M. Godet, J. Simar, M. Closset, J. Hecq, M. Braibant, L. Soumoy, P. Gillet, J. Jamart, B. Bihin, L. Galanti
Abstract Background Vancomycin is increasingly administrated by continuous infusion. But the treatment of patient in intensive care need restricted volume to prevent fluid overload. The aim of the study was to evaluate the physical and chemical stability of solutions of a high concentration of vancomycin hydrochloride in 5 % glucose or 0.9 % NaCl. Methods Eight syringes of 50 mL, containing 41.66 mg/mL of vancomycin hydrochloride four syringes in 5 % glucose and four in 0.9 % NaCl were prepared and stored at ambient temperature during 48 h. Immediately after preparation and during 48 h, vancomycin hydrochloride concentrations were measured by a high-performance liquid chromatography (HPLC). Spectrophotometric absorbance at different wavelengths, pH measurement and microscopic observations were also performed. Results All solutions were physico-chemically stable during the whole period storage at ambient temperature: no color change, turbidity, precipitation or opacity, no significant pH variations or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. Solutions are considered chemically stable as the lower limit of the 95 % unilateral confidence interval on the mean remained above 90 % of the initial concentration for at least 48 h. Conclusions Solutions of vancomycin hydrochloride 41.66 mg/mL in syringe of 5 % glucose or 0.9 % NaCl are physically and chemically stable for at least 48 h when stored in syringes at ambient temperature.
{"title":"Stability of Concentrated Solution of Vancomycin Hydrochloride in Syringes for Intensive Care Units","authors":"M. Godet, J. Simar, M. Closset, J. Hecq, M. Braibant, L. Soumoy, P. Gillet, J. Jamart, B. Bihin, L. Galanti","doi":"10.1515/PTHP-2017-0031","DOIUrl":"https://doi.org/10.1515/PTHP-2017-0031","url":null,"abstract":"Abstract Background Vancomycin is increasingly administrated by continuous infusion. But the treatment of patient in intensive care need restricted volume to prevent fluid overload. The aim of the study was to evaluate the physical and chemical stability of solutions of a high concentration of vancomycin hydrochloride in 5 % glucose or 0.9 % NaCl. Methods Eight syringes of 50 mL, containing 41.66 mg/mL of vancomycin hydrochloride four syringes in 5 % glucose and four in 0.9 % NaCl were prepared and stored at ambient temperature during 48 h. Immediately after preparation and during 48 h, vancomycin hydrochloride concentrations were measured by a high-performance liquid chromatography (HPLC). Spectrophotometric absorbance at different wavelengths, pH measurement and microscopic observations were also performed. Results All solutions were physico-chemically stable during the whole period storage at ambient temperature: no color change, turbidity, precipitation or opacity, no significant pH variations or optic densities were observed in the solutions. Any crystals were seen by microscopic analysis. Solutions are considered chemically stable as the lower limit of the 95 % unilateral confidence interval on the mean remained above 90 % of the initial concentration for at least 48 h. Conclusions Solutions of vancomycin hydrochloride 41.66 mg/mL in syringe of 5 % glucose or 0.9 % NaCl are physically and chemically stable for at least 48 h when stored in syringes at ambient temperature.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"30 1","pages":"23 - 30"},"PeriodicalIF":0.0,"publicationDate":"2018-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78620058","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 Preservative free ophthalmic formulations need to be packaged either as single doses, or using specially designed sterility preserving multidose eyedroppers. Our objective was to evaluate potential sorption phenomena between a device with a silicone sterility preserving membrane and the delivered drops of several ophthalmic solutions. Cyclosporine, rifamycin, latanoprost, timolol and norfloxacin were used as model drugs. Quantification of the active substance in delivered drops (1 to 4 drops per day) from low density polyethylene (LDPE) bottles without any sterility preserving device and from LDPE bottles with a sterility preserving silicone membrane (LDPE-Si) was performed for 14 days (n≥3), using validated HPLC methods. For cyclosporine, mean concentrations did not vary by more than 10 % from reference concentrations for either LDPE or LDPE-Si eyedroppers, but for LDPE-Si, the concentrations of the 1 mg.ml-1 cyclosporine micellar solution were found to be significantly lower than for those from LDPE eyedroppers (p=0.0127). For LDPE-Si, rifamycin mean concentrations decreased by 11.2 % throughout the 14 day study period, but didn’t vary by more than 10 % for LDPE and glass eyedroppers. However, rifamycin concentrations from LDPE-Si were not significantly different from those from LDPE eyedroppers. For latanoprost, whilst mean concentrations did not vary by more than 10 % from reference concentration for LDPE eyedroppers, for LDPE-Si eyedroppers concentrations decreased by 76.4 % at their lowest concentration and never returned to their initial level. For timolol and norfloxacin, mean concentrations did not vary by more than 10 % for either LDPE or LDPE-Si eyedroppers and no significant difference was found between the 2 eyedroppers concentrations. Our results are in favor of an absence of significant sorption between LDPE-Si eyedroppers for timolol or norfloxacin ophthalmic solutions. Further studies should be performed on cyclosporine ophthalmic micellar solutions and rifamycin ophthalmic solutions before any definite conclusions can be made. Finally, our results show that latanoprost ophthalmic solutions shouldn’t be used with LDPE-Si eyedroppers as the loss of active substance would cause a sever under-dosing.
