A. Adoum, Pho V. Le, S. Faisant, Pauline Legendre, M. Lester, P. Boivin
Abstract Objectives Amiodarone hydrochloride is a class III antiarrhythmic drug indicated for the treatment of ventricular and supraventricular tachycardias. Oral amiodarone is only available in a tablet dosage form, which is not suitable for pediatric use. The stability of amiodarone hydrochloride suspension at 5 mg/mL was assessed in SyrSpend® SF PH4 (liquid) but oral amiodarone is typically given as a loading dose of 10–15 mg/kg/day for 4–10 days and then reduced to a maintenance dose of 5 mg/kg/day, making the 20 mg/mL concentration a better option. A hospital preparation of 20 mg/mL amiodarone hydrochloride oral suspension was developed. The purpose of this study was to determine the physicochemical stability of a 20 mg/mL amiodarone hydrochloride oral multidose suspension in a commercial compounding excipient, SyrSpend® SF PH4 (liquid) at ambient temperature and under dark conditions. Methods Three batches of oral suspension were prepared using amiodarone hydrochloride powder and SyrSpend SF PH4 (liquid). The suspensions were stored at room temperature and protected from light (amber glass vials). A sample was withdrawn from each bottle immediately after preparation and at 1, 2, 5, 10, 15, 30, 60, and 90 days. After additional dilution to an expected concentration of 100 μg/mL with methanol, the samples were assayed in triplicate using a stability-indicating high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. The physicochemical properties (pH, osmolality, amiodarone concentration, macroscopic changes) were assessed over 90 days at each day of analysis. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point and defined as retention of at least 95% of the initial concentration of amiodarone hydrochloride. Results After 90 days, the study showed that amiodarone hydrochloride concentrations did not go below 95% of the initial drug concentration. Neither degradation products nor changes of physicochemical properties were detected. Conclusions Compounded oral suspensions of 20 mg/mL amiodarone hydrochloride in SyrSpend® SF PH4 (liquid) were stable for at least 90 days when stored in amber glass bottles at room temperature.
{"title":"Physicochemical stability of 20 mg/mL amiodarone hydrochloride oral suspension in SyrSpend® SF PH4 (liquid)","authors":"A. Adoum, Pho V. Le, S. Faisant, Pauline Legendre, M. Lester, P. Boivin","doi":"10.1515/pthp-2022-0005","DOIUrl":"https://doi.org/10.1515/pthp-2022-0005","url":null,"abstract":"Abstract Objectives Amiodarone hydrochloride is a class III antiarrhythmic drug indicated for the treatment of ventricular and supraventricular tachycardias. Oral amiodarone is only available in a tablet dosage form, which is not suitable for pediatric use. The stability of amiodarone hydrochloride suspension at 5 mg/mL was assessed in SyrSpend® SF PH4 (liquid) but oral amiodarone is typically given as a loading dose of 10–15 mg/kg/day for 4–10 days and then reduced to a maintenance dose of 5 mg/kg/day, making the 20 mg/mL concentration a better option. A hospital preparation of 20 mg/mL amiodarone hydrochloride oral suspension was developed. The purpose of this study was to determine the physicochemical stability of a 20 mg/mL amiodarone hydrochloride oral multidose suspension in a commercial compounding excipient, SyrSpend® SF PH4 (liquid) at ambient temperature and under dark conditions. Methods Three batches of oral suspension were prepared using amiodarone hydrochloride powder and SyrSpend SF PH4 (liquid). The suspensions were stored at room temperature and protected from light (amber glass vials). A sample was withdrawn from each bottle immediately after preparation and at 1, 2, 5, 10, 15, 30, 60, and 90 days. After additional dilution to an expected concentration of 100 μg/mL with methanol, the samples were assayed in triplicate using a stability-indicating high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection. The physicochemical properties (pH, osmolality, amiodarone concentration, macroscopic changes) were assessed over 90 days at each day of analysis. Stability was determined by evaluating the percentage of the initial concentration remaining at each time point and defined as retention of at least 95% of the initial concentration of amiodarone hydrochloride. Results After 90 days, the study showed that amiodarone hydrochloride concentrations did not go below 95% of the initial drug concentration. Neither degradation products nor changes of physicochemical properties were detected. Conclusions Compounded oral suspensions of 20 mg/mL amiodarone hydrochloride in SyrSpend® SF PH4 (liquid) were stable for at least 90 days when stored in amber glass bottles at room temperature.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76066993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives In adult intensive care patients, epinephrine is mostly administered by continuous injection with syringe pumps. The objective of this study was to investigate the physicochemical stability of pharmacy prepared ready-to-use epinephrine (E) 0.02 mg/mL injection solutions (total volume 50 mL) for assigning shelf-life. Methods E 0.02 mg/mL injection solution in 50 mL amber type l glass vials was produced batch-wise in the pharmacy department. Stability of the refrigerated (2–8 °C) product was investigated in real time over a period of 36 months by analyzing E concentrations, osmolality, pH, and sub-visible particles at predefined time-points. For E concentration measurements a stability-indicating, validated reversed-phase HPLC-PDA assay was used. Results The autoclaving process of E 0.02 mg/mL injection solution in 50 mL amber type I glass vials caused 5% loss of the active substance. The finished product remained stable over the study period of 36 months when stored refrigerated. Conclusions Batch-wise production of ready-to-use E injection solution 0.02 mg/mL in 50 mL amber glass vials was successfully implemented in our pharmacy department. According to the stability tests, a shelf-life of 36 months can be assigned to the finished product stored refrigerated. Studies concerning stability at room temperature would be useful.
