Indomethacin Concentration Research Articles

Functional biobased resin from a blend of tannin and crude black liquor and its application as an adsorbent for dexamethasone and indomethacin removal

A novel route is proposed to synthesize a functional biobased resin and its carbonized counterpart by sol-gel polymerization of a blend of tannin and crude Kraft black liquor. The potential of the synthesized biomaterial as adsorbents for dexamethasone and indomethacin removal from contaminated water was also evaluated. The characterization points out the great variety of surface functional groups, promoting different adsorbent-adsorbate interfacial interactions. As a result, the diversified functional groups favor the adsorption by electrostatic interactions, hydrogen bonds, and π-π interactions. Moreover, the thermal treatment decreased the functionality and oxygenated groups of the carbonized counterpart, increasing the hydrophobic interactions. It also increased the specific area of the material (2–98 m2 g−1) and the average pore size diameter (1.6–4.2 nm). Consequently, the carbonized counterpart exhibits superior adsorption of the model pollutants. The adsorption of dexamethasone occurred in multilayers, whose maximum adsorption capacity obtained experimentally were 11.38 mg g−1 and 22.22 mg g−1 for resin and the carbonized resin. Furthermore, the study concerning the adsorption of indomethacin showed that the indomethacin concentration must be controlled to optimize the adsorption process and avoid precipitation. Finally, the equilibrium studies disclosed an atypical isothermal profile, which is hardly found in the literature. Therefore, the ability to remediate the pollutants demonstrates this novel material potential for future application in water remediation technologies.

Effect of Ester Derivative of Indomethacin on Immune Inflammation.

The anti-inflammatory effect of the ester derivative of indomethacin (IML) in doses of 6.25, 12.5, and 25 mg/kg was studied in rats with modeled rheumatoid arthritis (adjuvant arthritis) and compared to the effects of the reference drug indomethacin in a dose of 1 mg/kg. IML in doses of 12.5 and 25 mg/kg reduced joint inflammation and promoted recovery of the microstructure of the synovial membrane and articular cartilage better than indomethacin. IML produced no ulcerogenic effect, while indomethacin concentration in the stomach wall after administration of IML was 1.8-3.4 times lower than after administration of the reference drug (p<0.05).

Противовоспалительное и анальгетическое действие нового сложноэфирного производного индометацина

Сложный эфир индометацина и ментола (ИМЛ) при введении внутрь в дозе 12,5 мг/кг оказывает профилактическое противовоспалительное действие на моделях острого экссудативного воспаления, вызванного каррагенином, гистамином и серотонином, и хронического пролиферативного воспаления у крыс. При введении за 12 ч до каррагенина антиэкссудативное действие ИМЛ превосходит эффект индометацина на 36 % (p &lt; 0,05), при введении ИМЛ за 8 ч до применения гистамина и серотонина — на 32 % (p &lt; 0,05). Максимальная концентрация индометацина, освобождаемого при гидролизе ИМЛ, создается в плазме крови крыс через (8 ± 0,3) ч, а максимальная концентрация индометацина — через (4 ± 0,5) ч. ИМЛ тормозит развитие грануляционной ткани слабее индометацина на 25,6 % (p &lt; 0,05), подавляет гипералгезию у мышей больше, чем индометацин на 16 % (p &lt; 0,05), не повреждает слизистую оболочку желудка крыс и создает в ней концентрацию индометацина в 3,2 – 5,3 раза более низкую, чем та, которая возникает при применении индометацина (p &lt; 0,05).

T2 Relaxation Study to Evaluate the Crystalline State of Indomethacin Containing Solid Dispersions Using Time-Domain NMR.

