Impact of mesoporous silica on the chemical degradation of Praziquantel upon grinding

Praziquantel and Syloid 244 FP (amorphous silicon dioxide) were ground in a vibrational mill in standard conditions (15 or 30 min at 25 Hz). Amorphous solid dispersions were obtained in a very short grinding time (15 min), as testified by DSC, PXRD and ESEM analyses. Samples ground at 15 min and 30 min showed the presence of the same degradation product, as was evident from UPLC, MS and NMR analyses. This short paper brings to light the tremendous lattice de-structuration ability of Syloid 244 FP upon grinding toward Praziquantel as well as its detrimental influence on promoting chemical degradation through ring opening and oxidation

Impact of mesoporous silica on the chemical degradation of Praziquantel upon grinding

Praziquantel and Syloid 244 FP (amorphous silicon dioxide) were ground in a vibrational mill in standard conditions ($15^{\prime}$ or $30^{\prime}$ at 25 Hz). Amorphous solid dispersions were obtained in a very short grinding time (15 min), as testified by DSC, PXRD and ESEM analyses. Samples ground at $15^{\prime}$ and $30^{\prime}$ showed the presence of the same degradation product, as was evident from UPLC, MS and NMR analyses. This short paper brings to light the tremendous lattice de-structuration ability of Syloid 244 FP upon grinding toward Praziquantel as well as its detrimental influence on promoting chemical degradation through ring opening and oxidation

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

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

Azelaic Acid: A Bio-Based Building Block for Biodegradable Polymers

The production of fine chemicals, new materials and products from renewable feedstocks represents a continuous challenge. Several procedures have been reported in the literature or patented in the last decade for the main biomass components: carbohydrates (75%), lignins (20%), fats and oils (5%) [1]. Regarding oleochemical developments, the oxidative cleavage of unsaturated fatty acids to produce dicarboxylic acids, hydroxy acids, and amino acids has received great attention in the last decade [2]. Two main oleochemical products obtained by the cleavage of unsaturated fatty acids are sebacic acid and azelaic acid. Azelaic acid (AzA) is a naturally occurring saturated nine carbon atom dicarboxylic acid found in whole grains, wheat, rye and barley [2], first detected in rancid fats. It can be formed endogenously from substrates such as longer-chain dicarboxylic acids and processes like the metabolism of oleic acid, and ψ-oxidation of monocarboxylic acids. The azelaic acid market is predicted to reach USD 160 million by 2023 and the applications include pharmacological ingredients, polymers, plastics, lubricants and materials for electronics [3]. The aim of the present review is to highlight the potential of azelaic acid as powerful building block for the synthesis of bio-based and biodegradable polymers, with a special emphasis on the green synthetic routes, embracing both chemical and enzymatic methods

New Multicomponent Porous Architecture of Self-Assembled Porphyrins/Calixarenes Driven by Nickel Ions

A new multicomponent material with nanoporous structure has been synthesized by co-crystallization of a mixture of cationic meso-tetrakis(4-N-methylpyridyl)porphyrin (H2T4) and meso-tri(4-N-methylpyridyl)porphyrin (H2T3py) with polyanionic 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis(hydroxylcarbonylmethoxy)calix[4]arene (C4TsTc) in the presence of Ni2+ ions. The structural analysis indicates that the overall architecture is assembled by interpenetrated two-dimensional (2D) meshes where the nodes are built up by a central tetracationic H2T4 porphyrin with arms hosted in sulphonated rims of four cavitands. The approximately 2D square network is formed by Ni2+ ions bridging the calixarene carboxylate rims in a tail-to-tail fashion. The central H2T4 stacks with two external H2T3py molecules having the neutral pyridine arm N-coordinated to Ni2+ ions. These metal centers interconnect the orthogonal 2D meshes by further coordination of calixarene\u2013carboxylate groups. Self-organization of the new multicomponent material, featuring large channels (60% of volume accessible to solvent molecules) and potential readily accessible metal active sites, has been driven by both supramolecular host\u2013guest recognition and coordinative assembly. The thermal behavior of native and nickel-containing crystals was studied by hot stage microscopy and differential scanning calorimetry. The decomposition temperatures of the multicomponent materials, 465\u2013470 \ub0C, are about 100 \ub0C higher than those of the single building blocks

An explorative analysis of process and formulation variables affecting comilling in a vibrational mill: The case of praziquantel

