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 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 Synthesis and Deblocking Investigations of Phenol Blocked Aliphatic Isocyanates and Their Application in the Development of Epoxy-Polyurethane Films

2022 ◽  
Vol 34 (2) ◽  
pp. 361-370
Author(s):  
Karthi Rajendran ◽  
Vennila Srinivasan ◽  
Sankar Govindarajan
Keyword(s):  
Tensile Strength ◽  
Mechanical Characteristics ◽  
13C Nmr Spectroscopy ◽  
Strength Analysis ◽  
Co2 Evolution ◽  
Structure Property ◽  
Gel Time ◽  
Solubility Study ◽  
Time Period ◽  
Atr Spectroscopy

Phenol blocked hexamethylenediisocyanate adducts and polyisocyanates were synthesized and their structure was validated by FTIR, 1H & 13C NMR spectroscopy, TGA, DSC and CO2 evolution techniques were used to evaluate the deblocking temperature of blocked isocyanates. Gel time studies of blocked isocyanates with terathane polyol and solubility study of blocked isocyanates with different polyols were conducted to demonstrate the structure-property correlation. Epoxy-polyurethane films were produced utilizing the blocked isocyanates reported in this work with epoxy resin and their structure was verified by ATR Spectroscopy. TGA, DSC, shore A hardness, tensile strength and flexural strength analysis were used to investigate the thermal and mechanical characteristics of these films. The findings of deblocking temperature and gel time revealed that unsubstituted phenol blocked isocyanates and polyisocyanates deblock at lower temperatures and cure for a shorter time period than substituted phenol blocked isocyanates. Thermal and mechanical characteristics of epoxy-polyurethane films based on blocked polyisocyanates are satisfactory.

Cocrystal formation of loratadine-succinic acid and its improved solubility

2021 ◽  
Vol 32 (4) ◽  
pp. 623-630
Author(s):  
Dwi Setyawan ◽  
Firdaus Rendra Adyaksa ◽  
Hanny Lystia Sari ◽  
Diajeng Putri Paramita ◽  
Retno Sari
Keyword(s):  
Succinic Acid ◽  
Solution Method ◽  
Intermolecular Hydrogen Bond ◽  
X Ray Diffraction ◽  
Citrate Buffer ◽  
Solubility Study ◽  
Lower Melting Point ◽  
Diffraction Peaks ◽  
Low Solubility ◽  
Biopharmaceutics Classification

Abstract Objectives Loratadine belongs to Class II compound of biopharmaceutics classification system (BCS) due its low solubility and high membrane permeability. Cocrystal is a system of multicomponent crystalline that mostly employed to improve solubility. Succinic acid is one of common coformer in cocrystal modification. This research aims to investigate cocrystal formation between loratadine and succinic acid and its effect on solubility property of loratadine. Methods Cocrystal of loratadine-succinic acid was prepared by solution method using methanol as the solvent. Cocrystal formation was identified under observation of polarization microscope and analysis of the binary phase diagram. The cocrystal phase was characterized by differential thermal analysis (DTA), powder X-ray diffraction (PXRD), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM). Solubility study was conducted in phosphate-citrate buffer pH 7.0 ± 0.5 at 30 ± 0.5 °C. Results Loratadine is known to form cocrystal with succinic acid in 1:1 M ratio. Cocrystal phase has lower melting point at 110.9 °C. Powder diffractograms exhibited new diffraction peaks at 2θ of 5.28, 10.09, 12.06, 15.74, 21.89, and 28.59° for cocrystal phase. IR spectra showed that there was a shift in C=O and O–H vibration, indicating intermolecular hydrogen bond between loratadine and succinic acid. SEM microphotographs showed different morphology for cocrystal phase. Loratadine solubility in cocrystal phase was increased up to 2-fold compared to loratadine alone. Conclusions Cocrystal of loratadine and succinic acid is formed by stoichiometry of 1:1 via C=O and H–O interaction. Cocrystal phase shows different physicochemical properties and responding to those properties, it shows improved loratadine solubility as well.

scholarly journals Preparation of Galla Chinensis Oral Solution as well as Its Stability, Safety, and Antidiarrheal Activity Evaluation

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Yi Yang ◽  
Huihui Luo ◽  
Xu Song ◽  
Li Yu ◽  
Juan Xie ◽  
...  
Keyword(s):  
Castor Oil ◽  
Lethal Dose ◽  
Pharmaceutical Preparations ◽  
Oral Solution ◽  
Tannin Content ◽  
Tannin Extract ◽  
Fluid Accumulation ◽  
Microbiological Stability ◽  
Antidiarrheal Activity ◽  
Oral Acute Toxicity