{"title":"Long-term stability of ready-to-use epinephrine 0.02 mg/mL injection solution in 50 mL glass vials","authors":"R. Heeb, F. Erdnüss, J. Reichhold, I. Krämer","doi":"10.1515/pthp-2021-0015","DOIUrl":"https://doi.org/10.1515/pthp-2021-0015","url":null,"abstract":"Abstract Objectives In adult intensive care patients, epinephrine is mostly administered by continuous injection with syringe pumps. The objective of this study was to investigate the physicochemical stability of pharmacy prepared ready-to-use epinephrine (E) 0.02 mg/mL injection solutions (total volume 50 mL) for assigning shelf-life. Methods E 0.02 mg/mL injection solution in 50 mL amber type l glass vials was produced batch-wise in the pharmacy department. Stability of the refrigerated (2–8 °C) product was investigated in real time over a period of 36 months by analyzing E concentrations, osmolality, pH, and sub-visible particles at predefined time-points. For E concentration measurements a stability-indicating, validated reversed-phase HPLC-PDA assay was used. Results The autoclaving process of E 0.02 mg/mL injection solution in 50 mL amber type I glass vials caused 5% loss of the active substance. The finished product remained stable over the study period of 36 months when stored refrigerated. Conclusions Batch-wise production of ready-to-use E injection solution 0.02 mg/mL in 50 mL amber glass vials was successfully implemented in our pharmacy department. According to the stability tests, a shelf-life of 36 months can be assigned to the finished product stored refrigerated. Studies concerning stability at room temperature would be useful.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86041185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aasfa Khan, Arnaud Venet, J. Bernadou, Sylvie Cresto, V. Servant, H. Boulestreau, F. Xuereb, S. Crauste-Manciet
Abstract Objectives Fungal keratitis is a rare but severe cause of infectious keratitis and can lead to blindness. To cure fungal keratitis, antifungal like voriconazole eye drops must be immediately administered. As no brand is available on the market, voriconazole ophthalmic solution is compounded in hospital pharmacies using voriconazole powder for intravenous infusion. The aims of our study were to both assess the physico-chemical and microbiological stability of eye drop solutions stored at +2 to 8 °C. Two different High-Density-Polyethylene (HDPE) eye drop dispensing containers were assessed, one with a sterility preserving cap Novelia®(Nemera) and the other without sterility preserving cap both provided by CAT laboratory. In addition microbiological quality was assessed during 15 days simulated patient use. Methods Multiple batches of voriconazole 10 mg/mL eye drops were prepared and stored at +2 to 8 °C to study their stability over 90 days. All analyses were performed in triplicate. Physical stability was determined, pH determination, osmolarity measurement, and a particle count test was also performed. A high performance liquid chromatography (HPLC-UV) stability indicating method was used to determine chemical stability of the ophthalmic solution over 90 days of storage. For microbiological stability, a sterility test was performed using closed membrane filtration method (Steritest®, Merck Millipore) at D0, D90 and D90+15 days after simulated administration of eye drops (D90+15). Results For both containers, no variation of visual aspect, pH, osmolality, particle count and final concentration were observed. No microbiological growth was observed after 90 days of storage. At the end of the simulated administration period (D+15), unconstant microbiological growth was only observed in HDPE vials without sterility preserving cap, whereas HDPE vials with a sterility preserving cap Novelia®(Nemera) remained sterile. Conclusions Voriconazole 10 mg/mL ophtalmic solution was stable during 90 days at +2 to 8 °C in lightproof HDPE vials without sterility preserving cap and HDPE vials with a sterility preserving cap Novelia®(Nemera). However, vials with classical cap which are not airtight systems, may microbiologically contaminated during patient’s use than vials with Novelia® cap thanks to their innovative valve system.
