Supramolecular eutectogel as new oral paediatric delivery system to enhance benznidazole bioavailability.

Benznidazole (BNZ) serves as the primary drug for treating Chagas Disease and is listed in the WHO Model List of Essential Medicines for Children. Herein, a new child-friendly oral BNZ delivery platform is developed in the form of supramolecular eutectogels (EGs). EGs address BNZ's poor oral bioavailability and provide a flexible twice-daily dose in stick-pack format. This green and sustainable formulation strategy relies on the gelation of drug-loaded Natural Deep Eutectic Solvents (NaDES) with xanthan gum (XG) and water. Specifically, choline chloride-based NaDES form stable and biocompatible 5 mg/mL BNZ-loaded EGs. Rheological and Low-field NMR investigations indicate that EGs are viscoelastic materials comprised of two co-existing regions in the XG network generated by different crosslink distributions between the biopolymer, NaDES and water. Remarkably, the shear modulus and relaxation spectrum of EGs remain unaffected by temperature variations. Upon dilution with simulated gastrointestinal fluids, EGs results in BNZ supersaturation, serving as the primary driving force for its absorption. Interestingly, after oral administration of EGs to rats, drug bioavailability increases by 2.6-fold, with a similar increase detected in their cerebrospinal fluid. The noteworthy correlation between in vivo results and in vitro release profiles confirms the efficacy of EGs in enhancing both peripheral and central BNZ oral bioavailability.

Enantiospecific crystallisation behaviour of malic acid in mechanochemical reactions with vinpocetine.

We report an intriguing example of enantioselectivity in the formation of new multicomponent crystalline solid containing vinpocetine and malic acid. Several experimental data sets confirmed that the multicomponent system presents a clear enantiospecific crystallisation behaviour both in the solid-state and in solution: only the system consisting of vinpocetine and L-malic acid produces a free-flowing solid consisting of a new crystalline form, while the experiments with D-malic acid produced an amorphous and often deliquescent material. The new vinpocetine-L-malic system crystallizes in the monoclinic space group of P21 and in a 1:1 M ratio, where the two molecules are linked through intermolecular hydrogen bonds in the asymmetric unit. The vinpocetine-DL-malic system was partially crystalline (with also traces of unreacted vinpocetine) with diffraction peaks corresponding to those of vinpocetine-L-malic acid. Solid-state NMR experiments revealed strong ionic interactions in all the three systems. However, while vinpocetine-L-malic acid system was a pure and crystalline phase, in the other two systems the presence of unreacted vinpocetine was always detected. This resulted in a significant worsening of the dissolution profile with respect to vinpocetine-L-malic pure crystalline salt, whose dissolution kinetics appeared superior.

Shifting the Focus from Dissolution to Permeation: Introducing the Meso-fluidic Chip for Permeability Assessment (MCPA).

In response to the growing ethical and environmental concerns associated with animal testing, numerous in vitro tools of varying complexity and biorelevance have been developed and adopted in pharmaceutical research and development. In this work, we present one of these tools, i.e., the Meso-fluidic Chip for Permeability Assessment (MCPA), for the first time. The MCPA combines an artificial barrier (PermeaPad®) with an organ-on-chip device (MIVO®) and real-time automated concentration measurements, to yield a sustainable, yet effortless method for permeation testing. The system offers three major physiological aspects, i.e., a biomimetic membrane, an optimal membrane interfacial area-to-donor-volume-ratio (A/V) and a physiological flow on the acceptor/basolateral side, which makes the MPCA an ideal candidate for mechanistic studies and excellent in vivo bioavailability predictions. We validated the method with a handful of assorted drug compounds in unstirred and stirred donor conditions, before exploring its applicability as a tool for dissolution/permeation testing on a BCS class III/I drug (pyrazinamide) crystalline adducts and BCS class II/IV (hydrocortisone) amorphous solid dispersions. The results were highly reproducible and clearly displayed the method's potential for evaluating the performance of enabling formulations, and possibly even predicting in vivo performance. We believe that, upon further development, the MCPA will serve as a useful in vitro tool that could push sustainability into pharmaceutics by refining, reducing and replacing animal testing in early-stage drug development.

