Simultaneous determination of tandospirone and its active metabolite, 1-[2-pyrimidyl]-piperazine in rat plasma by LC-MS/MS and its application to a pharmacokinetic study.

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry method for the detection of tandospirone (TDS) and its active metabolite 1-[2-pyrimidyl]-piperazine (1-PP) in Sprague-Dawley rat plasma is described. It was employed in a pharmacokinetic study. These analytes and the internal standards were extracted from plasma using protein precipitation with acetonitrile, then separated on a CAPCELL PAK ADME C18 column using a mobile phase of acetonitrile and 5 mm ammonium formate acidified with formic acid (0.1%, v/v) at a total flow rate of 0.4 mL/min. The detection was performed with a tandem mass spectrometer equipped with an electrospray ionization source. The method was validated to quantify the concentration ranges of 1.000-500.0 ng/mL for TDS and 10.00-500.0 ng/mL for 1-PP. Total time for each chromatograph was 3.0 min. The intra-day precision was between 1.42 and 6.69% and the accuracy ranged from 95.74 to 110.18% for all analytes. Inter-day precision and accuracy ranged from 2.47 to 6.02% and from 98.37 to 105.62%, respectively. The lower limits of quantification were 1.000 ng/mL for TDS and 10.00 ng/mL for 1-PP. This method provided a fast, sensitive and selective analytical tool for quantification of tandospirone and its metabolite 1-PP in plasma necessary for the pharmacokinetic investigation.

Buspirone Hydrochloride Loaded In Situ Nanovesicular Gel as an Anxiolytic Nasal Drug Delivery System: In Vitro and Animal Studies.

Nasal nanovesicular gels of buspirone hydrochloride (BH) were prepared and characterized aiming for sustained delivery and enhancing bioavailability. Buspirone hydrochloride has low bioavailability of about 4% after oral administration due to first pass metabolism. Buspirone hydrochloride nanovesicles were formulated by thin film hydration method (TFH). The selected nanovesicular formulation was incorporated into two types of in situ gels (pH-induced and thermoreversible) using carbopol 974P and poloxamer 407 (P407), respectively, together with different mucoadhesive polymers. The in situ gels were examined for pH, gelling capability, viscosity, content uniformity, mucoadhesiveness, and in vitro drug release. The ex vivo permeation performance of the in situ gel formulations that showed the most sustained release was also assessed. The in vivo study was done by the determination of BH blood level in albino rabbits after nasal administration. Results revealed that nanovesicles prepared using Span 60 and cholesterol in a ratio of 80:20 showed the highest EE% (70.57 ± 1.00%). The ex vivo permeation data confirmed higher permeability figures for carbopol formulation in comparison to poloxamer formulations. The in vivo study data showed an increase of 3.26 times in BH bioavailability when formulated into the carbopol nanovesicular in situ gel relative to control (nasal drug solution).

TiO2 Photocatalysis-DESI-MS Rotating Array Platform for High-Throughput Investigation of Oxidation Reactions.

We present a new high-throughput platform for studying titanium dioxide (TiO2) photocatalytic oxidation reactions by performing reactions on a TiO2-coated surface, followed by direct analysis of oxidation products from the surface by desorption electrospray ionization mass spectrometry (DESI-MS). For this purpose, we coated a round glass wafer with photocatalytically active anatase-phase TiO2 using atomic layer deposition. Approximately 70 aqueous 1 µL samples can be injected onto the rim of the TiO2-coated glass wafer, before the entire wafer is exposed to UV irradiation. After evaporation of water, the oxidation products can be directly analyzed from the sample spots by DESI-MS, using a commercial rotating sample platform. The method was shown to provide fast photocatalytic oxidation reactions and analysis with throughput of about four samples per minute. The feasibility of the method was examined for mimicking phase I metabolism reactions of amodiaquine, buspirone and verapamil. Their main photocatalytic reaction products were mostly similar to the products observed earlier in TiO2 photocatalysis and in in vitro phase I metabolism assays performed using human liver microsomes.

Azapirones for Attention Deficit Hyperactivity Disorder: A Systematic Review.

