A. Hausherr, Clara Roessle, Emma Pinet, V. Vasseur, T. Abarou, Samira Benakouche, O. Bourdon, T. Storme
Abstract Objectives Drugs are developed for adults, making it difficult to find suitable treatments for children. Hospital pharmacy has developed alternatives to respond to this medical need. The objective of this study is to present a new liquid formulation of ursodeoxycholic acid (UDCA) at a concentration suitable for treatment of neonatal jaundice, and to introduce a novel high pressure liquid chromatography (HPLC) assay method. Methods Four formulations have been developed using suspension vehicles due to the low solubility of the active ingredient, and different concentrations of excipient, xanthan gum, needed to facilitate resuspension. An HPLC method coupled to a diode array detector (DAD) has been developed. This method was used to analyze chemical and microbiologic stabilities, as well as physicochemical properties and palatability. Results After formulation was chosen, our new HPLC method assay was developed and validated for the quantification of chemical and microbiological stabilities of our product. Both parameters were stable over three months. Palatability has been improved thanks to the addition of universal suspension adjuvants. Odor, appearance and taste were judged pleasant despite a bitter aftertaste, with a persistence of the UDCA resuspension after one month. Conclusions Three months after informing neonatal department about the availability of the drug, patients and caregivers are satisfied, and production campaigns are routinely planned.
{"title":"Development and validation of a new HPLC method for the analysis of a novel oral suspension formulation of 50 mg/ml ursodeoxycholic acid for newborns","authors":"A. Hausherr, Clara Roessle, Emma Pinet, V. Vasseur, T. Abarou, Samira Benakouche, O. Bourdon, T. Storme","doi":"10.1515/pthp-2020-0006","DOIUrl":"https://doi.org/10.1515/pthp-2020-0006","url":null,"abstract":"Abstract Objectives Drugs are developed for adults, making it difficult to find suitable treatments for children. Hospital pharmacy has developed alternatives to respond to this medical need. The objective of this study is to present a new liquid formulation of ursodeoxycholic acid (UDCA) at a concentration suitable for treatment of neonatal jaundice, and to introduce a novel high pressure liquid chromatography (HPLC) assay method. Methods Four formulations have been developed using suspension vehicles due to the low solubility of the active ingredient, and different concentrations of excipient, xanthan gum, needed to facilitate resuspension. An HPLC method coupled to a diode array detector (DAD) has been developed. This method was used to analyze chemical and microbiologic stabilities, as well as physicochemical properties and palatability. Results After formulation was chosen, our new HPLC method assay was developed and validated for the quantification of chemical and microbiological stabilities of our product. Both parameters were stable over three months. Palatability has been improved thanks to the addition of universal suspension adjuvants. Odor, appearance and taste were judged pleasant despite a bitter aftertaste, with a persistence of the UDCA resuspension after one month. Conclusions Three months after informing neonatal department about the availability of the drug, patients and caregivers are satisfied, and production campaigns are routinely planned.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76208360","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}
C. Merienne, C. Marchand, S. Filali, D. Salmon, C. Pivot, F. Pirot
Abstract Background Stability of low amoxicillin oral dosage form (5 mg) used in reintroduction drug test was not fully documented. Furthermore, the impact of (1) salt moiety of amoxicillin and (2) amoxicillin – excipient interactions upon the antibiotic formulation stability during the storage was not characterized so that the estimation of the pharmaceutical expiration date from shelf-life was uncertain. Thus, the main goal of this study was to estimate the shelf-life of two formulations of amoxicillin, using a semi-predictive methodology. Methods Amoxicillin sodium (AS) and amoxicillin trihydrate (ATH), corresponding to 5-mg amoxicillin, were compounded with microcrystalline cellulose (MCC) in oral hard capsules which were, then, submitted to four environmental conditions (25 °C / 60% or 80% relative humidity (RH); 40 °C / 75% RH; 60 °C / 5% RH) in climatic chambers for 45 and 84 days. Therefore, the characterization of amoxicillin-MCC mixture was assessed by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) The profiles of amoxicillin content (determined by stability indicating chromatographic method) as a function of storage time, temperature and RH were fitted to pre-defined kinetic models performed by accelerated predictive stability (APS). Results ATR-FTIR analysis of AS, ATH, MCC and bulk specimens stored in heated and humid atmosphere confirmed water sorption to cellulose described by a broad and unresolved 3600 to 3000 cm−1 band associated with (1) general intramolecular and intermolecular hydrogen bonding between water and hydroxyl groups of the cellulose, and with (2) free hydroxyl in cellulose. Moreover, a dramatic decrease of absorption at 1776 and 1687 cm−1 respectively characteristic of the β-lactam ring (ν C=O) and amide group (ν