The Fabrication, Drug Loading, and Release Behavior of Porous Mannitol.

Porous materials are widely used as an effective strategy for the solubilization of insoluble drugs. In order to improve the solubility and bioavailability of low water-solubility drugs, it is necessary to prepare porous materials. Mannitol is one of the most popular excipients in food and drug formulations. In this study, porous mannitol was investigated as a drug carrier for low water solubility drugs. Its fabrication, drug loading, and drug release mechanisms were investigated. Porous mannitol was fabricated using the co-spray-antisolvent process and utilizing polyvinylpyrrolidone K30 (PVP K30) as the template agent. Porous mannitol particles were prepared by changing the proportion of the template agent, spraying the particles with mannitol, and eluting with ethanol in order to regulate their pore structure. In subsequent studies, porous mannitol morphology and characteristics were determined systematically. Furthermore, curcumin and ibuprofen, two poorly water-soluble drugs, were loaded into porous mannitol, and their release profiles were analyzed. The results of the study indicated that porous mannitol can be prepared using PVP K30 as a template and that the amount of template agent can be adjusted in order to control the structure of the porous mannitol. When the template agent was added in amounts of 1%, 3%, and 5%, the mannitol pore size increased by 167.80%, 95.16%, and 163.98%, respectively, compared to raw mannitol. Molecular docking revealed that mannitol and drugs are adsorbents and adhere to each other by force interaction. The cumulative dissolution of curcumin and ibuprofen-loaded porous mannitol reached 69% and 70%, respectively. The release mechanism of curcumin and ibuprofen from drug-loaded mannitol was suitable for the Korsmeyer-Peppas kinetic model. In summary, the co-spray-antisolvent method proved effective in fabricating porous materials rapidly, and porous mannitol had a remarkable effect on drug solubilization. The results obtained are conducive to the development of porous materials.

A review on the calculation and application of lignin Hansen solubility parameters.

Hansen solubility parameters (HSPs) play a critical role in the majority of processes involving lignin depolymerization, separation, fractionation, and polymer blending, which are directly related to dissolution properties. However, the calculation of lignin HSPs is highly complicated due to the diversity of sources and the complexity of lignin structures. Despite their important role, lignin HSPs have been undervalued, attracting insufficient attention. This review summarizes the calculation methods for lignin HSPs and proposes a straightforward method based on lignin subunits. Furthermore, it highlights the crucial applications of lignin HSPs, such as identifying ideal solvents for lignin dissolution, selecting suitable solvents for lignin depolymerization and extraction, designing green solvents for lignin fractionation, and guiding the preparation of lignin-based composites. For instance, leveraging HSPs to design a series of solvents could potentially achieve sequential controllable lignin fractionation, addressing issues of low value-added applications of lignin resulting from poor homogeneity. Notably, HSPs serve as valuable tools for understanding the dissolution behavior of lignin. Consequently, we expect this review to be of great interest to researchers specializing in lignin and other macromolecules.

Ecological restoration affects the dynamic response of alkaline minerals dissolution in bauxite residue.

Regulating alkalinity is the key process to eliminating environmental risk and implementing sustainable management of bauxite residue. Nevertheless, continuous release of free alkali from the solid phase (mainly sodalite and cancrinite) is a major challenge for long-term stability of alkalinity in amended bauxite residue. In order to understand the dissolution behavior of sodalite and cancrinite, their dissolution kinetics under simulated pH conditions of 8, 9 and 10 were investigated. Additionally, PHREEQC software and shrinking core model (SCM) were employed to analyze the release pattern of saline ions. The results revealed that the ratio of Na/Si and Na/Al values exhibited greater stability in sodalite than in cancrinite. The dissolution of elemental Na, Si, and Al in sodalite and cancrinite was matched with non-chemometric characteristics. The kinetic calculations by the shrinking core model (SCM) suggested that both sodalite and cancrinite exhibited slow dissolution kinetics, and their dissolution processes belong to internal diffusion control and external diffusion control, respectively. pH controlled the dissolution kinetic rates of sodalite and cancrinite mainly by changing their coupled dissolution-precipitation processes. More importantly, these findings can predict the change of alkaline components accurately, thus facilitating the implementation of efficient alkalinity regulation strategies for the ecological restoration of bauxite residue disposal areas.

