Physicochemical and microbiological stability of two new oral liquid formulations of clonidine hydrochloride for pediatric patients

2018 ◽  
Vol 24 (4) ◽  
pp. 465-478
Author(s):  
V. Merino-Bohórquez ◽  
M. Delgado-Valverde ◽  
M. García-Palomo ◽  
M.C. Dávila-Pousa ◽  
C. Cañete ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Oral Liquid ◽  
Clonidine Hydrochloride ◽  
Microbiological Stability

scholarly journals Formulation and Stability Study of Omeprazole Oral Liquid Suspension for Pediatric Patients

2019 ◽  
Vol 55 (5) ◽  
pp. 314-322
Author(s):  
Oriana Boscolo ◽  
Francesco Perra ◽  
Leandro Salvo ◽  
Fabián Buontempo ◽  
Silvia Lucangioli
Keyword(s):  
High Performance ◽  
Pediatric Patients ◽  
Hplc Method ◽  
Stability Study ◽  
Oral Formulations ◽  
Liquid Suspension ◽  
Oral Liquid ◽  
Microbiological Stability ◽  
Pediatric Use ◽  
Liquid Suspensions

Objectives: To develop and to study the physicochemical and microbiological stability of omeprazole liquid oral formulations used as therapeutic agent in many acid-related disorders, for pediatric use. Furthermore, to optimize and validate a stability-indicating high-performance liquid chromatography (HPLC) method for the analysis of omeprazole in the studied formulations. Method: Oral liquid suspensions of omeprazole were prepared at 2 mg/mL using crushed omeprazole pellets (formulation A) and pure omeprazole (formulation B) with a complete vehicle including humectant, suspending, sweetening, antioxidant, and flavoring agents. Samples were stored at 4°C and 25°C. Omeprazole content of each formulation was analyzed in triplicate using micro-HPLC at 0, 3, 7, 14, 30, 60, 90, 120, and 150 days. Other parameters were also determined, such as appearance, pH, resuspendibility, and viscosity. Microbiological studies were conducted according to the United Stated Pharmacopeia (USP) guidelines for non-sterile products. Results: Formulation A stayed physicochemical and microbiologically stable at refrigerated (4°C) conditions during at least 150 days and it only stayed stable during 14 days at 25°C. Formulation B was stayed physicochemical and microbiologically stable at refrigerated (4°C) conditions at least 90 days, but it is not recommended to store at 25°C for more than 1 day. Conclusions: Formulation A and formulation B can be stored for at least 150 and 90 days, respectively, at refrigerated conditions. Formulation A can be stored at room temperature for 14 days. Both formulations are perfectly suitable for pediatric patients who are usually notable to swallow solid oral formulations. The proposed analytical method was suitable for the study of stability of different formulations.

scholarly journals Investigation of the Physical, Chemical and Microbiological Stability of Losartan Potassium 5 mg/mL Extemporaneous Oral Liquid Suspension

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 301
Author(s):  
Lisa Foley ◽  
Jennifer Toney ◽  
James W. Barlow ◽  
Maura O’Connor ◽  
Deirdre Fitzgerald-Hughes ◽  
...  
Keyword(s):  
Shelf Life ◽  
Storage Conditions ◽  
Losartan Potassium ◽  
Microbial Count ◽  
E Coli ◽  
Physical Chemical ◽  
Liquid Suspension ◽  
Oral Liquid ◽  
Microbiological Stability ◽  
Stability Data

Extemporaneous oral liquid preparations are commonly used when there is no commercially available dosage form for adjustable dosing. In most cases, there is a lack of stability data to allow for an accurately assigned shelf life and storage conditions to give greater confidence of product safety and efficacy over its shelf life. The aim of this study was to evaluate the physical, chemical and microbiological stability of an extemporaneous oral liquid suspension of losartan potassium, 5 mg/mL, used to treat paediatric hypertension in Our Lady’s Children’s Hospital Crumlin, Ireland. The losartan content of extemporaneous oral suspensions, prepared with and without addition of water, was measured by UV and confirmed by HPLC analysis. Suspensions were stored at 4 °C and room temperature (RT) and were monitored for changes in; pH, colour, odour, re-dispersibility, Total Aerobic Microbial Count, Total Yeast and Mould Count and absence of E. coli. Results showed that suspensions prepared by both methods, stored at 4 °C and RT, were physically and microbiologically stable over 28 days. Initial losartan content of all suspensions was lower than expected at 80–81% and did not change significantly over the 28 days. HPLC and NMR did not detect degradation of losartan in the samples. Suspensions prepared in water showed 100% losartan content. The reduced initial losartan content was confirmed by HPLC and was related to the acidic pH of the suspension vehicle. Physiochemical properties of the drug are important factors for consideration in the selection of suspension vehicle for extemporaneous compounding of oral suspensions as they can influence the quality, homogeneity and efficacy of these preparations.

