Low Water-soluble Compounds Research Articles

Development and Evaluation of Microemulsion Formualatons of Valsartan for Solubility Enhancement

Microemulsions have attracted considerable amount of interest as potential drug delivery vehicles largely due to their simple method of preparation, stability and their abilities to incorporate a wide range of drugs of varying solubility. O/W microemulsion is expected to increase the solubility by dissolving low water solubility compounds into its dispersed phase and to enhance the oral bioavailability by protecting the drug increasing the rate of absorption and wettability due to surfactants induced permeability changes and smaller droplet size (< 100 nm) and most importantly able to target lymphatic system. 
 In the present study, the drug delivery system contains Valsartan, a hydrophilic component, a lipophillic component, surfactants and co-surfactants. The objective is to provide an increased release of valsartan and increased bioavailability of valsartan. Prepared microemulsion formulations by phase-titration method were evaluated for viscosity, drug content, thermodynamic stability studies and in-vitro dissolution. Resultant microemulsion optimized formulation (ME5) shows drug release (88.2±0.16%.%). Hence, micro-emulsion of valsartan was successfully developed and evaluated.
 Keywords: Microemulsion, Valsartan, solubility, evaluation.

Lipid based formulations as supersaturating oral delivery systems: From current to future industrial applications

Lipid-based formulations, in particular supersaturated lipid-based formulations, are important delivery approaches when formulating challenging compounds, as especially low water-soluble compounds profit from delivery in a pre-dissolved state. In this article, the classification of lipid-based formulation is described, followed by a detailed discussion of different supersaturated lipid-based formulations and the recent advances reported in the literature. The supersaturated lipid-based formulations discussed include both the in situ forming supersaturated systems as well as the thermally induced supersaturated lipid-based formulations. The in situ forming drug supersaturation by lipid-based formulations has been widely employed and numerous clinically available products are on the market. There are some scientific gaps in the field, but in general there is a good understanding of the mechanisms driving the success of these systems. For thermally induced supersaturation, the technology is not yet fully understood and developed, hence more research is required in this field to explore the formulations beyond preclinical studies and initial clinical trials.

Solid lipid nanoparticles to improve bioaccessibility and permeability of orally administered maslinic acid

Maslinic acid (MA) is a plant-derived, low water-soluble compound with antitumor activity. We have formulated MA in the form of solid lipid nanoparticles (SLNs) with three different shell compositions: Poloxamer 407 (PMA), dicarboxylic acid-Poloxamer 407 (PCMA), and HA-coated PCMA (PCMA-HA). These SLNs improved the solubility of MA up to 7.5 mg/mL, are stable in a wide range of pH, and increase the bioaccessibility of MA after in vitro gastrointestinal (GI) digestion. Gastrointestinal digested SLNs afforded MA delivery across in vitro gut barrier models (21 days old Caco-2 and mucus-producing Caco-2/HT29-MTX co-cultures). The cellular fraction of Caco-2/HT29-MTX co-cultures retained more MA from GI digested PCMA-HA than the Caco-2 monolayers. The concentration of MA reached in the basolateral chamber inhibited growth of pancreatic cancer cells, BxPC3. Finally, confocal microscopy images provided evidence that Nile Red incorporated in MA SLNs was capable of crossing Caco-2 monolayers to be taken up by basolaterally located BxPC3 cells. We have demonstrated that SLNs can be used as nanocarriers of hydrophobic antitumor compounds and that these SLNs are suitable for oral consumption and delivery of the bioactive across the gut barrier.

Assessment of Pharmacokinetic Parameters of Daidzein-Containing Nanosuspension and Nanoemulsion Formulations After Oral Administration to Rats

