scholarly journals Stability of Extemporaneously Compounded Suspensions of Trimethoprim and Sulfamethoxazole in Amber Plastic Bottles and Amber Plastic Syringes

2021 ◽  
Vol 74 (4) ◽  
Author(s):  
Isabelle St-Jean ◽  
M Mihaela Friciu ◽  
Anaëlle Monfort ◽  
Jessica MacMahon ◽  
Jean-Marc Forest ◽  
...  
Keyword(s):  
High Performance ◽  
Detection Method ◽  
Physical Stability ◽  
Oral Formulation ◽  
Initial Concentration ◽  
Bulk Powder ◽  
Organoleptic Characteristics ◽  
Polyethylene Terephtalate ◽  
The Stability ◽  
Stability Results

Background: Trimethoprim (TMP) and sulfamethoxazole (SMX) are widely used, in combination, to treat or prevent various infections. Unfortunately, no liquid oral formulation is currently available in Canada for patients who are unable to swallow tablets. Objective: To evaluate the stability of suspensions of TMP and SMX (8 and 40 mg/mL, respectively) prepared in Oral Mix or Oral Mix SF vehicle (Medisca Pharmaceutique Inc) and stored for up to 90 days in amber plastic bottles or amber plastic syringes at 5°C or 25°C. Methods: Suspensions were prepared from bulk powder and from tablets in Oral Mix and Oral Mix SF vehicles, then transferred to amber plastic (polyethylene terephthalate glycol) bottles and plastic oral syringes and stored at 5°C and 25°C. Samples were collected on predetermined study days (0, 7, 14, 23, 45, 60, 75, and 90 days) and analyzed using a validated high-performance liquid chromatography – ultraviolet detection method. A suspension was considered stable if it maintained at least 90% of its initial concentration with 95% confidence. Observations of organoleptic characteristics such as colour and odour, as well as pH, were used to assess physical stability. Results: Suspensions prepared from bulk powder maintained concentrations of TMP and SMX of at least 97% of the initial concentration over the 90-day study period. No obvious changes in colour, odour, or pH were observed. However, acceptable suspensions could not be prepared from the commercial tablets. A persistent foam that developed at the surface of all suspensions prepared from tablets could result in inconsistent dosing. Conclusions: Extemporaneously compounded oral suspensions of TMP and SMX (8 and 40 mg/mL, respectively) prepared from bulk powder in Oral Mix and Oral Mix SF vehicles and stored in amber plastic bottles or syringes at 5°C or 25°C remained stable for at least 90 days. Suspensions made from tablets produced unacceptable formulations. RÉSUMÉ Contexte : Le triméthoprime (TMP) et le sulfaméthoxazole (SMX) sont largement utilisés conjointement pour traiter ou prévenir diverses infections. Malheureusement, aucune formulation liquide orale n’est actuellement disponible au Canada pour les patients incapables d’avaler des comprimés. Objectif : Évaluer la stabilité des suspensions de TMP et de SMX (respectivement 8 et 40 mg/mL) préparées dans un véhicule Oral Mix ou Oral Mix SF (Medisca Pharmaceutique Inc.) et stockées pendant 90 jours dans des flacons ou des seringues en plastique ambré à 5 °C ou 25 °C. Méthodes : Les suspensions ont été préparées à partir de poudre en vrac et de comprimés dans les véhicules Oral Mix et Oral Mix SF, puis transférées dans des flacons en plastique ambré (polyéthylène téréphtalate glycol) et dans des seringues orales en plastique et stockées à 5 °C et 25 °C. Des échantillons ont été recueillis à des jours prédéterminés (0, 7, 14, 23, 45, 60, 75 et 90 jours) et analysés à l’aide d’une méthode de détection par ultraviolet validée de chromatographie en phase liquide à haute performance. La suspension était jugée stable si elle préservait au moins 90 % de sa concentration initiale avec un seuil de confiance de 95 %. Les observations des caractéristiques organoleptiques, comme la couleur et l’odeur, ainsi que le pH, ont été faites pour évaluer la stabilité physique. Résultats : Les suspensions préparées à partir de poudre en vrac préservaient au moins 97 % de la concentration initiale de TMP et de SMX pendant la période d’étude de 90 jours. Aucun changement manifeste de couleur, d’odeur ou de pH n’a été observé. Cependant, les suspensions acceptables n’ont pas pu être préparées à partir des comprimés commerciaux. Une mousse homogène se formait à la surface de ces suspensions, ce qui pourrait entraîner un dosage incohérent. Conclusions : Les suspensions orales composées extemporanées de TMP et SMX (respectivement 8 et 40 mg/mL) préparées à partir de poudre en vrac dans des véhicules Oral Mix et Oral Mix SF et stockées dans des flacons ou des seringues en plastique ambré à 5 °C ou 25°C sont restées stables pendant au moins 90 jours. Les suspensions préparées à partir de comprimés ont donné des formulations inacceptables.

