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Oral drug therapy in elderly with dysphagia: between a rock and a hard place!

Demographic indicators forecast that by 2050, the elderly will account for about one-third of the global population. Geriatric patients require a large number of medicines, and in most cases, these products are administered as solid oral solid dosage forms, as they are by far the most common formulations on the market. However, this population tends to suffer difficulties with swallowing. Caregivers in hospital geriatric units routinely compound in solid oral dosage forms for dysphagic patients by crushing the tablets or opening the capsules to facilitate administration. The manipulation of a tablet or a capsule, if not clearly indicated in the product labeling, is an off-label use of the medicine, and must be supported by documented scientific evidence and requires the patient’s informed consent. Compounding of marketed products has been recognized as being responsible for an increased number of adverse events and medical errors. Since extemporaneous compounding is the rule and not the exception in geriatrics departments, the seriousness and scope of issues caused by this daily practice are probably underestimated. In this article, the potential problems associated with the manipulation of authorized solid oral dosage forms are discussed.

Development and validation of a high-resolution LTQ Orbitrap MS method for the quantification of isoflavones in wastewater effluent.

Isoflavones and coumestranes are the most important classes of compounds among phytoestrogens; by binding to estrogen receptors, they mimic or modulate the effect on the endogenous receptors. Little information can be found in literature about the presence of isoflavones and coumestrol in the environment, even if it is known that this may have significance, being these substances classified as endocrine disrupting compounds. In this research, we aim to explore the capabilities of the LTQ Orbitrap Discovery hybrid MS in full-scan acquisition mode, with high resolution, to validate an analytical method for the quantification of nine isoflavones (genistein, genistin, glycitein, daidzein, daidzin, (R,S)-equol, biochanin A, formononetin and coumestrol) in wastewater samples. The correlation coefficients of calibration curves of the nine analyzed compounds were in a range of 0.996-0.999; recoveries at two different levels of concentration (0.05 and 0.5 µg/l) were in the range 73-98%, and the limits of detection ranged between 0.0014 and 0.017 µg/l, proving that this method is sensitive enough in comparison with other methods available in literature. This method has been applied for the analysis of 20 wastewater treatment plants in County Cork, Ireland.

High-performance liquid chromatography LTQ-Orbitrap mass spectrometry method for tomatidine and non-target metabolites quantification in organic and normal tomatoes.

Abstract Tomatoes, members of the Solanaceae plant family, produce biologically active secondary metabolites, including glycoalkaloids and aglycons, which may have both adverse and beneficial biological effects. A new liquid chromatography method that utilized LTQ-Orbitrap MS was developed for the analysis of tomatidine, the main aglycon in tomatoes. Recoveries of tomatidine were >98.3% with the relative standard deviations (RSDs) below 6.1%. The limit of detection (LODs) was 0.0003 mg kg−1. The limit of quantitation (LOQs) is 0.001 mg kg−1. The linear range was between with 0.0025 and 1 mg kg−1 with an excellent correlation coefficient (R2) equal to 0.9990. Various tomato samples were analyzed and the level of tomatidine in the 11 samples analysed was higher in normal respect to organic tomatoes. The capability of the set-up Full Scan LTQ-Orbitrap MS method allowed us to quantified two non-target analytes. The m/z 1032 was identified as dehydrotomatine, confirmed through accurate mass studies (mass error in ppm equal to 1.5017) meanwhile m/z 902 as (Glc)2–Gal-Tomatidine (β1-Tomatine) (mass error in ppm equal to 2.0719).

Water-in-Oil Microemulsions for Protein Delivery: Loading Optimization and Stability

