Variable Bioavailability Research Articles

Preparation and evaluation of famotidine nanosuspension

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. There are many methods used to increase dissolution rate of drug and in this study, the dissolution of the drug was enhanced by the preparation of nanosuspension. Famotidine nanosuspension was prepared by antisolvent precipitation method, where famotidine dissolved in methanol at room temperature and emptied into water containing different types of stabilizers (single and in combination). The optimum formula (F9) was selected according to particle size (362.8nm) and release profile (80 % of drug release within the 10 minutes) in comparison to pure famotidine powder release. The influence of formulation variables like the type and concentration of stabilizers Polyvinyl pyrrolidone K30, polyvinyl alcohol and poloxamer 188 (PVP K-30, PVA and poloxamer 188) in addition to combination of stabilizers on particle size of drug nanosuspensions were studied. The result showed that single stabilizer (poloxamer 188) has perfect surface affinity and could form a substantial mechanical and thermodynamic barrier at the interface of dug molecule. As the concentration of stabilizer increases the particle size decreases at fixed drug concentration (drug: stabilizer ratio 1:2).

Novel Combination for Self-Nanoemulsifying Drug Delivery System of Candesartan Cilexetil

Solubility problem of many of effective pharmaceutical molecules are still one of the major obstacle in theformulation of such molecules. Candesartan cilexetil (CC) is angiotensin II receptor antagonist with very low water solubility and this result in low and variable bioavailability. Self- emulsifying drug delivery system (SEDDS) showed promising result in overcoming solubility problem of many drug molecules. CC was prepared as SEDDS by using novel combination of two surfactants (tween 80 and cremophore EL) and tetraglycol as cosurfactant, in addition to the use of triacetin as oil. Different tests were performed in order to confirm the stability of the final product which includes thermodynamic study, determination of self-emulsification time, particle size and zeta potential measurement, and in-vitro drug release. The results showed that the particle size of the best formula was 13.3 nm and zeta potential of -37.45 mV with approximately 100% release after 45 minutes .These results suggest that the preparation of CC. as SEDDS with the use of the above combination of surfactant and cosurfactant is a promising maneuver for oral delivery of CC. in order to improve its bioavailability.

Preparation and evaluation of famotidine nanosuspension

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. There are many methods used to increase dissolution rate of drug and in this study, the dissolution of the drug was enhanced by the preparation of nanosuspension. Famotidine nanosuspension was prepared by antisolvent precipitation method, where famotidine dissolved in methanol at room temperature and emptied into water containing different types of stabilizers (single and in combination). The optimum formula (F9) was selected according to particle size (362.8nm) and release profile (80 % of drug release within the 10 minutes) in comparison to pure famotidine powder release. The influence of formulation variables like the type and concentration of stabilizers Polyvinyl pyrrolidone K30, polyvinyl alcohol and poloxamer 188 (PVP K-30, PVA and poloxamer 188) in addition to combination of stabilizers on particle size of drug nanosuspensions were studied. The result showed that single stabilizer (poloxamer 188) has perfect surface affinity and could form a substantial mechanical and thermodynamic barrier at the interface of dug molecule. As the concentration of stabilizer increases the particle size decreases at fixed drug concentration (drug: stabilizer ratio 1:2).

Preparation and evaluation of famotidine nanosuspension

Famotidine (FM) is a potent H2-receptor antagonist used for the treatment of peptic ulcer. It has a low and variable bioavailability which is attributed to its low water solubility. There are many methods used to increase dissolution rate of drug and in this study, the dissolution of the drug was enhanced by the preparation of nanosuspension. Famotidine nanosuspension was prepared by antisolvent precipitation method, where famotidine dissolved in methanol at room temperature and emptied into water containing different types of stabilizers (single and in combination). The optimum formula (F9) was selected according to particle size (362.8nm) and release profile (80 % of drug release within the 10 minutes) in comparison to pure famotidine powder release. The influence of formulation variables like the type and concentration of stabilizers Polyvinyl pyrrolidone K30, polyvinyl alcohol and poloxamer 188 (PVP K-30, PVA and poloxamer 188) in addition to combination of stabilizers on particle size of drug nanosuspensions were studied. The result showed that single stabilizer (poloxamer 188) has perfect surface affinity and could form a substantial mechanical and thermodynamic barrier at the interface of dug molecule. As the concentration of stabilizer increases the particle size decreases at fixed drug concentration (drug: stabilizer ratio 1:2).