The aim of this study was to demonstrate the usefulness of T2 measurements conducted with a time-domain NMR (TD-NMR) for the characterization of active pharmaceutical ingredients (APIs) containing solid dosage forms. A solid dispersion (SD) and a physical mixture (PM) consisting of indomethacin (IMC) and polyvinylpyrrolidone (PVP) were prepared at different weight ratios as test samples, and then their T2 relaxation curves were measured by TD-NMR. The T2 relaxation curve of IMC was quite different from that of PVP by nature. T2 values of the SD and PM samples became gradually shortened with increasing IMC content. No difference in T2 relaxation curves was observed between SD and PM. By analyzing the T2 relaxation curves in detail, we succeeded in precisely quantifying the IMC contents incorporated in the samples. Next, this study evaluated the T2 relaxation curves of amorphous and crystalline states of powdered IMC. T2 relaxation rate of crystalline IMC was slightly but significantly higher than that of amorphous IMC, proving that the T2 measurement was sensitive enough to detect these differences. Finally, a thermal stress was imposed on SD and PM samples at 60°C for 7 d, and then an amorphous-to-crystalline transformation occurred in IMC in the PM sample and was successfully monitored by T2 measurement. We believe that T2 measurement by TD-NMR is a promising analysis for the characterization of APIs in solid dosage forms, including SD-based pharmaceuticals.

ANTI-INFLAMMATORY ACTIVITY OF BAWANG DAYAK (ELEUTHERINE BULBOSA (MILL. URB.))ETHANOL BULB EXTRACTS

Background: Inflammation is a normal process in response to injury, but causes problems for the patient, including the appearance of pain, swelling, or fever. Anti-inflammatory agents generally used for those conditions, have several side effects to patients. Purpose: The objective of this research was to find alternative anti-inflammatory agents, especially from natural sources. Eleutherine bulbosa (Mill.) Urb. knew as “Bawang Dayak” belong to family Iridaceae is one of the natural sources for anti-inflammatory agents. This plant is known as traditional medicine in East Kalimantan and used as material in this research. Method: The experimental method of anti-inflammatory measurement using membrane stabilization activity for E. Bulbosa ethanol bulbs extracts. Result: The results showed that significant differences of EC50(p &lt; 0.05) were achieved between indomethacin (26.39 ± 2.91) as the positive control with E. Bulbosa (52.87 ± 2.29). EC50 of E. bulbosa showed the potential anti-inflammatory activities with similar effectiveness to half indomethacin concentration. Conclusion: It could be concluded that E. bulbosa could be further developed as a new natural source of the anti-inflammatory agents.

Skin permeability and transdermal delivery route of 50-nm indomethacin-loaded PLGA nanoparticles

Recently, nano-seized systems for transdermal delivery have attracted attention. To efficiently deliver drugs to hair follicles, we focused on poly(DL-lactide-co-glycolide) (PLGA) nanoparticles prepared using a combination of an antisolvent diffusion method with preferential solvation. The PLGA nanoparticles prepared using this method are suitable for iontophoresis because of their high surface charge number density. It has been reported that PLGA nanoparticles were delivered to hair follicles by applying iontophoresis, however research on PLGA nanoparticles with a size of less than 100nm was lacking. In this study, we prepared 50-nm and 100-nm PLGA nanoparticles. Indomethacin was used as a hydrophobic drug model and the nanoparticles were evaluated their skin permeability using the abdominal skin of a rat. Two hours after administration, the skin permeation indomethacin amounts of 50-nm and 100-nm PLGA nanoparticles with iontophoresis were significantly higher than those of passively diffused nanoparticles and indomethacin solution. Moreover, when iontophoresis was applied, the indomethacin concentration in the rat skin of 50-nm PLGA nanoparticles was 1.7 times higher than that of 100-nm PLGA nanoparticles. We also prepared coumarin-6-loaded 50-nm and 100-nm PLGA nanoparticles having surface characteristics equivalent to those of indomethacin-loaded PLGA nanoparticles to investigate transdermal delivery route of indomethacin-loaded PLGA nanoparticles. The 50-nm nanoparticles reached a deeper portion of the hair follicle when applying iontophoresis. Therefore, it was shown that this nanoparticle was useful for targeting to hair follicles.

