711 research outputs found
Dysphagia: daily concerns and formulative approaches for drug therapy
No full textThis doctoral thesis aimed to argue about the specific subject of dysphagia and its relative concerns. Dysphagia is defined as the sensation of delayed passage of the bolus from the mouth to the stomach and issues regarding swallowing of drug therapy are going to be discussed and faced in this work. In fact, focus was mainly pointed on the difficulty of solid oral dosage forms deglutition and, on problems related to compounding and administration of drug therapy. Two model drugs were examined: pravastatin sodium and potassium canrenoate. Their diffuse prescription makes them two interesting molecules in order to optimize alternative dosage forms with respect to the solid one.
The pharmaceutical market offers a wide availability of dosage forms but solid ones are by far the most common due to some advantages that they have in terms of production, stability of the molecule, and costs. Sometimes, not all active molecules are formulated in the preferable form suitable to dysphagic people as well. Population with swallowing inability requires some specific arrangements to assume the prescribed drug therapy.
Compounding commercial dosage forms is not always possible, for example in case of gastro-enteric or controlled-release formulations. Nevertheless, the lack of awareness and proper background make errors happen in the several care settings (hospital, nursing homes, long-term care facilities) where dysphagic patients are admitted. Other problems may occur during manipulation process such as, for example, invaluable drug losses, active molecule instability, palatability decrease, cross-contamination among the drug powders crushed in the same device.
To overcome some issues related to drug intake in dysphagic people, the purpose of the work was to optimize compounding process in order to produce suitable dosage forms for this specific target population.
The work was organized in the following parts. After a general introduction of dysphagia issue, biopharmaceutics considerations concerning drug compounding were argued in the first part of the thesis.
In the second chapter, current clinical practice was dealt with. Whatever was daily performed in the hospital setting, for instance, tablet splitting to facilitate drug intake reducing tablet size, or inappropriate prescriptions of solid oral dosage forms when other therapeutic forms would be available, or occupation risks related to hospital workers during bedside compounding were discussed.
The third chapter of the work addressed the optimization of some dosage forms. Liquid dispersions of pravastatin sodium and potassium canrenoate were set up and enteral delivery via feeding tubes was analyzed for both of them. Pravastatin sodium was further studied to prepare a gelified form to replace tablet. Rheological and kinetic release profile studies were evaluated. The same statin was used to refine an orodispersible film able to disintegrate in the mouth after contact with saliva.
All these dosage forms, studied and tuned in the laboratory, might be able to replace commercial tablets. They might guarantee drug therapy to those who, due to their inability to swallow solid forms, would not have therapeutic alternative with the exception of extemporaneously and bedside produced preparations
Effect of amino acid-based surfactants on Caco-2 cell permeability of macromolecular drugs
No full textBackgroundsSurfactants are amphiphilic molecules of large interest in the pharmaceutical field. An
interesting technological application of surfactants is their use as permeability enhancers. At this end,
different amphiphilic compounds have been investigated both iAimsThe aim of the study was to
evaluate the effect of N-acyl serine and N-acyl alanine on Caco-2 cell monolayer permeability of
fluorescein isothiocyanate–dextran 4kDa (as model for macromolecular drug) in comparison to
SDS, a well-knMethodsN-acyl serine and N-acyl alanine, with different lengths of the hydrocarbon
chains (from C10 to C16) were synthesized. Transepithelial electrical resistance (TEER) at not-toxic
concentrations (100% cell viability) across Caco-2 cell monoResultsA decrease in TEER was observed
after exposure to N-acyl surfactants. Particularly, the decrease in TEER was proportional to the length of
the hydrocarbon chain, reaching values comparable to SDS, when C16 derivatives were tested.