BACKGROUND Microemulsions are attractive delivery systems for therapeutic proteins and peptides due to their ability to enhance bioavailability. Although different proteins and peptides have been successfully delivered through such ternary systems, no information can be found about protein loading and the formulation stability when such microemulsions are prepared with pharmaceuticallyapproved oils and surfactants. The aim of this work was to optimise a ternary system consisting of water/ ethyl oleate/Span® 80-Tween® 80 and to determine its protein loading capacity and stability, using bovine serum albumin (BSA) as a model of biomolecule. METHODS The optimization was carried out using a Central Composite Design and all the prepared formulations were characterised through dynamic light scattering, rheology, optical and polarized microscopy. Subsequently, the maximum loading capacity was determined and the stability of the final microemulsion with the highest content of protein was followed over six months. To investigate the structural features of the protein, BSA was recovered from the microemulsion and analysed through fluorescence spectroscopy. RESULTS After incorporation of the protein in the microemulsion, a decrease of its aqueous solubility was observed. However, the formulation remained stable over six months and the native-like state of the recovered protein was demonstrated by fluorescence spectroscopy Conclusion: This study demonstrated the feasibility of preparing microemulsions with the highest content of protein and their long-term stability.

Chemical and microbiological stability studies of an aqueous solution of pravastatin sodium salt for drug therapy of the dysphagic patients

Objective This study is aimed to improve dysphagic patient compliance under therapy with cholesterol-lowering drugs. Patients suffering severe dysphagia, who do not feed independently, receive enteral nutrition through feeding tube and they need alternative oral route also for the administration of pharmacological therapy. This research deals with the development and stability (chemical and microbiological) of an aqueous solution of pravastatin sodium salt that will be administered orally directly in the feeding tube starting from commercial tablets. Tablets formulation is the only pharmaceutical dosage form available on the market for this type of drug. Methods Pravastatin sodium salt tablets are dissolved in a preserved sodium bicarbonate solution at the final concentration of 4 mg/mL. Samples are stored in two different conditions until 60 days. The samples are prepared for high-performance liquid chromatography analysis coupled to a diode array detector (HPLC-DAD), microbiological analysis and pH measurements. Results The chemical stability of the solution performed with HPLC-DAD analysis shows peaks’ overlapping, which are characteristic of pravastatin, and correspondence of the concentration of the active ingredient in the solution. The detected values are analysed by one-way analysis of variance showing no statistically significant differences. Microbiological analyses proved that there is not microbial growth. By considering the dilution factor applied, it was possible to express the result as <10 CFU/mL in the two different culture media. Conclusion This study demonstrated the possibility to reformulate pravastatin tablets as liquid pharmaceutical formulation for enteral administration with the aim of improving drug therapy in dysphagic patients.

Potassium canrenoate compounding for administration via enteral feeding tubes: a physical and microbiological stability study

Background Swallowing difficulties are arising in an increasing number of patients, especially in elderly people. When deglutition ability is completely compromised, enteral administration of a drug via feeding tubes is used. Licensed pharmacists have to compound the original solid forms to enable this drug therapy. Objectives To evaluate the possibility of compounding original commercial tablets to produce a liquid formulation suitable for administering via a feeding tube. Methods Two liquid formulations containing potassium canrenoate 5 mg/mL were prepared: a standard solution obtained by solubilising raw material and an extemporaneous preparation obtained by dissolving film-coated 100 mg tablets. Spectrophotometric determinations (UV range) of the drug established chemical stability of the analyte up to 60 days. Samples were tested for microbial growth. Gravimetric quantifications of liquid formulations were used to check any weight loss during the different steps before enteral administration. Results UV data confirmed the chemical stability of potassium canrenoate up to 60 days. Samples showed no microbial growth. A higher weight loss was recorded in extemporaneous preparations than in the standard solution (10.7% vs 7.6%) according to the gravimetric quantification. Conclusion It is possible to compound the original tablets into a liquid formulation suitable for administration via a feeding tube.

PP-023 Gravimetric and spectrophotometric quantification of pravastatin sodium salt extemporaneous solutions administered through feeding tube: Effect of preparation methods

