Novel nano-cellulose excipient for generating non-Newtonian droplets for targeted nasal drug delivery

Purpose: Thickening polymers have been used as excipients in nasal formulations to avoid nasal run-off (nasal drip) post-administration. However, increasing the viscosity of the formulation can have a negative impact on the quality of the aerosols generated. Therefore, the study aims to investigate the use of a novel smart nano-cellulose excipient to generate suitable droplets for nasal drug delivery that simultaneously has only marginally increased viscosity while still reducing nasal drips.

Methods: Nasal sprays containing nano-cellulose at different concentrations were investigated for the additive’s potential as an excipient. The formulations were characterized for their rheological and aerosol properties. This was then compared to conventional nasal spray formulation containing the single-component hydroxyl-propyl methyl cellulose (HPMC) viscosity enhancing excipient.

Results: The HPMC-containing nasal formulations behave in a Newtonian manner while the nano-cellulose formulations have a yield stress and shear-thinning properties. At higher excipient concentrations and shear rates, the nano-cellulose solutions have significantly lower viscosities compared to the HPMC solution, resulting in improved droplet formation when actuated through conventional nasal spray.

Conclusions: Nano-cellulose materials could potentially be used as a suitable excipient for nasal drug delivery, producing consistent aerosol droplet size, and enhanced residence time within the nasal cavity with reduced run-offs compared to conventional polymer thickeners.     

Applying the approximation method PAINT and the interactive method NIMBUS to the multiobjective optimization of operating a wastewater treatment plant

Using an interactive multiobjective optimization method called NIMBUS and an approximation method called PAINT, preferable solutions to a five-objective problem of operating a wastewater treatment plant are found. The decision maker giving preference information is an expert in wastewater treatment plant design at the engineering company Pöyry Finland Ltd. The wastewater treatment problem is computationally expensive and requires running a simulator to evaluate the values of the objective functions. This often leads to problems with interactive methods as the decision maker may get frustrated while waiting for new solutions to be computed. Thus, a newly developed PAINT method is used to speed up the iterations of the NIMBUS method. The PAINT method interpolates between a given set of Pareto optimal outcomes and constructs a computationally inexpensive mixed integer linear surrogate problem for the original wastewater treatment problem. With the mixed integer surrogate problem, the time required from the decision maker is comparatively short. In addition, a new IND-NIMBUS^® PAINT module is developed to allow the smooth interoperability of the NIMBUS method and the PAINT method.     

Application of cyclodextrins in antibody microparticles: potentials for antibody protection in spray drying

Objectives: Dry powder formulations are extensively used to improve the stability of antibodies. Spray drying is one of important methods for protein drying. This study investigated the effects of trehalose, hydroxypropyl beta cyclodextrin (HPBCD) and beta cyclodextrin (BCD) on the stability and particle properties of spray-dried IgG.

Methods: D-optimal design was employed for both experimental design and analysis and optimization of the variables. The size and aerodynamic behavior of particles were determined using laser light scattering and glass twin impinger, respectively. In addition, stability, ratio of beta sheets and morphology of antibody were analyzed using size exclusion chromatography, IR spectroscopy and electron microscopy, respectively.

Results: Particle properties and antibody stability were significantly improved in the presence of HPBCD. In addition, particle aerodynamic behavior, in terms of fine-particle fraction (FPF), enhanced up to 52.23%. Furthermore, antibody was better preserved not only during spray drying, but also during long-term storage. In contrast, application of BCD resulted in the formation of larger particles. Although trehalose caused inappropriate aerodynamic property, it efficiently decreased antibody aggregation.

Conclusion: HPBCD is an efficient excipient for the development of inhalable protein formulations. In this regard, optimal particle property and antibody stability was obtained with proper combination of cyclodextrins and simple sugars, such as trehalose.     

Reduction of tablet weight variability by optimizing paddle speed in the forced feeder of a high-speed rotary tablet press

Context: Tableting is a complex process due to the large number of process parameters that can be varied. Knowledge and understanding of the influence of these parameters on the final product quality is of great importance for the industry, allowing economic efficiency and parametric release.

Objective: The aim of this study was to investigate the influence of paddle speeds and fill depth at different tableting speeds on the weight and weight variability of tablets.

Materials and methods: Two excipients possessing different flow behavior, microcrystalline cellulose (MCC) and dibasic calcium phosphate dihydrate (DCP), were selected as model powders. Tablets were manufactured via a high-speed rotary tablet press using design of experiments (DoE). During each experiment also the volume of powder in the forced feeder was measured.

