Tablet splitting in elderly patients with dementia: The case of quetiapine

Quetiapine is an atypical antipsychotic approved for treating schizophrenia, bipolar depression, and mania but is frequently used in an off-label manner to control the behavioral and psychological symptoms of dementia in elderly patients with dementia. Due to the need to personalize doses for elderly patients with dementia, quetiapine tablet manipulation is widespread in hospital settings, long-term care facilities, and patient homes. The aim of this study was to assess the impact of the different splitting techniques on quetiapine fumarate tablets by analysing the obtained sub-divided tablets and to discuss compliance with the European Pharmacopoeia limits on whole and split tablets. Quetiapine fumarate tablets of two dose strengths were taken at random (in a number able to assure a power of 0.8 during statistical comparison) and were split with a kitchen knife or tablet cutter. The weight and the drug content were determined for each half tablet. The obtained data were compared to the European Pharmacopoeia limits. The differences between the different splitting techniques were statistically tested. Data showed that split tablets, independently of the dose strength and the technique employed, were not compliant with the European Pharmacopoeia specifications for both entire and subdivided tablets in terms of weight and content uniformity. Thus, such a common practice could have potential effects on treatment efficacy and toxicity, especially when also considering the fragility of the elderly target population in which polypharmacotherapy is very common. These results indicate a compelling need for flexible quetiapine formulations that can assure more accurate dose personalization

Management of solid oral dosage forms according to ministerial recommendation n. 19: Development of a web-based decision support tool

Introduction. The increase in life expectancy has led to a large number of patients suffering from multiple chronic diseases that need to be treated with an increasing number of drugs. The use of Solid Oral Dosage forms (SODF) for the therapy of these patients is more complex in case of difficulty in swallowing. This implies that many commercially available drugs are not suitable for administration and therefore they must be compounded with possible risks for patients and caregivers. For these reasons a web-based decision support, was realized with the aim to help prescribers and caregivers in the correct management of oral therapy in patients with swallowing disorders as suggested by the 19° Ministerial Recommendation (RM19). The web-application is based on a database of about 9.000 drugs. Every drug in the database is associated to an Information Sheet available online, that can contain risk symbols, galenic formulations and compounding methods. The aim of the present study is to analyze the knowledge of all users registered in web application about RM19 and the risks related to manipulation as well as collecting suggestions to improve the service offered by the web-application. Materials and methods. All users registered were invited by email to fill an anonymous survey on line structured on 11 compulsory questions. Results. From the 100 questionnaires examined, it emerged that only 45 users (45%) know RM19 and only 26 users (26%) have a procedure to standardize the compounding of SODFs in the workplace. The SODFs manipulation is also mainly performed by a nurse in the ward, often in the absence of a prior risk assessment. Conclusions. A wider spreading among healthcare professionals and a potentially integration with the computerized prescribing systems of general practitioners and with the computerized medical records of hospitals and healthcare residences could make web application a useful tool to comply with the RM19

N-acyl amino acids as a new class of permeability enhancers: in vitro study on Caco-2 cells.

N-acyl amino acids are attractive anionic surfactant molecules. They are made up of an amino acid as polar head chemically linked via an amide bond to a linear fatty acid (Bordes et al, 2015). These surfactants, especially glutamate derivates, have been several times proposed in cosmetics as promising detergents and foaming agents. Generally, they are referred as “mild surfactants” because less irritant and commonly considered safer than sulfates, the most used anionic surfactants e.g. sodium dodecyl sulphate (SDS). Anionic surfactants are also commonly employed in several pharmaceutical formulations and SDS is still the most used anionic surfactant despite its not favorable toxicological profile. N-acyl amino acid surfactants could represent an alternative option to SDS. However, most of the potentialities of such surfactants as pharmaceutical excipients remained unexplored. Several studies have demonstrated the effect of SDS as permeability enhancer for the oral route using Caco-2 cell monolayer (Deli M.A, 2009; Anderberg E.K., 1993). However, its use has surely been limited by toxicity concerns. The aim of this work was to investigate the cell viability profiles (MTS assay) on Caco-2 cell of N-acyl surfactants derived from alanine and serine, in comparison to SDS. Moreover, their ability to modulate transepithelial electrical resistance (TEER) and affect the permeability of fluorescein isothiocyanate (FITC) labeled dextran as model drug across Caco-2 cell monolayer was evaluated at non-toxic concentrations (100% of cell viability) as determined by MTS assay

Mucoadhesive hydrogel loaded with nanoparticles for the vaginal release of saquinavir mesylate

Nowadays HIV/AIDS is recognized as one of the most significant health concerns of our society. Although HIV infections have slowed in recent years, the continued presence on global level of a large number of untreated HIV-infected patients means that the infected population is likely to grow [1]. In absence of vaccines, current research has been focused on the developing of new strategies that can prevent/reduce the heterosexual transmission of the virus. The aim of this project was to formulate and characterize an intravaginal delivery system for saquinavir mesylate (the first protease inhibitor approved by the FDA and widely used in the antiHIV therapy). The drug was encapsulated in polymeric nanoparticles and then formulated into a vaginal hydrogel to enhance the retention time within the vaginal cavity and to provide an easy selfadministration [2]. The physiological removal mechanism, that is a limiting factor in the vaginal administration, can in fact be avoided using a mucoadhesive formulation, able to prolong the drug residence time into the vaginal cavity. In this study, mPEG-PLGA di-block copolymers were employed to prepare nanoparticles loaded with saquinavir mesylate, which were then incorporated into a 1.5% Carbopol ® 974 hydrogel.Various mPEG-PLGA di-block copolymers (with different mPEG/PLGA ratio) were screened for their ability to form stable nanoparticles. Different concentrations of nanoparticles were then tested to evaluate their influence on the gel strength in order to obtain a system with the desired rheological properties. The presence of nanoparticles was found to cause a decrease in the strength of the hydrogel. Nevertheless, Carbopol ®974 gives a hydrogel (from a rheological point of view) at any tested concentration of nanoparticles. Encapsulation efficiency of saquinavir mesylate loaded nanoparticles was finally determined by HPLC analysis resulting in 55%