scholarly journals Physicochemical Stability of Vancomycin at High Concentrations in Polypropylene Syringes

2019 ◽  
Vol 72 (5) ◽  
Author(s):  
Élise D’Huart ◽  
Jean Vigneron ◽  
Alexandre Charmillon ◽  
Igor Clarot ◽  
Béatrice Demoré
Keyword(s):  
High Performance ◽  
Room Temperature ◽  
Physical Stability ◽  
Syringe Pump ◽  
High Concentration ◽  
Initial Concentration ◽  
Infusion Line ◽  
Severe Infections ◽  
High Concentrations ◽  
The Stability

ABSTRACTBackground: In severe infections, high-concentration vancomycin may be administered by continuous infusion. The dosage of vancomycin may reach 60 mg/kg per day. Objectives: To study the feasibility of preparing high-concentration vancomycin solutions (40 to 83.3 mg/mL), to study the effect of an electric syringe pump on the physical stability of high-concentration vancomycin, and to study the stability of vancomycin 62.5 and 83.3 mg/mL in 0.9% sodium chloride (0.9% NaCl) or 5% dextrose in water (D5W) with storage up to 48 h at room temperature. Methods: The following sets of syringes were prepared: (1) 4 syringes of vancomycin in 0.9% NaCl for each of 5 concentrations between 40 and 83.3 mg/mL (total 20 syringes); (2) 6 syringes at 83.3 mg/mL in 0.9%NaCl and 6 syringes at 83.3 mg/mL in D5W; and (3) 30 syringes at 83.3 mg/mL in D5W. Visual inspection was performed for all 3 syringe sets, and subvisual inspection for sets 1 and 2 (for periods of 24 h for set 1 and 48 h for sets 2 and 3). One syringe of vancomycin 83.3 mg/mL with each solvent was inserted into an electric syringe pump, and samples from the infusion line and collected after transit through the pump were inspected visually. Chemical stability was evaluated by high-performance liquid chromatography, and physical stability, pH, and osmolality were investigated. Results: For all sets of syringes, no physical modification was observed over time, nor were any changes observed after transit through the electric syringe pump. In 0.9% NaCl, vancomycin 62.5 and 83.3 mg/mL retained more than 90% of the initial concentration after 48 and 24 h, respectively; however, for the 83.3 mg/mL solution, precipitate was visible after 48 h. In D5W, vancomycin at 62.5 and 83.3 mg/mL retained more than 90%of the initial concentration after 48 h. Conclusion: It was feasible to prepare high-concentration solutions of vancomycin. The electric syringe pump did not cause any precipitation. Vancomycin in D5W at 62.5 and 83.3 mg/mL was stable over 48 h at room temperature. Precipitation occurred in 0.9% NaCl. D5W is therefore recommended as the solvent for this drug.RÉSUMÉContexte : En cas d’infection grave, de la vancomycine à forte concentration peut être administrée par perfusion continue à une dose pouvant atteindre 60 mg/kg par jour. Objectifs : Mener une étude de faisabilité portant sur la préparation de solutions de vancomycine à forte concentration (de 40 à 83,3 mg/mL); étudier l’effet d’un pousse-seringue électrique sur la stabilité physique de la vancomycine à forte concentration; et étudier la stabilité de la vancomycine (62,5 et 83,3 mg/mL) dans une solution de chlorure de sodium à 0,9 % (NaCl à 0,9 %) ou dans une solution aqueuse de dextrose à 5 % (D5W) après 48 h à la température ambiante.Méthodes : Trois ensembles de seringues ont été préparés : (1) quatre seringues de vancomycine dans une solution de NaCl à 0,9 %, à chacune des cinq concentrations comprises entre 40 et 83,3 mg/mL (20 seringues au total); (2) six seringues à 83,3 mg/mL dans une solution de NaCl à 0,9 % et six seringues à 83,3 mg/mL dans une solution de D5W; et (3) 30 seringues à 83,3 mg/mL dans une solution de D5W. Une inspection visuelle des trois ensembles de seringues et une inspection « sous-visuelle » des ensembles 1 et 2 ont eu lieu (période de 24 h pour l’ensemble 1 et de 48 h pour les ensembles 2 et 3). Une seringue contenant de la vancomycine à 83,3 mg/mL mélangée à chaque solvant a été insérée dans un pousse-seringue électrique, et les échantillons prélevés dans le tube de perfusion et ceux recueillis après leur passage dans la pompe ont été inspectés visuellement. La stabilité chimique a été évaluée par chromatographie liquide à haute performance et la stabilité physique, le pH ainsi que l’osmolalité ont eux aussi été étudiés. Résultats : Les trois ensembles de seringues n’ont présenté aucune modification physique avec le temps. Aucun changement n’a non plus été observé après le passage dans le pousse-seringue électrique. Dans la solution de NaCl à 0,9 %, la vancomycine à 62,5 et à 83,3 mg/mL a conservé plus de 90 % de sa concentration initiale respectivement après 48 et 24 h. Cependant, le précipité de la solution à 83,3 mg/mL était visible après 48 h. Dans la solution de D5W, la vancomycine à 62,5 et à 83,3 mg/mL a conservé plus de 90 % de sa concentration initiale après 48 h. Conclusion : La préparation de solutions de vancomycine à forte concentration est faisable. Le pousse-seringue électrique n’a pas causé de précipitation. La vancomycine dans la solution de D5W à 62,5 et à 83,3 mg/mL est restée stable pendant plus de 48 h à la température ambiante. Les précipitations se sont produites dans les solutions de NaCl à 0,9 %. On recommande donc la solution de D5W comme solvant pour ce médicament.