{"title":"Stability of voriconazole 10 mg/mL ophthalmic solution during 90 days","authors":"Aasfa Khan, Arnaud Venet, J. Bernadou, Sylvie Cresto, V. Servant, H. Boulestreau, F. Xuereb, S. Crauste-Manciet","doi":"10.1515/pthp-2021-0010","DOIUrl":"https://doi.org/10.1515/pthp-2021-0010","url":null,"abstract":"Abstract Objectives Fungal keratitis is a rare but severe cause of infectious keratitis and can lead to blindness. To cure fungal keratitis, antifungal like voriconazole eye drops must be immediately administered. As no brand is available on the market, voriconazole ophthalmic solution is compounded in hospital pharmacies using voriconazole powder for intravenous infusion. The aims of our study were to both assess the physico-chemical and microbiological stability of eye drop solutions stored at +2 to 8 °C. Two different High-Density-Polyethylene (HDPE) eye drop dispensing containers were assessed, one with a sterility preserving cap Novelia®(Nemera) and the other without sterility preserving cap both provided by CAT laboratory. In addition microbiological quality was assessed during 15 days simulated patient use. Methods Multiple batches of voriconazole 10 mg/mL eye drops were prepared and stored at +2 to 8 °C to study their stability over 90 days. All analyses were performed in triplicate. Physical stability was determined, pH determination, osmolarity measurement, and a particle count test was also performed. A high performance liquid chromatography (HPLC-UV) stability indicating method was used to determine chemical stability of the ophthalmic solution over 90 days of storage. For microbiological stability, a sterility test was performed using closed membrane filtration method (Steritest®, Merck Millipore) at D0, D90 and D90+15 days after simulated administration of eye drops (D90+15). Results For both containers, no variation of visual aspect, pH, osmolality, particle count and final concentration were observed. No microbiological growth was observed after 90 days of storage. At the end of the simulated administration period (D+15), unconstant microbiological growth was only observed in HDPE vials without sterility preserving cap, whereas HDPE vials with a sterility preserving cap Novelia®(Nemera) remained sterile. Conclusions Voriconazole 10 mg/mL ophtalmic solution was stable during 90 days at +2 to 8 °C in lightproof HDPE vials without sterility preserving cap and HDPE vials with a sterility preserving cap Novelia®(Nemera). However, vials with classical cap which are not airtight systems, may microbiologically contaminated during patient’s use than vials with Novelia® cap thanks to their innovative valve system.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87584000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sally Bishay, Malgorzata Michalowska-Suterska, A. Edling, Jason Battle
Abstract Objectives The compounding and administration of hazardous drugs present a potential risk to healthcare worker and patient safety. This study sought to evaluate the HD surface contamination in multiple pharmacy and nursing areas that include standardized cleaning techniques and utilization of closed system transfer devices. Methods This study was conducted at six different areas in the pharmacy and nursing areas. Each area was assessed three times for five different HD’s surface contamination at an initial, 3 month, and 6 month follow up. Hazardous drug surface testing was performed for five most compounded HDs. A total of 90 individual samples were taken and analyzed during the study. Results A total of 30 samples were collected at three different timepoints for a total of 90 individual samples and analysis results. All 90 samples were negative (below the lower limit of detection; 0.01 ng/cm2), for their respective drug residue. Conclusions The method and design described in this evaluation may offer a way to determine if a facility’s current HD work practices and controls retain reduced HD surface contamination based upon published threshold values. Adoption and utilization of standardized work, including use of a closed system transfer device, and cleaning practices, described in this study, may present an option for facilities to retain reduced HD surface contamination, based upon previously determined threshold values.