Solid state properties and drug release behavior of co-amorphous indomethacin-arginine tablets coated with Kollicoat® Protect.

A promising approach to improve the solubility of poorly water-soluble drugs and to overcome the stability issues related to the plain amorphous form of the drugs, is the formulation of drugs as co-amorphous systems. Although polymer coatings have been proven very useful with regard to tablet stability and modifying drug release, there is little known on coating co-amorphous formulations. Hence, the aim of the present study was to investigate whether polymer coating of co-amorphous formulations is possible without inducing recrystallization. Tablets containing either a physical mixture of crystalline indomethacin and arginine or co-amorphous indomethacin-arginine were coated with a water soluble polyvinyl alcohol-polyethylene glycol graft copolymer (Kollicoat® Protect) and stored at 23°C/0% RH and 23°C/75% RH. The solid state properties of the coated tablets were analyzed by XRPD and FTIR and the drug release behavior was tested for up to 4h in phosphate buffer pH 4.5. The results showed that the co-amorphous formulation did not recrystallize during the coating process or during storage at both storage conditions for up to three months, which confirmed the high physical stability of this co-amorphous system. Furthermore, the applied coating could partially inhibit recrystallization of indomethacin during drug release testing, as coated tablets reached a higher level of supersaturation compared to the respective uncoated formulations and showed a lower decrease of the dissolved indomethacin concentration upon precipitation. Thus, the applied coating enhanced the AUC of the dissolution curve of the co-amorphous tablets by about 30%. In conclusion, coatings might improve the bioavailability of co-amorphous formulations.

Solid nanofoams based on cellulose nanofibers and indomethacin—the effect of processing parameters and drug content on material structure

The unique colloidal properties of cellulose nanofibers (CNF), makes CNF a very interesting new excipient in pharmaceutical formulations, as CNF in combination with some poorly-soluble drugs can create nanofoams with closed cells. Previous nanofoams, created with the model drug indomethacin, demonstrated a prolonged release compared to films, owing to the tortuous diffusion path that the drug needs to take around the intact air-bubbles. However, the nanofoam was only obtained at a relatively low drug content of 21wt% using fixed processing parameters. Herein, the effect of indomethacin content and processing parameters on the foaming properties was analysed. Results demonstrate that a certain amount of dissolved drug is needed to stabilize air-bubbles. At the same time, larger fractions of dissolved drug promote coarsening/collapse of the wet foam. The pendant drop/bubble profile tensiometry was used to verify the wet-foam stability at different pHs. The pH influenced the amount of solubilized drug and the processing-window was very narrow at high drug loadings. The results were compared to real foaming-experiments and solid state analysis of the final cellular solids. The parameters were assembled into a processing chart, highlighting the importance of the right combination of processing parameters (pH and time-point of pH adjustment) in order to successfully prepare cellular solid materials with up to 46 wt% drug loading.

Effect of indomethacin-loaded nanocapsules incorporation in a dentin adhesive resin.