Long-term stability of ready-to-use 1-mg/mL midazolam solution

2020 ◽  
Vol 77 (9) ◽  
pp. 681-689
Author(s):  
Sixtine Gilliot ◽  
Morgane Masse ◽  
Frédéric Feutry ◽  
Christine Barthélémy ◽  
Bertrand Décaudin ◽  
...  
Keyword(s):  
High Performance ◽  
Detection Method ◽  
Degradation Products ◽  
Storage Conditions ◽  
Target Concentration ◽  
Long Term Stability ◽  
Ph Values ◽  
Particle Contamination ◽  
The Stability

Abstract Purpose Midazolam is a benzodiazepine derivative commonly used in intensive care units to control sedation. Its use requires dilution of a 5-mg/mL commercial solution to a target concentration of 1 mg/mL. A study was conducted to evaluate the stability of diluted ready-to-use 1-mg/mL midazolam solutions over 365 days when stored in cyclic olefin copolymer vials or polypropylene syringes. Methods A specific stability-indicating high-performance liquid chromatography coupled with UV detection method was developed for midazolam hydrochloride and validated for selectivity, linearity, sensitivity, precision, and accuracy. Three storage conditions were tested: –20°C ± 5°C, 5°C ± 3°C, and 25°C ± 2°C at 60% ± 5% relative humidity. Half of the vials were stored upside down to test for the absence of interaction between midazolam and the stopper. Particle contamination, sterility, and pH were assessed. Results The limit of stability was set at 90% of the initial concentration. After 1 year’s storage at –20°C and 5°C, concentrations remained superior to 90% under all storage conditions. At 25°C, stability was maintained up to day 90 in syringes (mean [SD], 92.71% [1.43%]) and to day 180 in upright and upside-down vials (92.12% [0.15%] and 91.57% [0.15%], respectively). No degradation products were apparent, no variations in pH values were detected, and containers retained their sterility and conformity with regard to any specific contamination during the study. Conclusion The evaluated 1-mg/mL midazolam solution was stable over a 1-year period when stored at a refrigerated (5°C) or frozen (–20°C) temperature in both vials and syringes; with storage at 25°C, the stability duration was lower. The preparation of ready-to-use midazolam solutions by a hospital pharmacy is compatible with clinical practice and could help to decrease risks inherent in dilution in care units.