{"title":"A Sorption Study between Ophthalmic Drugs and Multi Dose Eyedroppers in Simulated Use Conditions","authors":"Y. Le Basle, P. Chennell, V. Sautou","doi":"10.1515/pthp-2017-0026","DOIUrl":"https://doi.org/10.1515/pthp-2017-0026","url":null,"abstract":"Abstract Preservative free ophthalmic formulations need to be packaged either as single doses, or using specially designed sterility preserving multidose eyedroppers. Our objective was to evaluate potential sorption phenomena between a device with a silicone sterility preserving membrane and the delivered drops of several ophthalmic solutions. Cyclosporine, rifamycin, latanoprost, timolol and norfloxacin were used as model drugs. Quantification of the active substance in delivered drops (1 to 4 drops per day) from low density polyethylene (LDPE) bottles without any sterility preserving device and from LDPE bottles with a sterility preserving silicone membrane (LDPE-Si) was performed for 14 days (n≥3), using validated HPLC methods. For cyclosporine, mean concentrations did not vary by more than 10 % from reference concentrations for either LDPE or LDPE-Si eyedroppers, but for LDPE-Si, the concentrations of the 1 mg.ml-1 cyclosporine micellar solution were found to be significantly lower than for those from LDPE eyedroppers (p=0.0127). For LDPE-Si, rifamycin mean concentrations decreased by 11.2 % throughout the 14 day study period, but didn’t vary by more than 10 % for LDPE and glass eyedroppers. However, rifamycin concentrations from LDPE-Si were not significantly different from those from LDPE eyedroppers. For latanoprost, whilst mean concentrations did not vary by more than 10 % from reference concentration for LDPE eyedroppers, for LDPE-Si eyedroppers concentrations decreased by 76.4 % at their lowest concentration and never returned to their initial level. For timolol and norfloxacin, mean concentrations did not vary by more than 10 % for either LDPE or LDPE-Si eyedroppers and no significant difference was found between the 2 eyedroppers concentrations. Our results are in favor of an absence of significant sorption between LDPE-Si eyedroppers for timolol or norfloxacin ophthalmic solutions. Further studies should be performed on cyclosporine ophthalmic micellar solutions and rifamycin ophthalmic solutions before any definite conclusions can be made. Finally, our results show that latanoprost ophthalmic solutions shouldn’t be used with LDPE-Si eyedroppers as the loss of active substance would cause a sever under-dosing.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"37 1","pages":"181 - 191"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72934622","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}
R. Heeb, B. Stollhof, J. Reichhold, J. Thiesen, I. Krämer
Abstract Background In the University Medical Centre Mainz, standard concentrations are defined for medicinal products to be administered by continuous injection with syringe pumps in adult intensive care patients. The objective of this study was to evaluate the physicochemical stability of ready-to-use and ready-to-administer preparations containing Epinephrine (E) and Norepinephrine (NE) in standardized concentrations and prepared batch wise in the pharmacy department as basis for assigning shelf-lives. Methods E 20 µg/mL and NE 10 µg/mL in disposable syringes and NE 40, 100, 200, 400 µg/ml in 50 ml amber type I glass vials were prepared batch wise and the concentrations were analyzed by stability-indicating, validated reversed-phase HPLC-PDA assays. Test solutions for long-term stability studies were stored under refrigeration (2–8 °C) for 6–12 months or at elevated temperatures (21–27 °C) light protected for up to 6 months or without light protection for up to one month. Osmolality and pH were measured on predefined intervals. Results The concentrations of E in 50 mL syringes and NE in 10 mL syringes remained unchanged over a period of 6 months when stored at 2–8 °C. NE preparations of different concentrations prepared in amber glass vials remained stable over a study period of 12 months. At RT the shelf-life decreased to about 6 months and the exposure to mixed daylight at RT caused loss of stability in only few days. Conclusions Batch wise preparation of ready-to-administer (RTA) preparations containing 20 µg/mL E or 10 µg/mL NE in disposable syringes as well as ready-to-use (RTU) preparations containing 40, 100, 200 and 400 µg/mL NE was successfully implemented in a pharmacy department. Storage of the preparations at refrigerated temperatures is required to obtain acceptable shelf-lives of 6–12 months. Elevated temperatures and especially exposure to mixed daylight significantly decreased the shelf life.
