From Bitter to Sweet: a preliminary study towards a patient-friendly Praziquantel dosage form

Praziquantel (PZQ) is an antihelmintic drug used worldwide against Schistosomiasis, despite its low solubility, bioavailability and the disgusting taste. This research represents a preliminary screening of 6 selected sweeteners in terms of their aptitude to be ground with PZQ, towards the development of a patient-friendly dosage form, capable of overcoming both dissolution and taste drawbacks. A vibrational mill was used to process equimolar mixtures of PZQ and each sweetener, and the dispersions were characterized by means of Differential Scanning Calorimetry, Powder X-ray Diffraction, Fourier Transform-Infrared Spectrometry, water solubility and Intrinsic Dissolution Rate. Physical stability of the coground systems was checked over a period of 1 year. The grinding for a short period (such as 30 min) of PZQ and selected sweeteners led to several very interesting products, with prevalent amorphous character, enhanced solubility and Intrinsic Dissolution Rate comparing to the raw drug. Peculiar behavior was found in the case of xylitol:PZQ ground mixtures where the appearance of traces of PZQ anhydrous Form B was noticed. Therefore, this research highlights the possibility of using binary premixes of PZQ and sweeteners in order to obtain an increase in the biopharmaceutical and organoleptic properties of the anthelmintic drug, underlining also the need for a careful screening of sweetener to design a PZQ patient-friendly dosage form

Rapidly-Disintegrating Laminar Extrudates: Preliminary Experiments upon an Age Appropriate Pediatric Formulation

The aim of the present investigation is to produce rapidly disintegrating laminar extrudates for delivering ibuprofen in the mouth of paediatric patients. This laminar shape is particularly convenient for drug delivering in the mouth and can be easily cut in cut in different sizes allowing for a convenient adjustment of the drug dose depending on the age of the patient. Due to the fact that in paediatric formulations, the selection of the excipients is always a challenging issue and the reduction of their amount is always highly desirable, in this study to select the most appropriate composition to achieve a rapid disintegration and simultaneously permit a high amount of ibuprofen in the system, an experimental design for mixtures was employed and the disintegration time in simulated saliva was used as experimental response. In addition, after solid state analyses to check possible insurgence of drug-excipients interactions, laminar extrudates were characterised in terms of mechanical properties and in vitro dissolution performances. Extrudates with the desired uniform laminar shape, constant thickness (2 mm) and a very high content of drug (82% wt) were produced. These products exhibited a short disintegration time. The dose for a patient of 6-12 years corresponded to a length of extrudate between 1-1.5 cm, perfectly compatible with a formulation orodispersible thin laminar extrudate intended for a paediatric patient (Figure 1)

Competitive Mechanochemical Solvate Formation of Theophylline in the Presence of Miscible Liquid Mixtures

In this study, we investigated the mechanochemical competitive solvate formation of polymorphic Form II of theophylline in the presence of two solvate/hydrate-forming miscible liquids, namely, water and 2-pyrrolidone. It is known that theophylline transforms into a monohydrate in the presence of water, while 2-pyrrolidone gives a monosolvate or a sesquisolvate, depending on the experimental conditions. Different theophylline-to-liquid molar ratios and several water:2-pyrrolidone mixtures were used to understand the competitive formation and/or transformation between these solvates. Interconversion studies between hydrate/monosolvate/sesquisolvate forms were also conducted. The obtained results suggest that water:2-pyrrolidone mixtures have a detrimental effect on the formation of multicomponent phases, as they dramatically reduce the efficiency of incorporation of both liquids in the crystal. In fact, all milling experiments performed in the presence of water:2-pyrrolidone mixtures suggested that a higher stoichiometric ratio is needed to obtain a pure form of a specific solvate. Importantly, additional competitive milling experiments revealed a preferential inclusion of 2-pyrrolidone over water. Based on several experimental datasets performed, we conclude that the propensity of solvate formation in the presence of liquid mixtures is a consequence of a complex interplaying of physicochemical and kinetic factors

Co-Crystalline Solid Solution Affords a High-Soluble and Fast-Absorbing Form of Praziquantel

Praziquantel (PZQ) is a chiral class-II drug, and it is used as a racemate for the treatment of schistosomiasis. The knowledge of several cocrystals with dicarboxylic acids has prompted the realization of solid solutions of PZQ with both enantiomers of malic acid and tartaric acid. Here, the solid form landscape of such a six-component system has been investigated. In the process, two new cocrystals were structural-characterized and three non-stoichiometric, mixed crystal forms identified and isolated. Thermal and solubility analysis indicates a fourfold solubility advantage for the newly prepared solid solutions over the pure drug. In addition, a pharmacokinetic study was conducted in rats, which involved innovative mini-capsules for the oral administration of the solid samples. The available data indicate that the faster dissolution rate of the solid solutions translates in faster absorption of the drug and helps maintain a constant steady-state concentration