Development of Oral Microemulsions of Morus alba Extract for Osteoarthritis

2014 ◽  
Vol 1060 ◽  
pp. 41-44
Author(s):  
Thapani Noi-Ang ◽  
Anusorn Charoensin ◽  
Aksiporn Warangkanagool ◽  
Athid Kulkong ◽  
Nattaporn Soonthornsit ◽  
...  
Keyword(s):  
Phase Diagrams ◽  
High Performance ◽  
Room Temperature ◽  
Ternary Phase ◽  
Physical Stability ◽  
Visual Observation ◽  
Stability Study ◽  
Ternary Phase Diagrams ◽  
The Stability ◽  
Precipitation Phase

This study aimed to develop oral microemulsions (MEs) containing M. alba extract. The stability study of the extract incorporated in the ME was also included. First, pseudo-ternary phase diagrams were constructed using caprylic/capric triglyceride (oil), PEG-8 caprylic/capric glycerides (S), polyglyceryl-3 diisostearate (CoS). Propylene glycol (PG) was used as a cosolvent. Then, the formulations were chosen to incorporate MSE and subjected to stability testing at 4o C, room temperature (RT) and 45o C at 75% RH for 8 weeks. Physical stability of the formulations was assessed by visual observation on the precipitation, phase separation and cloud point. Chemical stability was determined by quantitative analysis of oxyresveratrol using high performance liquid chromatography (HPLC). The results showed that with increasing the ratio of S/CoS, the area of ME existing region in phase diagrams increased. The addition of PG into aqueous phase at ratio 1:1 slightly affected the formation of MEs. Physical stability was not affected by temperature but was influenced by the components of the formulations. However, degradation of the extract was affected by both temperature and components of the formulations. The extract was stable at 4o C and RT. However, at 45o C, it degraded about 16-57%, depending on the components of the formulations. The best ME formulation consisted of 10% caprylic/capric triglyceride, 80% PEG-8 caprylic/capric glycerides and polyglyceryl-3 diisostearate (4:1), and 10% water and PG (1:1).

Stability of Sotalol in Two Liquid Formulations at Two Temperatures

2003 ◽  
Vol 37 (4) ◽  
pp. 506-509 ◽  
Author(s):  
Milap C Nahata ◽  
Richard S Morosco
Keyword(s):  
Dosage Form ◽  
Physical Stability ◽  
Initial Concentration ◽  
Three Samples ◽  
Life Threatening ◽  
Two Temperatures ◽  
The Mean ◽  
The Stability ◽  
Liquid Dosage Form ◽  
Mean Concentration

BACKGROUND: Sotalol is used in certain pediatric patients to treat, suppress, or prevent the recurrence of life-threatening ventricular arrhythmias. However, it is commercially unavailable in a liquid dosage form. The use of an extemporaneously prepared liquid dosage form must be supported by the documentation of the chemical and physical stability of sotalol. OBJECTIVE: To determine the stability of sotalol hydrochloride extemporaneously prepared from tablets in 2 oral suspensions stored at 2 temperatures. METHODS: Five bottles contained Ora Plus: Ora Sweet (1:1) and the other 5 bottles had 1% methylcellulose:simple syrup NF (1:9), with a sotalol concentration of 5 mg/mL. Three samples were collected from each bottle at 0, 7, 14, 28, 42, 56, 70, and 91 days and analyzed by a stability-indicating HPLC analytical method (n = 15). RESULTS: At 4°C, the mean concentration of sotalol was at least 98.9% of the original concentration in Ora Plus: Ora Sweet suspension and 95.5% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. At 25°C, the mean concentration of sotalol was ≥95.5% of the original concentration in Ora Plus: Ora Sweet suspension and 94.4% of the initial concentration in 1% methylcellulose:simple syrup during storage for 3 months. The pH did not change substantially during the study period. Further, no changes in physical appearance were seen during the study. CONCLUSIONS: Sotalol hydrochloride can be prepared in either of 2 liquid dosage forms and stored in plastic bottles for 13 weeks at 4 or 25°C without substantial loss of potency.

scholarly journals Stability of the Combination of Ceftazidime and Cephazolin in Icodextrin or PH Neutral Peritoneal Dialysis Solution

2014 ◽  
Vol 34 (2) ◽  
pp. 212-218 ◽  
Author(s):  
Rahul P. Patel ◽  
Madhur D. Shastri ◽  
Mohammad Bakkari ◽  
Troy Wanandy ◽  
Matthew D. Jose
Keyword(s):  
Peritoneal Dialysis ◽  
Body Temperature ◽  
High Performance ◽  
Room Temperature ◽  
Storage Conditions ◽  
Initial Concentration ◽  
Dialysis Solution ◽  
Different Temperatures ◽  
Colour Changes ◽  
The Stability