{"title":"Stability of Ready-to-Administer and Ready-to-Use Epinephrine and Norepinephrine Injection Solutions","authors":"R. Heeb, B. Stollhof, J. Reichhold, J. Thiesen, I. Krämer","doi":"10.1515/pthp-2017-0024","DOIUrl":"https://doi.org/10.1515/pthp-2017-0024","url":null,"abstract":"Abstract Background In the University Medical Centre Mainz, standard concentrations are defined for medicinal products to be administered by continuous injection with syringe pumps in adult intensive care patients. The objective of this study was to evaluate the physicochemical stability of ready-to-use and ready-to-administer preparations containing Epinephrine (E) and Norepinephrine (NE) in standardized concentrations and prepared batch wise in the pharmacy department as basis for assigning shelf-lives. Methods E 20 µg/mL and NE 10 µg/mL in disposable syringes and NE 40, 100, 200, 400 µg/ml in 50 ml amber type I glass vials were prepared batch wise and the concentrations were analyzed by stability-indicating, validated reversed-phase HPLC-PDA assays. Test solutions for long-term stability studies were stored under refrigeration (2–8 °C) for 6–12 months or at elevated temperatures (21–27 °C) light protected for up to 6 months or without light protection for up to one month. Osmolality and pH were measured on predefined intervals. Results The concentrations of E in 50 mL syringes and NE in 10 mL syringes remained unchanged over a period of 6 months when stored at 2–8 °C. NE preparations of different concentrations prepared in amber glass vials remained stable over a study period of 12 months. At RT the shelf-life decreased to about 6 months and the exposure to mixed daylight at RT caused loss of stability in only few days. Conclusions Batch wise preparation of ready-to-administer (RTA) preparations containing 20 µg/mL E or 10 µg/mL NE in disposable syringes as well as ready-to-use (RTU) preparations containing 40, 100, 200 and 400 µg/mL NE was successfully implemented in a pharmacy department. Storage of the preparations at refrigerated temperatures is required to obtain acceptable shelf-lives of 6–12 months. Elevated temperatures and especially exposure to mixed daylight significantly decreased the shelf life.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"245 1","pages":"159 - 171"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74115812","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}
G. Binson, N. Venisse, A. Bacle, K. Beuzit, A. Dupuis
Abstract Background Dexamethasone is commonly used to treat a wide variety of diseases including oncological disorders. The aim of this study was to propose a liquid formulation of dexamethasone. Therefore we have developed and assessed the stability of a 5 mg/mL dexamethasone oral suspension. Methods A stability-indicating analytical method, using HPLC-UV, was developed and fully validated according to well-recognized international guidelines. The dexamethasone suspension was prepared using dexamethasone acetate powder and Ora-Sweet® plus Ora-Plus® suspending vehicles (1:1, v:v). Compounded oral suspension were packaged in amber type I glass bottles. In order to assess physical and chemical stability of dexamethasone in oral suspension, six batches of the formulation were prepared and stored at 4±2 °C or at 21±3 °C. Physical parameters (appearance, pH) were assessed as well as dexamethasone content, at day 0, 7, 14, 30 and 60. Results The mean dexamethasone concentration of the compounded oral suspensions was equal to 5.07±0.17 mg/mL. No colour modifications, precipitate or suspending troubles was observed throughout the storage period and the pH of the oral suspensions was decreased slightly, from 4.41±0.01 to 4.20±0.02. According to the dexamethasone content determined by HPLC-UV, whatever storage condition was used, no significant degradation of dexamethasone occurred over the 60 days of the study period. Conclusion Dexamethasone oral suspension prepared according to our conditions is stable over 60 days under regular storage temperatures (at 4±2 °C or at 21±3 °C).