Results and discussion: Analysis of the DoE revealed that paddle speeds are of minor importance for tablet weight but significantly affect volume of powder inside the feeder in case of powders with excellent flowability (DCP). The opposite effect of paddle speed was observed for fairly flowing powders (MCC). Tableting speed played a role in weight and weight variability, whereas changing fill depth exclusively influenced tablet weight.

Conclusion: The DoE approach allowed predicting the optimum combination of process parameters leading to minimum tablet weight variability. Monte Carlo simulations allowed assessing the probability to exceed the acceptable response limits if factor settings were varied around their optimum. This multi-dimensional combination and interaction of input variables leading to response criteria with acceptable probability reflected the design space.     

In vitro characterization studies of self-microemulsified bosentan systems

Context: Bosentan is a poorly soluble drug and pose challenges in designing of drug delivery systems.

Objective: The objective of this study is to enhance the solubility, dissolution and shelf-life of bosentan by formulating it as S-SMEDDS capsules.

Materials and methods: Solubility of bosentan was tested in various liquid vehicles such as oils (rice bran and sunflower), surfactants (span 20 and tween 80) and co-surfactants (PEG 400 and propylene glycol) and microemulsions were developed. Bosentan was incorporated into appropriate microemulsion systems which were previously identified from pseudo ternary phase diagrams. Bosentan-loaded SMEDDS were evaluated for drug content, drug release, zeta potential, and droplet size. The selected liquid SMEDDS were converted into solid SMEDDS by employing adsorption and melt granulation. Solid SMEDDS were characterized for micromeritics and evaluated for drug content, drug release, and shelf-life.

Results: Isotropic systems R5, R13, S5, and S13 with submicron droplet size had exhibited 85.45, 94.12, 81.67, and 96.64% drug release, respectively. Solid SMEDDS of MR13 and AS13 formulations with rapid reconstitution ability, exhibited 84.85 and 86.74% of on par drug release. The formulations were physicochemically intact for 1.02 and 1.56 years.

Discussion: Liquid SMEDDS composed with PEG400 had displayed optimal characters. Solid SMEDDS had high-dissolution profiles than bosentan due to modification in the crystalline structure of drug upon microemulsification.

Conclusion: Thus, solid SMEDDS addressed the solubility, dissolution, and stability issues of bosentan and becomes an alternate for clinical convenience.     

Evaluation of the tamper-resistant properties of biphasic immediate-release/extended-release oxycodone/acetaminophen tablets

Context: Abuse potential of extended-release (ER) opioid tablets increases if tampering causes rapid opioid release.

Objective: To evaluate the susceptibility to tampering of biphasic immediate-release (IR)/ER oxycodone (OC)/acetaminophen (APAP) tablets compared with IR OC/APAP tablets.

Materials and methods: IR/ER OC/APAP and IR OC/APAP tablets were tested at room temperature and after heating, freezing and microwaving. Resistance to crushing was tested using manual and powered tools (e.g. spoons, mortar and pestle, blender, coffee grinder). Tampered tablets were tested for suitability for snorting, OC extraction in solvents and ease of drawing into a syringe. Dissolution of IR/ER OC/APAP in gastric fluid with and without ethanol was tested to determine the potential for facilitating precipitous release of opioid from the tablet.

Results: IR/ER OC/APAP tablets were more crush resistant than IR OC/APAP tablets. Heating, freezing and microwaving had no effect on crush resistance of IR/ER OC/APAP tablets. Although a mortar and pestle pulverized IR/ER OC/APAP tablets, upon contact with solvent, the powder formed a thick gel judged unsuitable for absorption through the nasal mucosa and could not be drawn into a syringe. In contrast, powder from crushed IR OC/APAP tablets dissolved readily, was judged suitable for snorting, and was easily drawn into a syringe. Dissolution of IR/ER OC/APAP tablets in gastric fluid was slowed by the addition of ethanol.

Discussion: IR/ER OC/APAP tablets are resistant to crushing and dissolution compared with IR OC/APAP tablets.

Conclusion: IR/ER OC/APAP tablets may have less potential for abuse involving tampering compared with IR OC/APAP tablets.     

Enhancing the solubility and masking the bitter taste of propiverine using crystalline complex formation

Context: Patient compliance can be reduced when bitter-tasting compounds, such as propiverine hydrochloride, are administered orally. Propiverine hydrochloride is an example of a drug with a bitter taste, used for the treatment of overactive bladders.