C=O), was revealed as a consequence of AS and ATH degradation caused by moisturization of bulk. Amoxicillin degradation was established by chromatographic analysis showing faster AS degradation than ATH throughout time exposure. The combined effects of temperature – RH were successfully modeled by APS, where AS and ATH showed accelerated (auto-catalysis degradation mechanism) and linear degradation, respectively. The faster AS degradation was assumed to be linked to lower hydrogen donor to hydrogen acceptor count ratio and polar surface than ATH, increasing the probability of AS hydrolysis by water adsorption to AS-MCC solid dispersion (e.g., by reduction of protective intramolecular hydrogen bonds between AS molecules). Furthermore, the compounding which involved a drastic homogenization of solids may have affected the crystalline degree of MCC with an increase of amorphous phase more sensitive to water adsorption. Conclusions The improvement of amoxicillin compounding for oral dose forms might be rationalized by taking into account the molecular descriptors of salt moiety and excipients, improved by the choice of an appropriate process of production, characterized from in
{"title":"Measurement, analysis and prediction of amoxicillin oral dose stability from integrated molecular description approach and accelerated predictive stability (APS)","authors":"C. Merienne, C. Marchand, S. Filali, D. Salmon, C. Pivot, F. Pirot","doi":"10.1515/pthp-2020-0009","DOIUrl":"https://doi.org/10.1515/pthp-2020-0009","url":null,"abstract":"Abstract Background Stability of low amoxicillin oral dosage form (5 mg) used in reintroduction drug test was not fully documented. Furthermore, the impact of (1) salt moiety of amoxicillin and (2) amoxicillin – excipient interactions upon the antibiotic formulation stability during the storage was not characterized so that the estimation of the pharmaceutical expiration date from shelf-life was uncertain. Thus, the main goal of this study was to estimate the shelf-life of two formulations of amoxicillin, using a semi-predictive methodology. Methods Amoxicillin sodium (AS) and amoxicillin trihydrate (ATH), corresponding to 5-mg amoxicillin, were compounded with microcrystalline cellulose (MCC) in oral hard capsules which were, then, submitted to four environmental conditions (25 °C / 60% or 80% relative humidity (RH); 40 °C / 75% RH; 60 °C / 5% RH) in climatic chambers for 45 and 84 days. Therefore, the characterization of amoxicillin-MCC mixture was assessed by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR) The profiles of amoxicillin content (determined by stability indicating chromatographic method) as a function of storage time, temperature and RH were fitted to pre-defined kinetic models performed by accelerated predictive stability (APS). Results ATR-FTIR analysis of AS, ATH, MCC and bulk specimens stored in heated and humid atmosphere confirmed water sorption to cellulose described by a broad and unresolved 3600 to 3000 cm−1 band associated with (1) general intramolecular and intermolecular hydrogen bonding between water and hydroxyl groups of the cellulose, and with (2) free hydroxyl in cellulose. Moreover, a dramatic decrease of absorption at 1776 and 1687 cm−1 respectively characteristic of the β-lactam ring (ν C=O) and amide group (ν C=O), was revealed as a consequence of AS and ATH degradation caused by moisturization of bulk. Amoxicillin degradation was established by chromatographic analysis showing faster AS degradation than ATH throughout time exposure. The combined effects of temperature – RH were successfully modeled by APS, where AS and ATH showed accelerated (auto-catalysis degradation mechanism) and linear degradation, respectively. The faster AS degradation was assumed to be linked to lower hydrogen donor to hydrogen acceptor count ratio and polar surface than ATH, increasing the probability of AS hydrolysis by water adsorption to AS-MCC solid dispersion (e.g., by reduction of protective intramolecular hydrogen bonds between AS molecules). Furthermore, the compounding which involved a drastic homogenization of solids may have affected the crystalline degree of MCC with an increase of amorphous phase more sensitive to water adsorption. Conclusions The improvement of amoxicillin compounding for oral dose forms might be rationalized by taking into account the molecular descriptors of salt moiety and excipients, improved by the choice of an appropriate process of production, characterized from in","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84276028","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}
S. Crauste-Manciet, I. Krämer, F. Lagarce, V. Sautou, A. Beaney, Julian Smith, V’Iain Fenton-May, J. Hecq, F. Sadeghipour, P. L. Brun
Abstract All dosage forms prepared in hospital pharmacies should be labelled with an appropriate shelf-life. This shelf-life should be validated taking chemical, physical and microbiological data into consideration. This guidance focuses on parenteral aseptically prepared products, as they are high-risk preparations. The risk is exacerbated by a requirement for longer shelf lives for reasons of economy and efficiency. The scope of this guidance includes individual patient preparations, preparations prepared in series (same type of preparation being repeatedly prepared) and batch preparations prepared from the same initial bulk admixture.