Praziquantel, a BCS II class anthelmintic drug used for the treatment of schistosome infections, was coground in a vibrational mill with different polymers (linear and crosslinked povidone, copovidone and sodium starch glycolate). An explorative analysis of formulation variables (drug-polymer wt ratio and polymer type) and process parameters (type of grinding media, grinding time and frequency) was carried out with the help of an experimental screening design. The influence of the above mentioned factors on three PZQ characteristics (residual crystallinity, water solubility enhancement and drug recovery) was studied. The variation of carrier amount proved to be by far the most important variable affecting all the experimental responses. A lower impact and, in some cases, rather null effect, had the variation of the process variables. All coground systems were characterized by a high amorphous degree and a solubility significantly higher than the API. A very promising product was obtained by processing at 20 Hz for 4 h, using 3 spheres of 15 mm as grinding media, i.e. a coground having a 50% API content, showing a 4.6-fold greater solubility at 20 °C than pure praziquantel. This product maintained the same antischistosomal activity of pure API and was both physically and chemically stable for at least 6 months

New Multicomponent Porous Architecture of Self-Assembled Porphyrins/Calixarenes Driven by Nickel Ions

A new multicomponent material with nanoporous structure has been synthesized by co-crystallization of a mixture of cationic <i>meso</i>-tetrakis­(4-<i>N</i>-methylpyridyl)­porphyrin (H₂T₄) and <i>meso</i>-tri­(4-<i>N</i>-methylpyridyl)­porphyrin (H₂T₃py) with polyanionic 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis­(hydroxylcarbonylmethoxy)­calix[4]­arene (C₄TsTc) in the presence of Ni²⁺ ions. The structural analysis indicates that the overall architecture is assembled by interpenetrated two-dimensional (2D) meshes where the nodes are built up by a central tetracationic H₂T₄ porphyrin with arms hosted in sulphonated rims of four cavitands. The approximately 2D square network is formed by Ni²⁺ ions bridging the calixarene carboxylate rims in a tail-to-tail fashion. The central H₂T₄ stacks with two external H₂T₃py molecules having the neutral pyridine arm <i>N</i>-coordinated to Ni²⁺ ions. These metal centers interconnect the orthogonal 2D meshes by further coordination of calixarene–carboxylate groups. Self-organization of the new multicomponent material, featuring large channels (60% of volume accessible to solvent molecules) and potential readily accessible metal active sites, has been driven by both supramolecular host–guest recognition and coordinative assembly. The thermal behavior of native and nickel-containing crystals was studied by hot stage microscopy and differential scanning calorimetry. The decomposition temperatures of the multicomponent materials, 465–470 °C, are about 100 °C higher than those of the single building blocks

New Multicomponent Porous Architecture of Self-Assembled Porphyrins/Calixarenes Driven by Nickel Ions

A new multicomponent material with nanoporous structure has been synthesized by co-crystallization of a mixture of cationic <i>meso</i>-tetrakis­(4-<i>N</i>-methylpyridyl)­porphyrin (H₂T₄) and <i>meso</i>-tri­(4-<i>N</i>-methylpyridyl)­porphyrin (H₂T₃py) with polyanionic 5,11,17,23-tetrasulfonato-25,26,27,28-tetrakis­(hydroxylcarbonylmethoxy)­calix[4]­arene (C₄TsTc) in the presence of Ni²⁺ ions. The structural analysis indicates that the overall architecture is assembled by interpenetrated two-dimensional (2D) meshes where the nodes are built up by a central tetracationic H₂T₄ porphyrin with arms hosted in sulphonated rims of four cavitands. The approximately 2D square network is formed by Ni²⁺ ions bridging the calixarene carboxylate rims in a tail-to-tail fashion. The central H₂T₄ stacks with two external H₂T₃py molecules having the neutral pyridine arm <i>N</i>-coordinated to Ni²⁺ ions. These metal centers interconnect the orthogonal 2D meshes by further coordination of calixarene–carboxylate groups. Self-organization of the new multicomponent material, featuring large channels (60% of volume accessible to solvent molecules) and potential readily accessible metal active sites, has been driven by both supramolecular host–guest recognition and coordinative assembly. The thermal behavior of native and nickel-containing crystals was studied by hot stage microscopy and differential scanning calorimetry. The decomposition temperatures of the multicomponent materials, 465–470 °C, are about 100 °C higher than those of the single building blocks