{"title":"Evaluation of the hazardous drug surface contamination in pharmacy compounding and administration clinical setting after adoption of standardized cleaning workflow and a closed system transfer device","authors":"Sally Bishay, Malgorzata Michalowska-Suterska, A. Edling, Jason Battle","doi":"10.1515/pthp-2022-0004","DOIUrl":"https://doi.org/10.1515/pthp-2022-0004","url":null,"abstract":"Abstract Objectives The compounding and administration of hazardous drugs present a potential risk to healthcare worker and patient safety. This study sought to evaluate the HD surface contamination in multiple pharmacy and nursing areas that include standardized cleaning techniques and utilization of closed system transfer devices. Methods This study was conducted at six different areas in the pharmacy and nursing areas. Each area was assessed three times for five different HD’s surface contamination at an initial, 3 month, and 6 month follow up. Hazardous drug surface testing was performed for five most compounded HDs. A total of 90 individual samples were taken and analyzed during the study. Results A total of 30 samples were collected at three different timepoints for a total of 90 individual samples and analysis results. All 90 samples were negative (below the lower limit of detection; 0.01 ng/cm2), for their respective drug residue. Conclusions The method and design described in this evaluation may offer a way to determine if a facility’s current HD work practices and controls retain reduced HD surface contamination based upon published threshold values. Adoption and utilization of standardized work, including use of a closed system transfer device, and cleaning practices, described in this study, may present an option for facilities to retain reduced HD surface contamination, based upon previously determined threshold values.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86378381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives The objective of this study was to investigate the physicochemical stability of ready-to-adminster human insulin (HI) 1 I.U./mL injection solutions of two different brand products diluted with 0.9% NaCl solution under different storage conditions either in 50 mL disposable plastic syringes or as bulk solution in infusion bags. Methods HI test solutions 1 I.U./mL were prepared with Huminsulin® Normal 100 and Actrapid® Penfill®, diluted with 0.9% sodium chloride infusion solution, and filled in Original-Perfusor® syringes or BD® Perfusion syringes. Test solutions were stored for 90 days at 2–8 °C/dark or at 20–25 °C/diffuse room light. Bulk solutions 1 I.U./mL prepared with Huminsulin® Normal 100 were stored in two different 3 L infusion bags (Ecobag® click and ExactaMix® EVA bag) at 2–8 °C/dark for five days. HI concentrations were determined by reversed-phase high-performance liquid chromatography at predefined time points. Beside regular visual inspection, subvisible particles and pH values were measured. Results Ready-to-adminster Huminsulin® Normal and Actrapid® Penfill® injection solutions 1 I.U./mL prepared in 50 mL Original-Perfusor® syringes or BD® Perfusion syringes remained physicochemically stable for up to 90 days when stored at 2–8 °C/dark and for at least 14 days when kept at 20–25 °C/diffuse room light. Prefilled 3 L polyolefin infusion bags (Ecobag® click) are suitable for the preparation of Huminsulin® 1 I.U./mL bulk solutions. In ethylene vinyl acetate (EVA) bags, HI concentrations decreased rapidly. Conclusions Ready-to-administer Huminsulin® Normal and Actrapid® Penfill® injection solutions 1 I.U./mL can be prepared in advance by dilution with 0.9% sodium chloride infusion solution and filled into 50 mL Original-Perfusor® syringes or BD® Perfusion syringes; subsequent storage at 2–8 °C/dark is possible for up to 90 days. For preparation of bulk solutions, the prefilled polyolefin infusion bag is appropriate.
摘要目的研究两种不同品牌的人胰岛素(HI) 1 iu /mL注射溶液经0.9% NaCl溶液稀释后，在50ml一次性塑料注射器和输液袋中作为散装溶液，在不同储存条件下的理化稳定性。方法用Huminsulin®Normal 100和Actrapid®Penfill®配制1 iu /mL HI试验溶液，用0.9%氯化钠输注液稀释后，分别充入Original-Perfusor®注射器或BD®Perfusion注射器。测试溶液在2-8°C/黑暗或20-25°C/漫射室内光下保存90天。用Huminsulin®Normal 100配制1 iu /mL的散装溶液，分别存放在两个不同的3 L输注袋(Ecobag®click和ExactaMix®EVA袋)中，在2-8°C/暗处保存5天。在预定时间点用反相高效液相色谱法测定HI浓度。除了定期目视检查外，还测量了不可见颗粒和pH值。1 iu /mL制备于50 mL Original-Perfusor®注射器或BD®灌注注射器中，在2-8°C/黑暗条件下保存可达90天，在20-25°C/漫射室内光条件下保存可达14天。预充3l聚烯烃输注袋(Ecobag®点击)适用于制备Huminsulin®1iu /mL散装溶液。在醋酸乙烯(EVA)袋中，HI浓度迅速下降。结论Huminsulin®Normal和Actrapid®Penfill®注射液可提前配制1 iu /mL，用0.9%氯化钠注射液稀释后充入50 mL Original-Perfusor®注射器或BD®Perfusion注射器中;随后在2-8°C/暗处储存可达90天。对于散装溶液的制备，预填充的聚烯烃输液袋是合适的。