Objective: This study tested whether propiverine free base palatability and aqueous solubility could be improved by crystalline complex formation.

Materials and methods: We used 42 compounds, and found 9 new propiverine crystalline complexes. The properties and solubility of these complexes were studied using a range of techniques. A taste perception study was carried out using a taste sensor to evaluate the taste masking ability of the crystalline complex formation.

Results: The melting points of the crystalline complexes were higher than that of propiverine. The dissolution rates of the crystalline complexes in aqueous buffer solution (pH 6.8) and in purified water were much faster than that of propiverine. Propiverine salicylic acid crystalline complex had substantially less bitterness than propiverine hydrochloride, which was extremely bitter.

Discussion: The present findings indicated that crystalline complex formation provided an effective approach to enhancing propiverine solubility, and to masking its bitter taste.

Conclusion: Crystalline complex formation represents a useful and valuable technique for the preparation of orally disintegrating tablets and improving patient compliance, even for substances with bitter tastes.     

Composition specification of teicoplanin based on its estimated relative bioavailability

Context: Teicoplanin is a fermentative antibiotic consisting of several active components that contribute similarly to the antibacterial activity, but exhibit different pharmacokinetic properties. Differences in systemic exposure between batches of teicoplanin are possible within pharmacopeial specifications as the proportion of subcomponents may vary from batch to batch.

Objective: The aim of this paper is to study the possible modification of the present pharmacopeial specification for teicoplanin composition to ensure an a priori pharmacokinetic equivalence between all pharmacopoeial-compliant batches.

Methods: The expectable whole Area Under the Curve (AUC) of plasma levels of teicoplanin was predicted for different experimental batches and also for the theoretical extreme batches within pharmacopeial specifications. Calculations were done based on the AUC of each teicoplanin active subcomponent. Subsequently, the equivalence between a generic teicoplanin and a reference drug product was investigated by means of the ratio of AUCs.

Results: Batches under study, complying with current pharmacopoeial specifications, showed a maximum predicted difference in AUC slightly larger than 40%. The observed variability in teicoplanin compositions surpasses the conventional ±5% specification used for drugs obtained by chemical synthesis, but no 5% differences have been observed for any of the AUC means of the reference product when compared with the whole pooled data.

Discussion and conclusion: Alternative specifications of actives composition can be defined to ensure that all batches complying with the pharmacopoeia are inside ±10% interval between them.     

Determining osmotic pressure of drug solutions by air humidity in equilibrium method

Objective: To establish a new osmotic pressure measuring method with a wide measuring range.

Method: The osmotic pressure of drug solutions is determined by measuring the relative air humidity in equilibrium with the solution. The freezing point osmometry is used as a control.

Results: The data obtained by the proposed method are comparable to those by the control method, and the measuring range of the proposed method is significantly wider than that of the control method.

Conclusion: The proposed method is performed in an isothermal and equilibrium state, so it overcomes the defects of the freezing point and dew point osmometries which result from the heterothermal process in the measurement, and therefore is not limited to diluted solutions.     

Mechanical and electrical properties of electrospun CNT/PVDF nanofiber for micro-actuator applications

Electrospun polyvinylidene fluoride (PVDF)-containing carbon nanotubes (CNT) were prepared for use in fabricating actuator materials. Actuating displacement was measured in an electrochemical environment. The electrospun nanofibers were arranged using a drum-type collector, and morphology was investigated using a field emission-scanning electron microscope. The uniformity of dispersion of CNT in the PVDF nanofibers was monitored by electron probe X-ray micro-analysis. Tensile strength and electrical resistivity results were used as an indication of the state of alignment. The electrospun CNT/PVDF nanofiber sheets exhibited better mechanical and electrical properties in the arranged direction. The efficiency and electrical capacities of electrospun CNT/PVDF nanofiber sheet were compared with those of cast PVDF sheets for use in actuator applications in electrochemical environments. The electrospun CNT/PVDF nanofiber sheets exhibited much better actuator performance than PVDF sheets, which are attributed to their superior electrical properties.

Highlights

(1) The interfacial durability of CNT/PVDF nanofibers was enhanced to increase contact area by reinforcing CNT.

(2) The efficiency of CNT/PVDF actuators was improved due to interfacial properties.

(3) Thin thickness drum-type collector was made to enhance nanofiber alignment.

