Topical Meloxicam Hydroxypropyl Guar Hydrogels Based on Low-Substituted Hydroxypropyl Cellulose Solid Dispersions.

Meloxicam (MX) is a poorly water-soluble drug with severe gastrointestinal side effects. Topical hydrogel of hydroxypropyl guar (HPG) was formulated using a solid dispersion (SD) of MX with hydroxypropyl cellulose (LHPC) as an alternative to oral administration. The development of a solid dispersion with an adequate MX:LHPC ratio could increase the topical delivery of meloxicam. Solid dispersions showed high MX solubility values and were related to an increase in hydrophilicity. The drug/polymer and polymer/polymer interactions of solid dispersions within the HPG hydrogels were evaluated by SEM, DSC, FTIR, and viscosity studies. A porous structure was observed in the solid dispersion hydrogel MX:LHPC (1:2.5) and its higher viscosity was related to a high increase in hydrogen bonds among the -OH groups from LHPC and HPG with water molecules. In vitro drug release studies showed increases of 3.20 and 3.97-fold for hydrogels with MX:LHPC ratios of (1:1) and (1:2.5), respectively, at 2 h compared to hydrogel with pure MX. Finally, a fitting transition from zero to first-order model was observed for these hydrogels containing solid dispersions, while the n value of Korsmeyer-Peppas model indicated that release mechanism is governed by diffusion through an important relaxation of the polymer.

Development of Chitosan/Sodium Carboxymethylcellulose Complexes to Improve the Simvastatin Release Rate: Polymer/Polymer and Drug/Polymer Interactions' Effects on Kinetic Models.

Simvastatin (SIM) is a potent lipid-lowering drug used to control hyper-cholesterolemia and prevent cardiovascular diseases. SIM presents low oral bioavailability (5%) because of its low aqueous solubility. In this work, polyelectrolyte complexes (PEC) are developed with different chitosan (CS) and carboxymethylcellulose (CMC) ratios that will allow for an increase in the SIM dissolution rate (2.54-fold) in simulated intestinal medium (pH 4.5). Scanning Electron Microscopy (SEM) images revealed highly porous structures. The changes between both complexes, PEC-SIM:CS:CMC (1:1:2) and (1:2:1), were related to the relaxation of the polymer chains upon absorption of the dissolution medium. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and powder X-ray diffraction (XRPD) studies were used to evaluate the polymer/polymer and drug/polymer interactions on the different PEC-SIM:CS:CMC ratios. In addition, the PEC-SIM:CS:CMC (1:2:1) complex exhibited a high ratio of protonated amino groups (NH3+) and an increase in intramolecular hydrogen bonds, which were correlated with a high expansion of the interpolymer chains and an increase in the SIM dissolution rate. Different kinetic models such as zero-order, first-order, Higuchi and Korsmeyer-Peppas were studied to evaluate the influence of CS/CMC ionic interactions on the ability to improve the release rate of poorly soluble drugs.

Solid dispersions of atorvastatin with Kolliphor RH40: Enhanced supersaturation and improvement in a hyperlipidemic rat model.

Atorvastatin is a potent lipid-lowering drug with poor solubility and high presystemic clearance that limits its therapeutic efficacy. The aim of this study was to develop solid dispersions and micellar systems to obtain fast-dissolving atorvastatin systems that enhances their anti-hyperlipidemic effect. Solubility and wettability studies allow the development of solid dispersions with low proportions of croscarmellose sodium as hydrophilic carrier. Solid state characterization studies indicated that the addition of Kolliphor® RH40 surfactant to solid dispersions increases intermolecular hydrogen bonding between drug and polymer chains. Dissolution studies in biorelevant Fasted State Simulate Intestinal Fluid (FaSSIF pH 6.5) medium showed for atorvastatin solid dispersion a supersaturation peak of atorvastatin followed by an aggregation/precipitation process. Only the presence of a surfactant such as Kolliphor® RH40 in atorvastatin micellar system, promotes the presence of micelles that achieve delayed recrystallization. Efficacy studies were carried out using a hyperlipidemic model of rats fed with a high- fat diet. The atorvastatin micellar system at doses of 10 mg/kg, revealed a significant improvement in serum levels of total cholesterol, low-density lipoproteins, and triglycerides compared to atorvastatin raw material. This micellar system also exhibited more beneficial effects on liver steatosis, inflammation and ballooning injury.