{"title":"Preparation and Physico-Chemical Stability of Dexamethasone Oral Suspension","authors":"G. Binson, N. Venisse, A. Bacle, K. Beuzit, A. Dupuis","doi":"10.1515/pthp-2017-0029","DOIUrl":"https://doi.org/10.1515/pthp-2017-0029","url":null,"abstract":"Abstract Background Dexamethasone is commonly used to treat a wide variety of diseases including oncological disorders. The aim of this study was to propose a liquid formulation of dexamethasone. Therefore we have developed and assessed the stability of a 5 mg/mL dexamethasone oral suspension. Methods A stability-indicating analytical method, using HPLC-UV, was developed and fully validated according to well-recognized international guidelines. The dexamethasone suspension was prepared using dexamethasone acetate powder and Ora-Sweet® plus Ora-Plus® suspending vehicles (1:1, v:v). Compounded oral suspension were packaged in amber type I glass bottles. In order to assess physical and chemical stability of dexamethasone in oral suspension, six batches of the formulation were prepared and stored at 4±2 °C or at 21±3 °C. Physical parameters (appearance, pH) were assessed as well as dexamethasone content, at day 0, 7, 14, 30 and 60. Results The mean dexamethasone concentration of the compounded oral suspensions was equal to 5.07±0.17 mg/mL. No colour modifications, precipitate or suspending troubles was observed throughout the storage period and the pH of the oral suspensions was decreased slightly, from 4.41±0.01 to 4.20±0.02. According to the dexamethasone content determined by HPLC-UV, whatever storage condition was used, no significant degradation of dexamethasone occurred over the 60 days of the study period. Conclusion Dexamethasone oral suspension prepared according to our conditions is stable over 60 days under regular storage temperatures (at 4±2 °C or at 21±3 °C).","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"12 1","pages":"193 - 201"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85344265","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 Background Profound knowledge about the physicochemical stability is necessary in order to determine the “beyond-use-dates” of ready-to-administer preparations after reconstitution and dilution. This is especially true for unstable azanucleoside drugs like decitabine. The aim of this study was to determine the physicochemical stability of decitabine after reconstitution and dilution of Dacogen® 50 mg lyophilized powder. Decitabine concentration of Dacogen® powder reconstituted with cold water for injections (5 mg/mL) has been determined after storage in the original vials under refrigeration for 48 hours and in single use syringes in a freezer at –25 °C for 28 days. Concentration of diluted decitabine infusion solutions (0.5 mg/mL) prepared in prefilled 0.9 % NaCl polyolefine (PO) infusion bags has been determined after storage under refrigeration (2–8 °C) for 48 hours. Methods To determine the stability of frozen Dacogen® solutions the powder was reconstituted with 10 mL of cold (2–8 °C) sterile water for injections, transferred into 1 mL plastic polycarbonate (PC)/polypropylene (PP) syringes and stored at –25 °C. Decitabine concentrations were determined on day 0, 22 and 28 after thawing at room temperature immediately before assaying. In parallel, pH-values were determined. To determine the stability of reconstituted Dacogen® 50 mg powder in the original glass vials, three Dacogen® 50 mg vials were aseptically reconstituted with 10 mL of cold sterile water. The reconstituted solutions were stored under refrigeration and decitabine concentrations were determined at 0, 3, 7, 12 and 24 hours after reconstitution. The pH-values were determined at 0, 7 and 24 hours. Diluted Dacogen® test solutions were aseptically prepared by adding 2 mL of the reconstituted Dacogen® solution from each of the three vials to 18 mL cold (2–8 °C) 0.9 % NaCl solution in prefilled multi-layer PO infusion bags of the nominal value 50 mL. Test solutions of the nominal concentration 0.5 mg/mL were stored under refrigeration. Decitabine concentrations were determined at 0, 5, 8, 12, 24 and 48 hours after preparation. The pH-values were determined at 0, 8, 24 and 48 hours. Each sample was assayed by a validated stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with photodiode array detection. Results When test solutions of reconstituted Dacogen® solution were stored frozen at −25 °C, decitabine concentrations decreased less than 2 % and no degradation products were detected in the HPLC chromatograms over the storage period of 28 days. In reconstituted test solutions in glass vials and in diluted test solutions in infusion bags stored under refrigeration decitabine concentrations remained above 90 % of the initial concentration for 12 hours and 24 hours, respectively. Several peaks of degradation products were observed which explicitly increased over time. In all test solutions the pH-values amounted to pH 7 and remained uncha