Background of the Study. As a widely used traditional medicine, Galla Chinensis is rich in tannins. However, there are few detailed studies about pharmaceutical preparations of Galla Chinensis tannin extract (GTE). In the present experiments, for better application and to investigate the possibility that Galla Chinensis tannin extract can be used as an antidiarrheal drug, we prepared Galla Chinensis oral solution (GOS). Materials and Methods. GOS was prepared with GTE, and its physicochemical and microbiological stability was evaluated. The oral acute toxicity of GOS was calculated by the 50% lethal dose (LD50). The antidiarrheal activity was determined in a castor oil-induced diarrhea model in mice through diarrhea symptoms, fluid accumulation ratio, and percentage of distance moved by charcoal meal. Results. The tannin content of GTE was 47.75%. GOS could endure a high temperature without a significant decrease of tannin content. After storage for six months, the tannin content of GOS was still more than 90%. GOS was determined to be nontoxic. Meanwhile, GOS showed significant antidiarrheal activity in a castor oil-induced diarrhea model in mice (P<0.01). Conclusion. The results suggested that GOS is an effective and stable antidiarrheal drug that can be used to complement other therapies.

scholarly journals Physicochemical and Microbiological Stability of a New Oral Clonidine Solution for Paediatric Use

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Camille Verlhac ◽  
Damien Lannoy ◽  
Florence Bourdon ◽  
Marie Titecat ◽  
Emilie Frealle ◽  
...  
Keyword(s):  
Membrane Filtration ◽  
Degradation Products ◽  
Potassium Citrate ◽  
Oral Solution ◽  
Opiate Withdrawal ◽  
Potassium Sorbate ◽  
Physical Parameters ◽  
Forced Degradation ◽  
Microbiological Stability ◽  
Glass Bottles

AbstractBackgroundAs many drugs are unavailable for paediatric use, hospital pharmacies are often required to develop suitable formulations themselves. Clonidine is commonly used in paediatrics (in severe hypertension, in opiate withdrawal syndrome, in tics and Gilles de la Tourette syndrome or in anaesthetic premedication) but no appropriate formulation has been drawn up. The aims of this work were to develop an oral solution of clonidine dedicated to children and to assess its physicochemical and microbiological stability.MethodsFormulation of an oral solution of clonidine hydrochloride suitable for neonates and paediatrics was developed using the active pharmaceutical ingredient (API), with as few excipients as possible and without any complex excipient vehicle. A stability study was made according to GERPAC-SFPC guidelines. At each point in time (D0, D1, D7, D15, D29, D60 and D90), visual aspect (limpidity), pH and osmolality were established. Clonidine concentration was quantified using a stability-indicating HPLC-UV-DAD method previously developed from a forced degradation study and validated according to SFSTP Pharma. Microbiological stability was also tested according to the European Pharmacopeia monograph with the best adapted method (by comparing membrane filtration and inclusion). Solutions were stored in amber glass bottles with an oral adapter for up to 3 months in two different conditions: 5 °C +/– 3 °C and at 25 °C +/– 2 °C with 60 % residual humidity (climatic chamber).ResultsThe formulated oral solution is composed of API at a concentration of 10 µg/mL and of potassium sorbate (0.3 %), citric acid, potassium citrate (pH 5 buffer) and sodium saccharine (0.025 %). Forced degradation highlighted six degradation products and the method was validated in the acceptance limits of ± 5 %. On D29, the mean percentages of the initial clonidine concentrations (+/–standard deviation) were 92.95+/–1.28 % in the solution stored at 25 °C +/– 2 °C and 97.44+/–1.21 % when stored at 5 °C +/– 3 °C. On D90, means were respectively 81.82+/–0.41 % and 93.66+/–0.71 %. The visual aspect did not change. Physical parameters remained stable during the study: pH varied from 4.94 to 5.09 and osmolality from 82 to 92 mOsm/kg in the two conditions tested here. Membrane filtration appeared to be the more sensitive method. Whatever the storage conditions,<1 micro-organism/mL was identified (only environmental) with no detectedE.coli.ConclusionsThis formulation is stable for at least 3 months at 5 °C +/– 3 °C in amber glass bottles and for one month when stored at room temperature. Microbiological stability was proven in accordance with the European Pharmacopeia.

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).

Study on the Preparation of Stigma Maydis Polysaccharide Oral Liquid

2013 ◽  
Vol 634-638 ◽  
pp. 1362-1365
Author(s):  
Hong Li Zhou ◽  
Guo Qiang Song ◽  
Jian Hang Wang
Keyword(s):  
Quality Control ◽  
Citric Acid ◽  
Polyacrylic Acid ◽  
Uniform Design ◽  
Oral Solution ◽  
People’S Republic Of China ◽  
People's Republic Of China ◽  
Republic Of China ◽  
Oral Liquid

The optimal prescription of stigma maydis polysaccharide (SMPS)oral liquid was 1g of SMPS, 0.03g of Casson, 39g of xylitol, 1g of citric acid, 0.2g of polyacrylic acid sodium (In terms of 1L oral solution) by uniform design and the quality control was conducted according to the Pharmacopoeia of the People's Republic of China(2010).

PP-017 Physicochemical and microbiological stability of a new paediatric oral solution of clonidine

2017 ◽  
Author(s):  
C Verlhac ◽  
D Lannoy ◽  
F Bourdon ◽  
M Titecat ◽  
E Frealle ◽  
...  
Keyword(s):  
Oral Solution ◽  
Microbiological Stability

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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