Daidzein has several biological effects such as antioxidation, anti-inflammation, chemoprevention, and anticancer effects.The aim of this study was to evaluate the impact of nano-formulations (nanoemulsion-NE and nanosuspension-NS) prepared to increase the oral bioavailability of daidzein, a poorly water-soluble isoflavone, on the pharmacokinetic parameters of daidzein in rats. A high-performance liquid chromatography-ultraviolet (HPLC-UV) method was successfully developed for daidzein analysis in rat plasma.The pharmacokinetics studies of the nano-sized formulations, compared to coarse daidzein suspension, were carried out in the rats by a single oral dose at 10 mg/kg (n=6/group). Area under the plasma concentration-time curve from time zero to extrapolation to time infinity (AUC0-∞), maximum plasma concentration (Cmax), time to reach maximum plasma concentration (tmax), andelimination half life (t1/2)values for coarse daidzein suspension, daidzein-NS, and daidzein-NE were estimated by a non-compartmental analysis. The AUC values of daidzein-NE and daidzein-NS were approximately 2.62 and 2.65 times higher than that of coarse daidzein suspension, respectively (p<0.05). Relative bioavailability (Frel) (%) values of daidzein following oral administration of nanosuspension or nanoemulsion formulations were about 265.6% and 262.3%, respectively. It revealed that nanoscale size is an important factor to overcome any dissolution rate barriers to oral bioavailability of the low water-soluble compound. Nanoemulsion and nanosuspension formulations are beneficial dosage forms to increase the oral bioavailability of Biopharmaceutical Classification System (BCS) Class II and Class IV compounds.

Computational Insights Into the Influence of Substitution Groups on the Inclusion Complexation of β-Cyclodextrin.

Cyclodextrins (CDs) and their derivatives have good prospects in soil remediation application due to their ability to enhance the stability and solubility of low water-soluble compounds by inclusion performance. To investigate the effect of different structural properties of cyclodextrin and its derivatives on the inclusion complexation, molecular dynamic (MD) simulations were performed on the inclusion complexes formed by three kinds of CDs with polycyclic aromatic hydrocarbons (PAHs). Based on neutral β-CD, the other two CDs were modified by introducing substitutional groups, including 2-hydroxypropyl and sulfonated butyl (SBE) functional groups in the ring structure, called HP-CD and SBE-CD. MD results show that PAH can merely enter into the cavity of SBE–β-CD from its wide rim. The substitutional groups significantly affect the structure of CDs, which may also cause the flipping of the glucose units. However, the substitutional groups can also enlarge the volume of the hydrophobic cavity, resulting in a tight combination with the guest molecules.

Efficacy of nanoemulsion with Pterodon emarginatus Vogel oleoresin for topical treatment of cutaneous leishmaniasis

Cutaneous leishmaniasis (CL) is a neglected tropical skin disease caused by the protozoan genus Leishmania. The treatment is restricted to a handful number of drugs that exhibit toxic effects, limited efficacy, and drug resistance. Additionally, developing an effective topical treatment is still an enormous unmet medical challenge. Natural oils, e.g. the oleoresin from P. emarginatus fruits (SO), contain various bioactive molecules, especially terpenoid compounds such as diterpenes and sesquiterpenes. However, its use in topical formulations can be impaired due to the natural barrier of the skin for low water solubility compounds. Nanoemulsions (NE) are drug delivery systems able to increase penetration of lipophilic compounds throughout the skin, improving their topical effect. In this context, we propose the use of SO-containing NE (SO-NE) for CL treatment. The SO-NE was produced by a low energy method and presented suitable physicochemical characteristic: average diameter and polydispersity index lower than 180 nm and 0.2, respectively. Leishmania (Leishmania) amazonensis-infected BALB/c mice were given topical doses of SO or SO-NE. The topical use of a combination of SO-NE and intraperitoneal meglumine antimoniate reduced lesion size by 41 % and tissue regeneration was proven by histopathological analyses. In addition, a reduction in the parasitic load and decreased in the level of IFN-γ in the lesion may be associated, as well as a lower level of the cytokine IL-10 may be associated with a less intense inflammatory process. The present study suggests that SO-NE in combination meglumine antimoniate represents a promising alternative for the topical treatment of CL caused by L. (L.) amazonensis.

Design and preparation of nanostructures based on Krafft point of nonionic amphiphiles for delivery of poorly water-soluble compounds.

Micellar solubilization can effectively dissolve low water-soluble compounds in aqueous environment, however, the micellar systems are not able to withstand dilution and maintain solubilization of poorly water-soluble drugs below critical micelle concentration. To overcome the drawbacks of conventional micellar solubilization, nonionic polyoxyethylated surfactants with Krafft points at or higher than body temperature were chosen to create novel micelle-based nanostructures as a delivery vehicle for poorly water-soluble compounds. A technique "thermo-spray process" was developed for the preparation of the nanostructures-containing formulation, in which the drug-containing micelle solution was first prepared and maintained at the elevated temperature above the Krafft point of the surfactant, then spray dried to solidify the obtained micelle-like nanostructure at room temperature. Lactose was used as an excipient to embed the nanostructures in the thermo-spray products. Water insoluble spherical nanoparticles with size range from 80 to 250nm were obtained after reconstitution of the product at the temperature lower than Krafft point. When paclitaxel was used as model drug, the micelle-like nanostructures exhibited similar drug entrapment efficiency, solubility enhancement and drug release facilitation as conventional micelles, but provided lower critical micellar concentration at body temperature, and good encapsulation stability upon storage and dilution. These findings indicated that the developed thermo-spray product can serve as a promising delivery platform for drugs with low aqueous solubility.