{"title":"Physicochemical Stability of Reconstituted Decitabine (Dacogen®) Solutions and Ready-to-Administer Infusion Bags when Stored Refrigerated or Frozen","authors":"S. H. Kim, R. Heeb, I. Krämer","doi":"10.1515/pthp-2017-0025","DOIUrl":"https://doi.org/10.1515/pthp-2017-0025","url":null,"abstract":"Abstract Background Profound knowledge about the physicochemical stability is necessary in order to determine the “beyond-use-dates” of ready-to-administer preparations after reconstitution and dilution. This is especially true for unstable azanucleoside drugs like decitabine. The aim of this study was to determine the physicochemical stability of decitabine after reconstitution and dilution of Dacogen® 50 mg lyophilized powder. Decitabine concentration of Dacogen® powder reconstituted with cold water for injections (5 mg/mL) has been determined after storage in the original vials under refrigeration for 48 hours and in single use syringes in a freezer at –25 °C for 28 days. Concentration of diluted decitabine infusion solutions (0.5 mg/mL) prepared in prefilled 0.9 % NaCl polyolefine (PO) infusion bags has been determined after storage under refrigeration (2–8 °C) for 48 hours. Methods To determine the stability of frozen Dacogen® solutions the powder was reconstituted with 10 mL of cold (2–8 °C) sterile water for injections, transferred into 1 mL plastic polycarbonate (PC)/polypropylene (PP) syringes and stored at –25 °C. Decitabine concentrations were determined on day 0, 22 and 28 after thawing at room temperature immediately before assaying. In parallel, pH-values were determined. To determine the stability of reconstituted Dacogen® 50 mg powder in the original glass vials, three Dacogen® 50 mg vials were aseptically reconstituted with 10 mL of cold sterile water. The reconstituted solutions were stored under refrigeration and decitabine concentrations were determined at 0, 3, 7, 12 and 24 hours after reconstitution. The pH-values were determined at 0, 7 and 24 hours. Diluted Dacogen® test solutions were aseptically prepared by adding 2 mL of the reconstituted Dacogen® solution from each of the three vials to 18 mL cold (2–8 °C) 0.9 % NaCl solution in prefilled multi-layer PO infusion bags of the nominal value 50 mL. Test solutions of the nominal concentration 0.5 mg/mL were stored under refrigeration. Decitabine concentrations were determined at 0, 5, 8, 12, 24 and 48 hours after preparation. The pH-values were determined at 0, 8, 24 and 48 hours. Each sample was assayed by a validated stability-indicating reversed-phase high-performance liquid chromatography (RP-HPLC) assay with photodiode array detection. Results When test solutions of reconstituted Dacogen® solution were stored frozen at −25 °C, decitabine concentrations decreased less than 2 % and no degradation products were detected in the HPLC chromatograms over the storage period of 28 days. In reconstituted test solutions in glass vials and in diluted test solutions in infusion bags stored under refrigeration decitabine concentrations remained above 90 % of the initial concentration for 12 hours and 24 hours, respectively. Several peaks of degradation products were observed which explicitly increased over time. In all test solutions the pH-values amounted to pH 7 and remained uncha","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"50 1","pages":"145 - 157"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85651392","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. Robert, J. Sorrieul, H. Kieffer, C. Folliard, V. Gibory, D. Dupoiron, C. Devys
Abstract Background The association of morphine and baclofen is used for the treatment of spasticity related pain. Moving these patients is sometimes difficult. In order to transport these syringes for pump refilling, it could be interesting to demonstrate the stability of the mixture, and so to be able to ensure the best transport conditions of syringes. Methods A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Two mixtures of morphine and baclofen – a low concentration mixture (morphine 1 mg/mL – baclofen 0.08 mg/mL) and a high concentration mixture (morphine 10 mg/mL – baclofen 1.6 mg/mL) stored in 5±3 °C and 25±2 °C were evaluated for seven days and compared to the initial observed concentrations. Results The stability of the low and high mixture is demonstrated for both storage conditions for seven days thanks to relative concentrations (95 % confidence intervals of the mean of 3 samples) systematically positioned between 95 % and 105 %. No degradation product was observed during the stability study. Conclusion This study shows the stability of a weakly concentrated mixture and a highly concentrated mixture of morphine and baclofen. Extrapolation of these data to an intermediate mixture may be considered. Further studies will support this hypothesis. This result will allow the transport of the preparation under optimal conditions. Advance preparations for intrathecal pump refills could also be feasible.
