Preparation, characterization and in vitro/vivo evaluation of tectorigenin solid dispersion with improved dissolution and bioavailability.

PubMed

Shuai, Shuping; Yue, Shanlan; Huang, Qingting; Wang, Wei; Yang, Junyi; Lan, Ke; Ye, Liming

2016-08-01

The purpose of this study was to develop and evaluate a novel amorphous solid dispersion system for tectorigenin (TG). TG is one of isoflavone aglycones extracted from Iris tectorum and flowers of Pueraria thunbergiana, but its poor water solubility and low membrane permeability have severely restricted the clinical application. To increase the aqueous solubility and oral bioavailability of TG, we prepared the solid dispersions of tectorigenin (TG-SD) using a simple solvent evaporation process with TG, polyvinylpyrrolidone (PVP) and PEG4000 at weight ratio of 7:54:9 after tested in several ratios. The prepared solid dispersions of tectorigenin are duly characterized for drug morphological conversion, in vitro dissolution and in vivo bioavailability. The X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) studies have indicated the morphological conversion of tectorigenin to amorphous form. In vitro release profiles revealed that the % release of TG-SD was achieved 4.35-fold higher than that of the pure drug after 150 min. The oral bioavailability of the solid dispersion in rats was also increased based on AUC0-t and C max of TG-SD, which were 4.8- and 13.1-fold higher than that of TG crystal, respectively. It is worth noting that physical mixture containing TG, PEG4000 and PVP produced a similar level of oral exposure as TG-SD, suggesting that PEG4000 and PVP were able to enhance bioavailability of TG in rats. However, with the reduction of particle size, TG-SD provided the fastest oral absorption compared to physical mixture and pure drug. These results demonstrated that the efficacy of solid dispersions for the enhancement of TG oral bioavailability was by increasing its aqueous solubility and the solid dispersion formulation could be a viable option for enhancing the oral bioavailability of TG.

Preparation and characterization of fusion processed solid dispersions containing a viscous thermally labile polymeric carrier.

PubMed

Hughey, Justin R; Keen, Justin M; Miller, Dave A; Brough, Chris; McGinity, James W

2012-11-15

The primary aim of the present study was to investigate the ability of hydroxypropyl and methoxyl substituted cellulose ethers to stabilize supersaturated concentrations of itraconazole (ITZ), a poorly water-soluble weak base, after an acid-to-neutral pH transition. A secondary aim of the study was to evaluate the effect of fusion processes on polymer stability and molecular weight. Polymer screening studies showed that stabilization of ITZ supersaturation was related to the molecular weight of the polymer and levels of hydroxypropyl and methoxyl substitution. METHOCEL E50LV (E50LV), which is characterized as having a high melt viscosity, was selected for solid dispersion formulation studies. Hot-melt extrusion processing of E50LV based compositions resulted in high torque loads, low material throughput and polymer degradation. KinetiSol Dispersing, a novel fusion based processing technique, was evaluated as a method to prepare the solid dispersions with reduced levels of polymer degradation. An experimental design revealed that polymer molecular weight was sensitive to shearing forces and high temperatures. However, optimal processing conditions resulted in significantly reduced E50LV degradation relative to HME processing. The technique was effectively utilized to prepare homogenous solid solutions of E50LV and ITZ, characterized as having a single glass transition temperature over a wide range of drug loadings. All prepared compositions provided for a high degree of ITZ supersaturation stabilization. Copyright © 2012 Elsevier B.V. All rights reserved.

Surface Solid Dispersion and Solid Dispersion of Meloxicam: Comparison and Product Development.

PubMed

Chaturvedi, Mayank; Kumar, Manish; Pathak, Kamla; Bhatt, Shailendra; Saini, Vipin

2017-12-01

Purpose: A comparative study was carried out between surface solid dispersion (SSD) and solid dispersion (SD) of meloxicam (MLX) to assess the solubility and dissolution enhancement approach and thereafter develop as patient friendly orodispersible tablet. Methods: Crospovidone (CPV), a hydrophilic carrier was selected for SSD preparation on the basis of 89% in- vitro MLX adsorption, 19% hydration capacity and high swelling index. SD on the other hand was made with PEG4000. Both were prepared by co-grinding and solvent evaporation method using drug: carrier ratios of 1:1, 1:4, and 1:8. Formulation SSDS3 (MLX: CPV in 1:8 ratio) made by solvent evaporation method showed t 50% of 28 min and 80.9% DE 50min which was higher in comparison to the corresponding solid dispersion, SDS3 (t 50% of 35min and 76.4% DE 50min ). Both SSDS3 and SDS3 were developed as orodispersible tablets and evaluated. Results: Tablet formulation F3 made with SSD3 with a disintegration time of 11 secs, by wetting time= 6 sec, high water absorption of 78%by wt and cumulative drug release of 97% proved to be superior than the tablet made with SD3. Conclusion: Conclusively, the SSD of meloxicam has the potential to be developed as fast acing formulation that can ensure almost complete release of drug.

Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion, Part II.

PubMed

Six, Karel; Berghmans, Hugo; Leuner, Christian; Dressman, Jennifer; Van Werde, Kristof; Mullens, Jules; Benoist, Luc; Thimon, Mireille; Meublat, Laurent; Verreck, Geert; Peeters, Jef; Brewster, Marcus; Van den Mooter, Guy

2003-07-01

This study was done to elucidate the physical and pharmaceutical properties of itraconazole-HPMC dispersions and the influence of water on the phase separation. Extrudates were prepared using a corotating twin-screw hot-stage extruder with fixed process parameters. Modulated-temperature differential scanning calorimetry (MTDSC) and DSC 111 were used to examine the mixing behavior of itraconazole and the carrier by evaluation of the glass transition region. High temperature diffuse reflectance infrared transform spectroscopy (HT-DRIFT) was performed to reveal interactions between itraconazole and HPMC. Dissolution was performed to investigate the pharmaceutical performance of the dispersions. Although the dissolution rate of itraconazole significantly increased, we found that the solid dispersions do not form a homogeneous system. A different picture was obtained depending on the way MTDSC analysis was performed, i.e., using open or closed sample pans. Water can evaporate in open pans, which allows itraconazole to interact with HPMC and leads to a partially mixed phase. Analysis in hermetically closed pans revealed a further phase separation as water remains on the sample and impedes the interaction between drug and polymer. Solid dispersions of itraconazole and HPMC do not form a homogeneous phase.