Praziquantel meets Niclosamide: A dual-drug Antiparasitic Cocrystal.

In this paper we report a successful example of combining drugs through cocrystallization. Specifically, the novel solid is formed by two anthelminthic drugs, namely praziquantel (PZQ) and niclosamide (NCM) in a 1:3 molar ratio, and it can be obtained through a sustainable one-step mechanochemical process in the presence of micromolar amounts of methanol. The novel solid phase crystallizes in the monoclinic space group of P21/c, showing one PZQ and three NCM molecules linked through homo- and heteromolecular hydrogen bonds in the asymmetric unit, as also attested by SSNMR and FT-IR results. A plate-like habitus is evident from scanning electron microscopy analysis with a melting point of 202.89 °C, which is intermediate to those of the parent compounds. The supramolecular interactions confer favorable properties to the cocrystal, preventing NCM transformation into the insoluble monohydrate both in the solid state and in aqueous solution. Remarkably, the PZQ - NCM cocrystal exhibits higher anthelmintic activity against in vitro S. mansoni models than corresponding physical mixture of the APIs. Finally, due to in vitro promising results, in vivo preliminary tests on mice were also performed through the administration of minicapsules size M.

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.

Praziquantel Fifty Years on: A Comprehensive Overview of Its Solid State.

This review discusses the entire progress made on the anthelmintic drug praziquantel, focusing on the solid state and, therefore, on anhydrous crystalline polymorphs, amorphous forms, and multicomponent systems (i.e., hydrates, solvates, and cocrystals). Despite having been extensively studied over the last 50 years, new polymorphs and the greater part of their cocrystals have only been identified in the past decade. Progress in crystal engineering science (e.g., the use of mechanochemistry as a solid form screening tool and more strategic structure-based methods), along with the development of analytical techniques, including Synchrotron X-ray analyses, spectroscopy, and microscopy, have furthered the identification of unknown crystal structures of the drug. Also, computational modeling has significantly contributed to the prediction and design of new cocrystals by considering structural conformations and interactions energy. Whilst the insights on praziquantel polymorphs discussed in the present review will give a significant contribution to controlling their formation during manufacturing and drug formulation, the detailed multicomponent forms will help in designing and implementing future praziquantel-based functional materials. The latter will hopefully overcome praziquantel's numerous drawbacks and exploit its potential in the field of neglected tropical diseases.

Validation and testing of a new artificial biomimetic barrier for estimation of transdermal drug absorption.

Human skin remains the most reliable model for studying the transdermal permeation of active compounds. Due to the limited source, porcine skin has been used extensively for performing penetration tests. Performing penetration studies by using human and animal skin, however, would also involve a series of ethical issues and restrictions. For these reasons, new biomimetic artificial barriers are being developed as possible alternatives for transdermal testing. If appropriately optimized, such products can be cost-effective, easily standardized across laboratories, precisely controlled in specific experimental conditions, or even present additional properties compared to the human and animal skin models such as negligible variability between replicates. In this current work we use the skin mimicking barrier (SMB) for drug permeability tests. The aim was to evaluate the suitability of the new barrier for studying the percutaneous absorption of the lipophilic extract of the plant Zingiber officinale Roscoe in vitro and compare its permeability ability with the artificial membrane Permeapad® and porcine skin. Our results showed that the permeability values obtained through the SMB are comparable are comparable to those obtained by using the porcine skin, suggesting that the new barrier may be an acceptable in vitro model for conducting percutaneous penetration experiments.

Overcoming the Drawbacks of Sulpiride by Means of New Crystal Forms.

This study aims at developing new multicomponent crystal forms of sulpiride, an antipsychotic drug. The main goal was to improve its solubility since it belongs to class IV of the BCS. Nine new adducts were obtained by combining the active pharmaceutical ingredient with acid coformers: a salt cocrystal and eight molecular salts. In addition, three novel co-drugs, of which two are molecular salts and one is a cocrystal, were also achieved. All samples were characterized in the solid state by complementary techniques (i.e., infrared spectroscopy, powder X-ray diffraction and solid-state NMR). For systems for which it was possible to obtain good-quality single crystals, the structure was solved by single crystal X-ray diffraction (SCXRD). SCXRD combined with solid-state NMR were used to evaluate the ionic or neutral character of the adducts. In vitro dissolution tests of the new crystal forms were performed and all the adducts display remarkable dissolution properties with respect to pure sulpiride.