{"title":"Stability Study of Morphine and Baclofen Solution in Polypropylene Syringes","authors":"J. Robert, J. Sorrieul, H. Kieffer, C. Folliard, V. Gibory, D. Dupoiron, C. Devys","doi":"10.1515/pthp-2017-0028","DOIUrl":"https://doi.org/10.1515/pthp-2017-0028","url":null,"abstract":"Abstract Background The association of morphine and baclofen is used for the treatment of spasticity related pain. Moving these patients is sometimes difficult. In order to transport these syringes for pump refilling, it could be interesting to demonstrate the stability of the mixture, and so to be able to ensure the best transport conditions of syringes. Methods A stability indicating UPLC-DAD method was developed and validated according to the ICH guidelines. Two mixtures of morphine and baclofen – a low concentration mixture (morphine 1 mg/mL – baclofen 0.08 mg/mL) and a high concentration mixture (morphine 10 mg/mL – baclofen 1.6 mg/mL) stored in 5±3 °C and 25±2 °C were evaluated for seven days and compared to the initial observed concentrations. Results The stability of the low and high mixture is demonstrated for both storage conditions for seven days thanks to relative concentrations (95 % confidence intervals of the mean of 3 samples) systematically positioned between 95 % and 105 %. No degradation product was observed during the stability study. Conclusion This study shows the stability of a weakly concentrated mixture and a highly concentrated mixture of morphine and baclofen. Extrapolation of these data to an intermediate mixture may be considered. Further studies will support this hypothesis. This result will allow the transport of the preparation under optimal conditions. Advance preparations for intrathecal pump refills could also be feasible.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"24 1","pages":"173 - 180"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86752520","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}
The preparation of medications is a fundamental part of the pharmacist’s profession. Today, hospital pharmacists prepare mainly sterile products i. e. anticancer drugs, antibiotics, medications for intensive care units in Centralized Intravenous Additive Services (CIVAS), eye-drops or parenteral nutrition especially for pediatrics. Oral solutions are prepared for patients who have difficulties to swallow such as pediatric or elderly patients. The more traditional preparations (such as capsules or unguents) are still carried out but today represent a small part of the activity of pharmacotechnics. Nevertheless, for all these preparations, hospital pharmacists need stability data to assign a shelf life to their compounded products. The need for stability studies is huge and this field of activity is a part of our mission defined in the official Good Manufacturing Practices (GMP) for compounding pharmacies. These GMP guidelines are similar in many countries. For example, in the French guidelines, the text makes it clear in chapter 1 that “The shelf life of the preparations can be determined by using bibliographic references or by performing stability studies.” and in chapter 2 “Control”: The hospital pharmacist has various missions including ... “the control of stability” [1]. Here is a non-exhaustive list of examples of stability studies which can be performed by hospital or university teams: – intravenous (IV) mixtures used in intensive care units or oncology, – parenteral (IV or subcutaneous) new monoclonal antibodies that are often prepared in advance or can be conserved if the prescription is cancelled after the preparation, – oral solutions for pediatrics or geriatrics, – very expensive drugs in the case of limited stability data provided by the manufacturers, to save money, – dilutions of antibiotics in unusual solvents such as peritoneal dialysis solutions, – anticancer drugs at elevated temperatures for intraperitoneal hyperthermic chemotherapy, – leaching of plasticizers into the solutions from containers. Diethylhexylphtalate (DEHP) is a well-known example of potentially toxic additive used in polyvinyl chloride containers but other less known products can leach into the solution and be potentially harmful to the patient, – etc.