Prediction of recrystallization behavior of troglitazone/polyvinylpyrrolidone solid dispersion by solid-state NMR.

PubMed

Ito, Atsutoshi; Watanabe, Tomoyuki; Yada, Shuichi; Hamaura, Takeshi; Nakagami, Hiroaki; Higashi, Kenjirou; Moribe, Kunikazu; Yamamoto, Keiji

2010-01-04

The purpose of this study was to elaborate the relationship between the (13)C CP/MAS NMR spectra and the recrystallization behavior during the storage of troglitazone solid dispersions. The solid dispersions were prepared by either the solvent method or by co-grinding. The recrystallization behavior under storage conditions at 40 degrees C/94% RH was evaluated by the Kolmogorov-Johnson-Mehl-Avrami (KJMA) equation. Solid dispersions prepared by the solvent method or by prolonged grinding brought about inhibition of the nucleation and the nuclei growth at the same time. No differences in the PXRD profiles were found in the samples prepared by the co-grinding and solvent methods, however, (13)C CP/MAS NMR showed significant differences in the spectra. The correlation coefficients using partial least square regression analysis between the PXRD profiles and the apparent nuclei-growth constant or induction period to nucleation were 0.1305 or 0.6350, respectively. In contrast, those between the (13)C CP/MAS NMR spectra and the constant or the period were 0.9916 or 0.9838, respectively. The (13)C CP/MAS NMR spectra had good correlation with the recrystallization kinetic parameters evaluated by the KJMA equation. Consequently, solid-state NMR was judged to be a useful tool for the prediction of the recrystallization behavior of solid dispersions.

Rheology Guided Rational Selection of Processing Temperature To Prepare Copovidone-Nifedipine Amorphous Solid Dispersions via Hot Melt Extrusion (HME).

PubMed

Yang, Fengyuan; Su, Yongchao; Zhang, Jingtao; DiNunzio, James; Leone, Anthony; Huang, Chengbin; Brown, Chad D

2016-10-03

The production of amorphous solid dispersions via hot melt extrusion (HME) relies on elevated temperature and prolonged residence time, which can result in potential degradation and decomposition of thermally sensitive components. Herein, the rheological properties of a physical mixture of polymer and an active pharmaceutical ingredient (API) were utilized to guide the selection of appropriate HME processing temperature. In the currently studied copovidone-nifedipine system, a critical temperature, which is substantially lower (∼13 °C) than the melting point of crystalline API, was captured during a temperature ramp examination and regarded as the critical point at which the API could molecularly dissolve into the polymer. Based on the identification of this critical point, various solid dispersions were prepared by HME processing below, at, and above the critical temperature (both below and above the melting temperature (T m ) of crystalline API). In addition, the resultant extrudates along with two control solid dispersions prepared by physical mixing and cryogenic milling were assessed by X-ray diffraction, differential scanning calorimetry, hot stage microscopy, rheology, and solid-state NMR. Physicochemical properties of resultant solid dispersions indicated that the identified critical temperature is sufficient for the polymer-API system to reach a molecular-level mixing, manifested by the transparent and smooth appearance of extrudates, the absence of API crystalline diffraction and melting peaks, dramatically decreased rheological properties, and significantly improved polymer-API miscibility. Once the critical temperature has been achieved, further raising the processing temperature only results in limited improvement of API dispersion, reflected by slightly reduced storage modulus and complex viscosity and limited improvement in miscibility.

Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution: pros and cons.

PubMed

Chokshi, Rina J; Zia, Hossein; Sandhu, Harpreet K; Shah, Navnit H; Malick, Waseem A

2007-01-01

The solid dispersions with poloxamer 188 (P188) and solid solutions with polyvinylpyrrolidone K30 (PVPK30) were evaluated and compared in an effort to improve aqueous solubility and bioavailability of a model hydrophobic drug. All preparations were characterized by differential scanning calorimetry, powder X-ray diffraction, intrinsic dissolution rates, and contact angle measurements. Accelerated stability studies also were conducted to determine the effects of aging on the stability of various formulations. The selected solid dispersion and solid solution formulations were further evaluated in beagle dogs for in vivo testing. Solid dispersions were characterized to show that the drug retains its crystallinity and forms a two-phase system. Solid solutions were characterized to be an amorphous monophasic system with transition of crystalline drug to amorphous state. The evaluation of the intrinsic dissolution rates of various preparations indicated that the solid solutions have higher initial dissolution rates compared with solid dispersions. However, after storage at accelerated conditions, the dissolution rates of solid solutions were lower due to partial reversion to crystalline form. The drug in solid dispersion showed better bioavailability in comparison to solid solution. Therefore, considering physical stability and in vivo study results, the solid dispersion was the most suitable choice to improve dissolution rates and hence the bioavailability of the poorly water soluble drug.

Improving the chemical stability of amorphous solid dispersion with cocrystal technique by hot melt extrusion.

PubMed

Liu, Xu; Lu, Ming; Guo, Zhefei; Huang, Lin; Feng, Xin; Wu, Chuanbin

2012-03-01

To explore in-situ forming cocrystal as a single-step, efficient method to significantly depress the processing temperature and thus minimize the thermal degradation of heat-sensitive drug in preparation of solid dispersions by melting method (MM) and hot melt extrusion (HME). Carbamazepine (CBZ)-nicotinamide (NIC) cocrystal solid dispersions were prepared with polymer carriers PVP/VA, SOLUPLUS and HPMC by MM and/or HME. The formation of cocrystal was investigated by differential scanning calorimetry and hot stage polarized optical microscopy. State of CBZ in solid dispersion was characterized by X-ray powder diffraction and optical microscopy. Interactions between CBZ, NIC and polymers were investigated by FTIR. Dissolution behaviors of solid dispersions were compared with that of pure CBZ. CBZ-NIC cocrystal with melting point of 160°C was formed in polymer carriers during heating process, and the preparation temperature of amorphous CBZ solid dispersion was therefore depressed to 160°C. The dissolution rate of CBZ-NIC cocrystal solid dispersion was significantly increased. By in-situ forming cocrystal, chemically stable amorphous solid dispersions were prepared by MM and HME at a depressed processing temperature. This method provides an attractive opportunity for HME of heat-sensitive drugs.