(4) The arranged CNT/PVDF nanofibers exhibited better mechanical and actuating displacements.     

Processing of pharmaceutical materials by electrospraying under reduced pressure

Context: Electrospraying was used in drug particle production.

Objective: The aim of the research was to evaluate the possibilities to produce drug particles with desired pharmaceutical properties by electrospraying. In particular, the effect of drying pressure on particle properties was studied.

Materials and methods: A poorly water soluble model drug (budesonide) was dissolved in chloroform, and the solution was atomized by electrospraying. Following this, the charged droplets were neutralized and dried in a drying chamber. The pressure in the drying chamber was varied. The dried particles were collected and analyzed.

Results: The pressure reduction had a slight impact on particle size distribution. The particles produced in reduced pressure turned out to be notably more porous than the particles produced in atmospheric pressure. The pressure reduction also affects the degree of crystallinity of the product. The dissolution of the particles produced in reduced pressures was faster to a certain extent than that of the particles produced in atmospheric pressure.

Discussion and conclusions: A setup for electrospraying materials in a reduced pressure was presented. The pressure reduction had a notable impact on particle morphology. The possibilities to tailor the particle properties during electrospraying were studied.     

Potential technique for tiny crystalline detection in lycopene-loaded SLN and NLC development

Context: The advantage of solid nanocarriers like solid lipid nanoparticles (SLN) or nanostructured lipid carriers (NLC) is related to some degree of crystalline characteristics of the lipid. However, the detection of tiny content of crystalline structure in such nanoparticles is difficult.

Objective: The aim of this study was to explore a potential method for detection of low degree of crystalline characteristics of lycopene-loaded SLN and NLC.

Methods: Crystalline characteristics investigation was done by polarized light microscope (PLM), differential scanning calorimeter (DSC), X-ray diffractometer (XRD) and transmission electron microscope (TEM).

Results and discussion: It was found that high crystalline characteristics as anisotropic molecular organization crystal of pure orange wax and lycopene could be investigated by PLM, DSC and WAXS. Low crystallinity of lycopene-loaded SLN and NLC could not be detected by those techniques. Electron diffraction mode of TEM showed potential detection of tiny crystalline characteristics of such systems. The diffraction pattern of lycopene-loaded SLN and NLC exhibited obvious zero order laue zone indicating an isotropic fine grained polycrystalline of the nanoparticles.

Conclusion: It could be concluded that TEM is a promising method for detection of low-level crystallinity of solid nanocarriers.     

RGD peptide targeted lipid-coated nanoparticles for combinatorial delivery of sorafenib and quercetin against hepatocellular carcinoma

Context: Combination therapies provide a potential solution to address the tumor heterogeneity and drug resistance issues by taking advantage of distinct mechanisms of action of the multiple therapeutics.

Objective: To design arginine-glycineaspartic acid (RGD) modified lipid-coated nanoparticles (NPs) for the co-delivery of the hydrophobic drugs against hepatocellular carcinoma (HCC).

Materials and methods: RGD modified lipid-coated PLGA NPs were developed for the targeted delivery of both sorafenib (SRF) and quercetin (QT) (RGD-SRF-QT NPs). Chemical–physical characteristics and release profiles were evaluated. In vitro cell viability assays were carried out on HCC cells. In vivo antitumor efficacies were evaluated in HCC animal model.

Results and discussion: The combination of SRF and QT formulations was more effective than the single drug formulations in both NPs and solution groups. RGD-SRF-QT NPs achieved the most significant tumor growth inhibition effect in vitro and in vivo.

Conclusion: The resulting NPs could provide a promising platform for co-delivery of multiple anticancer drugs for achievement of combinational therapy and could offer potential for enhancing the therapeutic efficacy on HCC.     

Investigations on the transfer of porphyrin from o/w emulsion droplets to liposomes with two different methods

Context: Due to their small particle size, colloidal fat emulsions are suitable for intravenous administration. In order to obtain information on their potential in vivo performance, it is important to find a simple and effective in vitro assay to evaluate the drug release behavior of such particles.

Objective: Two in vitro methods were studied to measure the transfer of a lipophilic model drug from colloidal o/w emulsion droplets (donor) to liposomes (acceptor), which serve as model membranes mimicking cell membranes in the body. In the first method (column method) the acceptor particles were neutral unilamellar vesicles. In the second method (MLV method), multilamellar vesicles (MLV) were used as acceptor.