High-pressure homogenization-assisted extraction of bioactive compounds from Ruta chalepensis

High-pressure homogenization (HPH) was investigated to promote the extraction in water of bioactive molecules from Ruta chalepensis, a medicinal plant widely used in folk medicine. Aqueous suspensions (5% wt) of the pre-milled plant were treated by high-shear mixing (HSM), followed by HPH at 100 MPa for up to 10 passes. A considerable decrease in the size of the suspended particles was observed when applying HPH, which was related to cell deagglomeration and fragmentation. In contrast, no significant changes at the cellular level were observed when only maceration or HSM treatments were applied. Remarkably, HPH treatment did not significantly change the antioxidant activity of the aqueous extracts, but affected their composition: HPLC analysis revealed that HPH treatment significantly increased the content in the aqueous phase of quercetin (+ 452.7%), recovered by fractionation of the aqueous phase with ethyl acetate, and rutin (+ 29.8%), recovered with butanol. In addition, GC/MS analysis of the chloroform fractions obtained from the aqueous extracts revealed that the HPH treatment caused also a significant (p < 0.05) increase in γ-fagarine and chalepin of + 177% and + 1420%, respectively, whereas pteleine, skimmianine, kokusaginine, and arborinine levels were higher in the extracts obtained by maceration than the HPH-treated samples. These findings suggest that the recovery of low water-solubility compounds from R. chalepensis, such as rutin and quercetin, as well as of some alkaloids, such as γ-fagarine and chalepin, significantly improved by HPH-assisted extraction and associated cell disruption effect.

Development and Mechanistic Insight into the Enhanced Cytotoxic Potential of Parvifloron D Albumin Nanoparticles in EGFR-Overexpressing Pancreatic Cancer Cells.

Pancreatic cancer is one of the most lethal cancers, with an extremely poor prognosis. The development of more effective therapies is thus imperative. Natural origin compounds isolated from Plectranthus genus, such as parvifloron D (PvD), have cytotoxic and antiproliferative activity against human tumour cells. However, PvD is a very low water-soluble compound, being nanotechnology a promising alternative strategy to solve this problem. Therefore, the aim of this study was to optimize a nanosystem for preferential delivery of PvD to pancreatic tumour cells. Albumin nanoparticles (BSA NPs) were produced through a desolvation method. Glucose cross-linking and bioactive functionalization profiles of BSA platform were elucidated and analysed using static lattice atomistic simulations in vacuum. Using the optimized methodology, PvD was encapsulated (yield higher than 80%) while NPs were characterized in terms of size (100–400 nm) and morphology. Importantly, to achieve a preferential targeting to pancreatic cancer cells, erlotinib and cetuximab were attached to the PvD-loaded nanoparticle surface, and their antiproliferative effects were evaluated in BxPC3 and Panc-1 cell lines. Erlotinib conjugated NPs presented the highest antiproliferative effect toward pancreatic tumour cells. Accordingly, cell cycle analysis of the BxPC3 cell line showed marked accumulation of tumour cells in G1-phase and cell cycle arrest promoted by NPs. As a result, erlotinib conjugated PvD-loaded BSA NPs must be considered a suitable and promising carrier to deliver PvD at the tumour site, improving the treatment of pancreatic cancer.

The in vivo toxicological profile of cationic solid lipid nanoparticles.