Background Most drugs are available only as solid oral dosage forms. Patients with swallowing difficulties supplied by enteral nutrition (EN) are not able to consume these pharmaceutical forms. Therefore, to improve the management of their drug therapy, it is often necessary to handle original drug to prepare an extemporaneous liquid dosage form. Purpose The aim of this work was to perform a gravimetric and spectrophotometric quantification of different extemporaneous preparations (prepared starting from dissolved and crushed tablets) containing pravastatin sodium salt (PraNa) that are administered through a feeding tube for EN. Results were compared with a PraNa standard solution. Material and methods Solution A was prepared choosing standard PraNa, parabens and sodium bicarbonate 8.4% solution. Solution B was obtained using 20 mg PraNa tablets (Pensa SpA), parabens and sodium bicarbonate 8.4% solution. Solution C was prepared crushing tablets of PraNa in a mortar and then the obtained powder was dispersed with water. Final concentration in all 3 preparations was always 4 mg/mL. 10 mL of each solution were administered through an enteral syringe into the feeding tube and then collected downstream of the tube. After each administration, the tube was flushed with distilled water (10 mL). The total volume, weight and absorbance (238 nm) were measured to determine the drug concentration and amount delivered through the tube. Statistical analysis (t test or Anova) was performed to evaluate the obtained results. Results Gravimetric results about the upstream delivered weights of each different preparation were 20.52 ± 0.093 mg, 21.41 ± 0.060 mg and 19.96 ± 0.270 mg; instead, the collected quantities from the distal point of the tube were 18.92 ± 0.261 mg, 19.63 ± 0.151 mg and 18.71 ± 0.449 mg, respectively. Spectrophotometric quantifications provided these values: 41.92 ± 1.08 mg delivered by whole tablets versus 40.98 ± 0.270 mg, 43.79 ± 1.94 mg and 42.83 ± 1.69 mg delivered downstream by the 3 preparations, respectively. The t test (p < 0.005) revealed significant differences among the values obtained with the gravimetric method, but there were no significant differences in the amount of administered drug as quantified through spectrophotometer measurements. No differences were found among the drugs administered using the different preparation methods when tested with Anova. Conclusion Comparing the different preparation methods, significant differences were found only when gravimetric determination was used. Instead, spectrophotometric determination gave results in agreement with the real amount of administered drug. No conflict of interest.

Development and validation of a highresolutionLTQ Orbitrap MS method for thequantification of isoflavones inwastewater effluent

Isoflavones and coumestranes are the most important classes of compounds among phytoestrogens; by binding to estrogen receptors, they mimic or modulate the effect on the endogenous receptors. Little information can be found in literature about the presence of isoflavones and coumestrol in the environment, even if it is known that this may have significance, being these substances classified as endocrine disrupting compounds. In this research, we aim to explore the capabilities of the LTQ Orbitrap Discovery hybrid MS in full-scan acquisition mode, with high resolution, to validate an analytical method for the quantification of nine isoflavones (genistein, genistin, glycitein, daidzein, daidzin, (R,S)-equol, biochanin A, formononetin and coumestrol) in wastewater samples. The correlation coefficients of calibration curves of the nine analyzed compounds were in a range of 0.996-0.999; recoveries at two different levels of concentration (0.05 and 0.5 µg/l) were in the range 73-98%, and the limits of detection ranged between 0.0014 and 0.017 µg/l, proving that this method is sensitive enough in comparison with other methods available in literature. This method has been applied for the analysis of 20 wastewater treatment plants in County Cork, Ireland.

Development and validation of a high-resolution LTQ Orbitrap MS method for the quantification of isoflavones in wastewater effluent: Orbitrap method for isoflavones in wastewater

Isoflavones and coumestranes are the most important classes of compounds among phytoestrogens; by binding to estrogen receptors, they mimic or modulate the effect on the endogenous receptors. Little information can be found in literature about the presence of isoflavones and coumestrol in the environment, even if it is known that this may have significance, being these substances classified as endocrine disrupting compounds. In this research, we aim to explore the capabilities of the LTQ Orbitrap Discovery hybrid MS in full-scan acquisition mode, with high resolution, to validate an analytical method for the quantification of nine isoflavones (genistein, genistin, glycitein, daidzein, daidzin, (R,S)-equol, biochanin A, formononetin and coumestrol) in wastewater samples. The correlation coefficients of calibration curves of the nine analyzed compounds were in a range of 0.996-0.999; recoveries at two different levels of concentration (0.05 and 0.5 µg/l) were in the range 73-98%, and the limits of detection ranged between 0.0014 and 0.017 µg/l, proving that this method is sensitive enough in comparison with other methods available in literature. This method has been applied for the analysis of 20 wastewater treatment plants in County Cork, Ireland.