Materials and methods: The donor nanoemulsions were prepared by high pressure homogenization. Z-average particle size, polydispersity index and zeta potential were determined.

Results: The transfer of porphyrin was moderate to the acceptor MLV and rapid to the acceptor unilamellar vesicles. The amount of transferred porphyrin at the end of the experiment depended on the transfer method and the donor/acceptor ratio. With both acceptors the transfer of porphyrin stopped at a concentration lower than the theoretical equilibrium values.

Discussion: Many factors such as acceptor particle size and donor to acceptor lipid molar ratio affect the drug transfer from the donor particles to the different acceptors.

Conclusion: Both methods seem to be suitable to study the drug transfer from such colloidal emulsion and the use of lipophilic acceptor particles is a better approach to the conditions in blood.     

Evaluation of superabsorbent linseed-polysaccharides as a novel stimuli-responsive oral sustained release drug delivery system

Context: Advancement in technology has transformed the conventional dosage forms to intelligent drug delivery systems. Such systems are helpful for targeted and efficient drug delivery with minimum side effects. Drug release from these systems is governed and controlled by external stimuli (pH, enzymes, ions, glucose, etc.). Polymeric biomaterial having stimuli-responsive properties has opened a new area in drug delivery approach.

Objective: Potential of a polysaccharide (rhamnogalacturonan)-based hydrogel from Linseeds (Linum usitatissimum L.) was investigated as an intelligent drug delivery material.

Materials and methods: Different concentrations of Linseed hydrogel (LSH) were used to prepare caffeine and diacerein tablets and further investigated for pH and salt solution-responsive swelling, pH-dependent drug release, and release kinetics. Morphology of tablets was observed using SEM.

Results: LSH tablets exhibited dynamic swelling–deswelling behavior with tendency to swell at pH 7.4 and in deionized water while deswell at pH 1.2, in normal saline and ethanol. Consequently, pH controlled release of the drugs was observed from tablets with lower release (<10%) at pH 1.2 and higher release at pH 6.8 and 7.4. SEM showed elongated channels in swollen then freeze-dried tablets.

Discussion: The drug release was greatly influenced by the amount of LSH in the tablets. Drug release from LSH tablets was governed by the non-Fickian diffusion.

Conclusions: These finding indicates that LSH holds potential to be developed as sustained release material for tablet.     

A study of photostability and compatibility of the anti-chagas drug Benznidazole with pharmaceutics excipients

Context: Benznidazole (BNZ) is an antiparasitic with trypanocidal properties for the etiological treatment of Chagas disease since 1973. Monitoring the stability of this drug is one of the most effective methods of assessment, forecasting and prevention of problems related to quality product.

Objective: To investigate the direct and indirect photodegradation of BNZ and to evaluate the interference of the excipients used in the forms dosage solid as well as to shed light on the chemical structure of the degradation products obtained.

Materials and methods: To perform this work we adopted the “ICH Harmonised Tripartite Guideline: Photostability Testing of New Drug Substances and Products Q1B” (Guideline Q1B). We used benzonidazole (BNZ) (N-benzil-2-(2-nitroimidazol-1-il) acetamide) (LAFEPE®, Recife, Brazil) and various excipients; beyond high-performance liquid chromatography (HPLC), differential scanning calorimetry (DSC), infrared spectroscopy (IR) and mass spectrometry/mass spectrometry (MS/MS). The indirect photodegradation of BNZ was carried out using physical mixtures with 13 pharmaceutical excipients commonly used in the preparation of solid dosage forms.

Results: HPLC and MS/MS techniques were selected for the identification of two photoproducts (PPs) and photoreactions found in direct and indirect tests with the microcrystalline cellulose, considered a critical excipient.

Discussion: Despite variations in the infrared spectrometry, differential scanning calorimetry and differential thermogravimetry curves, these techniques are not conclusive since the study of photodegradation of the drug caused decay of 30%, according to the ICH.

Conclusions: The results show that BNZ only undergoes direct photodegradation, since no new PPs were found for a combination of the drug and excipients.     

A thermoplastic elastomer patch matrix for traditional Chinese medicine: design and evaluation

Objective: To design and evaluate a novel pressure sensitive adhesive (PSA) patch containing traditional Chinese medicine (TCM) using styrene–isoprene–styrene (SIS) copolymer.