{"title":"GERPAC Consensus Conference – Guidance on the Assignment of Microbiological Shelf-life for Hospital Pharmacy Aseptic Preparations","authors":"S. Crauste-Manciet, I. Krämer, F. Lagarce, V. Sautou, A. Beaney, Julian Smith, V’Iain Fenton-May, J. Hecq, F. Sadeghipour, P. L. Brun","doi":"10.1515/pthp-2020-0001","DOIUrl":"https://doi.org/10.1515/pthp-2020-0001","url":null,"abstract":"Abstract All dosage forms prepared in hospital pharmacies should be labelled with an appropriate shelf-life. This shelf-life should be validated taking chemical, physical and microbiological data into consideration. This guidance focuses on parenteral aseptically prepared products, as they are high-risk preparations. The risk is exacerbated by a requirement for longer shelf lives for reasons of economy and efficiency. The scope of this guidance includes individual patient preparations, preparations prepared in series (same type of preparation being repeatedly prepared) and batch preparations prepared from the same initial bulk admixture.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81849637","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}
C. Curti, F. Mathias, Morane Savelli, P. Garrigue, E. Lamy, B. Guillet, P. Vanelle
Abstract Background Carbidopa is a drug mainly used to treat Parkinson’s disease. Associations with levodopa or with levodopa/entacapone are commercialized, but there is no oral formulation of carbidopa alone available in Europe. As carbidopa can also be used as premedication of adult patients for insulinoma diagnosis, it must be compounded as single dose mg capsules. The single dose administration of a magistral preparation implies the compounding of only one capsule, or the loss of consequent quantities of active pharmaceutical ingredient. As an alternative solution, carbidopa capsules could be compounded as batches of hospital preparation. Method With this objective, a stability-indicating dosing method for 200 mg carbidopa capsules was developed. Then, the compounding process was assessed according to the European Pharmacopeia requirements. Finally, the stability of carbidopa capsules stored protected from light at room temperature was studied for one year. Results 200 mg carbidopa capsules compounding process was validated on three independent batches. The beyond use date was fixed at one year. Conclusion Our work confirms that carbidopa 200 mg capsules can be realized in hospital pharmacy and its stability allows the compounding of large batches.