INTRODUCTION: No meta-analysis has evaluated azapirones (serotonin1A receptor partial agonists) as anxiolytics for attention deficit hyperactivity disorder (ADHD). METHODS: Randomized controlled trials (RCTs) and single-arm trials published before October 27, 2015 were retrieved from major healthcare databases and clinical trial registries. Relative risk and 95% confidence intervals were calculated. RESULTS: 5 RCTs (n=429) and 3 single-arm studies (n=70) were identified. 3 RCTs compared buspirone vs. methylphenidate in children/adolescents, one buspirone patches vs. placebo patches in children/adolescents, and one atomoxetine plus buspirone vs. atomoxetine vs. placebo in adults. The single-arm studies were buspirone trails in children/adolescents. All-cause discontinuation rates and adverse events did not differ between pooled buspirone and methylphenidate groups. No other meta-analyses of buspirone efficacy and safety vs. comparators were conducted due to insufficient data. 2 RCTs found no significant differences in parent and teacher ADHD-Rating Scale total scores between buspirone and methylphenidate, while one reported that methylphenidate improved parent and teacher ADHD-RS total scores vs. buspirone. DISCUSSION: It remains unclear whether buspirone use has benefit for ADHD patients and therefore further evidence is needed for better clinical use of buspirone in patients with ADHD.

Development of HPLC Method for the Determination of Buspirone in Rat Plasma Using Fluorescence Detection and Its Application to a Pharmacokinetic Study.

A simple and sensitive analytical method for the quantitative determination of buspirone in rat plasma by HPLC with fluorescence detection was developed and validated using naproxen as an internal standard. A relatively small-volume (150 µL) aliquot of rat plasma sample was prepared by a simple deproteinization procedure using acetonitrile as a precipitating organic solvent. Chromatographic separation was performed using Kinetex® C8 column with an isocratic mobile phase consisting of acetonitrile and 10-mM potassium phosphate buffer (pH 6.0) at a flow rate of 1.0 mL/min. The eluent was monitored by fluorescence detector at a wavelength pair of 237/380 nm (excitation/emission). The linearity was established at 20.0-5000 ng/mL, and the limit of detection was 6.51 ng/mL. The precision (≤14.6%), accuracy (89.2-108%), and stability (89.1-101%) were within acceptable ranges. The newly developed method was successfully applied to intravenous and oral pharmacokinetic studies of buspirone in rats.

Lyophilized sustained release mucoadhesive chitosan sponges for buccal buspirone hydrochloride delivery: formulation and in vitro evaluation.

This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 3(2) factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.

Conformational analysis and geometry optimization of buspirone-A 5-HT1A receptor agonist.

Buspirone, a partial 5-HT1A receptor agonist, is a clinically prescribed anxiolytic. In the present study, conformational analysis and geometry optimization of buspirone were done as per Hartree-Fock (HF) calculation method by Argus Lab 4.0.1 software. The minimum potential energy was calculated by geometry convergence function by Argus Lab software. The results indicate that the best conformation of molecule is present at minimum potential energy of-100679.5513 kcal/mol. At this point, buspirone will be more active.

Preparation, Swelling, and Drug Release Studies of Chitosan-based Hydrogels for Controlled Delivery of Buspirone Hydrochloride.

BACKGROUND: Buspirone is used for the management of depression and anxiety disorders. Due to its short half-life and low bioavailability, it requires multiple daily doses and is associated with some side effects. AIM: This study aimed to develop chitosan-based hydrogels as drug-controlled release carriers. OBJECTIVE: The objective of this study is to prepare chitosan-based hydrogels as controlled release carriers in order to overcome the side effects of buspirone HCl and improve patients' compliance and their life quality. METHODS: Polymer chitosan was polymerized with two monomers, acrylic acid and itaconic acid, to synthesize pH-sensitive hydrogel. The Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis were performed to confirm the structure formation and thermal stability. Water penetration capability and loading of the drug were performed by porosity and drug loading studies. The swelling and dissolution tests were performed to analyze the pH-sensitive nature of the developed hydrogels. RESULTS: FTIR, TGA, and DSC demonstrated that the chitosan-based hydrogels were successfully prepared. An increase in water penetration and drug loading into the hydrogel network was seen with the high incorporation of chitosan, acrylic acid, and itaconic acid. The swelling and dissolution studies revealed that prepared hydrogel offered the greatest swelling and drug release at a high pH of 7.4. The swelling and drug release from the hydrogel were affected by the concentrations of the incorporated contents. A controlled release of the drug was achieved by using chitosan-based hydrogel as a delivery carrier compared to commercial tablets of buspirone. CONCLUSION: The results showed that the developed chitosan-based hydrogel can be considered one of the most suitable drug carrier systems for the controlled delivery of buspirone.