Better and greener: sustainable pharmaceutical manufacturing technologies for highly bioavailable solid dosage forms.

In the last decades, Green Chemistry has been gaining widespread attention within the pharmaceutical field. It is thus very important to bring more sustainable approaches into the design and manufacture of effective oral drug delivery systems. This review focuses on spray congealing and mechanochemical activation, two technologies endorsing different principles of green chemistry, and at the same time, addressing some of the challenges related to the transformation of poorly water-soluble drugs in highly bioavailable solid dosage forms. We therefore present an overview of the basic principles, equipment, and application of these particle-engineering technologies, with specific attention to case studies carried out by the groups working in Italian Universities.

Mechanochemical Synthesis and Physicochemical Characterization of Previously Unreported Praziquantel Solvates with 2-Pyrrolidone and Acetic Acid.

Two new solvates of the widely used anthelminthic Praziquantel (PZQ) were obtained through mechanochemical screening with different liquid additives. Specifically, 2-pyrrolidone and acetic acid gave solvates with 1:1 stoichiometry (PZQ-AA and PZQ-2P, respectively). A wide-ranging characterization of the new solid forms was carried out by means of powder X-ray diffraction, differential scanning calorimetry, FT-IR, solid-state NMR and biopharmaceutical analyses (solubility and intrinsic dissolution studies). Besides, the crystal structures of the two new solvates were solved from their Synchrotron-PXRD pattern: the solvates are isostructural, with equivalent triclinic packing. In both structures acetic acid and 2-pyrrolidone showed a strong interaction with the PZQ molecule via hydrogen bond. Even though previous studies have shown that PZQ is conformationally flexible, the same syn conformation as the PZQ Form A of the C=O groups of the piperazinone-cyclohexylcarbonyl segment is involved in these two new solid forms. In terms of biopharmaceutical properties, PZQ-AA and PZQ-2P exhibited water solubility and intrinsic dissolution rate much greater than those of anhydrous Form A.

Echinacea angustifolia DC. Lipophilic Extract Patch for Skin Application: Preparation, In Vitro and In Vivo Studies.

Dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamide (tetraene) is the main component of Echinacea angustifolia DC. lipophilic extract, the bioavailability and immunomodulatory effect after oral administration in soft gel capsules in healthy volunteers of which we have already demonstrated. In the present work, we assessed the transdermal administration as an alternative route of administration of such an alkamide. The first step, therefore, encompassed the preparation of a drug-in-adhesive patch with an area of 868 mm2 and containing a dose of 0.64 mg of tetraene. In vitro skin permeation studies in Franz-type diffusion chambers resulted in a tetraene flux of (103 ± 10) ng × cm-2 × h-1 with a very good linearity (r = 0.99). The relatively low lag time of just 13 min indicates low binding and the accumulation of tetraene in the skin. Finally, the patch was administered to six healthy volunteers, and the pharmacokinetic analysis was performed by nonlinear mixed effects modelling with soft gel oral capsules serving as the reference formulation. The in vivo results correlated well with the in vitro permeation and indicated an initial burst tetraene absorption from the patch that was in parallel with the zero-order kinetics of absorption. The rate of the latter process was in good agreement with the one estimated in vitro. The tetraene absorption rate was therefore slow and prolonged with time, resulting in a bioavailability of 39% relative to the soft gel capsules and a very flat plasma concentration profile.

Mechanochemical Formation of Racemic Praziquantel Hemihydrate with Improved Biopharmaceutical Properties.