{"title":"Longterm physicochemical stability of ready-to-administer human insulin injection solutions 1 I.U./mL in 50 mL plastic syringes","authors":"F. Erdnüss, André Mohr, I. Krämer","doi":"10.1515/pthp-2021-0014","DOIUrl":"https://doi.org/10.1515/pthp-2021-0014","url":null,"abstract":"Abstract Objectives The objective of this study was to investigate the physicochemical stability of ready-to-adminster human insulin (HI) 1 I.U./mL injection solutions of two different brand products diluted with 0.9% NaCl solution under different storage conditions either in 50 mL disposable plastic syringes or as bulk solution in infusion bags. Methods HI test solutions 1 I.U./mL were prepared with Huminsulin® Normal 100 and Actrapid® Penfill®, diluted with 0.9% sodium chloride infusion solution, and filled in Original-Perfusor® syringes or BD® Perfusion syringes. Test solutions were stored for 90 days at 2–8 °C/dark or at 20–25 °C/diffuse room light. Bulk solutions 1 I.U./mL prepared with Huminsulin® Normal 100 were stored in two different 3 L infusion bags (Ecobag® click and ExactaMix® EVA bag) at 2–8 °C/dark for five days. HI concentrations were determined by reversed-phase high-performance liquid chromatography at predefined time points. Beside regular visual inspection, subvisible particles and pH values were measured. Results Ready-to-adminster Huminsulin® Normal and Actrapid® Penfill® injection solutions 1 I.U./mL prepared in 50 mL Original-Perfusor® syringes or BD® Perfusion syringes remained physicochemically stable for up to 90 days when stored at 2–8 °C/dark and for at least 14 days when kept at 20–25 °C/diffuse room light. Prefilled 3 L polyolefin infusion bags (Ecobag® click) are suitable for the preparation of Huminsulin® 1 I.U./mL bulk solutions. In ethylene vinyl acetate (EVA) bags, HI concentrations decreased rapidly. Conclusions Ready-to-administer Huminsulin® Normal and Actrapid® Penfill® injection solutions 1 I.U./mL can be prepared in advance by dilution with 0.9% sodium chloride infusion solution and filled into 50 mL Original-Perfusor® syringes or BD® Perfusion syringes; subsequent storage at 2–8 °C/dark is possible for up to 90 days. For preparation of bulk solutions, the prefilled polyolefin infusion bag is appropriate.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"121 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79156029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives Patients hospitalized in intensive care units often require multiple drug infusions. Due to limited intravenous accesses, concomitant administration of drugs in the same infusion line is often necessary. Compatibility studies of Y-site administration are available in the literature, but data of several combinations are lacking. Previous work from d’Huart et al. have performed an observation of the administration of injectable drugs in three adults ICUs and identified a list of Y-site administration without compatibility data. The objective of this study was to test the physical compatibility of the main drugs of this list used in pairs in Y-site infusions in critical care units, in order to provide new compatibility data to the literature, and to secure the administration of intravenous drugs. Methods The physical compatibility in Y-site of nine drugs with other drugs commonly used in intensive care units has been tested. Examinations were performed on 75 mixtures after their preparation, after 1 and 4-h storage. This evaluation included a visual examination with a search for precipitation formation, color change, gas formation, and a subvisual evaluation: absorbance measurements by UV-visible spectrophotometry at 350, 410 and 550 nm, and Light Obscuration Particle Count Test. The pH evaluation was performed at each time of analysis. Results Laboratory tests led to an overall compatibility of 68.0% for all mixtures obtained in this study. Nefopam was found to be quite compatible with other drugs (95.0%). Amiodarone hydrochloride (84.6%), acetylsalicylic acid (80.0%), clonidine hydrochloride (75.0%) and insulin (71.4%) were compatible with other drugs too. Atenolol (42.9%), furosemide (25.0%), heparin sodium (25.0%) showed less compatible results. Pantoprazole sodium (0.0%) was not at all compatible with the other drugs analyzed. Conclusions By the results of these laboratory tests, missing compatibility data are now available, providing additional information to the literature.
