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At SHL Medical in Nacka, Sweden, autoinjectors are developed and during their developmentstage, the autoinjectors are tested on a soft tissue model made of gel. The gel however haschallenges with robustness and customization. To eliminate these challenges, a soft tissuemodel of silicone was created. The aim of this project was to determine whether the twomaterials could generate the same results and, if therefore, the gel model was replaceable. Four different autoinjector models were chosen to be tested on four different silicone modelswith different geometry and stiffness. This was done to obtain a broad observation of how thesilicone performed during testing. All autoinjectors were tested on all different siliconemodels and the gel model to compare their results. We could conclude that the silicone model generates similar results to the gel model and thatthe gel model can be replaced by the silicone model. Additionally, it was concluded whichstiffness and geometry of the silicone model generates the most similar results to the gelmodel. Apart from this, the project gave guidance of how the silicone model can further bedeveloped to better match the gel model., På SHL Medical i Nacka utvecklar man autoinjektorer och gör under utvecklingsprocessentester på en vävnadsmodell av gel. I utvecklingsyfte tog man fram en ny modell av silikonsom skulle kunna ersätta gelmodellen eftersom den hade förbättringspotential inom robusthetoch anpassningsbarhet. Målet med detta projekt var att dra en slutsats kring om den nyasilikonmodellen genererar tillräckligt lika resultat som gelmodellen, för att då kunna byta utgelmodellen mot silikon. Fyra olika modeller av autoinjektorer valdes ut, samt fyra silikonmodeller med olika geometrioch styvhet, för att få en bred bild av hur silikonet presterar under testning. Alla autoinjektorertestades på de olika silikonmodellerna, samt på gelen, för att kunna jämföra dess resultat. Vi kunde efter att ha analyserat alla resultat dra slutsatsen att silikonet kan ersätta gelen ochatt vissa silikonmodeller fungerar bättre än andra. Projektet gav också vägledning till hursilikonmodellerna kan fortsätta utvecklas och anpassas för att ännu bättre efterlikna gelen.

At SHL Medical in Nacka, Sweden, autoinjectors are developed and during their developmentstage, the autoinjectors are tested on a soft tissue model made of gel. The gel however haschallenges with robustness and customization. To eliminate these challenges, a soft tissuemodel of silicone was created. The aim of this project was to determine whether the twomaterials could generate the same results and, if therefore, the gel model was replaceable. Four different autoinjector models were chosen to be tested on four different silicone modelswith different geometry and stiffness. This was done to obtain a broad observation of how thesilicone performed during testing. All autoinjectors were tested on all different siliconemodels and the gel model to compare their results. We could conclude that the silicone model generates similar results to the gel model and thatthe gel model can be replaced by the silicone model. Additionally, it was concluded whichstiffness and geometry of the silicone model generates the most similar results to the gelmodel. Apart from this, the project gave guidance of how the silicone model can further bedeveloped to better match the gel model., På SHL Medical i Nacka utvecklar man autoinjektorer och gör under utvecklingsprocessentester på en vävnadsmodell av gel. I utvecklingsyfte tog man fram en ny modell av silikonsom skulle kunna ersätta gelmodellen eftersom den hade förbättringspotential inom robusthetoch anpassningsbarhet. Målet med detta projekt var att dra en slutsats kring om den nyasilikonmodellen genererar tillräckligt lika resultat som gelmodellen, för att då kunna byta utgelmodellen mot silikon. Fyra olika modeller av autoinjektorer valdes ut, samt fyra silikonmodeller med olika geometrioch styvhet, för att få en bred bild av hur silikonet presterar under testning. Alla autoinjektorertestades på de olika silikonmodellerna, samt på gelen, för att kunna jämföra dess resultat. Vi kunde efter att ha analyserat alla resultat dra slutsatsen att silikonet kan ersätta gelen ochatt vissa silikonmodeller fungerar bättre än andra. Projektet gav också vägledning till hursilikonmodellerna kan fortsätta utvecklas och anpassas för att ännu bättre efterlikna gelen.