{"title":"Carbidopa Capsules for Insulinoma Diagnostic: Compounding and Stability Study","authors":"C. Curti, F. Mathias, Morane Savelli, P. Garrigue, E. Lamy, B. Guillet, P. Vanelle","doi":"10.1515/pthp-2019-0013","DOIUrl":"https://doi.org/10.1515/pthp-2019-0013","url":null,"abstract":"Abstract Background Carbidopa is a drug mainly used to treat Parkinson’s disease. Associations with levodopa or with levodopa/entacapone are commercialized, but there is no oral formulation of carbidopa alone available in Europe. As carbidopa can also be used as premedication of adult patients for insulinoma diagnosis, it must be compounded as single dose mg capsules. The single dose administration of a magistral preparation implies the compounding of only one capsule, or the loss of consequent quantities of active pharmaceutical ingredient. As an alternative solution, carbidopa capsules could be compounded as batches of hospital preparation. Method With this objective, a stability-indicating dosing method for 200 mg carbidopa capsules was developed. Then, the compounding process was assessed according to the European Pharmacopeia requirements. Finally, the stability of carbidopa capsules stored protected from light at room temperature was studied for one year. Results 200 mg carbidopa capsules compounding process was validated on three independent batches. The beyond use date was fixed at one year. Conclusion Our work confirms that carbidopa 200 mg capsules can be realized in hospital pharmacy and its stability allows the compounding of large batches.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"16 1","pages":"104 - 99"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82085560","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 the hospital setting, trace contamination with hazardous medications comes primarily from the manipulation of containers used in preparing and administering drugs. However, some traces of medications also come from the excreta of patients. Methods This descriptive exploratory study involved direct observation and discussion. The aim was to map potential contamination associated with handling babies’ excreta through diaper management. The study was conducted at CHU Sainte Justine (Montréal, Québec, Canada), a 500-bed mother and child facility with 38 beds for hematology-oncology and bone marrow transplant. A list of key steps related to the management of diapers by a parent or caregiver on a pediatric unit was established by the investigators. A data collection grid was then developed and reviewed by a member of the research team. Results A total of six diaper changes, by six distinct individuals, were observed in August and September 2019. Transport of a soiled diaper for weighing outside the baby’s room by an additional caregiver was also observed and recorded. In total, 25 individual steps in diaper management and 28 potential failure modes were identified through mapping. Conclusions Changing a baby’s diaper involves many individual steps, which are subject to numerous failure modes that can contribute to contamination with traces of hazardous drugs. A good understanding of these process steps and failure modes is desirable to better train caregivers and parents to reduce trace contamination with hazardous drugs.
{"title":"Surface Contamination by Antineoplastics in Hospitals: An Observational Study for Mapping of Potential Contamination Associated with Handling Excreta of Babies through Diaper Management","authors":"Marie Palamini, G. Mercier, J. Bussières","doi":"10.1515/pthp-2019-0019","DOIUrl":"https://doi.org/10.1515/pthp-2019-0019","url":null,"abstract":"Abstract Background In the hospital setting, trace contamination with hazardous medications comes primarily from the manipulation of containers used in preparing and administering drugs. However, some traces of medications also come from the excreta of patients. Methods This descriptive exploratory study involved direct observation and discussion. The aim was to map potential contamination associated with handling babies’ excreta through diaper management. The study was conducted at CHU Sainte Justine (Montréal, Québec, Canada), a 500-bed mother and child facility with 38 beds for hematology-oncology and bone marrow transplant. A list of key steps related to the management of diapers by a parent or caregiver on a pediatric unit was established by the investigators. A data collection grid was then developed and reviewed by a member of the research team. Results A total of six diaper changes, by six distinct individuals, were observed in August and September 2019. Transport of a soiled diaper for weighing outside the baby’s room by an additional caregiver was also observed and recorded. In total, 25 individual steps in diaper management and 28 potential failure modes were identified through mapping. Conclusions Changing a baby’s diaper involves many individual steps, which are subject to numerous failure modes that can contribute to contamination with traces of hazardous drugs. A good understanding of these process steps and failure modes is desirable to better train caregivers and parents to reduce trace contamination with hazardous drugs.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"14 1","pages":"119 - 125"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79897845","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}
Mathilde Royer, Maïté Libessart, Jean-Marc Dubaele, P. Tourneux, F. Marçon
Abstract Parenteral nutrition (PN) in the neonatal intensive care unit (NICU) involves a succession of risky processes. The objective was to identify and prioritize the risks associated with PN in order to improve the quality of the pathway. A failure modes, effects, and criticality analysis (FMECA) was used to identify potential PN pathway failure modes. A multidisciplinary working group conducted a functional analysis of the processes, then listed the failure modes (FM). The FM criticality was assessed on a scale from 1 to 5 for occurrence (O), severity (S), and detection (D). The risk priority number (RPN), ranging from 1 to 125, was calculated. The FMECA identified 99 FM (prescription (n=28), preparation (n=48), and administration (n=23)). The median RPN was 12, with scores ranging from 3 to 48. 25 % of the scores had an RPN>21.75. Among them, 12 were associated with prescription FM, 5 were associated with FM related to preparation and 8 were associated with a FM linked to administration. It allowed us to prioritize areas of potential quality improvement for parenteral nutrition of the preterm infant. The results demonstrated the need for the presence of a clinical pharmacist in the NICU to ensure the quality of PN process.