Study of Different Chitosan/Sodium Carboxymethyl Cellulose Proportions in the Development of Polyelectrolyte Complexes for the Sustained Release of Clarithromycin from Matrix Tablets.

This study investigated the combination of different proportions of cationic chitosan and anionic carboxymethyl cellulose (CMC) for the development of polyelectrolyte complexes to be used as a carrier in a sustained-release system. Analysis via scanning electron microscopy (SEM) Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) confirmed ionic interactions occur between the chitosan and carboxymethyl cellulose chains, which increases drug entrapment. The results of the dissolution study in acetate buffer (pH 4.2) showed significant increases in the kinetic profiles of clarithromycin for low proportions of chitosan/carboxymethyl cellulose tablets, while the tablets containing only chitosan had high relaxation of chitosan chains and disintegrated rapidly. The Korsmeyer-Peppas kinetic model for the different interpolymer complexes demonstrated that the clarithromycin transport mechanism was controlled by Fickian diffusion. These results suggest that the matrix tablets with different proportions of chitosan/carboxymethyl cellulose enhanced the ionic interaction and enabled the prolonged release of clarithromycin.

Development of a Solid Dispersion of Nystatin with Maltodextrin as a Carrier Agent: Improvements in Antifungal Efficacy against Candida spp. Biofilm Infections.

The aim of this study was to improve the treatment of Candida albicans biofilms through the use of nystatin solid dispersions developed using maltodextrins as a hyperosmotic carrier. Characterization studies by differential scanning calorimetry, X-ray diffraction, dissolution studies, and particle size analysis were performed to evaluate changes in nystatin crystallinity. Antifungal activity and anti-biofilm efficacy were assessed by microbiological techniques. The results for nystatin solid dispersions showed that the enhancement of antifungal activity may be related to the high proportions of maltodextrins. Anti-biofilm assays showed a significant reduction (more than 80%) on biofilm formation with SD-N:MD [1:6] compared to the nystatin reference suspension. The elaboration process and physicochemical properties of SD-N:MD [1:6] could be a promising strategy for treatment of Candida biofilms.

Multiparticulate Systems of Ezetimibe Micellar System and Atorvastatin Solid Dispersion Efficacy of Low-Dose Ezetimibe/Atorvastatin on High-Fat Diet-Induced Hyperlipidemia and Hepatic Steatosis in Diabetic Rats.

The aim of this study was to develop multiparticulate systems with a combination of ezetimibe micellar systems and atorvastatin solid dispersions using croscarmellose as a hydrophilic vehicle and Kolliphor RH40 as a surfactant. The presence of a surfactant with low hydrophilic polymer ratios produces the rapid dissolution of ezetimibe through a drug-polymer interaction that reduces its crystallinity. The solid dispersion of atorvastatin with low proportions of croscarmellose showed drug-polymer interactions sufficient to produce the fast dissolution of atorvastatin. Efficacy studies were performed in diabetic Goto-Kakizaki rats with induced hyperlipidemia. The administration of multiparticulate systems of ezetimibe and atorvastatin at low (2 and 6.7 mg/kg) and high (3 and 10 mg/kg) doses showed similar improvements in levels of cholesterol, triglycerides, lipoproteins, alanine transaminase, and aspartate transaminase compared to the high-fat diet group. Multiparticulate systems at low doses (2 and 6.7 mg/kg of ezetimibe and atorvastatin) had a similar improvement in hepatic steatosis compared to the administration of ezetimibe and atorvastatin raw materials at high doses (3 and 10 mg/kg). These results confirm the effectiveness of solid dispersions with low doses of ezetimibe and atorvastatin to reduce high lipid levels and hepatic steatosis in diabetic rats fed a high-fat diet.

Improvement in the Oral Bioavailability and Efficacy of New Ezetimibe Formulations-Comparative Study of a Solid Dispersion and Different Micellar Systems.