[Study on solid dispersion of precipitated calcium carbonate-based oleanolic acid].

PubMed

Yan, Hong-mei; Zhang, Zhen-hai; Jia, Xiao-bin; Jiang, Yan-rong; Sun, E

2015-05-01

Oleanolic acid-precipitated calcium carbonate solid dispersion was prepared by using solvent evaporation method. The microscopic structure and physicochemical properties of solid dispersion were analyzed using differential scanning calorimetry and scanning electron microscopy (SEM). And its in vitro release also was investigated. The properties of the precipitated calcium carbonate was studied which was as a carrier of oleanolic acid solid dispersion. Differential scanning calorimetry analysis suggested that oleanolic acid may be present in solid dispersion as amorphous substance. The in vitro release determination results of oleanolic acid-precipitated calcium carbonate (1: 5) solid dispersion showed accumulated dissolution rate of.oleanolic acid was up to 90% at 45 min. Accelerating experiment showed that content and in vitro dissolution of oleanolic acid solid dispersion did not change after storing over 6 months. The results indicated that in vitro dissolution of oleanolic acid was improved greatly by the solid dispersion with precipitated calcium carbonate as a carrier. The solid dispersion is a stabilizing system which has actual applied value.

Microparticles Containing Curcumin Solid Dispersion: Stability, Bioavailability and Anti-Inflammatory Activity.

PubMed

Teixeira, C C C; Mendonça, L M; Bergamaschi, M M; Queiroz, R H C; Souza, G E P; Antunes, L M G; Freitas, L A P

2016-04-01

This work aimed at improving the solubility of curcumin by the preparation of spray-dried ternary solid dispersions containing Gelucire®50/13-Aerosil® and quantifying the resulting in vivo oral bioavailability and anti-inflammatory activity. The solid dispersion containing 40% of curcumin was characterised by calorimetry, infrared spectroscopy and X-ray powder diffraction. The solubility and dissolution rate of curcumin in aqueous HCl or phosphate buffer improved up to 3600- and 7.3-fold, respectively. Accelerated stability test demonstrated that the solid dispersion was stable for 9 months. The pharmacokinetic study showed a 5.5-fold increase in curcumin in rat blood plasma when compared to unprocessed curcumin. The solid dispersion also provided enhanced anti-inflammatory activity in rat paw oedema. Finally, the solid dispersion proposed here is a promising way to enhance curcumin bioavailability at an industrial pharmaceutical perspective, since its preparation applies the spray drying, which is an easy to scale up technique. The findings herein stimulate further in vivo evaluations and clinical tests as a cancer and Alzheimer chemoprevention agent.

Dissolution enhancement of efavirenz by solid dispersion and PEGylation techniques

PubMed Central

Madhavi, B. Bindu; Kusum, B.; Chatanya, CH. Krishna; Madhu, M. Naga; Harsha, V. Sri; Banji, David

2011-01-01

Background: Efavirenz is the preferred nonnucleotide reverse transcriptase inhibitor for first-line antiretroviral treatment in many countries. It is orally active and is specific for human immunodeficiency virus type 1. Its effectiveness can be attributed to its long half-life, which is 52–76 h after multiple doses. The drug is having poor water solubility. The formulation of poorly soluble drug for oral delivery will be one of the biggest challenges for formulation scientists in the research field. Among the available approaches, the solid dispersion technique has often proved to be the most commonly used method in improving dissolution and bioavailability of the drugs because of its simplicity and economy in preparation and evaluation. Materials and Methods: Solid dispersions were prepared by solvent evaporation and physical mixture methods by using polyethylene glycol as the hydrophilic carrier and PEGylated product was also prepared. The prepared products were evaluated for various parameters, such as polymer interaction, saturation solubility study, and drug release studies. The drug release data were analyzed by fitting it into various kinetic models. Results: There is an improvement in the dissolution from 16% to 70% with solid dispersion technology. Higuchi model was found to be the best fit model. Conclusion: Solid dispersion is the simple, efficient, and economic method to improve the dissolution of the poorly water-soluble drugs. PMID:23071917

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

PubMed

Lin, Shiuan-Pey; Hou, Yu-Chi; Liao, Tzu-Yun; Tsai, Shang-Yuan

2014-03-01

Preparation of magnolol-loaded amorphous solid dispersion was investigated for improving the bioavailability. 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. 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. Magnolol-loaded amorphous solid dispersion with PVP has demonstrated enhanced bioavailability of magnolol in rabbits.

Enhancement of solubility and dissolution of coenzyme Q10 using solid dispersion formulation.

PubMed

Nepal, Pushp R; Han, Hyo-Kyung; Choi, Hoo-Kyun

2010-01-04

This study aimed to develop a stable solid dispersion of Coenzyme Q(10) (CoQ(10)) with high aqueous solubility and dissolution rate. Among various carriers screened, poloxamer 407 was most effective to form a superior solid dispersion of CoQ(10) having significantly enhanced solubility. Particularly, solid dispersion of CoQ(10) with poloxamer 407 in the weight ratio of 1:5 prepared by melting method enhanced the solubility of CoQ(10) to the greatest extent. However, it exhibited poor stability and hence Aerosil 200 (colloidal silicon dioxide) was incorporated into the solid dispersion as an adsorbent to inhibit the recrystallization process. The solid dispersion of CoQ(10), poloxamer 407 and Aerosil 200 in the weight ratio of 1:5:6 exhibited improved stability with no significant change in solubility during the 1-month stability test. Moreover, the solid dispersion formulation containing Aerosil 200 significantly enhanced the extent of drug release (approx. 75% release) as well as the dissolution rate of CoQ(10). In conclusion, the present study has developed the stable solid dispersion formulation of CoQ(10) with poloxamer 407 and Aerosil 200 for the enhanced solubility and dissolution of CoQ(10), which could also offer some additional advantages including ease of preparation, good flowability and cost-effectiveness.

Effect of hydroxypropylcellulose and Tween 80 on physicochemical properties and bioavailability of ezetimibe-loaded solid dispersion.