Permeability studies refSummary/ConclusionThis study demonstrated that N-acyl serine and N-acyl
alanine can act as permeability enhancers for oral absorption of macromolecular drugs
STUDIO DI STABILITÀ DELLA PRAVASTATINA SODICA IN SOLUZIONE
No full textLa Pravastatina è un farmaco indicato nel trattamento dell’ipercolesterolemia
primaria o della dislipidemia mista, nella prevenzione
primaria/secondaria di eventi cardiovascolari e nella riduzione della
iperlipidemia in pazienti in terapia immunosoppressiva a seguito di trapianto
d’organo. La Pravastatina, è commercializzata unicamente sotto
forma di compresse, pertanto la mancanza di altre formulazioni (iniettabili,
orodispersibili, granulato effervescente ...) costituisce un grande limite
alla gestione della terapia nei pazienti disfagici in nutrizione enterale
(NE). Il nostro studio quindi, è volto a mettere a punto una formulazione
di Pravastatina sodica facilmente somministrabile attraverso il sondino
della NE e a valutare la stabilità del principio attivo fino a 60 giorni dalla
preparazione della soluzion
Elucidation of the mass fragmentation patways of tomatidine and β1-hydroxytomatine using orbitrap mass spectrometry
No full textTomatoes, members of the Solanaceae plant family, produce biologically active secondary metabolites, including glycoalkaloids, which may have both adverse and beneficial biological effects. Using the linear ion trap (LIT) mass spectrometry, multi-stage collision induced dissociation (CID) experiments (MSn) were performed to elucidate characteristic fragmentation pathways of the glycoalkaloid, tomatidine and of â1-hydroxytomatine. High resolution with high accuracy mass analysis using an Orbitrap fourier transform MS with higher-energy collisional induced dissociation (HCD) was used to produce mass spectra data across a wide spectral range for confirmation of proposed ion structures and formulae
Oral drug therapy in elderly with dysphagia: between a rock and a hard place!
No full textSerena Logrippo,1,2 Giovanna Ricci,3 Matteo Sestili,4 Marco Cespi,2 Letizia Ferrara,4 Giovanni F Palmieri,2 Roberta Ganzetti,4 Giulia Bonacucina,2 Paolo Blasi2 1School of Advanced Studies, 2School of Pharmacy, 3School of Law, University of Camerino, Camerino, 4Italian National Research Centers on Ageing (INRCA), Ancona, Italy Abstract: 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. Keywords: geriatric medicine, dysphagia, compounding, modified-release formulations, gastrointestinal tract toxicit
Development and validation of a high‐resolution LTQ Orbitrap MS method for the quantification of isoflavones in wastewater effluent
No full textIsoflavones 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 hybridMS in full-scan acquisitionmode, with high resolution, to validate an analyticalmethod 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 thismethod is sensitive enough in comparisonwith othermethods
available in literature. This method has been applied for the analysis of 20 wastewater treatment plants in County Cork, Ireland
Linear Viscoelastic Properties of Selected Polysaccharide Gums as Function of Concentration, pH, and Temperature
No full textHydrocolloids have been intensively investigated due to their ability to modify the rheology of the system where they are employed. They find application as thickening and gelling agents in many food, cosmetic, and pharmaceutical preparations, due to their biocompatibility and biodegradability. The present study aims to provide an exhaustive and comprehensive viscoelastic characterization of a series of hydrocolloid formulations, as function of concentration, pH, and temperature. Glucomannan, xanthan gum, tara gum, guar gum, konjac gum, and gellan gum have been analyzed at two concentrations (0.5% w/w and 1.5% w/w), using three different pH conditions (pH 1.2, 5.5, and 6.8). Their viscoelastic properties have been monitored measuring the main rheological parameters, namely, storage modulus G′ and loss modulus G′′ as function of frequency, time, and temperature. The results obtained show a clear dependence of the linear viscoelastic properties of the systems on concentration and pH, while the temperature was not a critical factor. Glucomannan, xanthan gum, tara gum, and guar gum samples prepared in phosphate buffer (pH 6.8) at the final concentration of 1.5% (w/w) have been selected as the most promising systems for further investigations, exploring the possibility of combinations to improve the rheological properties
Enteral Delivery of Pravastatin Sodium Tablets: Effect of Compounding into a Liquid Form and Co-Administration of Enteral Nutrition