IntroductionThe objective of this study was to investigate the stability of ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral peritoneal dialysis (PD) solution.MethodsCeftazidime and cephazolin were injected into either a 7.5% icodextrin or pH neutral PD bag to obtain the concentration of 125 mg/L of each antibiotic. A total of nine 7.5% icodextrin or pH neutral PD bags containing ceftazidime and cephazolin were prepared and stored at 1 of 3 different temperatures: 4°C in a domestic refrigerator; 25°C at room temperature; or 37°C (body temperature) in an incubator. An aliquot was withdrawn immediately before (0 hour) or after 12, 24, 48, 96, 120, 144, 168 and 336 hours of storage. Each sample was analyzed in duplicate for the concentration of ceftazidime and cephazolin using a stability-indicating high-performance liquid chromatography technique. Ceftazidime and cephazolin were considered stable if they retained more than 90% of their initial concentration. Samples were also assessed for pH, colour changes and evidence of precipitation immediately after preparation and on each day of analysis.ResultsCeftazidime and cephazolin in both types of PD solution retained more than 90% of their initial concentration for 168 and 336 hours respectively when stored at 4°C. Both of the antibiotics lost more than 10% of the initial concentration after 24 hours of storage at 25 or 37°C. There was no evidence of precipitation at any time under the tested storage conditions. Change in the pH and color was observed at 25 and 37°C, but not at 4°C.ConclusionPremixed ceftazidime and cephazolin in a 7.5% icodextrin or pH neutral PD solution is stable for at least 168 hours when refrigerated. This allows the preparation of PD bags in advance, avoiding the necessity for daily preparation. Both the antibiotics are stable for at least 24 hours at 25 and 37°C, permitting storage at room temperature and pre-warming of PD bags to body temperature prior to its administration.

scholarly journals Stability of N-Acetylcysteine 60 mg/mL in Extemporaneously Compounded Injectable Solutions

2021 ◽  
Vol 74 (4) ◽  
Author(s):  
M Mihaela Friciu ◽  
Anaëlle Monfort ◽  
Pierre-André Dubé ◽  
Grégoire Leclair
Keyword(s):  
Sodium Chloride ◽  
High Performance ◽  
Current Treatment ◽  
Chromatography Method ◽  
Initial Concentration ◽  
Health Authorities ◽  
All Solutions ◽  
Liquid Chromatography Method ◽  
The Stability ◽  
General Chapter

Background: N-Acetylcysteine (NAC) administered by the IV route is the current treatment of choice for acetaminophen overdose. However, the protocol approved by health authorities in most countries has a complex dosing regimen, which leads to dosage errors in one-third of cases. Therefore, the Canadian Antidote Guide in Acute Care Toxicology and individual poison centres have begun to recommend a simplified regimen using continuous IV infusion. Unfortunately, no study has demonstrated the stability of IV solutions of NAC at concentrations above 30 mg/mL or in solutions other than 5% dextrose. Objective: To evaluate the stability of solutions of NAC 60 mg/mL in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose, stored for up to 72 hours in polyvinyl chloride (PVC) bags at 25°C. Methods: Solutions of the desired concentration were prepared from a commercial solution of NAC 200 mg/mL, with dilution in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose, and were then stored at room temperature in PVC bags for up to 72 hours. At predetermined time points (0, 16, 24, 40, 48 and 72 h), samples were collected and analyzed using a stability-indicating high-performance liquid chromatography method. A solution was considered stable if it maintained at least 90.0% of its initial concentration. Particulate matter count was also evaluated to confirm chemical stability. Finally, organoleptic properties, such as odour and colour, were evaluated to assess the stability of the solutions. Results: All solutions maintained at least 98.7% of their initial concentration. No obvious changes in odour or colour were observed. Moreover, particle counts remained acceptable throughout the study, according to the criteria specified in United States Pharmacopeia (USP) General Chapter <788>. Conclusions: NAC 60 mg/mL, diluted in 0.9% sodium chloride, 0.45% sodium chloride, or 5% dextrose and stored in PVC bags at 25°C, was chemically and physically stable for a period of at least 72 hours. RÉSUMÉ Contexte : La N-acétylcystéine (NAC) administrée par IV est actuellement le traitement de choix en cas de surdose d’acétaminophène. Cependant, le protocole approuvé par les autorités sanitaires de la plupart des pays s’accompagne d’un schéma posologique complexe qui entraîne des erreurs de dosage dans un tiers des cas. C’est pourquoi, le Guide canadien des antidotes en toxicologie d’urgence et les centres antipoison ont commencé à recommander un schéma simplifié utilisant des perfusions IV. Malheureusement, aucune étude n’a permis de démontrer la stabilité des solutions IV de NAC à des concentrations supérieures à 30 mg/mL ou dans des solutions autres que 5 % de dextrose. Objectif : Évaluer la stabilité des solutions de 60 mg/mL de NAC dans 0,9 % de chlorure de sodium, 0,45 % de chlorure de sodium ou 5 % de dextrose, stockées jusqu’à 72 heures dans des pochettes de chlorure de polyvinyle (PVC) à 25 °C. Méthodes : Les solutions ont été préparées à partir d’une solution commerciale de 200 mg/mL de NAC, avec une dilution dans 0,9 % de chlorure de sodium, dans 0,45 % de chlorure de sodium ou dans 5 % de dextrose. Elles ont ensuite été stockées à température ambiante dans des pochettes en PVC pendant une période allant jusqu’à 72 h. À des instants prédéterminés (0, 16, 24, 40, 48 et 72 h), des échantillons étaient recueillis et analysés à l’aide d’une méthode de chromatographie en phase liquide à haute performance indiquant la stabilité. Si la solution préservait au moins 90 % de sa concentration initiale, elle était jugée stable. Un comptage de particules a aussi permis de confirmer la stabilité chimique. Finalement, les propriétés organoleptiques, comme l’odeur et la couleur, ont été examinées pour évaluer la stabilité des solutions de NAC. Résultats : Toutes les solutions préservaient au moins 98,7 % de leur concentration initiale. Aucun changement manifeste d’odeur ou de couleur n’a été observé. De plus, le nombre de particules est resté acceptable pendant toute la durée de l’étude selon les critères indiqués dans le chapitre général de la Pharmacopée américaine (USP) <788>. Conclusions : La solution de 60 mg/mL de NAC, diluée dans 0,9 % de chlorure de sodium, dans 0,45 % de chlorure de sodium ou dans 5 % de dextrose et stockée dans des pochettes en PVC à 25 °C était chimiquement et physiquement stable pendant au moins 72 h.  