Ezetimibe (EZ) is a poorly water-soluble drug with low bioavailability. Strategies such as solid dispersions (SD) and micellar systems (MS) were developed to identify the most effective drug delivery formulations with the highest oral bioavailability, and to improve their lipid-lowering effect. The EZ formulations were prepared with different proportions of Kolliphor® RH40 as a surfactant (1:0.25, 1:0.5 and 1:0.75) and croscarmellose as a hydrophilic carrier. These excipients, and the addition of microcrystalline cellulose during the production process, led to significant improvements in the dissolution profiles of MS. Powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) revealed an amorphous form of ezetimibe with different semicrystalline states of microcrystalline cellulose for MS-I (1:0.75) and MS-II (1:0.75). Pharmacokinetic analysis after administration of MS-II (1:0.75) demonstrated a 173.86% increase in maximum plasma concentration (Cmax) and a 142.99% increase in oral bioavailability compared to EZ raw material (EZ-RM). Efficacy studies with the micellar system MS-II (1:0.75) in rats with hyperlipidemia showed that total cholesterol, triglycerides and high-density lipoprotein were reduced to normal levels and revealed improvements in low-density lipoprotein, aspartate and alanine aminotransferase. The improvement in the dissolution rate with micellar systems increases bioavailability and enhances the anti-hyperlipidemic effect of EZ.

Self-Micellizing Technology Improves the Properties of Ezetimibe and Increases Its Effect on Hyperlipidemic Rats.

The aim of this work was to develop ezetimibe self-micellizing solid dispersions using Kolliphor® RH40 (MS-K) as a surfactant incorporating ezetimibe (EZ) into the croscarmellose hydrophilic carrier. Different ezetimibe:Kolliphor® ratios were studied to select micellar systems that improve the dissolution properties of ezetimibe. The different formulations were characterized by means of solid state analysis by SEM, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), and dissolution studies. These physicochemical studies showed a decrease from the crystalline structure of ezetimibe (EZ) to its amorphous state in the micellar systems (MS-K). A rapid dissolution profile was observed in these micellar systems compared to the drug raw material and physical mixture. Efficacy studies were conducted using a high-fat diet that induced hyperlipidemic rats. The micellar system selected (MS-K 1:0.75) revealed a significant improvement in serum levels of total cholesterol (TC), low-density lipoproteins (LDL), and triglycerides (TG) compared to ezetimibe raw material. The histopathological examination of liver tissue also showed that this micellar system exhibited more beneficial effects on liver steatosis compared to ezetimibe raw material (EZ-RM) and the high-fat diet group (HFD). This study suggests that EZ micellar systems using Kolliphor® RH40 could enhance the antihyperlipidemic effect of ezetimibe and reduce liver steatosis.

Submicellar liquid chromatography with fluorescence detection improves the analysis of naproxen in plasma and brain tissue.

Rapid, simple, and sensitive submicellar liquid chromatography with fluorescence detection was developed and validated to quantify naproxen in plasma and brain samples after oral administration of Naproxen formulations. The method used tramadol as an internal standard. Different submicellar mobile phases with organic phases ranging from 40 to 60% were studied to improve the native fluorescence of the Naproxen and decrease retention times. Separation was done in a Zorbax SB C8 column (250 × 4.6 mm, 5 µm) with a mobile phase containing acidic 0.007 M sodium dodecyl sulfate/acetonitrile (50:50, v/v) at a flow rate of 1 mL/min. Detection was performed with an excitation wavelength of 280 nm and emission of 310 nm and 360 nm for internal standard and Naproxen, respectively. The method was validated by International Conference of Harmonization standards. The method is specific, accurate, and precise (relative standard deviation <3%). Limits of detection and quantification were 0.08 and 0.25 µg/mL, respectively, for biological samples. This method was applied to analyze brain/plasma ratios in mice that had received oral administrations of Naproxen micellar formulations containing 10% w/w of sodium dodecyl sulfate, Cremophor RH 40, or Tween 80. The sodium dodecyl sulfate micelles were faster and more widely distributed in the mouse brains.

A multivariate investigation into the relationship between pharmaceutical characteristics and patient preferences of bioequivalent ibuprofen tablets.