PubMed

Rashid, Rehmana; Kim, Dong Wuk; Din, Fakhar Ud; Mustapha, Omer; Yousaf, Abid Mehmood; Park, Jong Hyuck; Kim, Jong Oh; Yong, Chul Soon; Choi, Han-Gon

2015-10-05

The purpose of this research was to evaluate the effect of the HPC (hydroxypropylcellulose) and Tween 80 on the physicochemical properties and oral bioavailability of ezetimibe-loaded solid dispersions. The binary solid dispersions were prepared with drug and various amounts of HPC. Likewise, ternary solid dispersions were prepared with different ratios of drug, HPC and Tween 80. Both types of solid dispersions were prepared using the solvent evaporation method. Their aqueous solubility, physicochemical properties, dissolution and oral bioavailability were investigated in comparison with the drug powder. All the solid dispersions significantly improved the drug solubility and dissolution. As the amount of HPC increased in the binary solid dispersions to 10-fold, the drug solubility and dissolution were increased accordingly. However, further increase in HPC did not result in significant differences among them. Similarly, up to 0.1-fold, Tween 80 increased the drug solubility in the ternary solid dispersions followed by no significant change. However, Tween 80 hardly affected the drug dissolution. The physicochemical analysis proved that the drug in binary and ternary solid dispersion was existed in the amorphous form. The particle-size measurements of these formulations were also not significantly different from each other, which showed that Tween 80 had no impact on physicochemical properties. The ezetimibe-loaded binary and ternary solid dispersions gave 1.6- and 1.8-fold increased oral bioavailability in rats, respectively, as compared to the drug powder; however, these values were not significantly different from each other. Thus, HPC greatly affected the solubility, dissolution and oral bioavailability of drug, but Tween 80 hardly did. Furthermore, this ezetimibe-loaded binary solid dispersion prepared only with HPC would be suggested as a potential formulation for oral administration of ezetimibe. Copyright © 2015 Elsevier Ltd. All rights reserved.

[Effect of stability and dissolution of realgar nano-particles using solid dispersion technology].

PubMed

Guo, Teng; Shi, Feng; Yang, Gang; Feng, Nian-Ping

2013-09-01

To improve the stability and dissolution of realgar nano-particles by solid dispersion. Using polyethylene glycol 6000 and poloxamer-188 as carriers, the solid dispersions were prepare by melting method. XRD, microscopic inspection were used to determine the status of realgar nano-particles in solid dispersions. The content and stability test of As(2)0(3) were determined by DDC-Ag method. Hydride generation atomic absorption spectrometry was used to determine the content of Arsenic and investigated the in vitro dissolution behavior of solid dispersions. The results of XRD and microscopic inspection showed that realgar nano-particles in solid dispersions were amorphous. The dissolution amount and rate of Arsenic from realgar nano-particles of all solid dispersions were increased significantly, the reunion of realgar nano-particles and content of As(2)0(3) were reduced for the formation of solid dispersions. The solid dispersion of realgar nano-particles with poloxamer-188 as carriers could obviously improve stability, dissolution and solubility.

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

PubMed

Nakanishi, Sayaka; Fujii, Makiko; Sugamura, Yuka; Suzuki, Ayako; Shibata, Yusuke; Koizumi, Naoya; Watanabe, Yoshiteru

2011-07-15

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 Polyplasdones 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. Copyright © 2011 Elsevier B.V. All rights reserved.

Enhanced solubility of piperine using hydrophilic carrier-based potent solid dispersion systems.

PubMed

Thenmozhi, Kathavarayan; Yoo, Young Je

2017-09-01

Piperine alkaloid, an important constituent of black pepper, exhibits numerous therapeutic properties, whereas its usage as a drug is limited due to its poor solubility in aqueous medium, which leads to poor bioavailability. Herein, a new method has been developed to improve the solubility of this drug based on the development of solid dispersions with improved dissolution rate using hydrophilic carriers such as sorbitol (Sor), polyethylene glycol (PEG) and polyvinyl pyrrolidone K30 (PVP) by solvent method. Physical mixtures of piperine and carriers were also prepared for comparison. The physicochemical properties of the prepared solid dispersions were examined using SEM, TEM, DSC, XRD and FT-IR. In vitro dissolution profile of the solid dispersions was recorded and compared with that of the pure piperine and physical mixtures. The effect of these carriers on the aqueous solubility of piperine has been investigated. The solid dispersions of piperine with Sor, PEG and PVP exhibited superior performance for the dissolution of piperine with a drug release of 70%, 76% and 89%, respectively after 2 h compared to physical mixtures and pure piperine, which could be due to its transformation from crystalline to amorphous form as well as the attachment of hydrophilic carriers to the surface of poorly water-soluble piperine. Results suggest that the piperine solid dispersions prepared with improved in vitro release exhibit potential advantage in delivering poorly water-soluble piperine as an oral supplement.

Thermal Processing of PVP- and HPMC-Based Amorphous Solid Dispersions.

PubMed

LaFountaine, Justin S; Prasad, Leena Kumari; Brough, Chris; Miller, Dave A; McGinity, James W; Williams, Robert O

2016-02-01

Thermal processing technologies continue to gain interest in pharmaceutical manufacturing. However, the types and grades of polymers that can be utilized in common thermal processing technologies, such as hot-melt extrusion (HME), are often limited by thermal or rheological factors. The objectives of the present study were to compare and contrast two thermal processing methods, HME and KinetiSol® Dispersing (KSD), and investigate the influence of polymer type, polymer molecular weight, and drug loading on the ability to produce amorphous solid dispersions (ASDs) containing the model compound griseofulvin (GRIS). Dispersions were analyzed by a variety of imaging, solid-state, thermal, and solution-state techniques. Dispersions were prepared by both HME and KSD using polyvinylpyrrolidone (PVP) K17 or hydroxypropyl methylcellulose (HPMC) E5. Dispersions were only prepared by KSD using higher molecular weight grades of HPMC and PVP, as these could not be extruded under the conditions selected. Powder X-ray diffraction (PXRD) analysis showed that dispersions prepared by HME were amorphous at 10% and 20% drug load; however, it showed significant crystallinity at 40% drug load. PXRD analysis of KSD samples showed all formulations and drug loads to be amorphous with the exception of trace crystallinity seen in PVP K17 and PVP K30 samples at 40% drug load. These results were further supported by other analytical techniques. KSD produced amorphous dispersions at higher drug loads than could be prepared by HME, as well as with higher molecular weight polymers that were not processable by HME, due to its higher rate of shear and torque output.

Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan.