Drug supersaturation during formulation digestion, including real-time analytical approaches.

Self-emulsifying and other lipid-based drug delivery systems have drawn considerable interest from pharmaceutical scientists for managing oral delivery of poorly water-soluble compounds. Following administration, self-emulsifying systems exhibit complex aqueous dispersion and digestion in the gastro-intestinal tract. These processes generally result in drug supersaturation, which leads to enhanced absorption or the high drug concentrations may cause precipitation with erratic and variable oral bioavailability. This review briefly outlines drug supersaturation obtained from self-emulsifying and other lipid-based formulations; recent advancements of in vitro lipolysis testing are also discussed. Further, a main focus is mechanisms by which supersaturation is triggered from gastro-intestinal processes, as well as analytical techniques that are promising from a research and development perspective. Comparatively simple approaches are presented together with more sophisticated process analytics to enable direct examination of kinetic changes. The analytical methods together with their sensor probes are discussed in detail to clarify opportunities as well as technical limitations. Some of the more sophisticated methods, including those based on synchrotron radiation, are primarily research oriented despite interesting experimental findings from an industrial viewpoint. The availability of kinetic data further opens the door to mathematical modeling of supersaturation and precipitation versus permeation, which lays the groundwork for better in vitro to in vivo correlations as well as for physiologically-based modeling of lipid-based systems.

Effects of generally recognized as safe (GRAS) and dietary compounds on phenylephrine metabolism in LS180 human intestinal cells.

Phenylephrine (PE) has low and variable oral bioavailability in humans, due in part to presystemic metabolism by sulfation. LS180 cells were used as a model of the human intestinal epithelium to examine phenylephrine metabolism and its inhibition by generally recognized as safe (GRAS) and dietary compounds. Curcumin, zingerone, resveratrol, guaiacol, pterostilbene and isoeugenol significantly inhibited phenylephrine disappearance, while vanillin, propylparaben and eugenol did not. However, when propylparaben was combined with either vanillin or eugenol, the phenylephrine disappearance was significantly inhibited. These data suggest that these compounds or combinations thereof may have potential to improve phenylephrine oral bioavailability.

Food for thought: formulating away the food effect – a PEARRL review

Co-ingestion of oral dosage forms with meals can cause substantial changes in bioavailability relative to the fasted state. Food-mediated effects on bioavailability can have significant consequences in drug development, regulatory and clinical settings. To date, the primary focus of research has focused on the ability to mechanistically understand the causes and predict the occurrence of these effects. The current review describes the mechanisms underpinning the occurrence of food effects, sheds new insights on the relative frequency for newly licensed medicines and describes the various methods by which they can be overcome. Analysis of oral medicines licensed by either the EMA or FDA since 2010 revealed that over 40% display significant food effects. Due to altered bioavailability, these medicines are often required to be dosed, rather restrictively, in either the fed or the fasted state, which can hinder clinical usefulness. There are clinical and commercial advantages to predicting the presence of food effects early in the drug development process, in order to mitigate this risk of variable food effect bioavailability. Formulation approaches aimed at reducing variable food-dependent bioavailability, through the use of bio-enabling formulations, are an essential tool in addressing this challenge and the latest state of the art in this field are summarised here.