{"title":"Stability Studies: A Scientific Mission of the Hospital Pharmacist","authors":"J. Vigneron","doi":"10.1515/pthp-2017-0032","DOIUrl":"https://doi.org/10.1515/pthp-2017-0032","url":null,"abstract":"The preparation of medications is a fundamental part of the pharmacist’s profession. Today, hospital pharmacists prepare mainly sterile products i. e. anticancer drugs, antibiotics, medications for intensive care units in Centralized Intravenous Additive Services (CIVAS), eye-drops or parenteral nutrition especially for pediatrics. Oral solutions are prepared for patients who have difficulties to swallow such as pediatric or elderly patients. The more traditional preparations (such as capsules or unguents) are still carried out but today represent a small part of the activity of pharmacotechnics. Nevertheless, for all these preparations, hospital pharmacists need stability data to assign a shelf life to their compounded products. The need for stability studies is huge and this field of activity is a part of our mission defined in the official Good Manufacturing Practices (GMP) for compounding pharmacies. These GMP guidelines are similar in many countries. For example, in the French guidelines, the text makes it clear in chapter 1 that “The shelf life of the preparations can be determined by using bibliographic references or by performing stability studies.” and in chapter 2 “Control”: The hospital pharmacist has various missions including ... “the control of stability” [1]. Here is a non-exhaustive list of examples of stability studies which can be performed by hospital or university teams: – intravenous (IV) mixtures used in intensive care units or oncology, – parenteral (IV or subcutaneous) new monoclonal antibodies that are often prepared in advance or can be conserved if the prescription is cancelled after the preparation, – oral solutions for pediatrics or geriatrics, – very expensive drugs in the case of limited stability data provided by the manufacturers, to save money, – dilutions of antibiotics in unusual solvents such as peritoneal dialysis solutions, – anticancer drugs at elevated temperatures for intraperitoneal hyperthermic chemotherapy, – leaching of plasticizers into the solutions from containers. Diethylhexylphtalate (DEHP) is a well-known example of potentially toxic additive used in polyvinyl chloride containers but other less known products can leach into the solution and be potentially harmful to the patient, – etc.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"44 1","pages":"143 - 144"},"PeriodicalIF":0.0,"publicationDate":"2017-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80067759","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}
{"title":"Quality Assurance in Hospital Pharmacy Compounding Units is a Multi Player Game","authors":"F. Lagarce","doi":"10.1515/pthp-2017-0027","DOIUrl":"https://doi.org/10.1515/pthp-2017-0027","url":null,"abstract":"","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"21 1","pages":"97 - 98"},"PeriodicalIF":0.0,"publicationDate":"2017-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73474946","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 Background A method for process monitoring of the Baxter ACD, Exactamix EM2400, by chemically analyzing the concentrations of the ingredients in parenteral nutrition test preparations was evaluated. Methods In the study, three different test preparations were developed consisting of four ingredients varying in volume and concentration, which simulated actual PN products. Each test preparation was produced in triplicate by a trained pharmacy technician using the Exactamix EM2400 from Baxter (Baxter International Inc.). The process was repeated on three consecutive days using the same conditions. The amount of each ingredient in the test preparation was measured in an external contract laboratory using European Pharmacopoeia methods. Based on USP monographies and the Guidelines on the Safe Use of Automated Compounding Devices for the Preparation of Parenteral Nutrition from the ASHP the device was tested to be accurate to deliver within 5 % of the amount programmed. Results The study showed that in most cases the ingredient delivery of the automated compounder deviated less than 3 % from the expected concentrations. For certain ingredients out of specification results were detected and analyzed. By resetting the flow factor, it was possible to optimize the performance of the ACD. Conclusion The study emphasizes the need for process monitoring of the Exactamix EM2400 during the initial installation and on a regular basis for each ingredient to ensure the accurate delivery of ingredients. Further methods need to be analyzed to determine the most feasible method to regularly conduct process monitoring tests on an ACD in a hospital pharmacy setting.
摘要背景通过分析肠外营养试验制剂中各成分的浓度，探讨了一种用于百特ACD (Exactamix EM2400)过程监测的方法。方法采用四种不同体积和浓度的成分组成三种不同的试验制剂，模拟实际生产的PN产品。每种制剂由训练有素的药学技术人员使用百特公司(Baxter International Inc.)的Exactamix EM2400生产，一式三份。在相同的条件下，连续三天重复该过程。试验制剂中每种成分的量在外部合同实验室使用欧洲药典方法进行测量。根据USP专著和安全使用自动配制设备从空气源热泵制备肠外营养的指南，该设备被测试准确地在程序量的5%内交付。结果研究表明，在大多数情况下，自动复合物的成分传递偏离预期浓度不到3%。对某些不合格成分进行了检测和分析。通过重置流量系数，可以优化ACD的性能。结论本研究强调了在初始安装过程中对Exactamix EM2400进行工艺监测的必要性，并对每种成分进行定期监测，以确保成分的准确输送。需要分析进一步的方法，以确定在医院药房环境中定期对ACD进行过程监测测试的最可行方法。
