity were proved to be within the limits. This method can be employed in routine analysis for simultaneous estimation of sorafenib andregorafenib drug substances in quality formulations and dissolution studies.

Human factors validation for a rheumatoid arthritis auto-injector for the adalimumab biosimilar FKB327

Rheumatoid arthritis (RA) is a chronic autoimmune disorder, often treated with adalimumab. This study was designed to validate usability of the adalimumab biosimilar FKB327 auto-injector (AI) and document risk associated with the device. A total of 136 participants were enrolled, including patients with RA, caregivers of patients with RA, and healthcare providers of patients with RA. Use errors and close calls were evaluated during 2 simulated injections. A full dose was administered by 90.4% and 97.8% of users for the first and second injections, respectively. The most common use errors were failure to squeeze injection site, check expiration date, check medication in viewing window, and rotate injection site during the second injection. The device, packaging, and instructions received favourable user ratings. FKB327-AI is an easy-to-use device for patients with RA, their caregivers, and healthcare providers. Errors that could lead to incorrect dose were infrequent and not associated with serious harm.

Epinephrine Auto-Injector Needle Length (Does Height or BMI add Valuable Information in Adults?)

Background: Some overweight and obese adults have an increased risk of subcutaneous injection using epinephrine auto injectors (EAIs). Needle lengths of EAIs vary between brands and lots. Objective: To study if BMI or height adds information to define adults at risk of having intraosseous or subcutaneous injection. Methods: Ninety-nine (99) food allergic adult patients, 32 men and 67 women, 18 – 72 years of age, prescribed EAIs were included. The skin to muscle and skin to bone distances were measured by ultrasonography. The effect of injection on naked skin or through thick clothing was analyzed. High and minimal pressure was applied to the ultrasound probe. Results: Two of three men and 1/5 women with BMI &lt;20 had a risk of intraosseous/periosteal injection using the high pressure auto injector Epipen® , thick clothing, 5/8. Injecting through naked skin using the shortest needle, 14/17 obese women had a high risk of subcutaneous injection (overweight 14/23), through thick clothing all 17 obese women would have a risk of subcutaneous injection (overweight 20/23). Injecting with LPEAIs through naked skin, using the shortest needle 8/17 obese and 4/23 overweight women would have a risk of subcutaneous injection, wearing thick clothing, 10/17 obese and 7/23 overweight women. Height had no predictive value. Conclusion: Using high pressure EAIs, high BMI predicted a very high risk for subcutaneous injection in women and in some men. Even injection with low pressure EAIs had some risk of subcutaneous injection, especially when injected through thick clothing. Height had no predictive value. Keywords: Auto-injector; epinephrine; intramuscular; subcutaneous; intraosseous; skin to bone distance; skin to muscle distance; clothing; overweight; obese; adults; women; men.

The SYDNEY Device Study: A Multicenter, Randomized, Open-label Usability Study of a 2-mL Alirocumab Autoinjector Device

PurposeThe proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has produced significant reductions in LDL-C at a dose of 300 mg q4w administered as 2 separate 150-mg injections via a 1-mL autoinjector (AI). A recently developed 2-mL device (SYDNEY) permits the administration of a single 300mg dose of alirocumab. MethodsWe assessed the usability and product technical complaints (PTCs) reported by patients using the 2-mL SYDNEY device in unsupervised settings, adverse events, and effects on LDL-C, in a multicenter, randomized, open-label, 16-week study conducted in the United States. For their first dose, 69 patients with hypercholesterolemia despite receiving statin with or without other lipid-lowering therapy randomly received supervised, self-administered alirocumab 300 mg via 1 × 300 mg injection with the SYDNEY device (n = 35) or 2 × 150-mg injections with the currently approved AI (n = 34). All continuing patients subsequently received unsupervised, self-administered alirocumab 300 mg q4w using the SYDNEY device at weeks 4, 8, and 12. The primary end point was the proportion of SYDNEY device–associated PTCs related to the use of the unsupervised injections. FindingsBaseline characteristics between the study arms varied only in a higher percentage of males being randomized to the study arm using the SYDNEY device (74.3%) compared with the AI arm (44.1%). A single PTC was reported during the unsupervised injections (0.5%; 1 of 196 injections; 95% CI, 0.0%–3.2%). This event was classified as patient related as opposed to device related. No PTCs occurred during supervised injections. Mean LDL-C reductions from baseline at week 4 were 66.2% with SYDNEY and 51.2% with the AI; after adjustment for sex differences between groups, mean LDL-C reductions were 63.5% and 53.9%, respectively. LDL-C reductions persisted for 16 weeks. The most common adverse event was upper respiratory tract infection (3 with SYDNEY and 0 with the AI during weeks 0–4). ImplicationsThe SYDNEY device allowed for a single 2-mL injection of alirocumab 300 mg, providing substantial LDL-C reductions with no new product technical issues or no new safety concerns compared with the currently marketed 1-mL AI device. In conclusion, the 2-mL SYDNEY device provides patients with the possibility of injecting the 300-mg alirocumab dose as a single injection. ClinicalTrials.gov identifier: NCT03415178.