Radiocaesium bioavailability to flooded paddy rice is related to soil solution radiocaesium and potassium concentrations

This study was established to better understand the mechanisms of the variable radiocaesium bioavailability observed in flooded rice. Paddy topsoils (n = 9) with contrasting soil properties were collected from the Fukushima-accident affected area, spiked with 134Cs and cropped in the greenhouse with rice under flooded conditions. Soil solution was collected. As a reference to earlier work, we cropped the same paddy soils and additional grassland soils (n = 22 in total) with ryegrass under unsaturated conditions. Rice shoot 134Cs concentrations varied 110-fold among soils and were unrelated to soil solution 134Cs concentrations. However, the rice shoot 134Cs concentrations clearly increased with the soil solution 134Cs:K concentration ratio (R2 = 0.79; P < 0.001). The same trend was true for ryegrass shoot 134Cs concentrations, which were, on average, 4.1-fold larger than those for flooded rice at an equal soil solution 134Cs:K ratio. Soil solution radiocaesium and K concentrations explain the radiocaesium bioavailability to flooded rice, confirming established knowledge for ryegrass. Transport modelling suggests that the overall smaller 134Cs bioavailability to flooded rice than to ryegrass in unsaturated soils is related to the smaller K uptake rate of rice, alleviating K depletion in its rhizosphere with locally higher K+, blocking the root uptake of radiocaesium.

PH-independent controlled release tablets containing nanonizing valsartan solid dispersions for less variable bioavailability in humans

The aims of this work were to design pH-independent controlled release (CR) tablet containing nanonizing solid dispersion (SD) adsorbed on hydrophilic silica (Aeroperl® 300/30). Valsartan (VAL) was chosen to simultaneously modulate solubility and release rate due to its poor water solubility in low pH condition and short elimination half-life. Based on extensive equilibrium solubility and compatibility studies, poloxamer 407 was selected as a SD carrier. The melted mixtures of drug and poloxamer 407 were adsorbed onto hydrophilic fumed silica (Aeroperl® 300/30). Ternary SD system changed crystalline drug into an amorphous state and had intermolecular hydrogen bonding as confirmed by FT-IR with poloxamer 407. The dissolution rate of SD system was markedly enhanced as compared with pure VAL or commercial Diovan® tablet in simulated gastric fluid (pH 1.2). Interestingly, the particle size of SD system was gradually nanonized for 2 hr, ranging from 600 nm to 150 nm during dissolution process. The SD-loaded CR (SD-CR) tablets using hydroxypropylmethylcellulose (HPMC 4000) showed pH-independent zero-order release and good stability at accelerated conditions for six months. The SD-CR tablet showed minimized inter-subject variation of maximum plasma concentration as compared with commercial Diovan® tablets in healthy human volunteers.

First-Pass CYP3A-Mediated Metabolism of Midazolam in the Gut Wall and Liver in Preterm Neonates.

To predict first‐pass and systemic cytochrome P450 (CYP) 3A‐mediated metabolism of midazolam in preterm neonates, a physiological population pharmacokinetic model was developed describing intestinal and hepatic midazolam clearance in preterm infants. On the basis of midazolam and 1‐OH‐midazolam concentrations from 37 preterm neonates (gestational age 26–34 weeks) receiving midazolam orally and/or via a 30‐minute intravenous infusion, intrinsic clearance in the gut wall and liver were found to be very low, with lower values in the gut wall (0.0196 and 6.7 L/h, respectively). This results in a highly variable and high total oral bioavailability of 92.1% (range, 67–95%) in preterm neonates, whereas this is around 30% in adults. This approach in which intestinal and hepatic clearance were separately estimated shows that the high bioavailability in preterm neonates is explained by, likely age‐related, low CYP3A activity in the liver and even lower CYP3A activity in the gut wall.

UV-vis Imaging of Piroxicam Supersaturation, Precipitation, and Dissolution in a Flow-Through Setup.