PubMed

Lee, Jae-Young; Kang, Wie-Soo; Piao, Jingpei; Yoon, In-Soo; Kim, Dae-Duk; Cho, Hyun-Jong

2015-01-01

Soluplus(®) (SP) and D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based solid dispersion (SD) formulations were developed by hot-melt extrusion (HME) to improve oral bioavailability of valsartan (VST). HME process with twin-screw configuration for generating a high shear stress was used to prepare VST SD formulations. The thermodynamic state of the drug and its dispersion in the polymers were evaluated by solid-state studies, including Fourier-transform infrared, X-ray diffraction, and differential scanning calorimetry. Drug release from the SD formulations was assessed at pH values of 1.2, 4.0, and 6.8. Pharmacokinetic study was performed in rats to estimate the oral absorption of VST. HME with a high shear rate produced by the twin-screw system was successfully applied to prepare VST-loaded SD formulations. Drug amorphization and its molecular dispersion in the polymer matrix were verified by several solid-state studies. Drug release from SD formulations was improved, compared to the pure drug, particularly at pH 6.8. Oral absorption of drug in rats was also enhanced in SP and TPGS-based SD groups compared to that in the pure drug group. SP and TPGS-based SDs, prepared by the HME process, could be used to improve aqueous solubility, dissolution, and oral absorption of poorly water-soluble drugs.

Development of solid dispersion systems of dapivirine to enhance its solubility.

PubMed

Gorajana, Adinarayana; Ying, Chan Chiew; Shuang, Yeen; Fong, Pooi; Tan, Zhi; Gupta, Jyoti; Talekar, Meghna; Sharma, Manisha; Garg, Sanjay

2013-06-01

Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.

Development of novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose.

PubMed

Baek, Hyung Hee; Kim, Dae-Hwan; Kwon, So Young; Rho, Shin-Joung; Kim, Dong-Wuk; Choi, Han-Gon; Kim, Yong-Ro; Yong, Chul Soon

2012-03-01

To develop a novel ibuprofen-loaded solid dispersion with enhanced bioavailability using cycloamylose, it was prepared using spray-drying techniques with cycloamylose at a weight ratio of 1:1. The effect of cycloamylose on aqueous solubility of ibuprofen was investigated. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction. The dissolution and bioavailability in rats were evaluated compared with ibuprofen powder. This ibuprofen-loaded solid dispersion improved about 14-fold drug solubility. Ibuprofen was present in an unchanged crystalline state, and cycloamylose played the simple role of a solubilizing agent in this solid dispersion. Moreover, the dispersion gave 2-fold higher AUC (area under the drug concentration-time curve) value compared with a ibuprofen powder, indicating that it improved the oral bioavailability of ibuprofen in rats. Thus, the solid dispersion may be useful to deliver ibuprofen with enhanced bioavailability without crystalline change.

Development and in-vivo assessment of the bioavailability of oridonin solid dispersions by the gas anti-solvent technique.

PubMed

Li, Songming; Liu, Ying; Liu, Tao; Zhao, Ling; Zhao, Jihui; Feng, Nianping

2011-06-15

We developed solid dispersions, using the gas anti-solvent technique (GAS), to improve the oral bioavailability of the poorly water-soluble active component oridonin. The solubility of oridonin in supercritical carbon dioxide was measured under various pressures and temperatures. To prepare oridonin solid dispersions using the GAS technique, ethanol was used as the solvent, CO(2) was used as the anti-solvent and the hydrophilic polymer polyvinylpyrrolidone K17 (PVP K17) was used as the drug carrier matrix. Characterization of the obtained preparations was undertaken using scanning electron microscopy (SEM), X-ray diffraction (XRD) analyses and a drug release study. Oridonin solid dispersions were formed and oridonin was present in an amorphous form in these dispersions. Oridonin solid dispersions significantly increased the drug dissolution rate compared with that of oridonin powder, primarily through drug amorphization. Compared with the physical mixture of oridonin and PVP K17, oridonin solid dispersions gave higher values of AUC and C(max), and the absorption of oridonin from solid dispersions resulted in 26.4-fold improvement in bioavailability. The present study illustrated the feasibility of applying the GAS technique to prepare oridonin solid dispersions, and of using them for the delivery of oridonin via the oral route. Copyright © 2011 Elsevier B.V. All rights reserved.

Comparison of HPMC based polymers performance as carriers for manufacture of solid dispersions using the melt extruder.

PubMed

Ghosh, Indrajit; Snyder, Jennifer; Vippagunta, Radha; Alvine, Marilyn; Vakil, Ronak; Tong, Wei-Qin; Vippagunta, Sudha

2011-10-31

Preparation of amorphous solid dispersions using hot-melt extrusion process for poorly water soluble compounds which degrade on melting remains a challenge due to exposure to high temperatures. The aim of this study was to develop a physically and chemically stable amorphous solid dispersion of a poorly water-soluble compound, NVS981, which is highly thermal sensitive and degrades upon melting at 165 °C. Hydroxypropyl Methyl Cellulose (HPMC) based polymers; HPMC 3cps, HPMC phthalate (HPMCP) and HPMC acetyl succinate (HPMCAS) were selected as carriers to prepare solid dispersions using hot melt extrusion because of their relatively low glass transition temperatures. The solid dispersions were compared for their ease of manufacturing, physical stability such as recrystallization potential, phase separation, molecular mobility and enhancement of drug dissolution. Two different drug loads of 20 and 50% (w/w) were studied in each polymer system. It was interesting to note that solid dispersions with 50% (w/w) drug load were easier to process in the melt extruder compared to 20% (w/w) drug load in all three carriers, which was attributed to the plasticizing behavior of the drug substance. Upon storage at accelerated stability conditions, no phase separation was observed in HPMC 3cps and HPMCAS solid dispersions at the lower and higher drug load, whereas for HPMCP, phase separation was observed at higher drug load after 3 months. The pharmaceutical performance of these solid dispersions was evaluated by studying drug dissolution in pH 6.8 phosphate buffer. Drug release from solid dispersion prepared from polymers used for enteric coating, i.e. HPMCP and HPMCAS was faster compared with the water soluble polymer HPMC 3cps. In conclusion, of the 3 polymers studied for preparing solid dispersions of thermally sensitive compound using hot melt extrusion, HPMCAS was found to be the most promising as it was easily processible and provided stable solid dispersions with enhanced

Solid dispersion of berberine-phospholipid complex/TPGS 1000/SiO₂: preparation, characterization and in vivo studies.