scholarly journals Evaluation of Physical-Chemical and Microbiological Stability of Fluconazole Oral Suspensions for Hospital Use

2020 ◽  
Vol 4 (1) ◽  
pp. 39-43
Author(s):  
Camilo Marques D'Amore ◽  
Elisa De Saldanha Simon ◽  
Martin Steppe
Keyword(s):  
Analytical Method ◽  
High Performance ◽  
Active Pharmaceutical Ingredient ◽  
Oral Formulation ◽  
Porto Alegre ◽  
Pet Bottles ◽  
Physical Chemical ◽  
Oral Liquid ◽  
Microbiological Stability ◽  
New Formulation

Fluconazole is an important drug in the treatment of cutaneous and systemic mycoses. The Hospital de Clínicas de Porto Alegre performs a derivation of fluconazole capsules to obtain an oral liquid formulation that is easily administered and whose dose can be adjusted. In order to replace the derivation for a formulation produced from an active pharmaceutical ingredient, this study sought to develop a liquid oral formulation, evaluate its physical chemical and microbiological stability and demonstrate suitability of the analytical method for the formulation assay. Seven different formulations of pharmaceutical suspension form were produced and evaluated for pH, viscosity, sedimentation volume and assay. The analytical method by High Performance Liquid Chromatography was demonstrated. Two most promising formulations were manipulated in the Farmácia Semi-Industrial do Hospital de Clínicas de Porto Alegre and stored in amber PET bottles under three different conditions: room temperature, under refrigeration (2 to 8 ºC) and in an oven (40 ° C). Samples were collected after 0, 7 and 14 days to evaluate physical-chemical stability, assay, pH and macroscopic aspects. Samples were collected after 0 and 21 days to evaluate microbiological stability. It was possible to demonstrate stability for one of the formulations for a 14-day period. Throughout the study, the chosen formulation presented adequate quantification of fluconazole, constant pH, no organoleptic changes and no microbial growth. The results suggest the incorporation of a new formulation for fluconazole to the Farmacia Semi-Industrial portfolio).

Tenfold Medication Dose Prescribing Errors

2002 ◽  
Vol 36 (12) ◽  
pp. 1833-1839 ◽  
Author(s):  
Timothy S Lesar
Keyword(s):  
Pediatric Patients ◽  
Dose Range ◽  
Tertiary Care ◽  
Oral Dosage ◽  
Prescribing Errors ◽  
Enabling Factors ◽  
Medication Dosage ◽  
Oral Liquid ◽  
Medication Dose ◽  
Central Nervous System Agents

BACKGROUND: Tenfold errors in medication dosing continue to occur despite being a well-recognized risk, particularly to pediatric patients. Few systematic evaluations of the characteristics and causes of tenfold medication dosage prescribing errors have been performed. OBJECTIVE: To identify and quantify the characteristics of tenfold medication dosage prescribing errors. DESIGN: Evaluation of 200 consecutively detected medication orders with tenfold errors in dosing in a 631-bed tertiary-care teaching hospital. MAIN OUTCOME MEASURES: Type, frequency, characteristics, causes, enabling factors, and potential for adverse effects of tenfold medication dosage prescribing errors. RESULTS: Two hundred cases of tenfold prescribing errors were detected over an 18-month period. Overdoses were prescribed in 61% of the cases and underdoses in 39% of the cases. Ninety (45%) of the errors were rated as potentially serious or severe; 19.5% of the errors ocurred in pediatric patients. Levothyroxine accounted for 19% of all errors. As a class, antimicrobials, cardiovascular agents, and central nervous system agents each accounted for ≥15% of errors. Errors were associated with multiple zeroes in the dose (45%), use of equations or calculations to determine dose (27% total cases, 92.3% of pediatric cases), dose amount less than 1 (25%), and expression of measure conversion (23%). The tenfold errors were produced by a misplaced decimal point in 87 cases (43.5%), adding an extra zero in 63 cases (31.5%), and omitting a zero in 50 cases (25%). Factors identified as enabling a tenfold error to be carried out as ordered were a wide dose range for the drug (76.5%), medication ordered and able to be given by injection (42%), ability to give ordered dose as ≤5 solid oral dosage forms (36%), and availability of an oral liquid dose form (15%). CONCLUSIONS: Prescribing of tenfold medication dose errors is common and is associated with identifiable risk factors. Implementing commonly recommended medication safety processes are likely to reduce risk to patients from such errors. This information should be considered in the development of strategies to prevent adverse patient outcomes resulting from such errors.