Cationic solid lipid nanoparticles (cSLNs) are considered as one of the most effective lipid nanocarriers for delivery of low water-solubility compounds and genetic materials. As the excipients used in the cSLN production are generally regarded as safe (GRAS), the formulations are granted as non-toxic. However, the toxicological profile of new SLN-based formulations should always be performed to confirm that the delivery systems themselves may not impose risks to the human health. Therefore, in this study, we delineate the toxicological profile of the cSLN formulation at 24 and 72h after single intravenous injection to male Wistar rats. Hematological, biochemical, and histopathological evaluations of the spleen, lungs, liver, and kidneys indicated short-lived alterations including neutrophilia. We found increases in the population of macrophages in the lungs, liver, and spleen and also migration of circulating neutrophils into inflamed tissue and a decrease in blood urea nitrogen. We also observed the presence of cSLNs within the brain parenchyma without any sign of damage to the blood-brain barrier. These side effects appeared to be mild and transitory (< 72h). These findings reinforce the importance of investigating the toxicity of SLN-based formulations before the incorporation of drugs/genetic material to the formulation and its translation to the clinic.

Removal of selected pharmaceuticals from aqueous matrices with activated carbon under batch conditions

Adsorption of diclofenac (DCL), naproxen (NPR) and carbamazepine (CRB) from aqueous matrices onto a commercial granulated activated carbon (GAC) has been studied. Data obtained for DCL and NPR were evaluated by applying different adsorption isotherm models. The best fitting was reached using Langmuir equation. The experimental maximal adsorption capacity values were 50 and 80 mg g−1 for DCL and NPR, respectively, which increased to 320 and 280 mg g−1 when pulverized activated carbon was used. Activation energy calculated at different temperatures was between 5 and 9 kJ mol−1 for each compound in the three-component systems. By evaluating adsorption kinetics data with various models, the best fitting was obtained by applying the pseudo first order model. The calculated rate constant was about 0.076 min−1 for each compound in the single solutions. However, the obtained values for the three-component solutions were 0.16, 0.13 and 0.11 min−1 for CRB, NPR and DCL, respectively. According to the model calculations, intra-particle diffusion has a role in the adsorption and it is the sole rate-determining step for CRB and NPR. Applying a semi-open system, removal efficiency was nearly 100% from model sewage water (MSW) and secondary sewage water (SSW) during several cycles using the same GAC. This semi-open system permitted study of i) adsorption of low water-solubility compounds (e.g. CRB), ii) adsorption of NRP, CRB and DCL at a concentration level similar to that in real aqueous matrices and iii) comparison of drug removal from MSW/SSW, iv) modeling for sewage water treatment plants.

Cavity Closure of 2-Hydroxypropyl-β-Cyclodextrin: Replica Exchange Molecular Dynamics Simulations.

2-Hydroxypropyl-β-cyclodextrin (HPβCD) has unique properties to enhance the stability and the solubility of low water-soluble compounds by inclusion complexation. An understanding of the structural properties of HPβCD and its derivatives, based on the number of 2-hydroxypropyl (HP) substituents at the α-d-glucopyranose subunits is rather important. In this work, replica exchange molecular dynamics simulations were performed to investigate the conformational changes of single- and double-sided HP-substitution, called 6-HPβCDs and 2,6-HPβCDs, respectively. The results show that the glucose subunits in both 6-HPβCDs and 2,6-HPβCDs have a lower chance of flipping than in βCD. Also, HP groups occasionally block the hydrophobic cavity of HPβCDs, thus hindering drug inclusion. We found that HPβCDs with a high number of HP-substitutions are more likely to be blocked, while HPβCDs with double-sided HP-substitutions have an even higher probability of being blocked. Overall, 6-HPβCDs with three and four HP-substitutions are highlighted as the most suitable structures for guest encapsulation, based on our conformational analyses, such as structural distortion, the radius of gyration, circularity, and cavity self-closure of the HPβCDs.

Development of Parvifloron D-loaded Smart Nanoparticles to Target Pancreatic Cancer.

Pancreatic cancer is the eighth leading cause of cancer death worldwide. For this reason, the development of more effective therapies is a major concern for the scientific community. Accordingly, plants belonging to Plectranthus genus and their isolated compounds, such as Parvifloron D, were found to have cytotoxic and antiproliferative activities. However, Parvifloron D is a very low water-soluble compound. Thus, nanotechnology can be a promising delivery system to enhance drug solubility and targeted delivery. The extraction of Parvifloron D from P. ecklonii was optimized through an acetone ultrasound-assisted method and isolated by Flash-Dry Column Chromatography. Then, its antiproliferative effect was selectivity evaluated against different cell lines (IC50 of 0.15 ± 0.05 μM, 11.9 ± 0.7 μM, 21.6 ± 0.5, 34.3 ± 4.1 μM, 35.1 ± 2.2 μM and 32.1 ± 4.3 μM for BxPC3, PANC-1, Ins1-E, MCF-7, HaCat and Caco-2, respectively). To obtain an optimized stable Parvifloron D pharmaceutical dosage form, albumin nanoparticles were produced through a desolvation method (yield of encapsulation of 91.2%) and characterized in terms of size (165 nm; PI 0.11), zeta potential (−7.88 mV) and morphology. In conclusion, Parvifloron D can be efficiently obtained from P. ecklonii and it has shown selective cytotoxicity to pancreatic cell lines. Parvifloron D nanoencapsulation can be considered as a possible efficient alternative approach in the treatment of pancreatic cancer.