Praziquantel (PZQ) is the first-line drug used against schistosomiasis, one of the most common parasitic diseases in the world. A series of crystalline structures including two new polymorphs of the pure drug and a series of cocrystals of PZQ have been discovered and deposited in the Cambridge Structural Database (CSD). This work adds to the list of multicomponent forms of PZQ a relevant example of a racemic hemihydrate (PZQ-HH), obtainable from commercial PZQ (polymorphic Form A) through mechanochemistry. Noteworthy, the formation of the new hemihydrate strongly depends on the initial polymorphic form of PZQ and on the experimental conditions used. The new PZQ-HH has been fully characterized by means of HPLC, Differential Scanning Calorimetry (DSC), Thermogravimetric Analysis (TGA), Hot-Stage Microscopy (SEM), Powder X-Ray Diffraction (PXRD), Scanning Electron Microscopy (SEM), FT-IR, polarimetry, solid-state NMR (SS-NMR), solubility and intrinsic dissolution rate (IDR), and in vitro tests on Schistosoma mansoni adults. The crystal structure was solved from the powder X-ray diffraction pattern and validated by periodic-DFT calculations. The new bioactive hemihydrate was physically stable for three months and showed peculiar biopharmaceutical features including enhanced solubility and a double intrinsic dissolution rate in water in comparison to the commercially available PZQ Form A.

Dissolution of an ensemble of differently shaped poly-dispersed drug particles undergoing solubility reduction: mathematical modelling.

The aim of this theoretical paper is to develop a mathematical model for describing the dissolution process, in a finite liquid environment, of an ensemble of poly-dispersed drug particles, in form of sphere, cylinder and parallelepiped that can undergo solubility reduction due to phase transition induced by dissolution. The main result of this work consists in its simplicity as, whatever the particular particles size distribution, only two ordinary differential equations are needed to describe the dissolution process. This, in turn, reflects in a very powerful and agile theoretical tool that can be easily implemented in electronic sheets, a widespread tool among the research community. Another model advantage lies on the possibility of determining its parameters by means of common independent techniques thus enabling the evaluation of the importance of solid wettability on the dissolution process.

Exploring mechanochemical parameters using a DoE approach: Crystal structure solution from synchrotron XRPD and characterization of a new praziquantel polymorph.

A rotated Doehlert matrix was utilized to explore the experimental design space around the milling parameters of Praziquantel (PZQ) polymorph B formation in terms of frequency and milling time. Three experimental responses were evaluated on the resulting ground samples: two quantitative responses, i.e. median particle size by Laser Light scattering (LLS) and drug recovery by HPLC, and one qualitative dependent variable, i.e. the obtained PZQ crystalline form, characterized through X-Ray Powder Diffraction (XRPD) and confirmed by Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). Temperature inside the jars was kept under constant control during the milling process by using temperature sensor equipped jars (thermojars), thus allowing evaluation of the obtained solid states at each experimental point, considering the specific temperature of the process. This explorative analysis led to the finding of a novel PZQ polymorph, named "Form C", produced without degradation, then fully characterized, including by means of Synchrotron XRPD, Polarimetric, FT-IR, SS-NMR, ESEM and saturation solubility. Crystal structure was solved from XRPD data and its geometry was optimized by DFT calculations (CASTEP). Finally, Form C and Form A activity against adult schistosoma mansoni were compared through in vitro testing, and Form C's physical stability checked. The new polymorph, crystallizing in space group I2/c, physically stable for approximately 2 months, showed a m.p. of 106.84 °C and displayed excellent biopharmaceutical properties (water solubility of 382.69±9.26 mg/l), while preserving excellent activity levels against adult schistosoma mansoni.

Combined extracts of Echinacea angustifolia DC. and Zingiber officinale Roscoe in softgel capsules: Pharmacokinetics and immunomodulatory effects assessed by gene expression profiling.