{"title":"Y-site compatibility of intravenous medications commonly used in intensive care units: laboratory tests on 75 mixtures involving nine main drugs","authors":"Gillian Ayari, E. D’huart, J. Vigneron, B. Demoré","doi":"10.1515/pthp-2022-0002","DOIUrl":"https://doi.org/10.1515/pthp-2022-0002","url":null,"abstract":"Abstract Objectives Patients hospitalized in intensive care units often require multiple drug infusions. Due to limited intravenous accesses, concomitant administration of drugs in the same infusion line is often necessary. Compatibility studies of Y-site administration are available in the literature, but data of several combinations are lacking. Previous work from d’Huart et al. have performed an observation of the administration of injectable drugs in three adults ICUs and identified a list of Y-site administration without compatibility data. The objective of this study was to test the physical compatibility of the main drugs of this list used in pairs in Y-site infusions in critical care units, in order to provide new compatibility data to the literature, and to secure the administration of intravenous drugs. Methods The physical compatibility in Y-site of nine drugs with other drugs commonly used in intensive care units has been tested. Examinations were performed on 75 mixtures after their preparation, after 1 and 4-h storage. This evaluation included a visual examination with a search for precipitation formation, color change, gas formation, and a subvisual evaluation: absorbance measurements by UV-visible spectrophotometry at 350, 410 and 550 nm, and Light Obscuration Particle Count Test. The pH evaluation was performed at each time of analysis. Results Laboratory tests led to an overall compatibility of 68.0% for all mixtures obtained in this study. Nefopam was found to be quite compatible with other drugs (95.0%). Amiodarone hydrochloride (84.6%), acetylsalicylic acid (80.0%), clonidine hydrochloride (75.0%) and insulin (71.4%) were compatible with other drugs too. Atenolol (42.9%), furosemide (25.0%), heparin sodium (25.0%) showed less compatible results. Pantoprazole sodium (0.0%) was not at all compatible with the other drugs analyzed. Conclusions By the results of these laboratory tests, missing compatibility data are now available, providing additional information to the literature.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81493767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Quentin Trambloy, J. Vigneron, I. Clarot, F. Blaise, E. D’huart, B. Demoré
Abstract Objectives Azacitidine is a pyrimidine nucleoside analogue whose stability is temperature dependent. Numerous publications have studied the stability of this drug with discordant results. The purpose of this work is to study the stability of azacitidine suspensions under different conditions to allow preparation in advance: vials stored at room temperature or between 2 and 8 °C, reconstituted with refrigerated water for injection (WFI) or frozen/thawed WFI, azacitidine suspensions stored at room temperature, 2–8 °C or at −20 °C. The feasibility of a vented ChemoClave® Spike vial was also tested to reconstitute and collect azacitidine to aid the preparation stage. Methods The stability study was performed by HPLC coupled to a photodiode array detector. The method was validated according to ICH Q2(R1). Two syringes were prepared for each analysis condition and two samples were realised for each syringe at each time of the analysis. For a storage at 2–8 °C, analyses were performed for up to 168 h. The stability was studied after 2 h at room temperature. For frozen storage, the stability was studied after 28 days. Results Azacitidine 25 mg/mL suspensions stored between 2 and 8 °C, prepared with refrigerated WFI or frozen/thawed WFI, retained more than 90% of the initial concentration for 96 h and then for 2 h at room temperature. Prepared with frozen/thawed WFI, azacitidine 25 mg/mL suspensions stored at −20 °C for 28 days and then 72 h between 2 and 8 °C after thawing, retained more than 90% of the initial concentration. When using a Spike system compared to using a needle for reconstitution and collection of the suspension, the results obtained by HPLC showed a decrease of 1.47% in the concentration of azacitidine. The comparisons of the volumes withdrawn after reconstitution were similar when using a Spike system or a needle. Conclusions Azacitidine 25 mg/mL suspensions reconstituted with refrigerated WFI were chemically stable for 4 days when stored at 2–8 °C whatever the storage of vials (refrigerator or room temperature), and 2 h at room temperature. A storage of azacitidine 25 mg/mL suspensions in syringes prepared with frozen/thawed WFI at −20 °C has been validated for up to 28 days, leading to the possibility to prepare in advance. A Spike device can be used to reconstitute and collect azacitidine.