Evaluation of drug precipitation is important in order to address challenges regarding low and variable bioavailability of poorly water-soluble drugs, to assess potential risk of patient safety with infusion therapy, and to explore injectable in situ suspension-forming drug delivery systems. Generally, drug precipitation is assessed in vitro through solution concentration analysis methods. Dual-wavelength UV-vis imaging is a novel imaging technique that may provide an opportunity for simultaneously monitoring changes in both solution and solid phases during precipitation. In the present study, a multimodal approach integrating UV-vis imaging, light microscopy, and Raman spectroscopy was developed for characterization of piroxicam supersaturation, precipitation, and dissolution in a flow-through setup. A solution of piroxicam dissolved in 1-methyl-2-pyrrolidinone was injected into a flowing aqueous environment (pH 7.4), causing piroxicam to precipitate. Imaging at 405 and 280 nm monitored piroxicam concentration distributions during precipitation and revealed different supersaturation levels dependent on the initial concentration of the piroxicam solution. The combination with imaging at 525 nm, light microscopy, and Raman spectroscopy measurements demonstrated concentration-dependent precipitation and the formation, growth, and dissolution of individual particles. Results emphasize the importance of the specific hydrodynamic conditions on the piroxicam precipitation. The approach used may facilitate comprehensive understanding of drug precipitation and dissolution processes and may be developed further into a basic tool for formulation screening and development.

Solubility and bioavailability improvement of pazopanib hydrochloride

The anti-cancer drug pazopanib hydrochloride (PZH) has a very low aqueous solubility and a variable oral bioavailability. A new pharmaceutical formulation with an improved solubility may enhance the bioavailability and reduce the variability. A broad selection of polymer excipients was tested for their compatibility and solubilizing properties by conventional microscopic, thermal and spectrometric techniques. A wet milling and mixing technique was used to produce homogenous powder mixtures. The dissolution properties of the formulation were tested by a pH-switch dissolution model. The final formulation was tested in vivo in cancer patient following a dose escalation design. Of the tested mixture formulations, the one containing the co-block polymer Soluplus® in a 8:1 ratio with PZH performed best in terms of in vitro dissolution properties. The in vivo results indicated that 300 mg of the developed formulation yields similar exposure and a lower variability (379 μg/mL∗h (36.7% CV)) than previously reported values for the standard PZH formulation (Votrient®) at the approved dose of 800 mg. Furthermore, the expected plasma-Cthrough levels (27.2 μg/mL) exceeds the defined therapeutic efficacy threshold of 20 μg/mL.

Vitamin D nanoemulsion enhances hepatoprotective effect of conventional vitamin D in rats fed with a high-fat diet

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with hyperlipidemia, obesity and type II diabetes. Due to increasing prevalence of these diseases globally, NAFLD is considered as a common form of chronic liver diseases. Vitamin D is a fat soluble vitamin with reported anti-inflammatory, anti-oxidant and immune modulating activity. Hypovitaminosis D often coexists with NAFLD and various studies reported beneficial role of vitamin D in modulating NAFLD. However, variable oral bioavailability, poor water solubility, and chemical degradation hinder the clinical application of vitamin D. PurposeWe evaluated the potential protective effect of Vitamin D nanoemulsion (developed by sonication and pH-Shifting of pea protein isolate and canola oil) compared to conventional vitamin D against liver injury in rats fed with high fat diet (HFD). MethodsWe analyzed liver function enzymes, lipid profile, lipid metabolism, levels and histopathology of inflammation and fibrosis in rat liver tissues. ResultsHFD fed rats exhibited deterioration of liver function, poor lipid profile, decreased fatty acid oxidation and up-regulation of inflammatory cytokines and extracellular matrix deposition. Vitamin D administration reduced elevated liver enzymes, improved lipid profile, enhanced fatty acid oxidation and attenuated liver inflammation and fibrosis. Interestingly, vitamin D nanoemulsion was superior to conventional vitamin D with remarkable hepatoprotective effect against HFD-induced liver injury. ConclusionThis study demonstrated vitamin D nanoemulsion as a more efficient formulation with more prominent hepatoprotective effect against HFD-induced liver injury compared to conventional oral vitamin D.