Influence Mechanism of Drug-Polymer Compatibility on Humidity Stability of Crystalline Solid Dispersion.

This study investigates the influence of humidity on the dissolution behavior and microstructure of drugs in crystalline solid dispersions (CSDs). Using Bifonazole (BFZ) as a model drug, CSDs were prepared through spray drying with carriers such as Poloxamer 188 (P188), Poloxamer 407 (P407), and polyethylene glycol 8000 (PEG8000). The solubilization effect and mechanism were initially evaluated, followed by an examination of the impact of humidity (RH10%) on the dissolution behavior of CSDs. Furthermore, the influence of humidity on the microstructure of CSDs was investigated, and factors affecting the humidity stability of CSDs were summarized. Significant enhancements in the intrinsic dissolution rate (IDR) of BFZ in CSDs were observed due to changes in crystalline size and crystallinity, with the CSD-P188 system exhibiting the best performance. Following humidity treatment, the CSD-P407 system demonstrated the least change in the IDR of BFZ, indicating superior stability. The CSD-P407 system was followed by the CSD-P188 system, with the CSD-PEG8000 system exhibiting the least stability. Further analysis of the microstructure revealed that while humidity had negligible effects on the crystalline size and crystallinity of BFZ in CSDs, it had a significant impact on the distribution of BFZ on the CSD surface. This can be attributed to the water's potent plasticizing effect, which significantly alters the molecular mobility of BFZ. Additionally, the compatibility of the three polymers with BFZ differs, with CSD-P407 > CSD-P188 > CSD-PEG8000. Under the continuous influence of water, stronger compatibility leads to lower molecular mobility and more uniform drug distribution on the CSD surface. Enhancing the compatibility of drugs with polymers can effectively reduce the mobility of BFZ in CSDs, thereby mitigating changes caused by water and ultimately stabilizing the surface composition and dissolution behavior of drugs in CSDs.

Structural Characteristics and Properties of Redissolved Silk Sericin.

Silk sericin has garnered the attention of researchers as a promising biomaterial because of its good biocompatibility and high water retention. However, despite its useful properties, the poor storage stability of sericin has restricted its extensive use in biorelated applications. This study extracted sericin from silkworm cocoon, dried and stored it as a solid, and then dissolved it in hot water conditions to improve the storage stability of sericin for its use. The dissolution behavior of the extracted sericin solids was examined in conjunction with the structural characteristics and properties of dissolved sericin. Consequently, the results of solution viscosity, gel strength, crystallinity index, and thermal decomposition temperature indicated that the molecular weight (MW) of the dissolved sericin remained constant until a dissolution time of 5 min, following which deterioration was observed. The optimum condition of dissolution of the extracted sericin solid was 5 min at 90 °C. Conclusively, the extracted sericin could be stored in a dry state and dissolved to prepare redissolved sericin aqueous solution with the same MW as extracted sericin, thereby improving the storage stability of the sericin aqueous solution.

Tailored ASD destabilization - Balancing shelf life stability and dissolution performance with hydroxypropyl cellulose.

Amorphous solid dispersion (ASD) formulations are preferred enabling formulations for poorly water soluble active pharmaceutical ingredients (API) as they reliably enhance the dissolution behavior and solubility. Balancing a high stability against unwanted transformations such as crystallization and amorphous phase separation during storage on the one hand and optimizing the dissolution behavior of the formulation (high supersaturation and maintenance for long time) on the other hand are essential during formulation development. This study assessed the potential of ternary ASDs (one API and two polymers) containing the polymers hydroxypropyl cellulose together with poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) or hydroxypropyl cellulose acetate succinate to stabilize the amorphously embedded APIs fenofibrate and simvastatin during storage and to enhance the dissolution performance. Thermodynamic predictions using the PC-SAFT model revealed for each combination of polymers the optimal polymer ratio, maximum API load that is thermodynamically stable as well as miscibility of the two polymers. The stability predictions were validated by three months enduring stability tests, followed by a characterization of the dissolution behavior. The thermodynamically most stable ASDs were found to be the ASDs with deteriorated dissolution performance. Within the investigated polymer combinations, physical stability and dissolution performance opposed each other.