BACKGROUND: In Spain the price of all ibuprofen 600 mg tablet generic products is the same due to reimbursement existing rules so for the patient there is not any economic incentive to choose a particular one. Bearing in mind that the quality of generic products should be similar, it could be questioned if differences in patient preferences evaluated as sales could be related to differences on their pharmaceutical properties. The aims of this work were to study the variability on the pharmaceutical characteristics of marketed bioequivalent tablet formulations and its impact on patient preferences. METHODS: Thirty-six batches corresponding to fourteen different generic products were chosen among the best-selling products of the Spanish market in the years 2011 and 2015 and were compared to the reference product. The effect on patient preferences of six variables was studied through a multivariate analysis. The first two variables were marketing characteristics: 1) years in the market and 2) the number of other generic products marketed by the same manufacturer, which could be related to the size and service provided by the manufacturer. The other four variables studied were pharmaceutical tablet properties: 3) mean weight, 4) hardness, 5) disintegration, and 6) dissolution. A multiple linear regression analysis was performed to identify the effect on sales of the six variables studied. RESULTS: The disintegration time was the most significant (P=0.018) factor affecting the sales of Ibuprofen tablets which may be related to the onset of action. CONCLUSION: The faster the tablet disintegration, the higher its sales. Two possible explanations are suggested: 1) the most specialized ibuprofen tablet manufacturer considers fast disintegration as a key parameter and/or 2) habitual consumers of ibuprofen can detect small differences on the onset of action among different marketed formulations. In this work, all marketed ibuprofen tablets comply with the pharmacopoeia specifications.

Efficacy, Biodistribution, and Nephrotoxicity of Experimental Amphotericin B-Deoxycholate Formulations for Pulmonary Aspergillosis.

An experimental micellar formulation of 1:1.5 amphotericin B-sodium deoxycholate (AMB:DCH 1:1.5) was obtained and characterized to determine its aggregation state and particle size. The biodistribution, nephrotoxicity, and efficacy against pulmonary aspergillosis in a murine model were studied and compared to the liposomal commercial formulation of amphotericin B after intravenous administration. The administration of 5 mg/kg AMB:DCH 1:1.5 presented 2.8-fold-higher lung concentrations (18.125 ± 3.985 µg/g after 6 daily doses) and lower kidney exposure (0.391 ± 0.167 µg/g) than liposomal commercial amphotericin B (6.567 ± 1.536 and 5.374 ± 1.157 µg/g in lungs and kidneys, respectively). The different biodistribution of AMB:DCH micelle systems compared to liposomal commercial amphotericin B was attributed to their different morphologies and particle sizes. The efficacy study has shown that both drugs administered at 5 mg/kg produced similar survival percentages and reductions of fungal burden. A slightly lower nephrotoxicity, associated with amphotericin B, was observed with AMB:DCH 1:1.5 than the one induced by the liposomal commercial formulation. However, AMB:DCH 1:1.5 reached higher AMB concentrations in lungs, which could represent a therapeutic advantage over liposomal commercial amphotericin B-based treatment of pulmonary aspergillosis. These results are encouraging to explore the usefulness of AMB:DCH 1:1.5 against this disease.

Improvement of the surface hydrophilic properties of naproxen particles with addition of hydroxypropylmethyl cellulose and sodium dodecyl sulphate: In vitro and in vivo studies.

In this study, a new surface-modified naproxen was developed to enhance brain concentration in acute migraine treatment. Fast-dissolving naproxen granules were made by mixing hydroxypropylmethylcellulose (HPMC) sodium dodecyl sulphate (SDS) and sodium croscarmellose with micronized naproxen particles. The aim of this study was to evaluate the effect of adding proportions of SDS to the HPMC film caused changes in the polymer chains of the HPMC, producing a new hydrophilic HPMC-SDS structure. These formulations with different HPMC/SDS ratios were characterised using electron microscopy (SEM), powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). SDS 10% (w/w) produced a highly hydrophilic HPMC-SDS structure on the surface of the naproxen microparticles. The fast dissolution granules (SF-10%) showed a significant improvement in the dissolution rate of naproxen. Pharmacokinetic studies were conducted with mice, showing an improvement of Cmax (1.38 and 1.41-fold) and AUC0-2h (30% and 10% higher) for plasma and brain samples compared to the reference naproxen suspension. The faster Tmax ratio for SF-10% may be related to increased hydration in the gastrointestinal environment, enabling the drug to permeate the gastrointestinal hydration layer more easily due to the presence of the hydrophilic HPMC-SDS structure in the formulation.