Bioremediation of Endocrine Disruptive Chemicals: The Power of Microbial Enzymes

Microbial enzymes have been established as a powerful tool in bioremediation. In this review, applications of microbial enzymes in degradation of endocrine disruptive chemicals are explained. Endocrine disruptive chemicals (EDCs) are a number of pollutants reported bringing negative impacts on human being and wildlife. Exposure to EDCs may cause effect on endocrine system thus detrimental to the health eminently on the developmental and reproductive abnormalities. Physical approaches such as ozonation, activated carbon, nanofiltration have been implemented to remove EDCs in waste water. Over the past decade, bioremediation has been a preference method in EDCs degradation due to its environmental friendly approach. Lignin-modifying enzymes; LMEs have been the attractive candidates in EDC treatment due to their characteristics such as broad selectivity in substrate affinity and ability to degrade either complex, individual pollutants or low water solubility compounds. Usage of microbial enzymes either by using the whole organism or free enzymes has been introduced in water treatment. Current technology by immobilizing enzymes to certain matrix allow the enzymatic recycling process thus giving an advantage in operational cost.

The Tritiated Water Skin Barrier Integrity Test: Considerations for Acceptance Criteria with and Without 14C-Octanol.

A study was designed to assess barrier integrity simultaneously using separate compounds (probes) for polar and non-polar pathways through the skin, 3H2O and 14C-octanol, respectively; and to determine whether the two probe approach could better define barrier integrity. A 5-min dose of water containing 3H2O and 14C -octanol was applied to ex vivo human skin mounted in Franz diffusion cells. The receptor solution was sampled at 30min, analyzed for 3H and 14C content, and the correlation between water and octanol absorption was determined by statistical tests suitable for non-normally distributed data. This study was conducted on skin from 37 donors with from 3 to 30 replicate skin sections per donor (a total of 426 sections). The correlation between 3H2O and 14C-octanol absorption was low (Pearson correlation coefficient = 0.3485). The 3H2O absorption cutoff used in this study to select for a normal skin barrier rejected some sections in which 14C-octanol absorption was within normal limits and accepted others in which 14C-octanol absorption was abnormally high. The converse was true for 3H2O absorption when the 14C-octanol-based cutoff was used. The results of the 3H2O test or of similar tests that primarily assess the permeability of polar pathways through the skin may not necessarily provide information relevant to the absorption of highly lipophilic compounds. Octanol, or another molecule that more closely matches the physicochemical attributes of the test compound, may characterize properties of the skin barrier that are more relevant to compounds of low water solubility.

Nanoemulsions containing a synthetic chalcone as an alternative for treating cutaneous leshmaniasis: optimization using a full factorial design.

Nanoemulsions are drug delivery systems that may increase the penetration of lipophilic compounds through the skin, enhancing their topical effect. Chalcones are compounds of low water solubility that have been described as promising molecules for the treatment of cutaneous leishmaniasis (CL). In this context, the aim of this work was to optimize the development of a nanoemulsion containing a synthetic chalcone for CL treatment using a 22 full factorial design. The formulations were prepared by spontaneous emulsification and the experimental design studied the influence of two independent variables (type of surfactant – soybean lecithin or sorbitan monooleate and type of co-surfactants – polysorbate 20 or polysorbate 80) on the physicochemical characteristics of the nanoemulsions, as well as on the skin permeation/retention of the synthetic chalcone in porcine skin. In order to evaluate the stability of the systems, the antileishmanial assay was performed against Leishmania amazonensis 24 hours and 60 days after the preparation of the nanoemulsions. The formulation composed of soybean lecithin and polysorbate 20 presented suitable physicochemical characteristics (droplet size 171.9 nm; polydispersity index 0.14; zeta potential −39.43 mV; pH 5.16; and viscosity 2.00 cP), drug content (91.09%) and the highest retention in dermis (3.03 µg·g−1) – the main response of interest – confirmed by confocal microscopy. This formulation also presented better stability of leishmanicidal activity in vitro against L. amazonensis amastigote forms (half maximal inhibitory concentration value 0.32±0.05 µM), which confirmed the potential of the nanoemulsion soybean lecithin and polysorbate 20 for CL treatment.