An efficient synthesis of aripiprazole, buspirone and NAN-190 by the reductive alkylation of amines procedure.

The reductive alkylation of amines procedure was applied for the synthesis of aripiprazole 1a, buspirone 1b, and NAN-190 1c.

Quantitative estimation of circulating metabolites without synthetic standards by ultra-high-performance liquid chromatography/high resolution accurate mass spectrometry in combination with UV correction.

An early assessment of metabolite exposure in preclinical species can provide quantitative estimation on possible active or toxic metabolites. Frequently, synthetic metabolite standards are not available at the preclinical stage, precluding the quantitation of metabolites by means of calibration curves and quality control (QC) samples. We present here an approach to determine the extent of circulating metabolites using 'metabolite standards' generated by in vitro incubations in combination with the correction for mass spectrometry response based on UV response. The study was done by coupling ultra-high-performance liquid chromatography (UHPLC) to LTQ-Orbitrap high-resolution mass spectrometry, and the quantitation was based on full scan high-resolution accurate mass analysis in combination with retention time. First, we investigated the separation capacity of a 10.5 min UHPLC method and the quantitative capability of an LTQ-Orbitrap for full scan accurate mass quantitation by spiking chemical standards of buspirone and its six metabolites in blank plasma. Then we demonstrated the use of a UV correction approach to quantitatively estimate buspirone and its metabolites in plasma samples from a rat pharmacokinetics study. We compared the concentration versus time profiles of buspirone and its six metabolites in rat plasma samples obtained using three different approaches, including using UV correction, using individual standard curves for each metabolite prepared from the synthetic standard, and using a calibration curve of the parent compound buspirone. We demonstrated the estimated metabolite exposure of buspirone using this UV correction approach resulted in rank ordering of metabolite exposure within three-fold of the value obtained with metabolite standards, in contrast to eight-fold without UV correction. The approach presented in this paper provides a practical solution to an unmet bioanalytical need for quantitative information on metabolites without standards in preclinical in vivo studies.

Study of potential inhibitors of thyroid iodide uptake by using CHO cells stably expressing the human sodium/iodide symporter (hNIS) protein.

BACKGROUND: Thyroid gland is highly dependent on dietary intake of iodine for normal function, so it is particularly subjected to "endocrine disruptor" action. The human sodium/iodide symporter (hNIS) is an integral plasma membrane glycoprotein mediating the active transport of iodide into thyroid follicular cells, a crucial step for thyroid hormone biosynthesis. Beyond to perchlorate and thyocianate ions a few other inhibitors of iodide uptake have been described. AIM: The aim of this study was to investigate if 10 substances usually used as drugs in clinical practice were able to inhibit NIS-mediated iodide uptake in vitro. MATERIALS AND METHODS: A CHO cell line stably expressing hNIS was used to test any inhibition of NIS-mediated iodide uptake exerted by drugs. Perchlorate and thyocianate ions were used as positive controls. RESULTS: None of the analyzed substances was able to significantly inhibit iodide uptake in our system. As we expected, perchlorate and thyocianate ions were able to inhibit iodide uptake in a dose-dependent manner. CONCLUSIONS: In conclusion, we carried out an in vitro assay to evaluate the potential inhibitory effect of common drugs on NISmediated iodide uptake by using CHO-hNIS cells. None of the analyzed substances was able to inhibit iodide uptake; only perchlorate and thyocianate were able to inhibit iodide uptake in a dose-dependent manner.

Formulation and optimization of solid lipid nanoparticles of buspirone HCl for enhancement of its oral bioavailability.