The aim of this study was to produce indomethacin-loaded nanocapsules (IndOH-NCs) and evaluate the influence of their incorporation into an adhesive resin. Indomethacin was encapsulated by the deposition of preformed polymer. IndOH-NCs were characterized by laser diffractometry, Fourier transformed infrared spectrometry, transmission electron microscopy (TEM), scanning electron microscopy, high-performance liquid chromatography (HPLC), and MTT assay. Nanocapsules (NCs) were incorporated into an adhesive in concentrations of 1, 2, 5, and 10%. The addition was visualized by TEM and drug release was evaluated by HPLC until 120h of immersion in simulated body fluid (SBF). Drug diffusion through dentin was tested using a Franz diffusion cell apparatus and quantified by HPLC. The degree of conversion (DC), softening in ethanol, and microtensile bond strength (μTBS) were evaluated to determine whether the nanocapsules influenced the adhesive. Data were analyzed using one-way ANOVA and Tukey's post hoc test for DC, softening in ethanol, μTBS, and cytotoxicity, and paired t test for comparison between the initial and final Knoop microhardness. IndOH-NCs, with a spherical shape and a mean diameter of 165nm, were incorporated into an adhesive. Indomethacin content was 7mgdrug/gpowder. IndOH-NCs maintained high cell viability. At 120h, an amount of 13.83% of indomethacin was released, and after 7days, 7.07% of this drug was diffused through dentin for an adhesive containing 10% of nanocapsules. No alteration in the DC, softening in ethanol, and μTBS resulted from NC addition. IndOH-NCs may be incorporated into adhesive systems, without compromising properties, to add an anti-inflammatory drug controlled release for restorative procedures in deep cavities. Here is the first step toward the goal of providing agents to act at an inflammatory process of pulp tissue through dental adhesives via encapsulation of drug.

Solubility and hydrolytic stability of indomethacin in aqueous micellar solutions

The solubility of the indomethacin drug in aqueous micellar solutions of a series of dicationic surfactants was characterized by spectrophotometry. The use of these surfactants can significantly increase the indomethacin content in aqueous solutions without destruction of the drug. The increase in the solubility can be explained by the multifactorial mechanism of the influence of micelles involving the solubilization of the drug and its binding with surfactants due to electrostatic and specific interactions. The use of dicationic surfactants in alkaline solutions was shown to markedly accelerate the hydrolytic cleavage of indomethacin. The highest catalytic effect is observed for N,N´-(hexane-1,6-diyl)bis(2-hydroxyethyl)(methyl)(cetyl)ammonium dibromide: a 1200-fold increase in the reaction rate of alkaline hydrolysis of the drug.

Dissolution study of nanocrystal powders of a poorly soluble drug by UV imaging and channel flow methods

Application of drug nanocrystals provides advantageous options for the pharmaceutical formulation development of poorly soluble drugs. The objective of this study was to investigate the dissolution behavior improving effects of differently sized nanocrystals of a poorly soluble model drug, indomethacin. Nanocrystal suspensions were prepared using a top-down wet milling technique with three stabilizers: poloxamer F68, poloxamer F127 and polysorbate 80. The dissolution of the differently sized indomethacin nanocrystals were investigated using a channel flow dissolution method and by UV imaging. Unmilled bulk indomethacin and physical mixtures were used as references. According to both the dissolution methods, the dissolution properties of indomethacin were improved by the particle size reduction. UV imaging was used for the first time as a dissolution testing method for fast dissolving nanoscale material. The technique provided new information about the concentration of the dissolved drug next to the sample surface; with the smallest nanocrystals (580nm) the indomethacin concentration next to the particle surface exceeded five-fold the thermodynamic saturated indomethacin solution concentration. Thus the solubility improvement itself, not only the increased surface area for dissolution, may have an important role in the higher dissolution rates of nanocrystal formulations. Poloxamer F68 was the most optimal stabilizer in the preparation of the indomethacin nanocrystal suspensions and in the solubility and dissolution enhancement as well.

Polydimethylsiloxane-indomethacin blends and nanoparticles.

A series of blends of polydimethylsiloxane (PDMS) and indomethacin (IMC), containing 20-80 wt.% IMC were obtained and characterized by differential scanning calorimetry, Fourier transform-infrared spectroscopy, and powder X-ray diffraction in order to observe the mutual influence of the two components. The main thermal transitions of PDMS remained un-changed. Both the solvent (tetrahydrofuran, THF) and the PDMS influenced the crystalline form of IMC. The blends were subsequently re-dissolved in THF, with or without cross-linking reagents added and precipitated into diluted aqueous solutions of siloxane-based surfactants. The resulted nanoparticles were analyzed by dynamic light scattering and scanning electron microscopy. Most of the particles had diameters between 200 and 300 nm. The surfactants, the IMC content and the cross-linking influenced the particles size and polydispersity, as well as the nanoparticle yield. The maximum drug release from selected aqueous formulations was 30%.