Cinnamaldehyde in a Novel Intravenous Submicrometer Emulsion: Pharmacokinetics, Tissue Distribution, Antitumor Efficacy, and Toxicity.

The purpose of our research is to find a new lipid emulsion to deliver a low water-soluble compound, cinnamaldehyde (CA). Its characteristics, pharmacokinetics, antitumor efficacy, and toxicity were evaluated. The mean particle size, zeta potential, and encapsulation efficiency of the submicromemter emulsion of CA (SME-CA) were 130 ± 5.92 nm, -25.7 ± 6.00 mV, and 99.5 ± 0.25%, respectively. The area under the curve from 0 h to termination time (AUC(0-t)) of SME-CA showed a significantly higher value than that of CA (589 ± 59.2 vs 375 ± 83.5 ng h/L, P < 0.01). Tissue distribution study showed various changes; among them, a 27% higher concentration was found in brain tissue when using SME-CA at 15 min after administration. For the efficacy evaluation, SME-CA exhibited 8- and 11-fold antitumor activity in the depression of HeLa and A549 cell lines with the IC50 decreasing to 0.003 and 0.001 mmol/L, respectively. The LD50 values of CA and SME-CA in mice were 74.8 and 125 mg/kg, suggesting increased safety from the new formulation. The new formulation exhibited lower toxicity, higher antitumor activity, and a more satisfactory pharmacokinetic property, which displayed great potential for future pharmacological application.

Influence of Cosolvents on Low Water-Solubility Chemicals to Photobacterium phosphoreum in Acute Toxicity Test

Abstract There is little information about the influence of organic solvents for low water-solubility compounds on Photobacterium phosphoreum toxicity test, though it appears likely that much of data were obtained by using solutions prepared with the cosolvents or surfactants. In this study the influence of five stock solvents, including dimethyl sulphoxide (DMSO), acetone, aether, ethanol, tetrahydrofuran, on Photobacterium phosphoreum toxicity test were measured and different effective concentration (EC) values were obtained. DMSO was selected as the most suitable solvent of chemical compounds with low water-solubility according to its good characters and less toxicity effect to Photobacterium phospherum. Chlorobenzene and nitrobenzene, whose toxicity can be detected even if without any solvent, were selected to testify the effect of DMSO to toxicity of chemicals to Photobacterium phopherum. It was demonstrated that DMSO (its concentration no more than 0.20mol·L-1) had little effect on the toxicity of organic chemicals with EC value no more than 10%. The successful application of DMSO used as cosolvent provides a good example and a good idea to improve traditional acute toxicity test of Photobacterium phopherum.

Totally organic biphasic solvent systems for extraction and descriptor determinations

Partition between two immiscible solvents is widely used in sample preparation procedures for matrix simplification and isolation of target analytes, for separations using countercurrent, centrifugal partition, and liquid-liquid chromatography, and as a method for determining descriptors for use in modeling chemical, biological, and environmental processes. Until recently, most applications employed water as one component of the biphasic system. For compounds of low water solubility or stability, a series of totally organic biphasic systems have been developed to enhance the application range of liquid-liquid partition methods. These systems, their characterization using the solvation parameter model, and applications to sample preparation and the determination of descriptors are described in this review.

Oral bioavailability of a poorly aqueous drug from three different SBE7-β-cyclodextrin based formulations in beagle dogs

Oral administration of Lu 35-138, a low aqueous soluble compound, was investigated in three different formulations containing sulfobutylether β-cyclodextrin (SBE7βCD) in fasted beagle dogs. The evaluated formulations was (i) a SBE7βCD solution, (ii) a spray dried solution filled into hard gelatine capsules, and (iii) a direct compressible tablet containing SBE7βCD. The three formulations did not lead any significant differences in the obtained AUCs, though a trend was observed for the highest absorption when Lu 35-138 was dosed in the cyclodextrin solution. These results demonstrate that a solid formulation with a relative low content of cyclodextrins can be used to increase the bioavailability of a low water soluble compound to a relative high level when compared to a cyclodextrin solution.