PubMed

Zhang, Zhenhai; Chen, Yan; Deng, Jin; Jia, Xiaobin; Zhou, Jianping; Lv, Huixia

2014-04-25

Berberine (Ber), an isoquinoline alkaloid, arouses wide interests in many researchers in recent years because of its numerous new pharmacological actions. However Ber's low oral bioavailability restricts its wide application. In this study, a solid dispersion (BPTS-SD) composed of berberine-phospholipid complex (BPC), D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS 1000) and SiO₂ was prepared by simple solvent evaporation technique. BPC was employed to improve the liposolubility of Ber, and SiO₂ was used to improve the flowability of BPTS-SD, while TPGS 1000 played a dual role: firstly, as a solid dispersion carrier to improve the dissolution rate of BPC and secondly, as a P-glycoprotein (P-gp) inhibitor to enhance the intestinal absorption of Ber. FTIR, DSC and SEM analysis proved the formation of BPC and BPTS-SD. Po/w of BPC successfully increased from 0.25 to 8.75. In vitro dissolution study showed that the cumulative dissolution percentages of BPTS-SDs were nearly 2.67-4.78-folds of BPC. Single-pass intestinal perfusion studies showed that the absorption of Ber in BPC was increased nearly 1.4-2.0-folds compared to that of Ber which was mainly due to the improved liposolubility, and further increased by BPTS-SD around 0.1-1.3-folds compared to that of BPC through the P-gp inhibition of TPGS 1000. Significant improvements in Cmax and AUC₀→t of BPC and BPTS-SD were obtained in pharmacokinetic study (the highest improvement in oral relative bioavailability of BPTS-SD-1 was 322.66% of Ber). All these results indicated that BPTS-SD can be a promising drug delivery system to improve their oral bioavailability for the Ber's analogues. In particular this solid dispersion can be prepared just by a simple method and has a strong feasibility for industrialization. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Microwave generated solid dispersions containing Ibuprofen.

PubMed

Moneghini, Mariarosa; Bellich, Barbara; Baxa, Pietro; Princivalle, Francesco

2008-09-01

The purpose of this study was to apply the attractive technique of the microwaves irradiation (MW) for the preparation of solvent-free solid dispersions (SD). In particular, the microwave technology has been considered in order to prepare an enhanced release dosage form for the poorly soluble drug Ibuprofen (IBU), employing PVP/VA 60/40 (PVP/VA 64) and hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as hydrophilic carriers. Their physico-chemical characteristics and dissolution properties were compared to the corresponding physical mixtures and the drug alone. The results of physico-chemical characterization attested a correspondence of the solid state of the drug before and after irradiation treatment and that an amorphous form of the drug was obtained. This result, together with the presence of the hydrophilic polymers determined a remarkable enhancement of the in vitro dissolution rate of the drug suggesting that the microwave technique could be considered as a new and interesting method to prepare drug-polymer systems.

Development of novel sibutramine base-loaded solid dispersion with gelatin and HPMC: physicochemical characterization and pharmacokinetics in beagle dogs.

PubMed

Lim, Hyun-Tae; Balakrishnan, Prabagar; Oh, Dong Hoon; Joe, Kwan Hyung; Kim, Young Ran; Hwang, Doo Hyung; Lee, Yong-Bok; Yong, Chul Soon; Choi, Han-Gon

2010-09-15

To develop a novel sibutramine base-loaded solid dispersion with enhanced solubility and bioavailability, various solid dispersions were prepared using a spray drying technique with hydrophilic polymers such as gelatin, HPMC and citric acid. Their solubility, thermal characteristics and crystallinity were investigated. The dissolution and pharmacokinetics of the sibutramine base-loaded solid dispersion were then compared with a sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The solid dispersions prepared with gelatin gave higher drug solubility than those prepared without gelatin, irrespective of the amount of polymer. The sibutramine base-loaded solid dispersions containing hydrophilic polymer and citric acid showed higher drug solubility compared to sibutramine base and sibutramine hydrochloride monohydrate. Among the formulations tested, the solid dispersion composed of sibutramine base/gelatin/HPMC/citric acid at the weight ratio of 1/0.8/0.2/0.5 gave the highest solubility of 5.03+/-0.24 mg/ml. Our DSC and powder X-ray diffraction results showed that the drug was present in an altered amorphous form in this solid dispersion. The difference factor (f(1)) values between solid dispersion and commercial product were 2.82, 6.65 and 6.31 at pH 1.2, 4.0 and 6.8, respectively. Furthermore, they had the similarity factor (f(2)) value of 65.68, 53.43 and 58.97 at pH 1.2, 4.0 and 6.8, respectively. Our results suggested that the solid dispersion and commercial product produced a similar correlation of dissolution profiles at all pH ranges. The AUC, C(max) and T(max) of the parent drug and metabolite I and II from the solid dispersion were not significantly different from those of the commercial product, suggesting that the solid dispersion might be bioequivalent to the commercial product in beagle dogs. Thus, the sibutramine base-loaded solid dispersion prepared with gelatin, HPMC and citric acid is a promising candidate for improving the

Efficient sample preparation method based on solvent-assisted dispersive solid-phase extraction for the trace detection of butachlor in urine and waste water samples.

PubMed

Aladaghlo, Zolfaghar; Fakhari, Alireza; Behbahani, Mohammad

2016-10-01

In this work, an efficient sample preparation method termed solvent-assisted dispersive solid-phase extraction was applied. The used sample preparation method was based on the dispersion of the sorbent (benzophenone) into the aqueous sample to maximize the interaction surface. In this approach, the dispersion of the sorbent at a very low milligram level was achieved by inserting a solution of the sorbent and disperser solvent into the aqueous sample. The cloudy solution created from the dispersion of the sorbent in the bulk aqueous sample. After pre-concentration of the butachlor, the cloudy solution was centrifuged and butachlor in the sediment phase dissolved in ethanol and determined by gas chromatography with flame ionization detection. Under the optimized conditions (solution pH = 7.0, sorbent: benzophenone, 2%, disperser solvent: ethanol, 500 μL, centrifuged at 4000 rpm for 3 min), the method detection limit for butachlor was 2, 3 and 3 μg/L for distilled water, waste water, and urine sample, respectively. Furthermore, the preconcentration factor was 198.8, 175.0, and 174.2 in distilled water, waste water, and urine sample, respectively. Solvent-assisted dispersive solid-phase extraction was successfully used for the trace monitoring of butachlor in urine and waste water samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Physicochemical characterization of atorvastatin calcium/ezetimibe amorphous nano-solid dispersions prepared by electrospraying method.