Stability of a pyrimethamine suspension compounded from bulk powder

2017 ◽  
Vol 74 (24) ◽  
pp. 2060-2064 ◽  
Author(s):  
Paul O. Lewis ◽  
David B. Cluck ◽  
Jessica D. Huffman ◽  
Amanda P. Ogle ◽  
Stacy D. Brown
Keyword(s):  
High Performance ◽  
Room Temperature ◽  
Hplc Method ◽  
Stability Indicating ◽  
Color Changes ◽  
Stability Indicating Method ◽  
Bulk Powder ◽  
Subsequent Application ◽  
Temperature Ranges ◽  
The Stability

Abstract Purpose Development of a stability-indicating high-performance liquid chromatography (HPLC) method for pyrimethamine analysis, with subsequent application of that method to assess the 90-day stability of a pyrimethamine suspension compounded from bulk USP-grade pyrimethamine powder, is described. Methods A stability-indicating method of HPLC with ultraviolet detection specific to pyrimethamine was developed according to pharmacopeial recommendations and validated. The method was applied to investigate the stability of a 2-mg/mL pyrimethamine suspension in a vehicle consisting of Ora-Plus and Ora-Sweet (Perrigo) over a period of 90 days. Three replicate test preparations were stored at room temperature or refrigerated at 4.3–5.2 °C, and samples were analyzed in duplicate immediately after preparation and on study days 1, 2, 4, 7, 10, 14, 21, 30, 48, 60, 75, and 90. Results The 2-mg/mL suspension of pyrimethamine in Ora-Plus and Ora-Sweet retained 90–110% of the labeled potency to 90 days at both temperature ranges. However, color changes in the samples stored at room temperature observed at day 60 indicated that a beyond-use date less than 90 days from the preparation date should be specified when the suspension is to be stored at room temperature. Conclusion The study demonstrated that USP-grade pyrimethamine powder can be formulated as a 2-mg/mL suspension in a vehicle of Ora-Plus and Ora-Sweet and is stable when stored at room temperature and when refrigerated, in amber plastic bottles, for 48 and 90 days, respectively.

scholarly journals Stability of Extemporaneously Compounded Domperidone 5 mg/mL Suspension in Oral Mix in Plastic and Glass Bottles and Plastic Syringes

2018 ◽  
Vol 71 (3) ◽  
Author(s):  
Karen Lingertat-Walsh ◽  
Shirley Law ◽  
Scott E Walker
Keyword(s):  
Ethylene Terephthalate ◽  
Initial Concentration ◽  
Pet Bottles ◽  
Poly Ethylene Terephthalate ◽  
Polyethylene Terephtalate ◽  
Liquid Chromatographic Method ◽  
Glass Bottles ◽  
Poly Ethylene ◽  
The Stability ◽  
Liquid Chromatographic