TCH-024 Long-Term Stability of Indomethacin 0.2 mg/ml Ready-To-Use Solution For Intravenous Use

Background Indomethacin 1 mg is used in premature infants to close the patent ductus arteriosus. The commercial product Indocid PDA is no longer available in Switzerland. Nevertheless, on our paediatric...

Miscibility Studies of Indomethacin and Eudragit® E PO by Thermal, Rheological, and Spectroscopic Analysis

The objective of this study is to understand the underlying mechanisms responsible for the superior stability of indomethacin (INM)-Eudragit® E PO (E PO) system by exploring the miscibility and intermolecular interactions through the combination of thermal, rheological, and spectroscopic analysis. The zero shear-rate viscosity drops monotonically with the increase of INM concentration at 145 °C, suggesting that E PO and INM form a solution and the small molecular drug acts as a plasticizer. Flow activation energy was calculated from the viscosity data at different temperature. The glass transition temperature (T(g)) of the mixture at different composition was determined using differential scanning calorimetry. The T(g) and flow activation energy peak at the INM concentration around 60%-70%. Fourier transform infrared analysis provided direct evidence for the intermolecular ionic interactions, which may disrupt the dimer formation of amorphous INM. The study explained the superior stability of INM-E PO mixtures, and demonstrated that a combination of thermal, rheological, and spectroscopic technologies can help us to obtain a full picture of the drug-polymer interactions and to determine the formulation and processing conditions.

EICOSANOIDS MEDIATE CELLULAR IMMUNE RESPONSE AND PHENOLOXIDASE REACTION TO VIRAL INFECTION IN ADULT Pimpla turionellae

Nodulation is the predominant insect cellular immune response to microbial infections. We posed the hypothesis that parasitoid insects in their adulthood express melanotic nodulation reactions to viral challenge and that eicosanoids mediate nodulation reactions and phenoloxidase (PO) activation in response to viral challenge. To test this idea, we injected Pimpla turionellae adults with indomethacin, a nonsteroidal anti-inflammatory drug, immediately prior to intrahemocoelic injection of Bovine herpes simplex virus-1 (BHSV-1). Treating newly emerged adults of P. turionellae with BHSV-1 induced nodulation reactions, and decreased PO activity at high viral doses. Relative to vehicle-treated controls, indomethacin-treated adults produced significantly reduced numbers of nodules following viral infection (down from approximately 21 nodules per adult to less than six nodules per adult). In addition to injection treatments, increasing dietary indomethacin dosages (from 0.01% to 0.1%) were associated with decreasing nodulation (by six-fold) and PO (by about three-fold) reactions to BHSV-1 injection. Wasp adults orally fed with the lowest dietary indomethacin concentration (0.001%) expressed significantly increased PO activity (1.45 unit/min/mg protein) while nodulation reaction was not affected in response to viral challenge compared to control adults. We infer from these findings that cyclooxygenase (COX) products, at least prostaglandins, mediate nodulation response and PO action to viral infection in adults of these highly specialized insects.

Determination of Figures of Merit for Near-Infrared, Raman and Powder X-ray Diffraction by Net Analyte Signal Analysis for a Compacted Amorphous Dispersion with Spiked Crystallinity

With the growing interest in solubility enhancement of drugs via solid dispersion formulations, it is becoming more crucial to find appropriate analytical methods for detection of amorphous destabilization (i.e., crystallization). The objective of this work was to compare the performance of reflectance and transmittance near-infrared spectroscopy and Raman spectroscopy methods with powder X-ray diffraction. Specifically, the methods were compared on their ability to detect low concentrations (0–2 % w/w) of crystalline indomethacin-consolidated dispersions. Partial least squares regression and net analyte signal analyses were performed for the computation of figures of merit. Based on the calibration error statistics, all methods were suitable for the quantitative determination indomethacin content above 0.5 % (w/w) or 1 % (w/w) of drug content. However, the sensitivity, selectivity, limit of detection, and data collection time found for the near-infrared reflectance measurements provides the greatest promise for future online stability monitoring of consolidated dispersions.