BACKGROUND AND OBJECTIVE: Echinacea angustifolia DC. and Zingiber officinale Roscoe are two natural products with documented immunomodulatory activity, both able to modulate the expression of important immune-related genes. Thus, their use in combination seems to be particularly promising. In this context, we have considered the oral supplementation of a highly standardized lipophilic extract combining both above-mentioned phytocomplexes, formulated in attractive softgel capsules, with two objectives: on the one hand to study oral pharmacokinetic of main active extracts' components and on the other hand to examine the immunomodulation and anti-inflammatory properties by gene expression profiling. METHODS: Softgel capsules containing a combination of E. angustifolia DC. and Z. officinale Roscoe (5 mg and 25 mg, respectively) were given by oral administration to 10 healthy volunteers. The plasma concentrations of dodeca-2E,4E,8Z,10E/Z-tetraenoic isobutylamide (tetraene) for E. angustifolia DC., 6-gingerol and 6-shogaol (free and glucuronide) for Z. officinale Roscoe were determined by LC-MS analysis, and the pharmacokinetic analysis was performed. To understand the functional mechanisms responsible for the documented health benefits, we also examined the overall transcriptional remodeling induced in the peripheral blood mononuclear cells and performed an integrative functional analysis on the generated gene expression. RESULTS: All bioactive components were absorbed very rapidly, and their tmax were detected in plasma from 30 min to 1.40 h. The peak concentrations of tetraene, 6-gingerol, 6-shogaol and their glucuronide metabolites were 14.74, 5.66, 9.25, 29.2 and 22.24 ng/ml, respectively. Integrated analysis performed on the generated gene expression data highlighted immunomodulatory and anti-inflammatory effects similar to those exerted by hydrocortisone. CONCLUSION: These data demonstrated that the bioactive ingredients are highly and rapidly absorbed from softgel capsules containing the combination of the above-mentioned lipophilic extracts, providing evidence to support their immunomodulatory and anti-inflammatory properties. These data also help in defining the mechanistic pathways underlying the health benefits of these plant-derived bioactive compounds.

Activity and pharmacokinetics of a praziquantel crystalline polymorph in the Schistosoma mansoni mouse model.

Schistosomiasis is a global disease of significant public health relevance. Only one racemic drug, praziquantel, characterized by low bioavailability, low water solubility and extensive first pass metabolism, is currently available. We studied a new praziquantel formulation (polymorph B), which is based on a racemic praziquantel crystalline polymorph (TELCEU01). Its in vitro activity was tested on newly transformed schistosomula (NTS) and adult Schistosoma mansoni. In vivo studies were conducted in mice harboring chronic S. mansoni infections. Pharmacokinetic (PK) profiles of R- and S-praziquantel and R- and S- polymorph B following oral administration with both formulations were generated by sampling mice at 30, 60, 240 min and 24 h post-treatment, followed by LC-MS/MS analysis. PK parameters were calculated using a non-compartmental analysis with a linear trapezoidal model. In vitro, commercial praziquantel and the polymorph B performed similarly on both NTS (IC50 = 2.58 and 2.40 µg/mL at 72 h) and adults (IC50 = 0.05 and 0.07 µg/mL at 72 h). Praziquantel showed higher in vivo efficacy with an ED50 of 58.75 mg/kg compared to an ED50 of 122.61 mg/kg for the polymorph B. The PK profiles of the two drugs exhibited differences: R-praziquantel showed an overall 40% higher area under the plasma drug concentration-time curve (AUC0→24) (R-praziquantel = 3.42; R-polymorph B = 2.05 h*µg/mL) and an overall 30% lower apparent clearance (Cl/F) (R-praziquantel = 70.68 and R-polymorph B = 97.63 (mg)/(µg/mL)/h). Despite the lack of improved activity and PK properties of polymorph B against S. mansoni, here presented; research on pharmaceutical polymorphism remains a valid and cost-effective option for the development of new praziquantel formulations with enhanced properties such as increased solubility and/or dissolution.

Combining Mechanochemistry and Spray Congealing for New Praziquantel Pediatric Formulations in Schistosomiasis Treatment.

Praziquantel (PZQ) is the first line drug for the treatment of schistosome infections and is included in the WHO Model List of Essential Medicines for Children. In this study, the association of mechanochemical activation (MA) and the spray congealing (SC) technology was evaluated for developing a child-friendly PZQ dosage form, with better product handling and biopharmaceutical properties, compared to MA materials. A 1:1 by wt PZQ-Povidone coground-was prepared in a vibrational mill under cryogenic conditions, for favoring amorphization. PZQ was neat ground to obtain its polymorphic form (Form B), which has an improved solubility and bioactivity. Then, activated PZQ powders were loaded into microparticles (MPs) by the SC technology, using the self-emulsifying agent Gelucire® 50/13 as a carrier. Both, the activated powders and the corresponding loaded MPs were characterized for morphology, wettability, solubility, dissolution behavior, drug content, and drug solid state (Hot Stage Microscopy (HSM), Differential Scanning Calorimetry (DSC), X-Ray Powder Diffraction Studies (PXRD), and FT-IR). Samples were also in vitro tested for a comparison with PZQ against Schistosoma mansoni newly transformed schistosomula (NTS) and adults. MPs containing both MA systems showed a further increase of biopharmaceutical properties, compared to the milled powders, while maintaining PZQ bioactivity. MPs containing PZQ Form B represented the most promising product for designing a new PZQ formulation.