PubMed

Jahangiri, Azin; Barzegar-Jalali, Mohammad; Javadzadeh, Yousef; Hamishehkar, Hamed; Adibkia, Khosro

2017-09-01

In the present study, electrospraying was applied as a novel method for the fabrication of amorphous nano-solid dispersions (N-SDs) of atorvastatin calcium (ATV), ezetimibe (EZT), and ATV/EZT combination as poorly water-soluble drugs. N-SDs were prepared using polyvinylpyrrolidone K30 as an amorphous carrier in 1:1 and 1:5 drug to polymer ratios and the total solid (including drug and polymer) concentrations of 10 and 20% (w/v). The prepared formulations were further investigated for their morphological, physicochemical, and dissolution properties. Scanning electron microscopy studies indicated that the morphology and diameter of the electrosprayed samples (ESs) were influenced by the solution concentration and drug:polymer ratio, so that an increase in the solution concentration resulted in fiber formation while an increase in the polymer ratio led to enhancement of the particle diameter. Differential scanning calorimetry and X-ray powder diffraction studies together with in vitro dissolution test revealed that the ESs were present in an amorphous form with improved dissolution properties. Infrared spectroscopic studies showed hydrogen-bonding interaction between the drug and polymer in ESs. Since the electrospraying method benefits from the both amorphization and nanosizing effect, this novel approach seems to be an efficient method for the fabrication of N-SDs of poorly water-soluble drugs.

Physicochemical characterization of tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate.

PubMed

Park, Young-Joon; Ryu, Dong-Sung; Li, Dong Xun; Quan, Qi Zhe; Oh, Dong Hoon; Kim, Jong Oh; Seo, Youn Gee; Lee, Young-Im; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

2009-06-01

To develop a novel tacrolimus-loaded solid dispersion with improved solubility, various solid dispersions were prepared with various ratios of water, sodium lauryl sulfate, citric acid and carboxylmethylcellulose-Na using spray drying technique. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy, differential scanning calorimetery and powder X-ray diffraction. Furthermore, their solubility and dissolution were evaluated compared to drug powder. The solid dispersion at the tacrolimus/CMC-Na/sodium lauryl sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the drug solubility and dissolution compared to powder. The scanning electron microscopy result suggested that carriers might be attached to the surface of drug in this solid dispersion. Unlike traditional solid dispersion systems, the crystal form of drug in this solid dispersion could not be converted to amorphous form, which was confirmed by the analysis of DSC and powder X-ray diffraction. Thus, the solid dispersion system with water, sodium lauryl sulfate, citric acid and CMC-Na should be a potential candidate for delivering a poorly water-soluble tacrolimus with enhanced solubility and no convertible crystalline.

To evaluate the change in release from solid dispersion using sodium lauryl sulfate and model drug sulfathiazole.

PubMed

Dave, Rutesh H; Patel, Hardikkumar H; Donahue, Edward; Patel, Ashwinkumar D

2013-10-01

The solubility of drugs remains one of the most challenging aspects of formulation development. There are numerous ways to improve the solubility of drugs amongst which the most promising strategy is solid dispersion. Different ratios of sulfathiazole: PVP-K29/32: sodium lauryl sulfate (SLS) were prepared (1:1:0.1, 1:1:0.5, 1:1:1) and various methods were employed to characterize the prepared solid dispersions, namely modulated differential scanning calorimeter, X-ray powder diffraction, Fourier Transformed Infrared Spectroscopy and dissolution studies. Lack of crystallinity was observed in internal and external systems suggesting a loss of crystallinity, whereas the physical mixtures showed a characteristic peak of sulfathiazole. In vitro dissolution results clearly showed that the incorporation of a relatively small amount of surfactants (5, 20 or 33% w/w) into a solid dispersion can improve its dissolution rates compared to binary solid dispersion (SD) alone and pure sulfathiazole. In all ratios solid dispersion internal shows a higher dissolution rate compared to a physical mixture and solid dispersion external which suggests that the way that the surfactant is incorporated into the solid dispersion plays an important role in changing the solubility of a drug. The solubilization mechanism is mainly responsible for this higher dissolution rate when we incorporate the SLS in SD.

Improvement of solubility, dissolution and stability profile of artemether solid dispersions and self emulsified solid dispersions by solvent evaporation method.

PubMed

Tayyab Ansari, Muhammad; Arshad, Muhammad Sohail; Hussain, Altaf; Ahmad, Zeeshan

2016-12-08

The purpose of this study was to investigate changes in the water solubility of artemether; a poorly soluble drug used for the treatment of malaria. Different solid dispersions (SDs) of artemether were prepared using artemether and polyethylene glycol 6000 at ratio 12:88 (Group 1), self-emulsified solid dispersions (SESDs) containing artemether, polyethylene glycol 6000, cremophor-A-25, olive oil, hydroxypropylmethylcellulose and transcutol in the ratio 12:75:5:4:2:2, respectively (Group 2). SESDs were also prepared by substituting cremophor-A-25 in Group 2 with poloxamer 188 (noted as Group 3). Each of these preparations was formulated using physical mixing and the solvent evaporation method. Aqueous solubility of artemether improved 11-, 95- and 102-fold, while dissolution (in simulated gastric fluid) increased 3-, 13- and 14-fold, for formulation groups 1, 2 and 3, respectively. X-ray diffraction patterns of SDs indicated a decrease in peak intensities at 10° implying reduced artemether crystallinity. Scanning electron micrographs invariably revealed embedment of artemether by various excipients and a glassy appearance for solvent evaporated mixtures for all three formulation Groups. Our findings indicate improved hydrophilic interactions for drug particles yield greater solubility and dissolution in the following order for artemether formulating methods: solvent evaporation mixtures > physical mixtures > pure artemether.

Formulation and optimization of mouth dissolve tablets containing rofecoxib solid dispersion.