Study on the regulation mechanism of effective glass transition temperature on the crystallization of crystalline solid dispersion.

The focus of this investigation was to determine the mechanism of effective glass transition temperature (TgE) on the crystallization behavior and microstructure of drugs in crystalline solid dispersion (CSD). CSDs were prepared by rotary evaporation using ketoconazole (KET) as a model drug and the triblock copolymer poloxamer 188 as a carrier. The pharmaceutical properties of CSDs, such as crystallite size, crystallization kinetics, and dissolution behavior, were investigated to provide a foundation for studying the crystallization behavior and the microstructure of drugs in CSDs. According to classical nucleation theory, the relationship of treatment temperature-drug crystallite size-TgE of CSD was investigated. Voriconazole, a compound that is structurally similar to KET but with different physicochemical properties, was used to verify the conclusions. The dissolution behavior of KET was significantly enhanced compared to the raw drug due to smaller crystallite size. Crystallization kinetic studies revealed a two-step crystallization mechanism for KET-P188-CSD, in which P188 crystallized first and KET crystallized later. When the treatment temperature was near TgE, the drug crystallite size was smaller and more numerous, which suggests nucleation and slow growth. With the increase of temperature, the drug changed from nucleation to growth, and the number of crystallites decreased and the size of the drug increased. This result suggests it is possible to prepare CSDs with higher drug loading and smaller crystallite size by adjusting the treatment temperature and TgE, so as to maximize the drug dissolution rate. The VOR-P188-CSD maintained a relationship between treatment temperature, drug crystallite size, and TgE. The findings of our study demonstrate that TgE and the treatment temperature can be used to regulate the drug crystallite size and improve the drug solubility and dissolution rate.

Solubility Determination and Comprehensive Analysis of the New Heat-Resistant Energetic Material TNBP.

To improve the crystal quality of 4,8-bis(2,4,6-trinitrophenyl)difurazolo [3,4-b:3',4'-e] pyrazine (TNBP), the solubility of TNBP in organic solvents (six pure and four mixed solvents) was determined by the laser monitoring technique from 293.15 to 353.15 K. The results showed that the solubility was positively correlated with the increase in the experimental temperature and the main solvent content, except for the co-solvent phenomenon in the DMSO + ethyl acetate solvent mixture. To explain the dissolution behavior of TNBP, the KAT-SER model was analyzed for pure solvent systems, and it was found that hydrogen bonding alkalinity and self-cohesiveness were the main influencing factors. The free energy of solvation and radial distribution function of TNBP in mixed solvents were also obtained by molecular dynamics simulation, and the effect of solute-solvent and solvent-solvent interactions on the solubility trend was analyzed. The experimental data were correlated using three empirical equations (van't Hoff equation, modified Apelblat equation, and λh equation), and the deviation analysis showed the good applicability of the modified Apelblat model. Furthermore, the dissolution of TNBP was heat-absorbing and not spontaneous, according to the thermodynamic characteristics estimated by the van't Hoff equation.

The preparation, characterization, and application of porous core-shell composite particles produced with laboratory-scale spray dryer.

OBJECTIVE: To prepare porous core-shell composite particles (PCPs) in order to improve the flowability and compactibility of powder materials for direct compaction (DC), as well as the dissolution of tablets. SIGNIFICANCE: The results obtained are meaningful to boosting the development and further research of PCPs on DC. Methods: In this study, hydroxypropyl methylcellulose (HPMC E3) and polyvinylpyrrolidone (PVP K30) were selected as shell materials, the Xiao Er Xi Shi formulation powder (XEXS) was used as the core materials, ammonium bicarbonate (NH4HCO3), and sodium bicarbonate (NaHCO3) were employed as pore-forming agent. Using co-spray drying method to prepare composite particles (CPs). Then, the physical properties and comparison between different CPs were characterized comprehensively. Finally, the different CPs were directly compacted as tablets to explore the effect on the dissolution behavior of DC tablets, respectively. RESULTS: (i) The XEXS PCPs were prepared successfully by co-spray drying, and the yield of PCPs is almost 80%; (ii) The TS values of PCP-X-P-Na, PCP-X-P-NH4, PCP-X-H-Na and PCP-X-P-Na were 5.70, 7.56, 3.98, and 6.88 times higher than that of raw material (X); (iii) The disintegration time of PCPs tablets decreased 10-25% when compared with CPs tablets; (iv) The values of Carr's index (CI), Hausner ratio (HR), Caking strength (CS), and Cohesion index (CoI) of PCP-X-H-NH4 were 19.16%, 19.29%, 40.14%, and 6.39% lower than that of X, respectively. CONCLUSIONS: The PCPs prepared by co-spray drying did improve the flowability and compactibility of powder, as well as the dissolution of tablets.