scholarly journals Critical Aspects in the Preparation of Extemporaneous Flecainide Acetate Oral Solution for Paediatrics

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1963
Author(s):  
Antonella Casiraghi ◽  
Giorgio Centin ◽  
Francesca Selmin ◽  
Claudia Picozzi ◽  
Paola Minghetti ◽  
...  
Keyword(s):  
Sucrose Solution ◽  
Oral Solution ◽  
Citrate Buffer ◽  
Toxic Dose ◽  
Solubility Study ◽  
Time Period ◽  
Oral Liquid ◽  
Microbiological Stability ◽  
Flecainide Acetate ◽  
Microbiological Data

The availability of liquid oral preparations compounded by pharmacists is essential to meet paediatric needs which remain unanswered by the pharmaceutical industry. Unfortunately, compendial monographs are often not available and, in many cases, pre-formulation studies (e.g., compatibility with other excipients and solubility evaluations) are not performed in-depth, leading, in some rare cases, to the inadvertent administration of a toxic dose. In this study, the preparation of an oral liquid formulation for paediatric use, containing flecainide acetate at different strengths, was considered, taking into account the possible effects of conventionally used excipients. First, the optimal vehicle was selected based on a solubility study, evidencing some unexpected formations of precipitates. As a matter of fact, the buffers commonly used for oral solutions significantly reduced flecainide solubility, and the concomitant presence of citrate buffer and methylparaben even caused the formation of non-resuspendable crystals. Then, chemical, physical, and microbiological stability were assessed. Solutions at strengths of 10 and 20 mg/mL flecainide acetate were stable up to 8 weeks when compounded by using a 40% sucrose solution as a vehicle. Microbiological data showed that the use of methylparaben was not necessary over this time period.

scholarly journals Stability of clonidine hydrochloride in an oral powder form compounded for pediatric patients in Japan

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jumpei Saito ◽  
Takehisa Hanawa ◽  
Takahiro Matsumoto ◽  
Nozomi Yoshikawa ◽  
Tsutomu Harada ◽  
...  
Keyword(s):  
Relative Humidity ◽  
Pediatric Patients ◽  
Storage Conditions ◽  
Drug Dissolution ◽  
Powder Form ◽  
X Ray Diffraction ◽  
Oral Clonidine ◽  
Clonidine Hydrochloride ◽  
Array Detection ◽  
The Stability

Abstract Background Clonidine hydrochloride is used to treat sedative agent withdrawals, malignant hypertension, and anesthesia complications. Clonidine is also prescribed off-label to pediatric patients at a dose of 1 μg/kg. The commercially available enteral form of clonidine, Catapres® tablets, is often compounded into a powder form by pharmacists to achieve dosage adjustments for administration to pediatric patients. However, the stability and quality of compounded clonidine powder have not been verified. The objectives of this study were to formulate a 0.2 mg/g oral clonidine hydrochloride powder and assess the stability and physical properties of this compounded product in storage. Methods A 0.2 mg/g clonidine powder was prepared by adding lactose monohydrate to crushed and filtrated clonidine tablets. The powder was stored in polycarbonate amber bottles or coated paper packages laminated with cellophane and polyethylene. The stability of clonidine at 25 °C ± 2 °C and 60% ± 5% relative humidity was examined over a 120-d period in “bottle (closed),” “bottle (in use),” and “laminated paper” storage conditions. Drug dissolution and powder X-ray diffraction analysis were conducted to assess physicochemical stabilities. Validated liquid chromatography-diode array detection was used to detect and quantify clonidine and its degradation product, 2,6-dichloroaniline (2,6-DCA). Results Clonidine content was maintained between 90.0 and 110.0% of the initial contents in all packaging and storage conditions. After 120 d of storage, 2,6-DCA was not detected, and no crystallographic and dissolution changes were observed. Conclusions Compounded clonidine powder stability was maintained for 120 d at 25 °C ± 2 °C and 60% ± 5% relative humidity. This information may contribute to the management of clonidine compounded powder in community and hospital pharmacies in Japan.

scholarly journals Stability Study of 0.5 g/mL Urea Oral Solution in InOrpha®

2019 ◽  
Vol 4 (2) ◽  
pp. 69-76
Author(s):  
Johan Bourbon ◽  
Anne Dory ◽  
Laurent Perello ◽  
Laure Belotti ◽  
Fanny Reisz ◽  
...  
Keyword(s):  
Room Temperature ◽  
Liquid Solution ◽  
Urea Concentration ◽  
Urea Solution ◽  
Ph Change ◽  
Initial Concentration ◽  
Relative Standard ◽  
Oral Liquid ◽  
Microbiological Stability ◽  
Glass Bottles

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.

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