Enhanced kinetic solubility profiles of indomethacin amorphous solid dispersions in poly(2-hydroxyethyl methacrylate) hydrogels

The feasibility of forming solid molecular dispersions of poorly water-soluble drugs in crosslinked poly(2-hydroethyl methacrylate) (PHEMA) hydrogel has recently been reported by our group. The purpose of the present study is to investigate the extent of enhancement of kinetic solubility of amorphous solid dispersions (ASDs) of indomethacin (IND) in crosslinked PHEMA hydrogels as compared with those based on conventional water-soluble polymer carriers. Our results show that under non-sink conditions, the initial solubility enhancement is higher for ASDs based on polyvinylpyrrolidone (PVP) and hydroxypropylmethylcellulose acetate succinate (HMPCAS), but the ability to maintain this solubility enhancement at longer times is better for ASDs based on PHEMA over a period of 24h with the extent of solubility enhancement of IND ASDs in PHEMA falling between those in PVP and HPMCAS at 10.0% IND loading after 6h and outperforming those in PVP and HPMCAS at 32.9% IND loading after 8h. The observed kinetic solubility profiles reflect the fact that the amorphous IND is released from PHEMA by a different mechanism than those from water-soluble polymer carriers. In this case, the dissolution of IND ASD from water-soluble PVP and HPMCAS is almost instantaneous, resulting in an initial surge of IND concentration followed by a sharp decline due to the nucleation and crystallization events triggered by the rapid build-up of drug supersaturation. On the other hand, the dissolution of IND ASD from insoluble crosslinked PHEMA hydrogel beads is less rapid as it is regulated by a feedback-controlled diffusion mechanism, thus avoiding a sudden surge of supersaturation in the dissolution medium. The absence of an apparent decline in drug concentration during dissolution from IND-PHEMA ASD further reflects the diminished nucleation and crystallization events during IND dissolution from hydrogel-based solid molecular dispersions. Based on the XRD analyses, a threshold IND loading level of about 34% in PHEMA has been identified, above which amorphous to crystalline transition tends to occur. Also, by selecting the appropriate particle sizes, immediate to controlled release of IND from IND-PHEMA ASD can be readily achieved as the release rate increases with decreasing PHEMA bead size. Furthermore, a robust physical stability has been demonstrated in IND-PHEMA ASD with no drug precipitation for up to 8months at IND loadings below 16.7% under direct open cup exposure to accelerated stability conditions (40°C/75% RH).

Differential protective effects of quercetin, resveratrol, rutin and epigallocatechin gallate against mitochondrial dysfunction induced by indomethacin in Caco-2 cells