{"title":"Controlling Risks in the Compounding Process of Individually Formulated Parenteral Nutrition: Use of the FMECA Method (Failure modes, effects, and Criticality Analysis)","authors":"Mathilde Royer, Maïté Libessart, Jean-Marc Dubaele, P. Tourneux, F. Marçon","doi":"10.1515/pthp-2019-0020","DOIUrl":"https://doi.org/10.1515/pthp-2019-0020","url":null,"abstract":"Abstract Parenteral nutrition (PN) in the neonatal intensive care unit (NICU) involves a succession of risky processes. The objective was to identify and prioritize the risks associated with PN in order to improve the quality of the pathway. A failure modes, effects, and criticality analysis (FMECA) was used to identify potential PN pathway failure modes. A multidisciplinary working group conducted a functional analysis of the processes, then listed the failure modes (FM). The FM criticality was assessed on a scale from 1 to 5 for occurrence (O), severity (S), and detection (D). The risk priority number (RPN), ranging from 1 to 125, was calculated. The FMECA identified 99 FM (prescription (n=28), preparation (n=48), and administration (n=23)). The median RPN was 12, with scores ranging from 3 to 48. 25 % of the scores had an RPN>21.75. Among them, 12 were associated with prescription FM, 5 were associated with FM related to preparation and 8 were associated with a FM linked to administration. It allowed us to prioritize areas of potential quality improvement for parenteral nutrition of the preterm infant. The results demonstrated the need for the presence of a clinical pharmacist in the NICU to ensure the quality of PN process.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"37 1","pages":"105 - 112"},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75083890","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 Automated compounding systems appeared on the market during these last 15 years as an alternative for manual compounding of intravenous (IVD) drugs. A literature review was conducted on reconstitution of IVD. The following methods were identified: manual, semi- automatic and automatic. A classification was carried out in three categories: automatic syringes, peristaltic pumps, and compounding doses robots. The number of compounding robots is increasing. A table describes the different features of each device. The ampuls cannot be supported by these robots. Large doses vials improve the time of reconstitution compared to current dosage vials. Advantages of automated preparation are: higher consistency of process and products, higher accuracy of products, Integrated digitized processing, precise, complete documentation, reduced effort and wrist injuries, reduced personnel requirement, increased worker satisfaction. Disadvantages of automated preparation are: risk of failure/down time, dependency on power supply, software (updates), high investment costs/high maintenance costs, specialized personnel with additional training, decreased worker satisfaction (early adopter), complexity when products are switched or added, potential for new errors. This review allows the potential user to know the current availability on the market.
