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

THE USE OF SOUND SPEED MEASUREMENTS IN THE EVALUATION OF POLYMERS MUCOADHESIVENESS

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HIGH RESOLUTION ULTRASONIC SPECTROSCOPY IN THE ANALYSIS OF POLOXAMERS BEHAVIOUR

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Effect of Lactose on the thermogelation properties of Poloxamer 407.

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Characterization of ternary phase diagrams by means of thermal and rheological analyses

Context: Mixtures made of oil, water and surfactants give rise to a wide range of structure with different characteristics and phase manifestations. Objective: Aim of this paper is to build up and understand the phase diagram of a model ternary system (Water, Polysorbate 80 and isopropyl myristate) by the use of common techniques such as thermal analysis and rheology, in comparison with visual assessment and polarized light microscopy. Methods: Different ternary systems were prepared and analyzed by means of DSC and rheology in order to highlight the state of water (free, interphasal, bound water) and the samples structural characteristics. Results: The resultant phase diagram is divided into four different zones. Bound water zone is predominant at elevated surfactant/oil ratios, while as the surfactant/oil ratio decreases, DSC reveals the presence of free water. Interphasal water prevails at intermediate water and surfactant content which corresponds with gels systems. Mechanical spectra allow to discern between cubic (true gel) and lamellar mesophases (weak gel), while flow curves allow to distinguish among microemulsions, emulsions or lamellar mesophases. Discussion: A deeper characterization of a model ternary phase diagram is possible, with respect to the simple visual inspection, by the use of thermal analysis and rheology. The state of water molecules and the viscoelastic characteristics of the system allow to obtain important structural considerations. Conclusions: In conclusion, the knowledge of the state of water and of the viscoelastic characteristics of the systems allow a deeper understanding of the structural features of the ternary phase diagra

In situ composite ion-triggered gellan gum gel incorporating amino methacrylate copolymer microparticles: a therapeutic modality for buccal applicability

The aim of the current investigation is to delineate the buccal applicability of an in situ composite gel containing aceclofenac (AC) amino methacrylate copolymer microparticles (MPs), surmounting limitations of oral existing conventional therapy. AC Eudragit RL100 MPs were fabricated and statistically optimized using 2241 factorial design. Better buccal applicability and enhanced localization were achieved by combining the optimum MPs with in situ ion-activated gellan gum gel. The crosslinking and gelation of in situ gel were investigated by morphological and solid state characterizations. Suitability for buccal delivery and in vivo therapeutic efficacy in inflammation model of rats were also assessed. Results showed that the best performing formula displayed particle size (PS) of 51.00 µm and high entrapment efficiency (EE%) of 94.73%. MPs were successfully entrapped inside the gel network of the composite system. Gelation tendency, pH, shear-thinning properties and mucoadhesivity of the prepared in situ composite gel guaranteed its buccal suitability. Sustained AC release features and promising in vitro anti-arthritic response were also demonstrated. Moreover, consistent and prolonged in vivo anti-inflammatory effect was achieved, relative to standard AC. Taken together; this study proves the potential of in situ composite gel as an appropriate therapeutic proposal for AC buccal delivery

Rheological, adhesive and release characterisation of semisolid Carbopol/Tetraglycol systems

Gels dosage forms are successfully used as drug delivery systems considering their ability to control drug release and to protect medicaments from an hostile environment. This study deals with the gelation properties of Carbopol 971 e 974 polymeric systems in tetraglycol, a water-miscible cosolvent. In this paper, the attention was noted of the thickening properties of the different Carbopol in tetraglycol solvent at increasing temperatures, in order to obtain gels avoiding neutralisation and, at the same time, to make possible the dissolution in these gels of insoluble or poorly soluble water drugs. Samples were prepared by simply dispersing different Carbopols amount (0.5-4%) were added to tetraglycol and different systems were prepared at room temperature and by heating at 70 °C. All these systems were then characterised rheologically. Frequency sweep, creep-recovery, temperature sweep and time sweep analyses outlined that Carbopol 971 and 974 in tetraglycol gave rise after heating to gels with satisfactory rheological behaviour: the elastic modulus was greater than the viscous one and a remarkable elastic character was found to be present. Systems obtained by heating procedure were examined also from a mechanical point of view using a texture profile analysis. Besides, being Carbopols well known mucoadhesive polymers, gels adhesive properties were also studied using the ex vivo method. Texture and adhesion characterisation confirmed rheological results pointing out a certain greater elasticity and adhesiveness of Carbopol 974 systems. Then, the possible cutaneous irritation was also tested using the in vivo method (Draize test). No signs of cutaneous irritation were obtained for all the samples that were analysed. After rheological and mucoadhesive properties were set, paracetamol as a model drug was inserted in the composition of the gels and the release characteristics were defined. Dissolution tests pointed out the greater release control properties of tetraglycol/Carbopol 971 samples. These studies showed tetraglycol/Carbopol systems as a first-rate alternative to traditional water gels when low water-soluble drugs have to be added