The accumulation and toxicity of ZIF-8 nanoparticles in Corbicula fluminea.

Metal-organic frameworks (MOFs) are promising new materials that have been intensively studied and possibly applied to various environmental remediation. However, little is known about the fate and risk of MOFs to living organisms in the water environment. Here, the toxic effects of ZIF-8 nanoparticles (NPs) on benthic organisms were confirmed by sub-chronic toxicity experiments (7 and 14 days) using Corbicula fluminea as the model organism. With exposure doses ranging from 0 to 50 mg/L, ZIF-8 NPs induced oxidative stress behaviors similar to the hormesis effect in the tissues of C. fluminea. The oxidative stress induced by ZIF-8 NPs and the released Zn2+ was the crucial cause of the toxic effects. Besides, we also found that the ZIF-8 NPs and dissolved Zn2+ may result in different mechanisms of toxicity and accumulation depending on the dosages. The Zn2+ release rate of ZIF-8 NPs was high at low dosages, leading to a higher proportion of Zn2+ taken up by C. fluminea than the particulate ZIF-8. Conversely, at high dosages, C. fluminea mainly ingested the ZIF-8 NPs and resulted in increased mortality. The results have important implications for understanding the fate and biological effects of ZIF-8 in natural aquatic environments.

[Dissolution test and evaluation of Guizhi Fuling Capsules].

Because of the complex components, simple content determination can hardly reflect the overall quality of Guizhi Fuling Capsules. Therefore, it is necessary to carry out a multi-component dissolution test. The variability of quality among different batches of products from different manufacturers is a common problem of Chinese medicine solid preparations. To comprehensively control the quality of Guizhi Fuling Capsules, we studied the dissolution behaviors of 7 index components in the capsules under different conditions, and investigated the consistency of dissolution behaviors among different batches of products from the same manufacturer. The basket method of general rule 0931 in Chinese Pharmacopoeia was adopted, and the rotating speeds were set at 50, 75, and 100 r·min~(-1), respectively. The hydrochloric acid solution(pH 1.2), acetate buffer solution(pH 4.0), pure water, and phosphate buffer solution(pH 6.8) were used as the dissolution media. Automatic sampling was carried out at the time points of 5, 10, 20, 30, 45, and 60 min, respectively. The cumulative dissolution of 7 index components was measured through ultra-performance liquid chromatography(UPLC). The difference factor f_1 and similarity factor f_2 were calculated to comprehensively evaluate the similarity of the dissolution curves among 8 batches of Guizhi Fuling Capsules, and a variety of dissolution and release equations were fitted. The results showed that multiple components had faster dissolution rates at higher rotating speed and in hydrochloric acid medium. The 8 batches of Guizhi Fuling capsules showed the average f_1 value lower than 15 and the average f_2 value higher than 50, which indicated that different batches of products had similar dissolution behaviors. Most components had synchronous dissolution behaviors and similar release cha-racteristics. This study provides a reference for the quality consistency evaluation among batches, processing optimization, and dosage form improvement of Guizhi Fuling Capsules.

Atazanavir-Loaded Crosslinked Gamma-Cyclodextrin Nanoparticles to Improve Solubility and Dissolution Characteristics.