Solubility Enhancement of Poorly Water-Soluble Antifungal Drug Acyclovir by Nanocrystal Formulation Approach

Administration of an antiviral drug, acyclovir via the oral route leads to low and variable bioavailability (15-30%). Therefore, this research work was aimed to enhance bioavailability of acyclovir by nanocrystallization technique. The drug nanocrystals were prepared by anti-solvent precipitation method in which different stabilizers were used. The formed nanocrystals are subjected to biopharmaceutical characterization including solubility, particle size and in-vitro release. SEM studies showed nano-crystals were crystalline nature with sharp peaks. The formulated drug nanocrystals were found to be in the range of 600-900nm and formulations NC7 and NC8 showed marked improvement in dissolution velocity when compared to pure drug, thus providing greater bioavailability. FT-IR and DSC studies revealed the absence of any chemical interaction between drug and polymers used.

Prevention of Invasive Aspergillus Fungal Infections with the Suspension and Delayed-Release Tablet Formulations of Posaconazole in Patients with Haematologic Malignancies

Posaconazole is a triazole antifungal used to prevent invasive fungal infections (IFIs) in patients receiving chemotherapy or haemotopoietic stem cell transplantation. Due to highly variable bioavailability of the oral suspension formulation, a delayed-release tablet was developed which showed improved bioavailability. A minimal target posaconazole plasma concentration of 0.7 mg/L is recommended for prophylaxis of IFIs. However, the relationship between plasma concentration of posaconazole and its efficacy against IFIs remains unclear. We analysed trough posaconazole concentrations and response against IFIs in 50 and 104 patients with haematologic malignancies receiving prophylactic posaconazole as the tablet or suspension formulation, respectively. Mean plasma concentration of posaconazole was 1.91 ± 1.06 mg/L and 0.82 ± 0.57 mg/L in the tablet and the oral suspension group, respectively (p < 0.0001). The percentage of patients reaching the minimal target concentration of 0.7 mg/L was 92.0% and 47.1% in the tablet and oral suspension groups, respectively (p < 0.0001). Emergent aspergillosis occurred in 9 (8.7%) patients in the suspension group and in none of the patients taking the tablet formulation (p = 0.032). Our results show a relationship between plasma concentrations of posaconazole and its prophylactic efficacy in patients with haematologic malignancies. Target posaconazole concentrations are reached more efficiently with the tablet than with the suspension formulation.

Design, characterization and in vivo evaluation of nanostructured lipid carriers (NLC) as a new drug delivery system for hydrochlorothiazide oral administration in pediatric therapy

The hydrochlorothiazide (HCT) low solubility and permeability give rise to limited and variable bioavailability; its low stability makes it difficult to develop stable aqueous liquid formulations; its low dose makes the achievement of a homogeneous drug distribution very difficult. Thus, the aim of this study was to investigate the effectiveness of a strategy based on the development of nanostructured lipid carriers (NLC) as an innovative oral pediatric formulation of HCT with improved therapeutic efficacy. The performance of various synthetic and natural liquid lipids was examined and two different preparation methods were employed, i.e. homogenization-ultrasonication (HU) and microemulsion (ME), in order to evaluate their influence on the NLC properties in terms of size, polydispersity index, ζ-potential, entrapment efficiency, gastric stability, and drug release properties. Precirol®ATO5 was used as solid lipid and Tween®80 and Pluronic®F68 as surfactants, formerly selected in a previous study focused on the development of HCT-solid lipid nanoparticles (SLNs). The presence of Pluronic®F68 did not allow ME formation. On the contrary, using Tween®80, the ME method enabled a higher entrapment efficiency than the HU. Regardless of the preparation method, NLCs exhibited great entrapment efficiency values clearly higher than previous SLNs. Moreover, NLC-ME formulations provided a prolonged release, which lasted for 6 h. In particular, NLC-ME containing Tween®20 as Co-Surfactant showed the best performances, giving rise to a complete drug release, never achieved with previous SLN formulations, despite their successful results. In vivo studies on rats confirmed these results, displaying their best diuretic profile. Moreover, all HCT-loaded NLC formulations showed higher stability than the corresponding SLNs.

Solubility Enhancement of Domperidone by Solvent Change In situ Micronization Technique.