Antibacterial drug release from a biphasic gel system: Mathematical modelling.

Bacterial infections represent an important drawback in the orthopaedic field, as they can develop either immediately after surgery procedures or after some years. Specifically, in case of implants, they are alleged to be troublesome as their elimination often compels a surgical removal of the infected implant. A possible solution strategy could involve a local coating of the implant by an antibacterial system, which requires to be easily applicable, biocompatible and able to provide the desired release kinetics for the selected antibacterial drug. Thus, this work focusses on a biphasic system made up by a thermo-reversible gel matrix (Poloxamer 407/water system) hosting a dispersed phase (PLGA micro-particles), containing a model antibacterial drug (vancomycin hydrochloride). In order to understand the key parameters ruling the performance of this delivery system, we developed a mathematical model able to discriminate the drug diffusion inside micro-particles and within the gel phase, eventually providing to predict the drug release kinetics. The model reliability was confirmed by fitting to experimental data, proposing as a powerful theoretical approach to design and optimize such in situ delivery systems.

An investigation into the release behavior of solid lipid microparticles in different simulated gastrointestinal fluids.

In recent years there has been a growing interest in solid lipid-based systems, particularly in solid lipid microparticles (SLMs); however, only very few studies deeply investigated the dissolution behaviour of orally delivered-SLMs. The present study provides new insights about the release performance in different gastrointestinal fluids of SLMs containing a freely water soluble drug (caffeine, as BCS class I drug). Three different formulations of SLMs were prepared by spray congealing using lipid excipients belonging to three chemical classes: fatty acids, triglycerides and waxes. The dissolution profiles of caffeine were investigated using various updated biorelevant dissolution media simulating the conditions of the gastrointestinal tract (gastric tract and proximal human intestine). The profiles were statistically compared and the morphological changes of the particles after dissolution were assessed by SEM analysis. The influence of the SLMs composition resulted to be crucial on the dissolution behavior in the case of bigger particles (>250 µm), while smaller SLMs (100-250 µm) were mainly affected by the fluid composition. Moreover, regardless of the particle size, greater differences in drug release profiles were noted by using different intestinal media compared to those obtained in gastric media. In particular, the drug release from fatty acid and triglyceride-based SLMs was more controlled in the phosphate buffer than in the intestinal biorelevant media; while the opposite behavior was noticed for waxy-bases SLMs. Overall, the present study provides interesting insights which can be useful for the design of a multiparticulated solid lipid formulation.

Conformational polymorphic changes in the crystal structure of the chiral antiparasitic drug praziquantel and interactions with calcium carbonate.

Praziquantel is an antiparasitic drug used for decades. Currently, the praziquantel commercial preparation is a racemic mixture, in which only the levo-enantiomer possesses anthelmintic activity. The knowledge of its properties in the solid state and other chemical-physical properties is necessary for improving its efficacy and applications. Drug solid dispersions were prepared with calcium carbonate at 1:5 drug to excipient weight ratio by solvent evaporation method. Then, the modification of the crystal structure of the racemic polymorph of praziquantel in presence of calcium carbonate has been studied by means of several analytical techniques (DSC, TGA, XRD, SEM, FTIR, Raman spectroscopy and chiral liquid chromatography). This study has been completed with atomistic calculations based on empirical interatomic force fields and quantum mechanics methods applied to the crystal structure of praziquantel and of intermolecular interactions. The results evidenced that calcium carbonate provoked a conformational change in the praziquantel molecule yielding the formation of different polymorphs of praziquantel crystal. These alterations were not observed replacing calcium carbonate with colloidal silica as excipient in the solid dispersion.