{"title":"Automated Compounding of Intravenous Therapy in European Countries: A Review in 2019","authors":"L. Soumoy, J. Hecq","doi":"10.1515/pthp-2019-0008","DOIUrl":"https://doi.org/10.1515/pthp-2019-0008","url":null,"abstract":"Abstract Automated compounding systems appeared on the market during these last 15 years as an alternative for manual compounding of intravenous (IVD) drugs. A literature review was conducted on reconstitution of IVD. The following methods were identified: manual, semi- automatic and automatic. A classification was carried out in three categories: automatic syringes, peristaltic pumps, and compounding doses robots. The number of compounding robots is increasing. A table describes the different features of each device. The ampuls cannot be supported by these robots. Large doses vials improve the time of reconstitution compared to current dosage vials. Advantages of automated preparation are: higher consistency of process and products, higher accuracy of products, Integrated digitized processing, precise, complete documentation, reduced effort and wrist injuries, reduced personnel requirement, increased worker satisfaction. Disadvantages of automated preparation are: risk of failure/down time, dependency on power supply, software (updates), high investment costs/high maintenance costs, specialized personnel with additional training, decreased worker satisfaction (early adopter), complexity when products are switched or added, potential for new errors. This review allows the potential user to know the current availability on the market.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"149 1","pages":"51 - 57"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75884209","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 Propofol and remifentanil often need to be co-administered via the same intravenous catheter line, which predisposes to potential compatibility issues. Our aim was to determine and compare the emulsion stability of three propofol formulations, two with medium chain triglycerides and one with long chain triglycerides, when administered together with remifentanil hydrochloride. Methods Remifentanil hydrochloride (Ultiva®) 50 µg/mL was mixed with two concentrations (10 and 20 mg/mL) of each propofol formulation in mixing ratios 10+1, 20+1, 1+1 and 1+20. Emulsion stability was assessed immediately after mixing and 4 hours later by measurements of pH, mean droplet diameter, polydispersity index, and calculating percentage of fat residing in globules>5 µm (PFAT5). Results High PFAT5 values were observed in certain mixing ratios. The correlation between elevated PFAT5 and high propofol concentration (20 mg/mL), when remifentanil was in abundance and for long contact time indicated that these factors influenced the stability of the propofol emulsions. Conclusions Stability differences between the propofol formulations were identified under extreme test conditions. Co-administration of remifentanil and propofol in the same i.v. line is safe when propofol is in abundance. Caution is advised when remifentanil is present in equal parts or in abundance when co-administered with propofol 20 mg/mL.
{"title":"Emulsion Stability of Different Intravenous Propofol Formulations in Simulated Co-Administration with Remifentanil Hydrochloride","authors":"N. Nilsson, K. Nezvalova-Henriksen, I. Tho","doi":"10.1515/pthp-2019-0014","DOIUrl":"https://doi.org/10.1515/pthp-2019-0014","url":null,"abstract":"Abstract Background Propofol and remifentanil often need to be co-administered via the same intravenous catheter line, which predisposes to potential compatibility issues. Our aim was to determine and compare the emulsion stability of three propofol formulations, two with medium chain triglycerides and one with long chain triglycerides, when administered together with remifentanil hydrochloride. Methods Remifentanil hydrochloride (Ultiva®) 50 µg/mL was mixed with two concentrations (10 and 20 mg/mL) of each propofol formulation in mixing ratios 10+1, 20+1, 1+1 and 1+20. Emulsion stability was assessed immediately after mixing and 4 hours later by measurements of pH, mean droplet diameter, polydispersity index, and calculating percentage of fat residing in globules>5 µm (PFAT5). Results High PFAT5 values were observed in certain mixing ratios. The correlation between elevated PFAT5 and high propofol concentration (20 mg/mL), when remifentanil was in abundance and for long contact time indicated that these factors influenced the stability of the propofol emulsions. Conclusions Stability differences between the propofol formulations were identified under extreme test conditions. Co-administration of remifentanil and propofol in the same i.v. line is safe when propofol is in abundance. Caution is advised when remifentanil is present in equal parts or in abundance when co-administered with propofol 20 mg/mL.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"12 1","pages":"77 - 87"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89518706","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. Bourbon, A. Dory, L. Perello, Laure Belotti, F. Reisz, G. Ubeaud‐Séquier, B. Gourieux
Abstract Background Urea is recommended in the 2nd line treatment in moderate to severe hyponatraemia induced by syndrome of inappropriate antidiuretic hormone secretion (SIADH), when water restriction is insufficient. A posology of 0.25–0.5 g/kg daily is suggested. A usual but inadequate urea oral preparation, i. e. 10 g urea powder dissolved in 100 mL water before use, was classically compounded. Therefore the pharmacy has developed a 0.5 g/mL urea oral liquid solution in InOrpha® with better organoleptic characteristics to improve treatment adherence and reduce the preparation time. The aim of this study was to determine physicochemical and microbiological stability of the urea oral liquid solution in order to establish a shelf life of the preparation. Methods The 0.5 g/mL urea solution was compounded using urea powder in a commercial suspending vehicle: Inorpha®. A validated high-performance liquid chromatographic (HPLC) method with UV detection was performed for the assay of urea. The preparations were packaged in amber glass bottles and stored at fridge (5 °C±3 °C) or at room temperature (24 °C±1 °C). The physicochemical (urea concentration, macroscopic change) and microbiological stability of the preparation was tested over 90 days. Urea concentration measurement at day 0 was considered as the reference value (100 % stability) and urea concentration in subsequent samples greater than 90 % were definite stable without macroscopic changes. Results The developed HPLC-UV method was validated in terms of linearity, specificity, accuracy and fidelity (less than 5 % for relative standard deviation and relative error). After 90 days, no microbial growth was noted and urea concentrations were always higher than 90 % of the initial concentration. Macroscopic changes were observed for the samples stored at fridge (5 °C+/− 3 °C) with massive crystallization of urea solution. Conclusions Although, all the preparations retain more than 95 % of the initial concentration after 90 days in all storage conditions, macroscopic change and pH change (more than 1 unit after 15 days at room temperature) have to be taken into account. The 0.5 g/mL urea oral liquid solution in InOrpha® remains stable for 15 days at room temperature (24 °C±1 °C) in amber glass bottles.