A phase 1, randomized, open-label, single-dose study to assess the relative bioavailability of a subcutaneous dose of FKB327 when administered using a prefilled syringe, a prefilled auto-injector, or a vial with disposable syringe in healthy subjects

Background/objectiveFKB327 is a biosimilar of the adalimumab reference product (RP). The primary objective was to assess the relative bioavailability of FKB327 after a single subcutaneous (SC) dose via prefilled syringe (PFS), auto-injector (AI), or vial with a disposable syringe (vial), in healthy subjects.MethodsThis randomized, open-label, parallel-group, single SC-dose study was conducted in 195 healthy male and female subjects who were randomized 1:1:1 to receive FKB327 40 mg via PFS, AI, or vial. The primary pharmacokinetic (PK) parameters, areas under the serum concentration-time curve to the last detectable value (AUC0-t) and extrapolated to infinity (AUC0-∞), and maximum concentration (Cmax), were compared. Relative bioavailability was established if the ratio of geometric least squares (LS) means of the test product was within the predefined bioequivalence (BE) range of 0.80 to 1.25 of the RP for each comparison. Safety and immunogenicity were assessed.ResultsThe mean serum FKB327 concentration-time profiles appeared similar across all 3 presentations. AUC0-t, AUC0-∞, and Cmax were within the predefined BE range for PFS compared with vial, suggesting comparable bioavailability. AUC0-∞ and Cmax of AI compared with vial and PFS were fully contained within BE range, although the upper limit of 90% confidence intervals of the geometric LS means ratios for AUC0-t was slightly high. Treatment-emergent adverse events in all 3 groups were mild, with no new safety concern with FKB327 identified. Similar immunogenicity was observed among administrations.ConclusionAmong all 3 delivery methods, PK characteristics, safety profiles, and immunogenicity were similar.Trial registrationEU Clinical Trials Registry EudraCTN2014–004469-26, registered October 14, 2014.

P309 FORWARD STUDY REPORTS ALMOST 100 % OF CHILDREN WITH FOOD ALLERGIES HAD FILLED EPINEPHRINE PRESCRIPTIONS

In a large prospective multicenter, NIH sponsored, FORWARD trial, we analyzed intake surveys for racial differences in the prescribing of epinephrine auto injectors (EAI), differences in filling habits and if an EAI was filled based on the number of food allergies and other atopic conditions.

Single-Use Autoinjector Functionality And Reliability For At-Home Administration Of Benralizumab For Patients With Severe Asthma: GRECO Trial Results.

PurposeAccessorized prefilled syringes (APFS) have demonstrated functionality and reliability for subcutaneous (SC) delivery, including self-administration, of benralizumab 30 mg in the clinic or at home. The multicenter, open-label GRECO study (NCT02918071) assessed functionality and reliability of a single-use autoinjector (AI) for at-home benralizumab administration by patients or their caregivers.Patients and methodsAdults with severe asthma received benralizumab SC injections at the study site at Weeks 0, 4, and 8. The first dose was administered by health care providers. Patients/caregivers had the option of administering the second dose and were required to administer the third dose under supervision. At Weeks 12 and 16, patients/caregivers administered benralizumab via AI at home. After each administration, patients/caregivers completed questionnaires concerning administration and device functioning. All AI devices used were returned for evaluation.ResultsA total of 595 AIs were used for 121 patients (mean age 48.5 years; 64% female) in the clinic and at home. Of 116 participants, 113 (97.4%; 95% confidence interval [CI]: 92.63–99.46) and 112 (96.6%; 95% CI: 91.41–99.05) successfully administered benralizumab at home at Weeks 12 and 16, respectively; 108 (93.1%; 95% CI: 86.86–96.98) were successful on both occasions. Throughout the study, 10 (1.7%) AI administrations were unsuccessful: 8 (1.3%) because of user error, 1 (0.2%) with undetermined cause, and 1 (0.2%) because of a manufacturing defect. Benralizumab efficacy (assessed by Asthma Control Questionnaire 6 score) and pharmacokinetics for patients using the AI were comparable to published results for patients receiving benralizumab via syringe in a clinical setting. No new or unexpected safety findings were observed.ConclusionAIs were functional, reliable, and performed well in the clinic and at home. Nearly all patients and caregivers successfully administered SC benralizumab via AI. Benralizumab availability in AI and APFS could provide patients with choices for self-administration.

Evaluation of an interprofessional naloxone didactic and skills session with medical residents and physician assistant learners.