Solid lipid nanoparticles (SLNs) of buspirone HCl as a water-soluble drug were prepared by emulsification-evaporation, followed by the sonification method. A preliminary screening of the most effective parameters on the production of nanoparticles by a Taguchi L(8) orthogonal array showed that the lipid type, surfactant percentage, speed of homogenizer, and acetone:dichloromethane (DCM) ratio had a significant effect on particle size. In the next step, the lipid was fixed on cetyl alcohol, surfactant on Tween 20, lecithin:lipid weight ratio on 20:70, sonication time on 30 seconds, and the other effective, independent factors aforementioned were studied each at three levels by a three-factor, three-level Box-Behnken design. The percentage of drug entrapment, mean particle-size diameter, and zeta potential were studied as the responses. Contour plots were constructed to further elucidate the relationship between the independent and dependent variables. A pharmacokinetic study was conducted in male Wistar rats after oral administration of 15 mg.kg(-1) buspirone in the form of free drug or SLNs. The optimized SLNs had aq particle size of 345.7 nm, loading efficiency of 32.8%, and zeta potential of -6.8 mV. Buspirone released about 90% during 4.5 hours in vitro. It was found that the relative bioavailability of the drug in SLNs was significantly increased, compared to that of the drug solution.

Enhanced bioavailability of buspirone from reservoir-based transdermal therapeutic system, optimization of formulation employing Box-Behnken statistical design.

The purpose of the present study was to develop and optimize reservoir-based transdermal therapeutic system (TTS) for buspirone (BUSP), a low bioavailable drug. A three-factor, three-level Box-Behnken design was employed to optimize the TTS. Hydroxypropyl methylcellulose, D: -limonene and propylene glycol were varied as independent variables; cumulative amount permeated across rat abdominal skin in 24 h, flux and lag time were selected as dependent variables. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The statistical validity of polynomials was established, and optimized formulation factors were selected by feasibility and grid search. Validation of the optimization study with seven confirmatory runs indicated high degree of prognostic ability of response surface methodology. BUSP-OPT (optimized formulation) showed a flux 104.6 microg cm(-2) h(-1), which could meet target flux. The bioavailability studies in rabbits showed that about 2.65 times improvement (p < 0.05) in bioavailability, after transdermal administration of BUSP-OPT compared to oral solution. The ex vivo-in vivo correlation was found to have biphasic pattern and followed type A correlation. Reservoir-based TTS for BUSP was developed and optimized using Box-Behnken statistical design and could provide an effective treatment in the management of anxiety.

Carboxy group derivatization for enhanced electron-transfer dissociation mass spectrometric analysis of phosphopeptides.

A novel strategy based on carboxy group derivatization is presented for specific characterization of phosphopeptides. By tagging the carboxy group with 1-(2-pyrimidyl) piperazine (PP), the ion charge states of phosphopeptides can be largely enhanced, showing great advantages for sequencing phosphorylated peptides with electron-transfer dissociation MS. Besides, after PP-derivatization, most non-specific bindings can be avoided by eliminating the interaction between the carboxy group and TiO(2), greatly improving the specificity of TiO(2)-based phosphopeptide enrichment strategy. Moreover, being tagged with a hydrophobic group, the retention time of phosphopeptides in RPLC can be prolonged, overcoming the difficulty of separating phosphopeptides in RPLC-based approach. Together with several other advantages, such as ease of handling, rapid reaction time, broad applicability and good reproducibility, this PP-derivatization method is promising for high-throughput phosphoproteome research.

Two-injection workflow for a liquid chromatography/LTQ-Orbitrap system to complete in vivo biotransformation characterization: demonstration with buspirone metabolite identification.