Effect of temperature increase during the tableting of pharmaceutical materials

Scale-up of tableting process is particularly difficult due to specific concerns related exclusively to the process itself and that cannot be determined on a smaller scale, which are the effect of compression speed and the build-up of heat due to the length of the compaction operations. In this work, it has been simulated the rise of temperature observed during the tablets manufacturing in a full production scale by means of an appropriate modification of a R&D rotary tablet machine. Four common pharmaceutical excipients, characterized by different chemical nature, consolidation behaviour and temperature sensitiveness have been analysed in terms of compaction mechanism (Heckel and energy analysis) and tabletability, in order to verify any effect of the increase of temperature. The results showed a relevance of the temperature on mechanical tablets properties only on materials characterized by low temperature thermal transitions (melting or glass transition), while, for compounds which do not exhibit thermal events at low temperature, it becomes less important for ductile materials and irrelevant for brittle materials. Heckel analysis highlighted a noticeable increase of ductility only in those materials whose tablets mechanical properties depended on the temperature. On the other hand, energy analysis showed low sensitivity failing to identify any temperature effect on compaction materials properties. This work showed how to simulate the process of temperature rise on a small scale and the influence of temperature on materials compaction properties. The use of a modified tableting machine, able to control the temperature and moisture levels and also capable of monitoring the punch movements, resulted in identifying the effect of temperature both on mechanical and compaction properties on materials. Thus, it represents a valuable tool in order to provide useful information at an early stage during the development of tablets formulations

Mechanical characterization of pharmaceutical solids: a comparison between rheological tests performed under static and dynamic porosity conditions.

The aim of this work was to verify how and to what extent rheological tests, carried out under dynamic (Heckel) and static (creep, stress/strain) porosity conditions, may serve as a valuable complement to the classic Heckel tests in the characterization of viscoelastic and densification properties of solid materials for pharmaceutical use. Six different modified (pregelatinized) starches were compressed in a rotary tablet machine equipped to measure force and punch displacement. Tablets were obtained using flat-faced 6 mm diameter punches at different compression pressures. Compression cycles performed at the maximal pressure of 200 MPa were used to build the Heckel plots. Ejected tablets at the 10%, 20%, 30%, and 40% porosity levels were used for the stress/strain and creep tests. Parameters obtained with both types of tests were consistent with each other. In particular, among the six starches, lower viscosity values corresponded to lower PY values, and lower elastic modulus values corresponded to lower elastic recovery of the tablet. Mechanical properties of materials can be better characterized if viscoelastic tests performed under dynamic porosity conditions (Heckel analysis) are supported by classical viscoelastic tests carried out under conditions of static porosity

Dynamic mechanical thermal analysis of hypromellose 2910 free films

It is common practice to coat oral solid dosage forms with polymeric materials for controlled release purposes or for practical and aesthetic reasons. Good knowledge of thermo-mechanical film properties or their variation as a function of polymer grade, type and amount of additives or preparation method is of prime importance in developing solid dosage forms. This work focused on the dynamic mechanical thermal characteristics of free films of hypromellose 2910 (also known as HPMC), prepared using three grades of this polymer from two different manufacturers, in order to assess whether polymer chain length or origin affects the mechanical or thermo-mechanical properties of the final films. Hypromellose free films were obtained by casting their aqueous solutions prepared at a specific concentrations in order to obtain the same viscosity for each. The films were stored at room temperature until dried and then examined using a dynamic mechanical analyser. The results of the frequency scans showed no significant differences in the mechanical moduli E' and E" of the different samples when analysed at room temperature; however, the grade of the polymer affected material transitions during the heating process. Glass transition temperature, apparent activation energy and fragility parameters depended on polymer chain length, while the material brand showed little impact on film performance