{"title":"Stability Study of 0.5 g/mL Urea Oral Solution in InOrpha®","authors":"J. Bourbon, A. Dory, L. Perello, Laure Belotti, F. Reisz, G. Ubeaud‐Séquier, B. Gourieux","doi":"10.1515/pthp-2019-0015","DOIUrl":"https://doi.org/10.1515/pthp-2019-0015","url":null,"abstract":"Abstract Background Urea is recommended in the 2nd line treatment in moderate to severe hyponatraemia induced by syndrome of inappropriate antidiuretic hormone secretion (SIADH), when water restriction is insufficient. A posology of 0.25–0.5 g/kg daily is suggested. A usual but inadequate urea oral preparation, i. e. 10 g urea powder dissolved in 100 mL water before use, was classically compounded. Therefore the pharmacy has developed a 0.5 g/mL urea oral liquid solution in InOrpha® with better organoleptic characteristics to improve treatment adherence and reduce the preparation time. The aim of this study was to determine physicochemical and microbiological stability of the urea oral liquid solution in order to establish a shelf life of the preparation. Methods The 0.5 g/mL urea solution was compounded using urea powder in a commercial suspending vehicle: Inorpha®. A validated high-performance liquid chromatographic (HPLC) method with UV detection was performed for the assay of urea. The preparations were packaged in amber glass bottles and stored at fridge (5 °C±3 °C) or at room temperature (24 °C±1 °C). The physicochemical (urea concentration, macroscopic change) and microbiological stability of the preparation was tested over 90 days. Urea concentration measurement at day 0 was considered as the reference value (100 % stability) and urea concentration in subsequent samples greater than 90 % were definite stable without macroscopic changes. Results The developed HPLC-UV method was validated in terms of linearity, specificity, accuracy and fidelity (less than 5 % for relative standard deviation and relative error). After 90 days, no microbial growth was noted and urea concentrations were always higher than 90 % of the initial concentration. Macroscopic changes were observed for the samples stored at fridge (5 °C+/− 3 °C) with massive crystallization of urea solution. Conclusions Although, all the preparations retain more than 95 % of the initial concentration after 90 days in all storage conditions, macroscopic change and pH change (more than 1 unit after 15 days at room temperature) have to be taken into account. The 0.5 g/mL urea oral liquid solution in InOrpha® remains stable for 15 days at room temperature (24 °C±1 °C) in amber glass bottles.","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"99 1","pages":"69 - 76"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1515/pthp-2019-0015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72531875","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":"The Art of Compounding in Hospital Pharmacy","authors":"F. Lagarce","doi":"10.1515/pthp-2019-2011","DOIUrl":"https://doi.org/10.1515/pthp-2019-2011","url":null,"abstract":"","PeriodicalId":19802,"journal":{"name":"Pharmaceutical Technology in Hospital Pharmacy","volume":"46 1","pages":"49 - 49"},"PeriodicalIF":0.0,"publicationDate":"2019-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90610537","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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