<p>ABSTRACT</p><p>Background: Domperidone liquid for oral administration is not commercially available in Canada, but is needed for patients who cannot swallow intact tablets.</p><p>Objective: To evaluate the stability of domperidone 5 mg/mL suspensions prepared in Oral Mix vehicle and stored, for up to 91 days, in amber polyvinylchloride (PVC) bottles, amber glass bottles, or amber poly - ethylene terephthalate (PET) bottles at 4°C or 25°C or in polypropylene oral syringes at 25°C.</p><p>Methods: Three separate 300-mL batches of domperidone suspension 5 mg/mL were prepared with Oral Mix vehicle. Fifty-millilitre aliquots of the suspension were stored in 100-mL bottles (amber PVC, amber glass, or amber PET). Half of the bottles of each type were stored at 25°C and half at 4°C. On study days 0, 1, 2, 4, 7, 10, 14, 21, 28, 35, 42, 49, 63, 77, and 91, domperidone concentration was determined, with a validated reverse-phase, stability-indicating liquid chromatographic method, in samples drawn from each type of container stored at each temperature. In addition, 1.5-mL aliquots of a fourth 100-mL batch of suspension were stored in 3-mL oral syringes at 25°C and were tested on the same study days.</p><p>Results: The concentration of domperidone in all study samples remained above 93% of initial concentration after storage for 91 days. The percent remaining on day 91, based on fastest degradation rate (as represented by the lower limit of the 95% confidence interval [CI]), was at least 92.3% for suspensions stored at 4°C in PVC, glass, and PET bottles. With storage at 25°C, suspensions in PVC and glass bottles retained more than 90% of initial concentration, whereas suspensions in PET bottles and plastic syringes retained 88.9% and 88.0% of initial concentration, respectively.</p><p>Conclusions: Because suspensions of domperidone in PET bottles and oral syringes retained less than 90% of their initial concentration on day 91 (based on the 95% CI), it is suggested that such suspensions be stored at 4°C or 25°C in any bottle type or syringe with an assigned beyond-use date not exceeding 75 days.</p><p>RÉSUMÉ</p><p>Contexte : La dompéridone sous forme liquide pour administration orale n’est pas disponible sur le marché au Canada, mais elle est nécessaire pour les patients incapables d’avaler des comprimés entiers.<br />Objectif : Évaluer la stabilité de suspensions de dompéridone de 5 mg/mL préparées dans l’excipient Oral Mix et conservées jusqu’à 91 jours dans des flacons de polychlorure de vinyle (PVC) ambré, de verre ambré ou de polyéthylène téréphtalate (PET) ambré à 4 °C ou à 25 °C ou dans des seringues orales de polypropylène à 25 °C.</p><p>Méthodes : Trois différents lots de 300 mL de suspension de dompéridone de 5 mg/mL ont été préparés à l’aide de l’excipient Oral Mix. Des aliquotes de 50 mL de la suspension ont été entreposées dans des flacons de 100 mL de PVC ambré, de verre ambré ou de PET ambré. La moitié des flacons de chaque type était conservée à 25 °C et l’autre moitié était conservée à 4 °C. Aux jours 0, 1, 2, 4, 7, 10, 14, 21, 28, 35, 42, 49, 63, 77 et 91 de l’étude, les concentrations de dompéridone ont été évaluées sur des échantillons tirés de chaque type de flacons conservés aux deux températures à l’aide d’une épreuve validée mesurant la stabilité par chromatographie liquide en phase inverse. De plus, des aliquotes de 1,5 mL provenant d’un quatrième lot de suspension ont été entreposées dans des seringues orales de 3 mL à 25 °C et ont été analysées aux mêmes jours.</p><p>Résultats : Les concentrations de dompéridone dans l’ensemble des échantillons de l’étude conservaient plus de 93 % de la concentration initiale après un entreposage de 91 jours. Le pourcentage restant au jour 91, selon le taux de dégradation le plus rapide (correspondant à la limite inférieure de l’intervalle de confiance (IC) de 95 %), atteignait au moins 92,3 % pour les suspensions entreposées à 4 °C dans les flacons de PVC, de verre et de PET. Lorsqu’elles étaient entreposées à 25 °C, les suspensions contenues dans les flacons de PVC ou de verre conservaient plus de 90 % de la concentration initiale alors que les suspensions contenues dans les flacons de PET ou les seringues de plastique conservaient respectivement 88,9 % et 88,0 % de la concentration initiale.</p><p>Conclusions : Comme les suspensions entreposées dans les flacons de PET et les seringues orales conservaient moins de 90 % de leur concentration initiale au jour 91 (selon l’IC de 95 %), on suggère d’entreposer les suspensions de dompéridone à 4 °C ou à 25 °C dans n’importe lequel contenant en l’accompagnant d’une date limite d’utilisation ne dépassant pas 75 jours.</p>

scholarly journals Stability of Extemporaneously Prepared Acetazolamide Oral Suspensions at Two Temperatures