Objectives: Atazanavir sulfate (AS), a Biosafety Cabinet (BCS) class II antiretroviral drug, shows dissolution rate-limited bioavailability, therefore, it is necessary to improve its solubility and oral bioavailability. The present investigation is intended to improve the aqueous solubility by developing AS-loaded nanoparticles (ASNPs). Additionally, the immediate release formulation of AS capsules has gastrointestinal side effects such as nausea and abdominal pain, cardiovascular side effect, e.g. abnormal cardiac conduction, toxic effects on kidney and liver such as nephrolithiasis, hyperbilirubinemia, and jaundice. Therefore, ASNPs were designed to release the drug slowly for 12 h, so that these side effects could be reduced. Materials and Methods: ASNPs were prepared using gamma-cyclodextrin (γ-CD) and the crosslinker dimethyl carbonate were characterized by differential scanning calorimetry (DSC) and X-ray diffraction (XRD) to check the crystal characteristics of AS upon entrapment in NPs. Entrapment efficiency (EE), particle size, morphology, solubility, and dissolution behavior were also determined. Results: EE%, particle size, and zeta potential varied from 14.38 ± 0.16 to 75.97 ± 0.28%, 65.4 ± 1.25 nm to 439.6 ± 2.21 nm, and 28.3 ± 0.1 mV to 41.0 ± 0.3 mV, respectively. XRD and DSC confirmed the transformation of the crystalline AS to amorphous in NPs. There was 11.717 folds rise in AS solubility in water from NPs. The formulation having AS: γ-CD, 1:1 at 10 mg/mL, depicted 88.55 ± 0.58, 91.23 ± 0.80, and 86.8 ± 0.65% drug release in water, acid buffer, and phosphate buffer, respectively, in 12 h. Conclusion: Solubility enhancement could be attributed to the decrease in crystallinity of atazanavir, when dispersed in NPs.

Molecular simulations of the effects of substitutions on the dissolution properties of amorphous cellulose acetate.

The dissolution behavior of cellulose acetate (CA) is an extremely important property in its extensive applications and preparation of derivatives. In this paper, we proposed a molecular model building strategy to construct amorphous CA with various substituent distributions (different degrees of substitution and substitution positions). A protocol combing molecular dynamics simulation and density functional theory (DFT) was applied to systematically investigate the dissolution behavior of CAs, and the structural properties of CAs. The reduced cohesive energy and polarity of CAs caused by the increase in substituents would enhance its solubility. The interaction of solvent molecules and CAs and the diffusion of solvent molecules in CAs have a synergistic effect on the dissolution of CAs. The diffusion coefficient is the primary factor affecting the solubility. Moreover, substituents at different positions of the anhydroglucose units along the CAs chains would produce different steric hindrance effects, which in turn affect the dissolution behavior.

Dissolution behavior of representative elements from red mud (RM) by leaching with titanium white waste acid (TWWA).

Titanium white waste acid (TWWA) was used to dissolve the representative elements from red mud (RM) to achieve the goal of "treating waste with waste." The leaching parameters on the leaching efficiency of Na, Sc, and Al were investigated, in which the analysis of XRD and SEM-EDS on RM and leaching residue was performed. The leaching kinetics of Na, Sc, and Al was studied with unreacted shrinking core model (USCM). The results show that the dealkalization efficiency was close to 100%, and the leaching efficiency of Sc and Al was 82% and 75%, respectively. Cancrinite was dissolved from RM, and then the elements such as Na, Al, and Ca reacted with H2SO4 of TWWA. Na existed in the leaching liquor in the form of ions. Ca reacted with sulfuric acid to form anhydrite, which existed in the leaching residue. The particles of RM became smaller and dispersed with each other by acid leaching. The leaching apparent activation energy of Na, Sc, and Al was 4.947 kJ/mol, 6.361 kJ/mol, and 31.666 kJ/mol, respectively. The leaching kinetic equation of Na, Sc, and Al was 1 - (1 - a)2/3 = 0.084·exp[- 595.05/T]·t by external diffusion, 1 - 2a/3 - (1 - a)2/3 = 0.021·exp[- 765.16/T]·t by internal diffusion, and ln(1 - a)/3 + (1 - a)-2/3 - 1 = 67.12·exp[- 3808.8/T]·t by joint action, respectively.