Background:The CDC has reported 399,230 opioid-related deaths from 1999-2017. In 2018, the US surgeon general issued a public health advisory, advising all Americans to carry naloxone. Studies show that enhanced naloxone access directly reduces death from opioid overdose. Despite this, health care professional learners report low knowledge and confidence surrounding naloxone. Therefore, it becomes critical that medical education programs incorporate didactic and experiential sessions improving knowledge, skills and attitudes regarding harm reduction through naloxone.Objectives:1. Describe the components and evaluation of a replicable and adaptable naloxone didactic and skills session model for medical providers; 2. Report the results of the evaluation from a pilot session with family medicine residents and physician assistant students; and 3. Share the session toolkit, including evaluation surveys and list of materials used.Methods:In July 2017, a literature search was completed for naloxone skill training examining best practices on instruction and evaluation. A training session for family medicine residents and physician assistant learners was designed and led by University of Cincinnati College of Medicine and College of Pharmacy faculty. The same faculty designed a pre and post session evaluation form through internal review on elements targeting naloxone knowledge, attitude, and self-efficacy.Results:The training session included one hour for a didactic and one hour for small group live skills demonstration in four methods of naloxone administration (syringe and ampule, nasal atomizer, branded nasal spray and auto injector). Forty-eight participants showed statistically significant (p<0.05) improvement in knowledge (67.5% to 95.9%), attitudes (71.2% to 91.2%), and self-efficacy (62.1% to 97.8%) from pre to post assessment. Forty-four of 48 participants agreed that the pace of the training was appropriate and that the information will be of use in their respective primary care practices. Supply costs for the session were USD 1,200, with the majority being reusable on subsequent trainings.Conclusions:Our study of a naloxone didactic and skills session for primary care trainees demonstrated significant improvements in knowledge, self-efficacy, and attitudes. It provides an adaptable and efficient model for delivery of knowledge and skills in naloxone administration training. The pilot data suggest that the training was efficacious.

SIMULTANEOUS DETERMINATION OF BENZYDAMINE HYDROCHLORIDE, METHYLPARABEN AND PEPPERMINT OIL IN A SPRAY DOSAGE FORM BY GAS CHROMATOGRAPHY

Objective: To develop and validate an analytical procedure for simultaneous determination of benzydamine hydrochloride, methylparaben and peppermint oil in a spray dosage form by gas chromatography method (GC).&#x0D; Methods: The analytical method was conducted on Agilent 7890 gas chromatograph, equipped with HP-5 capillary column with helium as a mobile phase, split/splitless injector and flame ionization detector and an auto injector. Validation parameters, such as selectivity, linearity, precision, accuracy and, robustness were estimated.&#x0D; Results: A method for simultaneous determination of benzydamine hydrochloride, methylparaben and peppermint oil in a spray dosage form by GC was developed. The retention time of menthol (marker substance of peppermint oil) methylparaben and benzydamine hydrochloride, was 5.0, 9.2, and 19.4 respectively. Relative standard deviation (RSD)% for precision was 0.24, 0.13 and 0.12 respectively. The linearity of the method for given analytes was estimated in a concentration range of 80-120% to a nominal concentration with the respective correlation coefficients of more than 0.999. Accuracy of the method was within 98-102% for all analytes.&#x0D; Conclusion: The developed analytical procedure meets the acceptance criteria of validation parameters and can be used in quality control laboratories for determination of benzydamine hydrochloride, methylparaben and peppermint oil in a spray dosage form.

Comparison of autoinjector with accessorized prefilled syringe for benralizumab pharmacokinetic exposure: AMES trial results

Objective We compared the pharmacokinetic exposure following a single subcutaneous dose of benralizumab 30 mg using either autoinjectors (AI) or accessorized prefilled syringes (APFS). APFS and AI functionality and reliability for at-home benralizumab delivery have been demonstrated in the GREGALE and GRECO studies, respectively. Methods In the open-label AMES study (NCT02968914), 180 healthy adult men and women were randomized to one of two device (AI or APFS) and three injection site (upper arm, abdomen, or thigh) combinations. Randomization was stratified by weight (<70 kg, 70–84.9 kg, and ≥85 kg). Blood eosinophil counts were measured on Days 1, 8, 29, and 57. Results Benralizumab pharmacokinetic exposure was similar between AI and APFS. Geometric mean ratios (AI/APFS) (90% CI) were 92.8% (87.4–98.6) and 94.5% (88.2–101.2) for two area under the concentration‒time curve measurements (AUClast and AUCinf). Benralizumab exposure was approximately 15–30% greater for thigh vs. abdomen or upper arm administration. Exposure was slightly greater for APFS vs. AI regardless of injection site or weight class. These differences were unlikely to be clinically relevant, as eosinophil depletion was achieved consistently with both devices at all injection sites. No device malfunctions were reported. No new or unexpected safety findings were observed. Conclusion Benralizumab pharmacokinetic exposure was similar between AI and APFS, with consistent blood eosinophil count depletion observed with both devices. These results support benralizumab administration with either AI or APFS, providing patients and physicians increased choice, flexibility, and convenience for potential at-home delivery.