2020 ◽  
Vol 25 (8) ◽  
pp. 723-729
Author(s):  
Charlotte Gillium ◽  
Mihaela Friciu ◽  
Nicolas Abatzoglou ◽  
Grégoire Leclair
Keyword(s):  
High Performance ◽  
Room Temperature ◽  
Time Profile ◽  
Initial Concentration ◽  
Initial Ph ◽  
Different Temperatures ◽  
Two Temperatures ◽  
Clear Plastic ◽  
Bulk Drug ◽  
The Stability

OBJECTIVES Some drugs need to be compounded by the pharmacist before being administered to the patient. A study was conducted to determine the stability of acetazolamide suspensions in 2 different vehicles (Oral Mix and Oral Mix Sugar Free [SF]) from bulk drug and tablets at 2 different temperatures and in 2 different containers (amber plastic bottles and clear plastic syringes). METHODS Acetazolamide suspensions (25 mg/mL) were prepared from bulk drug or tablets. Each suspension, using Oral Mix or Oral Mix SF, was split between 2 types of containers—amber plastic bottles and clear plastic syringes—and stored either at room temperature (23°C–27°C) or under refrigeration (3°C–7°C). Samples were drawn from the suspensions right after preparation and on days 7, 14, 30, 45, 60, 75, and 90. They were then analyzed by high-performance liquid chromatography (HPLC) using a reverse-phase column. A validated stability-indicating HPLC with ultraviolet detection method was developed. A visual inspection and a pH measurement were also completed at each time point. Stability was defined as retention of at least 90% of the initial concentration of acetazolamide suspension. RESULTS At least 91.2% of the initial acetazolamide concentration in suspensions remained throughout the 90-day study period for both vehicles, both containers, and both temperatures. Assays varied between 91.2% and 105.0% of the initial concentration for all 112 tested conditions but 2 (105.2% and 109.0%). Linear regression was calculated for each time profile and remained above 95.0% at the end of the study in all cases. Similarly, pH remained within 0.1 unit of the initial pH, which was 4.2 for Oral Mix and 4.3 for Oral Mix SF. Furthermore, no changes in organoleptic properties were observed because the preparations remained as white fluid suspensions without sedimentation. CONCLUSIONS Acetazolamide suspensions were stable for at least 90 days in all tested conditions because the average drug concentration was not less than 90% of the initial concentration. The beyond-use date could be extended from 60 to 90 days.

Long-term stability of ganciclovir in polypropylene containers at room temperature

2017 ◽  
Vol 25 (2) ◽  
pp. 303-308 ◽  
Author(s):  
Nicolas Guichard ◽  
Pascal Bonnabry ◽  
Serge Rudaz ◽  
Sandrine Fleury-Souverain
Keyword(s):  
High Performance ◽  
Physical Stability ◽  
Significant Loss ◽  
Stability Indicating ◽  
Long Term Stability ◽  
Stability Indicating Method ◽  
All Solutions ◽  
Different Temperatures ◽  
The Stability

Purpose Ganciclovir is increasingly provided by hospital pharmacy production unit in a ready-to-use form, in order to improve the safety of healthcare workers and the efficiency of the organisation. The objective of this study was to develop a stability-indicating method to assay ganciclovir and determine the stability of ganciclovir in syringes (5 mg/mL) and infusion bags (0.25 and 5 mg/mL) at two different temperatures. Method Ganciclovir solutions (0.25 mg/mL and 5 mg/mL) in 0.9% sodium chloride were prepared in 50 mL polypropylene syringes or 100 mL polypropylene infusion bags and stored at 2–8℃ and 23–27℃. The chemical stability was measured using a stability-indicating Ultra High Performance Liquid Chromatography coupled to mass spectrometry method. Physical stability was assessed by visual inspection. Results No significant loss of ganciclovir under any of the tested conditions was observed in this study. All solutions remained clear through the study period. Conclusion All tested formulations remained stable for at least 185 days independently of container type, temperature or concentration studied.

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