Dissolution behavior of arabinoxylan from sugarcane bagasse in tetrabutylammonium hydroxide aqueous solution.

Arabinoxylan is one of the main components of xylan-rich hemicellulose of sugarcane bagasse. The study on the dissolution behavior of arabinoxylan from sugarcane bagasse (AXSB) is beneficial to its efficient utilization. The dissolution behavior of AXSB in a 50% TBAH aqueous solution was investigated by small angle X-ray scattering and rheological methods. SAXS analysis showed that the radius of gyration (Rg) of AXSB is between 8.5 nm and 21.6 nm, and Rg has a larger value with the rising AXSB concentration. Rheological measurements showed that AXSB is completely dissolved in TBAH aqueous solution at low concentration, aggregating after reaching a certain concentration. The estimated critical concentration is approximately 0.033 g mL-1. The rheological curves at the high concentration indicated shear thinning behavior, causing the failure of the Cox-Merz rule. The storage modulus grows gradually with the increasing AXSB concentration, inferring the probable formation of AXSB aggregation in TBAH aqueous solution.

The Novel Use of PVP K30 as Templating Agent in Production of Porous Lactose.

It is necessary to prepare porous lactose in order to improve the dissolution behavior of insoluble active ingredient. In this study, polyvinylpyrrolidone K30 (PVP K30) was firstly utilized as a templating agent with different use levels in preparing porous lactose. Then, the physical properties were profoundly characterized. Finally, the porous lactose was also employed as a health functional food/drug carrier to explore the effect on the dissolution behavior of curcumin. The results confirmed that (i) porous lactose was successfully prepared using PVP K30 as templating agent; (ii) PVP K30 significantly improved the yield of lactose in the spray drying; (iii) the improved powder properties of porous lactose were more conducive to the downstream operating process for the preparation of health functional food or drug; and (iv) the porous lactose significantly improved the dissolution behavior of curcumin. Therefore, the results obtained are beneficial to boosting the development of porous materials.

Dissolution magnitude and kinetics of ZnO nanoparticles mediated by water are dependent on O vacancy abundance: The environmental implications.

Metal oxide nanoparticles (NPs) dissolution in water environment is an important issue with regard to their environmental behaviors. The metal ion dissolves from surface defective site, but the effect of defect abundance remains largely unknown. This study aims to reveal this effect using ZnO NPs and O vacancy as the model system. The abundance of O vacancy is modulated by using different precursors and changing calcination atmosphere and temperature. X-ray photoelectron spectroscopy characterization shows that surface O vacancy abundance is effectively modulated to be distributed in a wide range from 15.3% to 41.8%. The deviation of O/Zn mole-ratio from 1.00 is used to denote O vacancy abundance in the bulk crystal, and the deviation reaches up to 0.32. Experiments show that the kinetics and magnitude of ZnO NPs dissolution vary in H2O, which are highly dependent on O vacancy abundance. In comparison, the specific surface area and aggregation state take minor roles. Particularly, Zn2+ dissolution rate in the first hour is more linearly correlated with surface O vacancy abundance than with specific surface area. Defects and their abundances should thus be co-considered with other physicochemical properties to fully understand the dissolution behaviors of metal oxide NPs in water environment. This study is of significance in comprehensively assessing and predicting the environmental risk of metal oxide NPs.

Structures and Dissolution Behaviors of Quaternary CaO-SrO-P2O5-TiO2 Glasses.