No full textBackground: Compounding solid oral dosage forms into liquid preparations is a common practice for administering drug therapy to patients with swallowing difficulties. This is particularly relevant for those on enteral nutrition, where factors such as the administration procedure and co-administration of enteral nutrition play crucial roles in effective drug delivery. Due to the limited studies focused on this practice, the impact of co-administered nutrition remains unclear. Methods: Pravastatin tablets were compounded into two liquid formulations and administered through three independent tubes for ten cycles. The drug amount was quantified upstream and downstream of the tubes both with and without different (fiber content) nutritional boluses. Results: The compounding procedure did not lower the drug amount with respect to the original tablets. However, when the liquid formulation was pumped through the tubes, a statistically significant reduction in the pravastatin administered (between 4.6% and 11.3%) was observed. The co-administration of different nutritional boluses or the compounding procedure did not affect the general results. Conclusions: Pravastatin loss appears unavoidable when administered via the enteral tube. Although, in this case, the loss was of limited clinical relevance, it is important not to underestimate this phenomenon, especially with drugs having a narrow therapeutic index
DESIGN AND DEVELOPMENT OF AN ORODISPERSIBLE FILM AS A NEW DRUG DELIVERY FILM-SYSTEM TO DYSPHAGIC PATIENTS
No full textPurpose: Oral route is generally the most preferable route of drug administration even though is not always accessible due to specific pathological conditions. The onset of swallowing difficulties may be a situation where oral solid medicines are not manageable. A quite new technology in the pharmaceutical field is focused on the development of orodispersible films (ODFs) as a good alternative to conventional solid forms (i.e., tablets or capsules).1,2 The aim of this work is to develop an ODF using electrospinning technique3 in order to tune a proper drug delivery film-system (DDFS) able to facilitate drug administration to dysphagic patients. Electrospinning apparatus allows to produce a nanofibers’ matrix disintegrating into the mouth. Specifications reported in European Pharmacopoeia 8th edition (Eu.Ph.)4 about orodispersible tablets are generally used as reference because there is still not a clear description on ODFs characterization methods.
Methods: The spinning solutions were prepared by dissolving two polymers polyvinylpyrrolidone K90 (PVP K90) 5% w/w and polyethylene oxide 300k Da (PEO 300k) 5% w/w in water under magnetic stirring. This blend was chosen for producing a placebo film after a selection of several polymers and electrospinning conditions to achieve proper film properties about disintegration time and handling. Additionally, a DDFS was prepared by adding pravastatin sodium 1% w/w in the placebo mixture. The electrospinning process was carried out applying the following parameters: voltage 15kV, 20cm needle-collector distance and flow-rate 0.5mL/hour in placebo system and drug-loaded system.
Surface morphology and dimensions of nanofibers were revealed and measured using a JSM-5900LV scanning electron microscope (SEM).
Disintegration tests were performed on squared pieces (2cm*2cm) of each produced film to evaluate the complete disappearance of the film when a proper volume (3-5mL) of artificial saliva (phosphate buffer solution pH 6.0) was added into a Petri dish to simulate oral cavity conditions. Disintegration time was recorded and tests were performed in triplicate.
Results: SEM pictures showed that nanofibers appeared straight and elongated in the entire mat. Their dimensions ranged within 445.50 ± 39.68nm and 439.60 ± 33.49nm in placebo film and in DDFS, respectively. Fiber size and fiber distribution looked homogeneous in all mat. Detection of cationic sodium related to pravastatin and determined by elemental analysis, confirmed the presence of the drug in the DDFS.
Disintegration of the films resulted into 120 and 60-75 seconds in placebo film and in DDFS, respectively, in accordance with specifications reported in Eu.Ph. for orodispersible tablets. In fact, Eu.Ph. establishes that tablets should disintegrates into the mouth within 3 minutes. Then, these results demonstrated a possible relationship existing between fiber dimension and speed of disintegration of the mat: decreasing diameter size, films revealed a quicker time for disappearance in the mouth. Mats exhibited a quite good manipulation and handling properties to guarantee a suitable administration on the tongue.
Conclusions: Orodispersible films may be considered promising drug delivery systems especially for patients who present specific alterations in deglutition process. ODFs may offer a valid alternative to conventional forms and the switch between the two forms may assure drug therapy compliance
Location-Based Discovery and Network Handover Management for Heterogeneous IEEE 802.11ah IoT Applications
No full textThis research was funded by the Flemish IDEAL-IoT project (FWO SBO, grant nr. S004017N). The author Serena Santi is funded by the Flemish FWO SB grant (nr. 1S82120N). The author Filip Lemic was supported by the EU MSCA grant (nr. 893760). The computational resources were provided by the VSC (Flemish Supercomputer Center), funded by FWO and the Flemish Government -department EWI
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