Application of multivariate techniques in the evaluation of melt granulation products

In this work, principal component analysis and cluster analysis were applied as helping tools to extract useful information in the development of formulations and manufacturing processes of melt granulates. Two melt granulation processes that differ in the shear stress applied to the solid bed during melting step were designed. These processes employ equipment frequently used in the local pharmaceutical industry. The selected binders include both hydrophilic and hydrophobic excipients, which were used alone or in binary mixtures. Granulates were characterized regarding their physicomechanical properties, including their compaction behavior. The resulting tablets were also evaluated. The selected multivariate statistical methods proved to be useful in facilitating the interpretation of the collected data and the study of the properties of granulates and tablets, as well as the selection of more efficient production processes.Neste trabalho, foram aplicadas as técnicas de análise de componentes principais e de análise de agrupamentos para extrair informações úteis no desenvolvimento de formulações e de processos de produção de granulados por fusão. Desenharam-se dois processos de granulação por fusão que apresentam diferenças na tensão de cisalhamento aplicada ao leito sólido durante a etapa de fusão. Esses processos empregam equipamentos frequentemente usados na indústria farmacêutica local. Os ligantes escolhidos incluíram excipientes tanto hidrofílicos quanto hidrofóbicos, utilizados de forma individual ou em misturas binárias. Os granulados foram caracterizados quanto às suas propriedades físico-mecânicas, incluindo seu desempenho no processo de compactação. Os comprimidos resultantes também foram avaliados. Os métodos de análise multivariada escolhidos provaram ser úteis para facilitar a interpretação dos dados coletados e o estudo das propriedades dos granulados e dos comprimidos, bem como a seleção de processos de produção mais eficientes

Drug Nanocrystals: Theoretical Background of Solubility Increase and Dissolution Rate Enhancement

The peculiar higher solubility of drug nanocrystals compared to macrocrystals appeals to the pharmaceutical field. Indeed, until now, about 70 % of the potential drug candidates are discarded due to low bioavailability related with poor solubility in water. Since a modern and efficient design strategy for nanocrystal-based delivery systems requires the knowledge of the theoretical relation between nanocrystal size and solubility, the aim of this paper is to build up a physically-oriented thermodynamic model relating to nanocrystal dimensions with their melting temperature, enthalpy, solubility and dissolution rate. In particular, the developed model will be applied to vinpocetine, a poorly soluble drug used in the treatment of various types of cerebrovascular circulatory disorders

Drug Nanocrystals: Theoretical Background of Solubility Increase and Dissolution Rate Enhancement

The peculiar higher solubility of drug nanocrystals compared to macrocrystals appeals to the pharmaceutical field. Indeed, until now, about 70 % of the potential drug candidates are discarded due to low bioavailability related with poor solubility in water. Since a modern and efficient design strategy for nanocrystal-based delivery systems requires the knowledge of the theoretical relation between nanocrystal size and solubility, the aim of this paper is to build up a physically-oriented thermodynamic model relating to nanocrystal dimensions with their melting temperature, enthalpy, solubility and dissolution rate. In particular, the developed model will be applied to vinpocetine, a poorly soluble drug used in the treatment of various types of cerebrovascular circulatory disorders

Trends in h2s-donors chemistry and their effects in cardiovascular diseases

Hydrogen sulfide (H2S) is an endogenous gasotransmitter recently emerged as an important regulatory mediator of numerous human cell functions in health and in disease. In fact, much evidence has suggested that hydrogen sulfide plays a significant role in many physio-pathological processes, such as inflammation, oxidation, neurophysiology, ion channels regulation, cardiovascular protection, endocrine regulation, and tumor progression. Considering the plethora of physiological effects of this gasotransmitter, the protective role of H2S donors in different disease models has been extensively studied. Based on the growing interest in H2S-releasing compounds and their importance as tools for biological and pharmacological studies, this review is an exploration of currently available H2S donors, classifying them by the H2S-releasing-triggered mechanism and highlighting those potentially useful as promising drugs in the treatment of cardiovascular diseases

Tecnologia para elaboração de vinhos finos licorosos tintos.

1. Vinhos Vinhos licorosos: classificação e importância; 2. Elaboração de vinhos licorosos de interesse; 2.1. Recioto della Valpolicella; 2.2. Vinho do Porto Vintage; 3. Objetivos da pesquisa geradora da tecnologia; 4. Metodologia; 4.1. Variedades de uva; 4.2. Desidratação das uvas; 4.3. Vinificações; 4.4. Análises de mostos e vinhos; 5. Resultados; 6. Protocolo de elaboração validado; 7. Características dos produtos originados do processo agroindustrial; 8. Conclusões e perspectivas de estudos visando ao aprimoramento dos produtos; 9. Referênciasbitstream/item/211450/1/SERIE-DOCUMENTOS-113-Publica-451-A4-CAPA-MIOLO-versao-2020-02-12.pd