Calcium phosphate glasses have a high potential for use as biomaterials because their composition is similar to that of the mineral phase of bone. Phosphate glasses can dissolve completely in aqueous solution and can contain various elements owing to their acidity. Thus, the glass can be a candidate for therapeutic ion carriers. Recently, we focused on the effect of strontium ions for bone formation, which exhibited dual effects of stimulating bone formation and inhibiting bone resorption. However, large amounts of strontium ions may induce a cytotoxic effect, and there is a need to control their releasing amount. This work reports fundamental data for designing quaternary CaO-SrO-P2O5-TiO2 glasses with pyro- and meta-phosphate compositions to control strontium ion-releasing behavior. The glasses were prepared by substituting CaO by SrO using the melt-quenching method. The SrO/CaO mixed composition exhibited a mixed cation effect on the glassification degree and ion-releasing behavior, which showed non-linear properties with mixed cation compositions of the glasses. Sr2+ ions have smaller field strength than Ca2+ ions, and the glass network structure may be weakened by the substitution of CaO by SrO. However, glassification degree and chemical durability of pyro- and meta-phosphate glasses increased with substituted all CaO by SrO. This is because titanium groups in the glasses are closely related to their glass network structure by SrO substitution. The P-O-Ti bonds in pyrophosphate glass series and TiO4 tetrahedra in metaphosphate glass series increased with substitution by SrO. The titanium groups in the glasses were crosslink and/or coordinate phosphate groups to improve glassification degree and chemical durability. Sr2+ ion releasing amount of pyrophosphate glasses with >83% SrO substitution was larger than 0.1 mM at day seven, an amount that reported enhanced bone formation by stimulation of osteogenic markers.

Towards functional characterization of excipients for oral solid dosage forms using UV-vis imaging. Liberation, release and dissolution.

The purpose of this study was to investigate whole-dosage form UV-vis imaging as a potential tool for functional characterization of excipients used in solid oral dosage forms. To this end, tablets (average mass 260.0 mg, 224.5 mg and 222.1 mg) containing theophylline anhydrate (20 % w/w), 1% (w/w) magnesium stearate, and 79 % (w/w) of either microcrystalline cellulose (MCC, Avicel PH 101) or hydroxypropyl methylcellulose (HPMC, Methocel K15 M or K100 M) were prepared as model systems. Drug liberation from tablets was studied in 0.01 M HCl at 37 °C using a Sirius SDi2 equipped with a USP IV type flow cell comprising a UV-vis imaging detector operating at 255 nm and 520 nm. The effluent from the flow cell was passed through a downstream spectrophotometer, and UV-vis spectra in the wavelength range 200-800 nm were recorded every 2 min. The erosion and swelling behavior of the MCC tablets and HPMC K15 M and K100 M tablets were visualized in real time. The swelling of HPMC K15 M and K100 M containing tablets was assessed quantitatively as changes in tablet diameter measured at 520 nm, and was clearly distinguished from the swelling of the MCC tablets. Namely, an increment of 2.5 mm in diameter was determined for the HPMC tablets while the MCC tablets increased by 0.5-1 mm in diameter. Gel layers of variable thickness were observed only for the HPMC K15 M and K100 M tablets. In addition, a relatively high initial liberation rate of theophylline was found for the MCC tablets as compared to the HPMC tablets. UV-vis imaging revealed features of liberation not revealed by simply measuring drug concentration in the dissolution media or by visual assessment. It may be sufficiently sensitive to be further developed for functional characterization of excipients and provide insights into drug-excipient interactions likely to be useful in formulation development.

Formulation and characterization of voriconazole nanospray dried powders.

Purpose: Voriconazole nanoparticles (API-NPs) were prepared by nanospray drying to improve the solubility of voriconazole and reduce its interindividual variability.Methods: The preparation procedure was optimized by central composite design-response surface methodology. The properties of the nanoparticles were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) analyses. The solubility, dissolution, and stability of the API-NPs were determined experimentally. The pharmacokinetics were assessed based on rat plasma levels of voriconazole. An acute oral toxicity test of the API-NPs was performed in mice.Results: The powers were formulated using cetyltrimethylammonium chloride (CTAC) as the carrier material. SEM and particle size results showed that the API-NPs had a narrow particle size distribution. The XRD, DSC, and FTIR analyses show a decrease in crystallinity and a polymorphic transformation of the nanoparticles after nanospray drying. The solubility in water was approximately 15 times higher than that of voriconazole. The API-NP tablets exhibited significantly higher plasma exposure, namely, longer acting times and lower variability. The acute administration of voriconazole showed no toxic histopathological effects on organ tissue.Conclusion: The solubility of voriconazole was greatly improved, it showed higher bioavailability and safety, and the interindividual variability in voriconazole pharmacokinetics was reduced by nanospray drying.