Efficacy and toxicity evaluation of new amphotericin B micelle systems for brain fungal infections.

The aim of this work is to study the micelle systems of amphotericin B (AmB) and surfactant sodium deoxycholate (NaDC) as possible formulations to treat brain fungal infections. Fungizone(®) and Ambisome(®) were used as AmB references. The particle size, aggregation state, toxicity and efficacy of AmB:NaDC micelles were studied with increasing proportions of NaDC. Differences in the size and aggregation state of the reference formulations and micellar NaDC formulations might explain the differences in their distribution and therefore in their toxicity and efficacy. AmB:NaDC 1:0.8 and 1:1.5 nano-sized micelle systems showed a poly-aggregated form of AmB and small mean particle size (450-750 nm). The AmB:NaDC 1:0.8 and AmB:NaDC 1:1.5 micelle systems studied showed an 8-fold lower toxicity than Fungizone(®). Efficacy was examined in a murine candidiasis model by determining the survival rate and tissue burden reduction in kidneys and brain. The AmB:NaDC 1:1.5 micellar system at 5mg/kg of AmB and the highest amount of NaDC (7.5 mg/kg) presented a good survival rate, and induced a major clearance of brain infection. The new AmB:NaDC 1:1.5 nano-sized micelle system is a promising formulation with a good efficacy/toxicity ratio, which can be attributed to its particle size, AmB aggregation state and NaDC content.

Novel solid dispersions of benznidazole: preparation, dissolution profile and biological evaluation as alternative antichagasic drug delivery system.

Solid dispersions (SD) of benznidazole (BNZ) in sodium deoxycholate (NaDC) or low-substituted hydroxypropylcellulose (L-HPC) were developed by freeze-drying process to improve the solubility of this low water-soluble drug and consequently, its trypanocidal activity. Although the dissolution studies showed a progressive decrease in the release rate of BNZ when formulated in the presence of NaDC, the increase in the surfactant concentration resulted in a better trypanocidal profile on epimastigotes, as well as in an enhancement of the unspecific cytotoxicity. However, such an effect was not so evident on amastigotes and in vivo (blood-trypomastigotes), where high concentrations of surfactant (BNZ:NaDC ≥ 1:6) experimented a loss of activity, correlating this fact with the minor cession of BNZ these formulations accomplished in acidic locations (i.e., dissolution test medium). According to the in vitro results, we reformulated the promising SD-1:3 (IC50 epimastigotes = 33.92 ± 6.41 µM, IC50 amastigotes = 0.40 ± 0.05 µM and LC50 = 183.87 ± 12.30 µM) replacing NaDC by L-HPC, which achieved the fastest dissolution profile. This fact, together with the safety this carrier ensures (LC50 > 256 µM), prompted us to evaluate the cellulose SD in vivo, improving the effectiveness of its NaDC equivalent (%AUPC = 96.65% and 91.93%, respectively). The results compiled in the present work suggest these solid dispersions as alternative drug delivery systems to improve the limited chemotherapy of Chagas disease.

Enhanced bioavailability and anthelmintic efficacy of mebendazole in redispersible microparticles with low-substituted hydroxypropylcellulose.