{"title":"Physicochemical stability of azacitidine suspensions at 25 mg/mL in polypropylene syringes stored under different conditions of storage","authors":"Quentin Trambloy, J. Vigneron, I. Clarot, F. Blaise, E. D’huart, B. Demoré","doi":"10.1515/pthp-2022-0003","DOIUrl":"https://doi.org/10.1515/pthp-2022-0003","url":null,"abstract":"Abstract Objectives Azacitidine is a pyrimidine nucleoside analogue whose stability is temperature dependent. Numerous publications have studied the stability of this drug with discordant results. The purpose of this work is to study the stability of azacitidine suspensions under different conditions to allow preparation in advance: vials stored at room temperature or between 2 and 8 °C, reconstituted with refrigerated water for injection (WFI) or frozen/thawed WFI, azacitidine suspensions stored at room temperature, 2–8 °C or at −20 °C. The feasibility of a vented ChemoClave® Spike vial was also tested to reconstitute and collect azacitidine to aid the preparation stage. Methods The stability study was performed by HPLC coupled to a photodiode array detector. The method was validated according to ICH Q2(R1). Two syringes were prepared for each analysis condition and two samples were realised for each syringe at each time of the analysis. For a storage at 2–8 °C, analyses were performed for up to 168 h. The stability was studied after 2 h at room temperature. For frozen storage, the stability was studied after 28 days. Results Azacitidine 25 mg/mL suspensions stored between 2 and 8 °C, prepared with refrigerated WFI or frozen/thawed WFI, retained more than 90% of the initial concentration for 96 h and then for 2 h at room temperature. Prepared with frozen/thawed WFI, azacitidine 25 mg/mL suspensions stored at −20 °C for 28 days and then 72 h between 2 and 8 °C after thawing, retained more than 90% of the initial concentration. When using a Spike system compared to using a needle for reconstitution and collection of the suspension, the results obtained by HPLC showed a decrease of 1.47% in the concentration of azacitidine. The comparisons of the volumes withdrawn after reconstitution were similar when using a Spike system or a needle. Conclusions Azacitidine 25 mg/mL suspensions reconstituted with refrigerated WFI were chemically stable for 4 days when stored at 2–8 °C whatever the storage of vials (refrigerator or room temperature), and 2 h at room temperature. A storage of azacitidine 25 mg/mL suspensions in syringes prepared with frozen/thawed WFI at −20 °C has been validated for up to 28 days, leading to the possibility to prepare in advance. A Spike device can be used to reconstitute and collect azacitidine.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85864549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marissa Rase, Mark Hanlon, Le Ho, D. Duriez, Cathy Zhao
Abstract Objectives Particles due to fragmentation present a clear risk to the patient. Reported fragmentation rates vary, and an insertion angle at 45°, as opposed to 90°, has been proposed as a mitigation strategy. So, this study evaluated the fragmentation rates induced by single-use hypodermic needles using different angled penetration techniques. Methods Needles underwent fragmentation testing using two penetration techniques. In method 1, the needle was inserted through the stopper at 45° and rotated to 90° upon exiting the stopper underside, and in method 2 the needle was rotated only after the bevel was fully enveloped by the stopper. Methods were tested with 18, 20, and 22-gauge needles with bevel faced up, down, and sideways. Fragmentation data sets were subjected to ANOVA and a fit to a General Linear Model was attempted to ascertain the significance of needle size, bevel position, and penetration method; p-values less than 0.05 indicated statistical significance. Results Incidence varied from 0 to 49% and depended on the test method. Needles larger than 22-gauge induced fragmentation the most when the bevel was down. The bevel up position induced fragmentation the least. Generation of large fragments designated “cores” depended on all factors examined, and generation of small fragments designated “fragments” depended on all factors except for the penetration method. Conclusions Clinical context and intended application need to be communicated to manufacturers and considered for functional testing when devising end-user recommendations which must reflect a combination of factors.
{"title":"Vial coring and fragmentation incidence after angled penetration of rubber stoppers with single-use hypodermic needles","authors":"Marissa Rase, Mark Hanlon, Le Ho, D. Duriez, Cathy Zhao","doi":"10.1515/pthp-2021-0004","DOIUrl":"https://doi.org/10.1515/pthp-2021-0004","url":null,"abstract":"Abstract Objectives Particles due to fragmentation present a clear risk to the patient. Reported fragmentation rates vary, and an insertion angle at 45°, as opposed to 90°, has been proposed as a mitigation strategy. So, this study evaluated the fragmentation rates induced by single-use hypodermic needles using different angled penetration techniques. Methods Needles underwent fragmentation testing using two penetration techniques. In method 1, the needle was inserted through the stopper at 45° and rotated to 90° upon exiting the stopper underside, and in method 2 the needle was rotated only after the bevel was fully enveloped by the stopper. Methods were tested with 18, 20, and 22-gauge needles with bevel faced up, down, and sideways. Fragmentation data sets were subjected to ANOVA and a fit to a General Linear Model was attempted to ascertain the significance of needle size, bevel position, and penetration method; p-values less than 0.05 indicated statistical significance. Results Incidence varied from 0 to 49% and depended on the test method. Needles larger than 22-gauge induced fragmentation the most when the bevel was down. The bevel up position induced fragmentation the least. Generation of large fragments designated “cores” depended on all factors examined, and generation of small fragments designated “fragments” depended on all factors except for the penetration method. Conclusions Clinical context and intended application need to be communicated to manufacturers and considered for functional testing when devising end-user recommendations which must reflect a combination of factors.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79729513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J. Hecq, J. Jamart, P. Odou, J. Vigneron, L. Galanti
Abstract The physico-chemical stability of an injectable preparation (IV) is conditioned by different parameters. A collaboration between the pharmacy, the chemistry laboratory and the statisticians of the scientific support unit was established in 1996, in order to carry out long-term chemical stability studies of commonly used IVs and to be able to take charge of their preparation in pharmacy. In 24 years of activity, the Drug Stability Research Group (DSRG) tested 39 IV at different concentration and temperature of storage. The DSRG has organized an annual symposium since 2015. The theme of the 2019 edition was devoted to the robotization of injectable reconstitution operations, focused on their impact on the workplace and the existing equipment.