{"title":"Evaluation of a Process Monitoring Method for Compounding Parenteral Nutrition with the Baxter EM2400 in a Hospital Pharmacy Department","authors":"C. Collins, I. Krämer","doi":"10.1515/pthp-2017-0019","DOIUrl":"https://doi.org/10.1515/pthp-2017-0019","url":null,"abstract":"Abstract Background A method for process monitoring of the Baxter ACD, Exactamix EM2400, by chemically analyzing the concentrations of the ingredients in parenteral nutrition test preparations was evaluated. Methods In the study, three different test preparations were developed consisting of four ingredients varying in volume and concentration, which simulated actual PN products. Each test preparation was produced in triplicate by a trained pharmacy technician using the Exactamix EM2400 from Baxter (Baxter International Inc.). The process was repeated on three consecutive days using the same conditions. The amount of each ingredient in the test preparation was measured in an external contract laboratory using European Pharmacopoeia methods. Based on USP monographies and the Guidelines on the Safe Use of Automated Compounding Devices for the Preparation of Parenteral Nutrition from the ASHP the device was tested to be accurate to deliver within 5 % of the amount programmed. Results The study showed that in most cases the ingredient delivery of the automated compounder deviated less than 3 % from the expected concentrations. For certain ingredients out of specification results were detected and analyzed. By resetting the flow factor, it was possible to optimize the performance of the ACD. Conclusion The study emphasizes the need for process monitoring of the Exactamix EM2400 during the initial installation and on a regular basis for each ingredient to ensure the accurate delivery of ingredients. Further methods need to be analyzed to determine the most feasible method to regularly conduct process monitoring tests on an ACD in a hospital pharmacy setting.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"27 3 1","pages":"107 - 115"},"PeriodicalIF":0.0,"publicationDate":"2017-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78169839","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 Background In France, control of chemotherapy preparations is highly recommended. Analytical control is a method of choice for identifying and quantifying drugs. Pediatric preparations, which often contain small quantities of drugs and are made in low final volumes were until then not analytically controlled. After the development and validation of a new sampling and assaying method for low volume chemotherapy preparations with an UV/Raman automaton (QCPrep +), the quality control results of the preparations intended for the patients were analyzed over a period of eighteen months Methods The results were studied by type of preparation (low and high volume), per molecule, manipulator, and conformity rates dispersion. Results Over the period, 7,548 controls were carried out, representing 87.7% of our production. 75.5% of these controls concerned low-volume preparations (<50mL). The overall conformity rate was 94.4%. The lowest conformity rates were found for vinca alkaloids, methotrexate and some rarely manipulated drugs (cisplatin, decitabine, epirubicin). The study of the results dispersion showed non-conformities increasing with low concentrations, specific to pediatrics. These results show the limits of analytical control for pediatric preparations. The low analytical sensitivity encountered for certain concentrations and drugs requires a complementary quality control tool, like camera or video. However this new analytical method allows us to improve the safety of the injectable chemotherapy circuit. Conclusion Young patients can benefit from the same level of safety and quality as adult patients. Some critical points could be highlighted: the homogenization of the preparations, the analytical sensitivity of some drugs and human factors. This data allow us to focus our work on staff training, improving our calibration ranges and on the development of complementary control tools.
{"title":"Analytical Control of Pediatric Chemotherapy Preparations with a UV-Raman Automaton: Results After 18 Months of Implementation and Development of A Suitable Method for Low Volume Preparations","authors":"T. Chouquet, G. Benoit, K. Morand","doi":"10.1515/pthp-2017-0021","DOIUrl":"https://doi.org/10.1515/pthp-2017-0021","url":null,"abstract":"Abstract Background In France, control of chemotherapy preparations is highly recommended. Analytical control is a method of choice for identifying and quantifying drugs. Pediatric preparations, which often contain small quantities of drugs and are made in low final volumes were until then not analytically controlled. After the development and validation of a new sampling and assaying method for low volume chemotherapy preparations with an UV/Raman automaton (QCPrep +), the quality control results of the preparations intended for the patients were analyzed over a period of eighteen months Methods The results were studied by type of preparation (low and high volume), per molecule, manipulator, and conformity rates dispersion. Results Over the period, 7,548 controls were carried out, representing 87.7% of our production. 75.5% of these controls concerned low-volume preparations (<50mL). The overall conformity rate was 94.4%. The lowest conformity rates were found for vinca alkaloids, methotrexate and some rarely manipulated drugs (cisplatin, decitabine, epirubicin). The study of the results dispersion showed non-conformities increasing with low concentrations, specific to pediatrics. These results show the limits of analytical control for pediatric preparations. The low analytical sensitivity encountered for certain concentrations and drugs requires a complementary quality control tool, like camera or video. However this new analytical method allows us to improve the safety of the injectable chemotherapy circuit. Conclusion Young patients can benefit from the same level of safety and quality as adult patients. Some critical points could be highlighted: the homogenization of the preparations, the analytical sensitivity of some drugs and human factors. This data allow us to focus our work on staff training, improving our calibration ranges and on the development of complementary control tools.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"19 1","pages":"117 - 129"},"PeriodicalIF":0.0,"publicationDate":"2017-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78981220","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：