Följande examensarbete är skrivet på Kungliga Tekniska Högskolan inom maskinteknik med inriktningen industriell ekonomi och produktion och utförd i ett ingenjörsföretag. ISO standarden 11608–1:2014 listar olika tester som måste genomföras för att få en autoinjektor godkänd för användning. Ett utav testerna är att man släpper autoinjektorn från en bestämd höjd och riktning i fritt fall. Det testet kallas för droptest. Minimikraven för ISO 11608–1 för droptest kan potentiellt ha begränsningar då de inte representerar verkligheten, som exempelvis att en autoinjektor kan falla från höjder och riktningar som inte tillhör minimikraven. Detta kan skapa osäkerheter hur en autoinjektor kan prestera under nödsituationer. Syftet med arbetet är att undersöka ifall man kan öka säkerheten vid användning av autoinjektorer vid nödsituationer, och då har man satt som mål att undersöka ifall det krävs att droptesta mer än minimikravet i ISO-standarden. Detta utförs genom att genomföra olika experiment för att avgöra om ISO-standarden räcker till. Där man experimenterar med att släppa autoinjektorer från högre höjder och fler riktningar samt utför hur detta har påverkat funktionen på apparaterna. Metoden genomförs i företaget, kommer ge data hur funktionen har påverkats. Mer specifikt data på om det krävs mer eller mindre kraft för att dra bort locket. Och data på hur aktiveringen av sprutan har påverkats. Med hjälp av lådagram så analyseras värdena då man skapar grafer för att hitta olika trender som kan uppstå. Resultatet efter genomföranden och analysen blev det att inga tydliga trender uppstod och inga tydliga indikationer att det krävs att drop testa över minimikravet. Däremot kan analysen från detta examensarbete användas som underlag vid diskussioner och planering av droptest på företaget, The following thesis will give the reader a better understanding about autoinjectors and drop tests. ISO standard 11608-1:2014 lists various tests that must be carried out to get an autoinjector approved for use. One of the tests is to drop the autoinjector from a certain height and direction in free fall. That test is called a drop test. The minimum requirements of ISO 11608-1 for drop testing can potentially have limitations as they do not represent reality, such as an autoinjector falling from heights and directions outside the minimum requirements. This can create uncertainties in how an autoinjector can perform during emergency situations. The purpose of this thesis is to investigate whether it is possible to increase safety when using autoinjectors in emergency situations, where the goal is to investigate whether droptests from higher heights and different directions are required. This is done by conducting various experiments to determine if the ISO standard is sufficient. Where one first performs dropstests from higher heights and more directions and secondly performs functional testing on the devices to see how they have been affected. The method is carried out in the company and will provide data on how the function has been affected. More specifically, data on whether force is required to pull the lid off. And data on how the activation of the syringe has been affected. Through using boxplots, the values are analysed when creating graphs to find different trends that may occur. The result after implementation and analysis was that no clear trends emerged and there were no clear indications that it is required to drop test above the minimum requirement. However, the analysis from this thesis can be used as a basis for discussions and planning of drop tests for others.

Följande examensarbete är skrivet på Kungliga Tekniska Högskolan inom maskinteknik med inriktningen industriell ekonomi och produktion och utförd i ett ingenjörsföretag. ISO standarden 11608–1:2014 listar olika tester som måste genomföras för att få en autoinjektor godkänd för användning. Ett utav testerna är att man släpper autoinjektorn från en bestämd höjd och riktning i fritt fall. Det testet kallas för droptest. Minimikraven för ISO 11608–1 för droptest kan potentiellt ha begränsningar då de inte representerar verkligheten, som exempelvis att en autoinjektor kan falla från höjder och riktningar som inte tillhör minimikraven. Detta kan skapa osäkerheter hur en autoinjektor kan prestera under nödsituationer. Syftet med arbetet är att undersöka ifall man kan öka säkerheten vid användning av autoinjektorer vid nödsituationer, och då har man satt som mål att undersöka ifall det krävs att droptesta mer än minimikravet i ISO-standarden. Detta utförs genom att genomföra olika experiment för att avgöra om ISO-standarden räcker till. Där man experimenterar med att släppa autoinjektorer från högre höjder och fler riktningar samt utför hur detta har påverkat funktionen på apparaterna. Metoden genomförs i företaget, kommer ge data hur funktionen har påverkats. Mer specifikt data på om det krävs mer eller mindre kraft för att dra bort locket. Och data på hur aktiveringen av sprutan har påverkats. Med hjälp av lådagram så analyseras värdena då man skapar grafer för att hitta olika trender som kan uppstå. Resultatet efter genomföranden och analysen blev det att inga tydliga trender uppstod och inga tydliga indikationer att det krävs att drop testa över minimikravet. Däremot kan analysen från detta examensarbete användas som underlag vid diskussioner och planering av droptest på företaget, The following thesis will give the reader a better understanding about autoinjectors and drop tests. ISO standard 11608-1:2014 lists various tests that must be carried out to get an autoinjector approved for use. One of the tests is to drop the autoinjector from a certain height and direction in free fall. That test is called a drop test. The minimum requirements of ISO 11608-1 for drop testing can potentially have limitations as they do not represent reality, such as an autoinjector falling from heights and directions outside the minimum requirements. This can create uncertainties in how an autoinjector can perform during emergency situations. The purpose of this thesis is to investigate whether it is possible to increase safety when using autoinjectors in emergency situations, where the goal is to investigate whether droptests from higher heights and different directions are required. This is done by conducting various experiments to determine if the ISO standard is sufficient. Where one first performs dropstests from higher heights and more directions and secondly performs functional testing on the devices to see how they have been affected. The method is carried out in the company and will provide data on how the function has been affected. More specifically, data on whether force is required to pull the lid off. And data on how the activation of the syringe has been affected. Through using boxplots, the values are analysed when creating graphs to find different trends that may occur. The result after implementation and analysis was that no clear trends emerged and there were no clear indications that it is required to drop test above the minimum requirement. However, the analysis from this thesis can be used as a basis for discussions and planning of drop tests for others.

Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C-max and AUC(0-20) when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C-max. Two discernable C-max's were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher C-max. There is a dose dependent increase in plasma concentration and AUC(0-20). Most investigators found two C-max's with T-max 5-10 min and 30-50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.

Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C-max and AUC(0-20) when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C-max. Two discernable C-max's were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher C-max. There is a dose dependent increase in plasma concentration and AUC(0-20). Most investigators found two C-max's with T-max 5-10 min and 30-50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.

Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C-max and AUC(0-20) when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C-max. Two discernable C-max's were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher C-max. There is a dose dependent increase in plasma concentration and AUC(0-20). Most investigators found two C-max's with T-max 5-10 min and 30-50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.

Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C-max and AUC(0-20) when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C-max. Two discernable C-max's were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher C-max. There is a dose dependent increase in plasma concentration and AUC(0-20). Most investigators found two C-max's with T-max 5-10 min and 30-50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.

Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C-max and AUC(0-20) when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C-max. Two discernable C-max's were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher C-max. There is a dose dependent increase in plasma concentration and AUC(0-20). Most investigators found two C-max's with T-max 5-10 min and 30-50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.

Background For a century, epinephrine has been the drug of choice for acute treatment of systemic allergic reactions/anaphylaxis. For 40 years, autoinjectors have been used for the treatment of anaphylaxis. Over the last 20 years, intramuscular epinephrine injected into the thigh has been recommended for optimal effect. Objective To review the literature on pharmacokinetics of epinephrine autoinjectors. Results Six studies assessing epinephrine autoinjector pharmacokinetics were identified. The studies, all on healthy volunteers, were completed by Simons, Edwards, Duvauchelle, Worm and Turner over the span of 2 decades. Simons et al. published two small studies that suggested that intramuscular injection was superior to subcutaneous injection. These findings were partially supported by Duvauchelle. Duvauchelle showed a proportional increase in C-max and AUC(0-20) when increasing the dose from 0.3 to 0.5 mg epinephrine intramuscularly. Turner confirmed these findings. Simons, Edwards and Duvauchelle documented the impact of epinephrine on heart rate and blood pressure. Turner confirmed a dose-dependent increase in heart rate, cardiac output and stroke volume. Based on limited data, confirmed intramuscular injections appeared to lead to faster C-max. Two discernable C-max's were identified in most of the studies. We identified similarities and discrepancies in a number of variables in the aforementioned studies. Conclusions Intramuscular injection with higher doses of epinephrine appears to lead to a higher C-max. There is a dose dependent increase in plasma concentration and AUC(0-20). Most investigators found two C-max's with T-max 5-10 min and 30-50 min, respectively. There is a need for conclusive trials to evaluate the differences between intramuscular and subcutaneous injections with the epinephrine delivery site confirmed with ultrasound.

Purpose: Simponi® (golimumab, MSD) is a fully human monoclonal antibody against tumor necrosis factor alpha administered subcutaneously using an autoinjector or a prefilled syringe. This study examined preference for administration of golimumab by autoinjector or prefilled syringe in patients with moderate-to-severe ulcerative colitis (UC). Patients and methods: This was a multicenter, open-label, randomized crossover trial (EudraCT no 2014-000656-29). Patients with moderate-to-severe UC were randomized 1:1 to receive 2 subcutaneous injections of 50 mg golimumab with the autoinjector followed by 2 injections of 50 mg with the prefilled syringe or the same 4 injections administered in the opposite order. Patients assessed preference, ease of use, and discomfort immediately after the injections and 2 weeks later. Results: Ninety-one patients were included (median age=42.7 years [range, 19.7–93.7]; 58% male). The autoinjector was preferred by 76.9% of patients immediately after injections and by 71.4% 2 weeks later. The autoinjector was more often considered extremely easy or easy to use (94.5%) than the prefilled syringe (73.6%). Moderate discomfort or worse was reported by more patients when using the prefilled syringe (20.9%) than when using the autoinjector (5.5%), and severe discomfort or discomfort preventing injection of future doses was reported by 8.8% for the prefilled syringe but not at all when using the autoinjector. A favorable or extremely favorable overall impression was reported by 89.0% for the autoinjector and 72.5% for the prefilled syringe. Conclusion: Most patients with moderate-to-severe UC preferred to self-administer golimumab with the autoinjector over a prefilled syringe., SCOPUS: ar.j, info:eu-repo/semantics/published

A study was instituted in sheep to compare efficacy against Soman and the pharmacokinetics of atropine and HI-6 by wet/dry autoinjector and by syringe. The efficacy in sheep against Soman of Atropine/HI-6 delivered by wet/ dry autoinjector was also compared to the efficacy of atropine/pralidoxime chloride when syringe. The aging rate of GD was also determined in sheep erytrocytes. There were no statistical differences in the LD50's of sheep treated with atropine/HI-6 using syringes of wet/dry autoinjectors. A PR was determined for atropine/HI-6 treatment. Based on analyses of HI-6 and atropine pharmacokinetic parameters there were no statistically significant differences in the two injection techniques. The aging rate of sheep RBC's is highly dependent upon the GD-AChE incubation temperature.