{"title":"Fifth DSRG symposium at CHU UCL Namur, 18/10/2019. “Centralization of injectables and robotization”","authors":"J. Hecq, J. Jamart, P. Odou, J. Vigneron, L. Galanti","doi":"10.1515/pthp-2020-0018","DOIUrl":"https://doi.org/10.1515/pthp-2020-0018","url":null,"abstract":"Abstract The physico-chemical stability of an injectable preparation (IV) is conditioned by different parameters. A collaboration between the pharmacy, the chemistry laboratory and the statisticians of the scientific support unit was established in 1996, in order to carry out long-term chemical stability studies of commonly used IVs and to be able to take charge of their preparation in pharmacy. In 24 years of activity, the Drug Stability Research Group (DSRG) tested 39 IV at different concentration and temperature of storage. The DSRG has organized an annual symposium since 2015. The theme of the 2019 edition was devoted to the robotization of injectable reconstitution operations, focused on their impact on the workplace and the existing equipment.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91033560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abstract Objectives An audit of the practices of our compounding unit was performed in 2016: areas of improvement were proposed, such as the automatization of our process. An automated compounder was acquired (MediMixmulti® MF4120R). The aim of the study was to anticipate the risks of the new process, in order to improve its security and to support the professionals during this evolution of our compounding process. Methods The Failure Modes, Effects and Criticality Analysis (FMECA) method was carried out in order to detect potential failures brought by the automatization of parenteral nutrition (PN) manufacturing in the new process. The FMECA method included four steps that were divided into five work sessions of one and a half hour each over a period of two months. A working group made up of professionals involved in the PN production process was set up (pharmacists, pharmacy resident, manager and pharmaceutical technician). Results Fifty failure modes were determined by this analysis, of which 96% could have an impact on the patient, 90% on the health staff and 74% on the product. The FMECA shows that 18 failure modes have a tolerable or unacceptable CI (CI≥100) for which it is necessary to implement preventive measures as a priority. This work also made it possible to review the barrier measures already in place for the current process. Conclusions The risk analysis allowed us to analyze the failures of both the actual and the future manufacturing processes. Once the most critical failure modes were identified, specific recommendations were proposed and an improvement plan was established. First, the compounder needs to be fully qualified. Then, the quality manual of the PN process will be reviewed and updated. Once these steps are completed, the pharmacy professionals (pharmacists, pharmacy technicians) will be trained and the PN production will be performed using the automated compounder on a daily basis.
{"title":"Risks associated with the evolution in the compounding process of parenteral nutrition solutions: use of the “FMECA” method","authors":"G. Dozias, J. Thiec, Gwenola Le Den, V. Cogulet","doi":"10.1515/pthp-2020-0017","DOIUrl":"https://doi.org/10.1515/pthp-2020-0017","url":null,"abstract":"Abstract Objectives An audit of the practices of our compounding unit was performed in 2016: areas of improvement were proposed, such as the automatization of our process. An automated compounder was acquired (MediMixmulti® MF4120R). The aim of the study was to anticipate the risks of the new process, in order to improve its security and to support the professionals during this evolution of our compounding process. Methods The Failure Modes, Effects and Criticality Analysis (FMECA) method was carried out in order to detect potential failures brought by the automatization of parenteral nutrition (PN) manufacturing in the new process. The FMECA method included four steps that were divided into five work sessions of one and a half hour each over a period of two months. A working group made up of professionals involved in the PN production process was set up (pharmacists, pharmacy resident, manager and pharmaceutical technician). Results Fifty failure modes were determined by this analysis, of which 96% could have an impact on the patient, 90% on the health staff and 74% on the product. The FMECA shows that 18 failure modes have a tolerable or unacceptable CI (CI≥100) for which it is necessary to implement preventive measures as a priority. This work also made it possible to review the barrier measures already in place for the current process. Conclusions The risk analysis allowed us to analyze the failures of both the actual and the future manufacturing processes. Once the most critical failure modes were identified, specific recommendations were proposed and an improvement plan was established. First, the compounder needs to be fully qualified. Then, the quality manual of the PN process will be reviewed and updated. Once these steps are completed, the pharmacy professionals (pharmacists, pharmacy technicians) will be trained and the PN production will be performed using the automated compounder on a daily basis.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86858270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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