The relatively high background matrix in in vivo samples typically poses difficulties in drug metabolite identification, and causes repeated analytical runs on unit resolution liquid chromatography/mass spectrometry (LC/MS) systems before the completion of biotransformation characterization. Ballpark parameter settings for the LTQ-Orbitrap are reported herein that enable complete in vivo metabolite identification within two HPLC/MS injections on the hybrid LTQ-Orbitrap data collection system. By setting the FT survey full scan at 60K resolution to trigger five dependent LTQ MS(2) scans, and proper parameters of Repeat Duration, Exclusion Duration and Repeat Count for the first run (exploratory), the Orbitrap achieved the optimal parallel data acquisition capability and collected maximum number of product ion scans. Biotransformation knowledge based prediction played the key role in exact mass ion extraction and multiple mass defect filtration when the initial data was processed. Meanwhile, product ion extraction and neutral loss extraction of the initial dependent data provided additional bonus in identifying metabolites. With updated parent mass list and the data-dependent setting to let only the ions on the parent mass list trigger dependent scans, the second run (confirmatory) ensures that all precursor ions of identified metabolites trigger not only dependent product ion scans, but also at or close to the highest concentration of the eluted metabolite peaks. This workflow has been developed for metabolite identification of in vivo or ADME studies, of which the samples typically contain a high level of complex matrix. However, due to the proprietary nature of the in vivo studies, this workflow is presented herein with in vitro buspirone sample incubated with human liver microsomes (HLM). The major HLM-mediated biotransformation on buspirone was identified as oxidation or hydroxylation since five mono- (+16 Da), seven di- (+32 Da) and at least three tri-oxygenated (+48 Da) metabolites were identified. Besides the metabolites 1-pyrimidinylpiperazine (1-PP) and hydroxylated 1-PP that formed by N-dealkylation, a new metabolite M308 was identified as the result of a second N-dealkylation of the pyrimidine unit. Two new metabolites containing the 8-butyl-8-azaspiro[4,5]decane-7,9-dione partial structure, M240 and M254, were also identified that were formed apparently due to the first N-dealkylation of the 1-PP moiety.

TiO2 Photocatalyzed Oxidation of Drugs Studied by Laser Ablation Electrospray Ionization Mass Spectrometry.

In drug discovery, it is important to identify phase I metabolic modifications as early as possible to screen for inactivation of drugs and/or activation of prodrugs. As the major class of reactions in phase I metabolism is oxidation reactions, oxidation of drugs with TiO2 photocatalysis can be used as a simple non-biological method to initially eliminate (pro)drug candidates with an undesired phase I oxidation metabolism. Analysis of reaction products is commonly achieved with mass spectrometry coupled to chromatography. However, sample throughput can be substantially increased by eliminating pretreatment steps and exploiting the potential of ambient ionization mass spectrometry (MS). Furthermore, online monitoring of reactions in a time-resolved way would identify sequential modification steps. Here, we introduce a novel (time-resolved) TiO2-photocatalysis laser ablation electrospray ionization (LAESI) MS method for the analysis of drug candidates. This method was proven to be compatible with both TiO2-coated glass slides as well as solutions containing suspended TiO2 nanoparticles, and the results were in excellent agreement with studies on biological oxidation of verapamil, buspirone, testosterone, andarine, and ostarine. Finally, a time-resolved LAESI MS setup was developed and initial results for verapamil showed excellent analytical stability for online photocatalyzed oxidation reactions within the set-up up to at least 1 h. Graphical Abstract.

Can in vitro metabolism-dependent covalent binding data in liver microsomes distinguish hepatotoxic from nonhepatotoxic drugs? An analysis of 18 drugs with consideration of intrinsic clearance and daily dose.

In vitro covalent binding assessments of drugs have been useful in providing retrospective insights into the association between drug metabolism and a resulting toxicological response. On the basis of these studies, it has been advocated that in vitro covalent binding to liver microsomal proteins in the presence and the absence of NADPH be used routinely to screen drug candidates. However, the utility of this approach in predicting toxicities of drug candidates accurately remains an unanswered question. Importantly, the years of research that have been invested in understanding metabolic bioactivation and covalent binding and its potential role in toxicity have focused only on those compounds that demonstrate toxicity. Investigations have not frequently queried whether in vitro covalent binding could be observed with drugs with good safety records. Eighteen drugs (nine hepatotoxins and nine nonhepatotoxins in humans) were assessed for in vitro covalent binding in NADPH-supplemented human liver microsomes. Of the two sets of nine drugs, seven in each set were shown to undergo some degree of covalent binding. Among hepatotoxic drugs, acetaminophen, carbamazepine, diclofenac, indomethacin, nefazodone, sudoxicam, and tienilic acid demonstrated covalent binding, while benoxaprofen and felbamate did not. Of the nonhepatotoxic drugs evaluated, buspirone, diphenhydramine, meloxicam, paroxetine, propranolol, raloxifene, and simvastatin demonstrated covalent binding, while ibuprofen and theophylline did not. A quantitative comparison of covalent binding in vitro intrinsic clearance did not separate the two groups of compounds, and in fact, paroxetine, a nonhepatotoxin, showed the greatest amount of covalent binding in microsomes. Including factors such as the fraction of total metabolism comprised by covalent binding and the total daily dose of each drug improved the discrimination between hepatotoxic and nontoxic drugs based on in vitro covalent binding data; however, the approach still would falsely identify some agents as potentially hepatotoxic.