Background:Domperidone (DOM), a dopamine receptor antagonist, is used as antiemetic for the treatment of gastroparesis, vomiting, and nausea. The low water solubility of DOM leads to a low dissolution rate and variable bioavailability. The aim of this study was to enhance the solubility of DOM by the preparation of micron-sized particles.Materials and Methods:The in situ micronization process was carried out using solvent change method in the presence of Soluplus® or PEG6000 as stabilizing agents. DOM was dissolved in appropriate solvent (acetone and methanol 1:1 v/v), and the stabilizing agent was dissolved in water (as nonsolvent). The nonsolvent was poured rapidly into the drug solution under stirring by a homogenizer, and the resultant was freeze dried. The crystalline shape and particle size of DOM and interaction of DOM with stabilizers were investigated by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetry (DSC), and then, dissolution test was carried out.Results:Optimum formulation was composed of DOM (0.5%) and PEG6000 (0.1%) with the lowest particle size (3 μm) and the highest DE60% (95.95%) as compared to pure DOM (particle size of 13.4 μm and DE60% 52.18%).Conclusion:SEM micrographs showed uniform and spherical shape of microcrystals. FTIR, XRD, and DSC studies indicated the micron size of the microcrystals and no interference between the drug and the stabilizer.

Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration

Nowadays, therapeutic indications for cannabinoids, specifically Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is that its composition of materials is approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (10.8mg, 10mg respectively) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments.Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has in serving as a standardized oral cannabinoid formulation. Moreover, the concept of improving oral bioavailability described here, can pave the way for other potential lipophilic active compounds requiring enhancement of their oral bioavailability.

Pharmacokinetic evaluation of oral itraconazole for antifungal prophylaxis in children.

Itraconazole is a first-generation triazole agent with an extended spectrum of activity; it is licensed in adults for superficial and systemic fungal infections; no recommendation has been yet established for use in children patients. Its variable and unpredictable oral bioavailability make it difficult to determine the optimal dosing regimen. Hence, therapeutic drug monitoring, highly available in clinical practice, may improve itraconazole treatment success and safety. The aim of the study was to describe in paediatrics the oral itraconazole pharmacokinetics, used for prophylaxis. Moreover, we evaluated the utility of its therapeutic drug monitoring in this cohort. A fully validated chromatographic method was used to quantify itraconazole concentration in plasma collected from paediatric patients, at the end of dosing interval. Associations between variables were tested using the Pearson test. Mann-Whitney U test has been used to probe the influence of categorical variables on continuous ones. Any predictive power of the considered variables was finally evaluated through univariate and multivariate linear and logistic regression analyses. A high inter-individual variability was shown; ethnicity (beta coefficient, β -0.161 and interval of confidence at 95%, IC -395.035; -62.383) and gender (β 0.123 and IC 9.590; 349.395) remained in the final linear regression model with P value of .007 and .038, respectively. This study highlights that therapeutic drug monitoring is required to achieve an adequate target itraconazole serum exposure.

Improving the solubility of nilotinib through novel spray-dried solid dispersions

The tyrosine kinase inhibitor nilotinib has a very low aqueous solubility and a low and variable oral bioavailability. A pharmaceutical formulation with an improved solubility may enhance the bioavailability and reduce the variability thereof and of the pharmacokinetics. The aim of this study was to enhance the solubility of nilotinib by developing a spray dried solid dispersion. A broad selection of polymer excipients were tested for solubilizing properties. The spray drying technique was used to produce solid dispersions of nilotinib hydrochloride (NH) in matrices of the best performing polymers. Both the dissolution and physicochemical characteristics of the formulations were studied using a pH-switch dissolution model and conventional microscopic, thermal and spectrometric techniques. Of the tested spray dried solid dispersions, the ones containing the co-block polymer Soluplus® performed best in terms of in vitro dissolution properties. Further testing led to an optimized weight ratio of 1:7 (NH:Soluplus®) that improved the solubility up to 630-fold compared to crystalline NH (1.5μg/mL) in simulated intestinal fluid. This effect can be attributed to the amorphization of NH and the solubilization of the drug due to micelle formation. A spray dried solid dispersion formulation of NH with Soluplus® in a ratio of 1:7 was developed that showed a significant increase in solubility.