Method: A mixture D-optimal design with ternary response surface diagram was employed in the optimization process. The proportions of SIS copolymer, tackifying resin and plasticizer were selected as the independent variables while tack force, peel strength of the patch and skin penetrability of methyl salicylate were selected as the dependent variables. The optimized patch was then evaluated including in vivo absorption, pharmacological activities and skin irritation, by comparing with a commercial patch based on natural rubber.

Results: The optimized patch, which comprised 30.0% SIS copolymer, 26.6% tackifying resin and 43.4% plasticizer, was superior to commercial patch in skin permeation, pharmacological activities and skin biocompatibility.

Conclusion: SIS copolymer was a suitable substitute to natural rubber in producing patches containing TCM formula.     

Preparation and evaluation of posaconazole-loaded enteric microparticles in rats

Objectives: Posaconazole (POS) is an antifungal compound which has a low oral bioavailability. The aim of this study was to prepare POS enteric microparticles to enhance its oral bioavailability.

Methods: POS enteric microparticles were prepared with hypromellose acetate succinate (HPMCAS) via the spray drying method. The solvent mixtures of acetone and ethanol used in the preparation of the microparticles were optimized to produce the ideal POS enteric microparticles. Multivariate data analysis using a principal component analysis (PCA) was used to find the relationship among the HPMCAS molecular characteristics, particle properties and drug release kinetics from the spray dried microparticles.

Key findings: The optimal spray solvent mixtures were critical to produce the POS microparticles with the defined polymer entanglement index, drug surface enrichment, particle size and drug loading. The HPMCAS molecular characteristics affected the microscopic connectivity and diffusivity of polymer matrix and eventually influenced the drug release behavior, and enhanced the bioavailability of POS.

Conclusions: These studies suggested that the selection of suitable solvent mixtures of acetone and ethanol used in the spray drying of the microparticles was quite important to produce the entangled polymer structures with preferred polymer molecular properties of polymer coiling, overlap concentration and entanglement index. Additional studies on particle size and surface drug enrichment eventually produced HPMCAS-based enteric microparticles to enhance the oral bioavailability of POS.     

To enhance the efficiency of nefopam transdermal iontophoresis by using a novel method based on ion-exchange fiber

Background: In the system of the iontophoresis, the external electric field made the ions in the system moving directly, then, the current was generated. Because the current was contributed by all ions in the system, and the small ions with large amount often had higher conductibility than the drug ions, the fraction of the total current contributed by the drug ions was often low. It was the main reason for the generally low efficiency of the transdermal iontophoretic drug delivery.

Objectives: The objective of this study was to find a novel method to increase the fraction of the total current contributed by the drug ions so as to enhance the drug's iontophoretic delivery.

Method: Iontophoretic transport of nefopam hydrochloride solution and iontophoretic transport of nefopam assisted by ion-exchange materials, including ion-exchange resin, ion-exchange membrane and ion-exchange fiber, across the rat skin were investigated.

Results: Both in vitro and in vivo iontophoretic transport experiments showed that the efficiency of the nefopam-fiber iontophoretic system for nefopam permeating across rat skin was the highest among four iontophoretic systems (nefopam solution, nefopam-resin, nefopam-membrane and nefopam-fiber).

Conclusion: The results of this study suggested that there was an enhancement of nefopam across rat skin by ion-exchange fibers in ion-exchange fibers assisted iontophoresis. The present study has demonstrated the potential of a new approach of using ion-exchange fibers to improve the efficiency of the transdermal iontophoresis for cationizable drugs.     

Enhancing the bioavailability of magnolol in rabbits using melting solid dispersion with polyvinylpyrrolidone

Objective: Preparation of magnolol-loaded amorphous solid dispersion was investigated for improving the bioavailability.

Materials and methods: A solid dispersion of magnolol was prepared with polyvinylpyrrolidone K-30 (PVP) by melting method, and the physical properties were characterized by using differential scanning calorimetry, powder X-ray diffractometry, Fourier transformation-infrared spectroscopy and scanning electron microscope. In addition, dissolution test was also performed. Subsequently, the bioavailability of magnolol pure compound, its physical mixture and solid dispersion were compared in rabbits. The blood samples withdrawn via marginal ear vein at specific time points were assayed by HPLC method.

Results: Oral administration of the solid dispersion of magnolol with PVP significantly increased the systemic exposures of magnolol and magnolol sulfates/glucuronides by 80.1% and 142.8%, respectively, compared to those given with magnolol pure compound.

Conclusion: Magnolol-loaded amorphous solid dispersion with PVP has demonstrated enhanced bioavailability of magnolol in rabbits.