The beneficial effects of dietary polyphenols on health are due not only to their antioxidant properties but also to their antibacterial, anti-inflammatory and/or anti-tumoral activities. It has recently been proposed that protection of mitochondrial function (which is altered in several diseases such as Alzheimer, Parkinson, obesity and diabetes) by these compounds, may be important in explaining the beneficial effects of polyphenols on health. The aim of this study was to evaluate the protective effects of dietary polyphenols quercetin, rutin, resveratrol and epigallocatechin gallate against the alterations of mitochondrial function induced by indomethacin (INDO) in intestinal epithelial Caco-2 cells, and to address the mechanism involved in such damaging effect by INDO, which generates oxidative stress. INDO concentration dependently decreases cellular ATP levels and mitochondrial membrane potential in Caco-2 cells after 20min of incubation. INDO also inhibits the activity of mitochondrial complex I and causes accumulation of NADH; leading to overproduction of mitochondrial O2−, since it is prevented by pyruvate. Quercetin (0.01mg/ml), resveratrol (0.1mg/ml) and rutin (1mg/ml) protected Caco-2 cells against INDO-induced mitochondrial dysfunction, while no protection was observed with epigallocatechin gallate. Quercetin was the most efficient in protecting against mitochondrial dysfunction; this could be due to its ability to enter cells and accumulate in mitochondria. Additionally its structural similarity with rotenone could favor its binding to the ubiquinone site of complex I, protecting it from inhibitors such as INDO or rotenone. These findings suggest a possible new protective role for dietary polyphenols for mitochondria, complementary of their antioxidant property. This new role might expand the preventive and/or therapeutic use of PPs in conditions involving mitochondrial dysfunction and associated with increased oxidative stress at the cellular or tissue levels.

Development of Nanofiber Coated Indomethacin—Eluting Stent for Tracheal Regeneration

In the case of tracheal rupture or stenosis, most effective way is to insert a commercially available metal stent. However, the implantation often causes a fever or a pain on the contact surface between trachea and the stent. And also the metal stent should be removed after a certain time implantation. Thus, we developed a functional tracheal drug eluting stent consisting of indomethacin, a nonsteroidal anti-inflammatory drug (NSAID), loaded nanofibers on a bare metal stent. To control the drug release kinetics and enhancement of mucosal regeneration, gelatin and PLCL were coated layer by layer on a metal stent by an electrospinning method. Indomethacin was loaded in the gelatin layer by soaking and drying method (0.1, 0.5, and 1 wt% in ethanol for 10 min). The morphology of functional drug eluting tracheal stent was characterized by scanning electron microscope (SEM). And mechanical properties of the constructs such as air leak pressure, ultimate tensile stress, and modulus were calculated and evaluated. Drug release was performed by a high performance liquid chromatography (HPLC). Stably coated gelatin and poly(L-lactide- co-epsilon-caprolactone) (PLCL) nanofibers were observed by SEM. Bi-layered nanofibers-coated stent showed enough mechanical properties as a tracheal stent, which confirmed by a custom-designed air leak mechanical test. For indomethacin loading on a stent, stent was immersed in a series of drug solutions (different concentrations) for 10 min. At the result of HPLC, total amounts of indomethacin on a stent were approximately 77, 323, and 670 ug/stent, respectively. Time dependent drug release kinetics of the tracheal stent showed a sustained release profile regardless of indomethacin content. Thus, functionally designed nanofiber coated tracheal stent with anti-inflammatory drug may be useful for tracheal regeneration.

Evaluation of the physicochemical characteristics of crospovidone that influence solid dispersion preparation

A solid dispersion (SD) powder of indomethacin (IM) with crospovidone (CrosPVP) shows useful characteristics for manufacturing dosage forms. Four types of commercial CroPVP, Polyplasdone ® XL (XL) used as the initial carrier, Polyplasdone ® XL10 and INF-10 ® manufactured by milling XL, and Kollidon ® CL (CL) marketed by another company, were compared. The limit of the IM–CrosPVP weight ratio with which an SD can be prepared (maximum IM content) was calculated on the basis of the heat of fusion of physical mixtures of IM and CrosPVP with various weight ratios. When Polyplasdone ®s were used, the maximum IM content increased with the specific surface area of the CrosPVP. When CL was used, however, it was about half of that obtained with XL, even though the difference between XL and CL was not observed in the physicochemical characteristics (particle size, specific surface area, flowability, glass transition temperature, IR spectra, and solid state NMR spectra). As determined by pore size distribution measurement, the volume of pore of which size is larger than the particle size of IM was less in CL than in XL. Therefore, the effective surface area of CrosPVP that comes in contact with IM is important for the preparation of the SD.