BACKGROUND: Mebendazole (MBZ) is an extremely insoluble and therefore poorly absorbed drug and the variable clinical results may correlate with blood concentrations. The necessity of a prolonged high dose treatment of this drug increases the risk of adverse effects. METHODS: In the present study we prepared redispersible microparticles (RDM) containing MBZ, an oral, poorly water-soluble drug, in different proportions of low-substituted hydroxypropylcellulose (L-HPC). We investigated the microparticulate structures that emerge spontaneously upon dispersion of an RDM in aqueous medium and elucidated their influence on dissolution, and also on their oral bioavailability and therapeutic efficiency using a murine model of infection with the nematode parasite Trichinella spiralis. RESULTS: Elevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s) under the curve (AUC)0-∞ values. Likewise, after oral administration of the RDM-1:2.5 and RDM-1:5 the AUC0-∞ were 2.67- and 2.97-fold higher, respectively, compared to those of pure MBZ. Therapeutic activity, assessed on the Trichinella spiralis life cycle, showed that RDM-1:5 was the most effective in reducing the number of parasites (4.56-fold) as compared to pure MBZ, on the encysted stage. CONCLUSION: THE MBZ: L-HPC RDM might be an effective way of improving oral bioavailability and therapeutic activity using low doses of MBZ (5 mg/kg), which implies a low degree of toxicity for humans.

Development of novel benznidazole formulations: physicochemical characterization and in vivo evaluation on parasitemia reduction in Chagas disease.

This work aims to develop novel benznidazole (BZN) solid dispersions (SD) to improve its solubility and bioavailability properties. Low-substituted hydroxypropylcellulose (L-HPC) and sodium deoxycholate (NaDC) were evaluated as carriers. BZN solid dispersions containing different ratios of carrier were prepared by a freeze-drying process and characterized by SEM, powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution studies. The reduced BNZ crystallinity in the new formulations was confirmed by XRD, and supported by DSC. BNZ:L-HPC solid dispersion at a 1:3 ratio (w/w) (SD-1:3 L-HPC) improved the BNZ dissolution rate (85% at 5 min) in comparison with BNZ raw material (23% at 5 min). However, NaDC formulations showed a prolonged release (24% at 30 min for SD-1:3 NaDC), due to the formation of a sustained release matrix in acidic medium. In vivo studies performed in a murine model of Chagas disease showed that the formulation achieving the highest parasitemia suppression at a low dose of 25mg/kg/day after five days of treatment was SD-1:3 L-HPC (60% of parasitemia suppression versus 33% of suppression exerted by BNZ), suggesting that BNZ:L-HPC systems enhance the bioavailability of the drug.

The influence of CYP2C19 genetic polymorphism on the pharmacokinetics/- pharmacodynamics of proton pump inhibitor-containing Helicobacter pylori treatments.

Proton pump inhibitors (PPIs) are the most potent acid suppressants available. PPIs undergo hepatic metabolism via the CYP2C system for the isoforms CYP2C19 and CYP3A4 in particular. Genetic polymorphisms in CYP2C19 may affect the metabolism of individual PPIs to different extents. Although PPIs are highly effective as a class, differences in their pharmacokinetics, such as bioavailability and metabolism, may translate into differences in clinical outcomes. In Helicobacter pylori infection, a significantly lower eradication rate was seen in extensive metabolizers with omeprazole but no with rabeprazole.

Changed crystallinity of mebendazole solid dispersion: improved anthelmintic activity.

To improve the efficacy of mebendazole (MBZ), a poorly water-soluble drug, MBZ solid dispersions containing different proportions of low-substituted hydroxypropylcellulose (L-HPC) were prepared by lyophilization process. The physical characteristics of recrystallized MBZ, and solid dispersions (SD) at different MBZ:L-HPC proportions were investigated in terms of morphology (scanning electron microscopy, SEM), powder X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dissolution rate. The in vivo performance was assessed by anthelmintic activity studies against enteral (pre-adult) stage of Trichinella spiralis in mice. The XRD, DSC and SEM revealed a characteristic decrease in crystallinity when increasing the L-HPC proportions in the solid dispersions. The dissolution studies demonstrated a marked increase in the dissolution rate in comparison with recrystallized drug. The considerable improvement in the dissolution rate of MBZ from solid dispersions was attributed to decreased drug crystallinity and altered surface morphology (major) and to the wetting effect of L-HPC (minor). The in vivo studies revealed that the anthelmintic effects of solid dispersions in mice were significantly increased in comparison with recrystallized MBZ (1.74-fold for SD-1:1, 3.20-fold for SD-1:2.5 and 3.80-fold for SD-1:5). These results have shown the suitability of MBZ:L-HPC solid dispersions for the treatment of enteral helmintic diseases at low doses.