The molecular interactions of buspirone analogues with the serotonin transporter.

A major problem with the selective serotonin reuptake inhibitors (SSRIs) is the delayed onset of action. A reason for that may be that the initial SSRI-induced increase in serotonin levels activates somatodendritic 5-HT(1A) autoreceptors, causing a decrease in serotonin release in major forebrain areas. It has been suggested that compounds combining inhibition of the serotonin transport protein with antagonistic effects on the 5-HT(1A) receptor will shorten the onset time. The anxiolytic drug buspirone is known as 5-HT(1A) partial agonist. In the present work, we are studying the inhibition of the serotonin transporter protein by a series of buspirone analogues by molecular modelling and by experimental affinity measurements. Models of the transporter protein were constructed using the crystal structure of the Escherichia coli major facilitator family transporter-LacY and the X-ray structure of the neurotransmitter symporter family (NSS) transporter-LeuT(Aa) as templates. The buspirone analogues were docked into both SERT models and the interactions with amino acids within the protein were analyzed. Two putative binding sites were identified on the LeuT(Aa) based model, one suggested to be a high-affinity site, and the other suggested to be a low-affinity binding site. Molecular dynamic simulations of the LacY based model in complex with ligands did not induce a helical architecture of the LacY based model into an arrangement more similar to that of the LeuT(Aa) based model.

Modulation of buspirone HCl release from hypromellose matrices using chitosan succinate: implications for pH-independent release.

Chitosan succinate (CS) was synthesized through the acylation of chitosan with succinic anhydride. The interaction of CS with buspirone HCl (BUSP) was evaluated using dialysis experiments and shown to result in complex with a stability constant of 2.26 mM and a capacity of 0.0362 micromol BUSP/mg CS. The extent of complexation upon dry and wet mixing of CS and BUSP was determined quantitatively using differential scanning calorimetry. The extent of the interaction was highest in wet mixtures and was found to be dependent on the pH of the granulation liquid. CS was incorporated in BUSP-containing hypromellose (HPMC) tablets using dry mixing and wet granulation with BUSP. Tablet dissolution was tested in 0.1N HCl and phosphate buffer, pH 6.8. According to f(2) and mean dissolution time results, the similarity of profiles increased as CS content increased with the highest f(2) value observed when CS was wet granulated with BUSP. Dissolution was also tested in deionized water and 5% NaCl; where increased ionic strength resulted in faster dissolution suggesting an ion exchange involvement in drug release. CS was proved effective in modulating BUSP release from HPMC matrices for pH-independent release through ionic complex formation.

Sustained-release of buspirone HCl by co spray-drying with aqueous polymeric dispersions.

Sustained-release of buspirone HCl (BUH) was attempted by spray drying after dissolving in two commercially available aqueous polymeric dispersions (Eudragit RS 30 D or Kollicoat SR 30 D) at five different drug:polymer ratios (1:1, 1:2, 1:3, 1:6 and 1:9). The produced spray-dried agglomerates were evaluated in terms of their particle size and morphology, production yield, encapsulation efficiency and in-vitro release of BUH. Possible drug-polymer interactions were checked by Differential Scanning Calorimetry (DSC) and FT-IR spectroscopy. Scanning electron microscopy (SEM) was employed for the qualitative characterization of particle size and morphology. Encapsulation efficiency was generally high (around 100%) and independent of the polymeric dispersion type, while production yield was generally low (7.2-31.0%) and significantly lower for the case of Kollicoat SR 30 D (KSR) than for Eudragit RS 30 D (ERS). Scanning electron micrographs showed remarkable changes in size and shape of agglomerates due to the type of aqueous polymeric dispersion and drug:polymer ratio. In-vitro release of BUH from compacted co spray-dried agglomerates was remarkably slower and incomplete for the case of Kollicoat at drug:polymer ratio below 1, presumably due to increased plastic deformation of the developed coating instead of fragmentation in the case of Eudragit coating during compaction.