PubMed

Sammour, Omaima A; Hammad, Mohammed A; Megrab, Nagia A; Zidan, Ahmed S

2006-06-16

The purpose of the present investigation was to increase the solubility and dissolution rate of rofecoxib by the preparation of its solid dispersion with polyvinyl pyrrolidone K30 (PVP K30) using solvent evaporation method. Drug-polymer interactions were investigated using differential scanning calorimetry (DSC), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). For the preparation of rofecoxib mouth dissolve tablets, its 1:9 solid dispersion with PVP K30 was used with various disintegrants and sublimable materials. In an attempt to construct a statistical model for the prediction of disintegration time and percentage friability, a 3(2) randomized full and reduced factorial design was used to optimize the influence of the amounts of superdisintegrant and subliming agent. The obtained results showed that dispersion of the drug in the polymer considerably enhanced the dissolution rate. The drug-to-carrier ratio was the controlling factor for dissolution improvement. FTIR spectra revealed no chemical incompatibility between the drug and PVP K30. As indicated from XRD and DSC data, rofecoxib was in the amorphous form, which explains the better dissolution rate of the drug from its solid dispersions. Concerning the optimization study, the multiple regression analysis revealed that an optimum concentration of camphor and a higher percentage of crospovidone are required for obtaining rapidly disintegrating tablets. In conclusion, this investigation demonstrated the potential of experimental design in understanding the effect of the formulation variables on the quality of mouth dissolve tablets containing solid dispersion of a hydrophobic drug.

Preparation and investigation of mefenamic acid - polyethylene glycol - sucrose ester solid dispersions.

PubMed

Fülöp, Ibolya; Gyéresi, Árpád; Kiss, Lóránd; Deli, Mária A; Croitoru, Mircea Dumitru; Szabó-Révész, Piroska; Aigner, Zoltán

2015-12-01

Mefenamic acid (MA) is a widely used non-steroidal antiinflammatory (NSAID) drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670) and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives.

Fusion production of solid dispersions containing a heat-sensitive active ingredient by hot melt extrusion and Kinetisol dispersing.

PubMed

Dinunzio, James C; Brough, Chris; Hughey, Justin R; Miller, Dave A; Williams, Robert O; McGinity, James W

2010-02-01

Many techniques for the production of solid dispersions rely on elevated temperatures and prolonged material residence times, which can result in decomposition of temperature-sensitive components. In this study, hydrocortisone was used as a model temperature-sensitive active ingredient to study the effect of formulation and processing techniques as well as to characterize the benefits of KinetiSol Dispersing for the production of solid dispersions. Preformulation studies were conducted using differential scanning calorimetry and hot stage microscopy to identify optimum carriers for the production of amorphous solid dispersions. After identification, solid dispersions were prepared by hot melt extrusion and KinetiSol Dispersing, with material characterized by X-ray diffraction, dissolution and potency testing to evaluate physicochemical properties. Results from the preformulation studies showed that vinylacetate:vinylpyrrolidone (PVPVA) copolymer allowed for hydrocortisone dissolution within the carrier at temperatures as low as 160 degrees C, while hydroxypropyl methylcellulose required temperatures upward of 180 degrees C to facilitate solubilization. Low substituted hydroxypropyl cellulose, a high glass transition temperature control, showed that the material was unable to solubilize hydrocortisone. Manufacturing process control studies using hot melt extruded compositions of hydrocortisone and PVPVA showed that increased temperatures and residence times negatively impacted product potency due to decomposition. Using KinetiSol Dispersing to reduce residence time and to facilitate lower temperature processing, it was possible to produce solid dispersions with improved product potency. This study clearly demonstrated the importance of carrier selection to facilitate lower temperature processing, as well as the effect of residence time on product potency. Furthermore, KinetiSol Dispersing provided significant advantages over hot melt extrusion due to the reduced

Current trends and future perspectives of solid dispersions containing poorly water-soluble drugs.

PubMed

Vo, Chau Le-Ngoc; Park, Chulhun; Lee, Beom-Jin

2013-11-01

Over 40% of active pharmaceutical ingredients (API) in development pipelines are poorly water-soluble drugs which limit formulation approaches, clinical application and marketability because of their low dissolution and bioavailability. Solid dispersion has been considered one of the major advancements in overcoming these issues with several successfully marketed products. A number of key references that describe state-of-the-art technologies have been collected in this review, which addresses various pharmaceutical strategies and future visions for the solubilization of poorly water-soluble drugs according to the four generations of solid dispersions. This article reviews critical aspects and recent advances in formulation, preparation and characterization of solid dispersions as well as in-depth pharmaceutical solutions to overcome some problems and issues that limit the development and marketability of solid dispersion products. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation of curcumin self-micelle solid dispersion with enhanced bioavailability and cytotoxic activity by mechanochemistry.

PubMed

Zhang, Qihong; Polyakov, Nikolay E; Chistyachenko, Yulia S; Khvostov, Mikhail V; Frolova, Tatjana S; Tolstikova, Tatjana G; Dushkin, Alexandr V; Su, Weike

2018-11-01

An amorphous solid dispersion (SD) of curcumin (Cur) with disodium glycyrrhizin (Na 2 GA) was prepared by mechanical ball milling. Curcumin loaded micelles were self-formed by Na 2 GA when SD dissolved in water. The physical properties of Cur SD in solid state were characterized by differential scanning calorimetry, X-ray diffraction studies, and scanning electron microscope. The characteristics of the sample solutions were analyzed by reverse phase HPLC, UV-visible spectroscopy, 1 H NMR spectroscopy, gel permeation LC, and transmission electron microscopy. In vitro cytotoxic tests demonstrated that Cur SD induced higher cytotoxicity against glioblastoma U-87 MG cells than free Cur. Besides, an improvement of membrane permeability of Cur SD was confirmed by parallel artificial membrane permeability assay. Further pharmacokinetic study of this SD formulation in rat showed a significant ∼19-fold increase of bioavailability as comparing to free Cur. Thus, Cur SD provide a more potent and efficacious formulation for Cur oral delivery.

Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process.

PubMed

Ha, Eun-Sol; Kim, Jeong-Soo; Baek, In-Hwan; Yoo, Jin-Wook; Jung, Yunjin; Moon, Hyung Ryong; Kim, Min-Soo

2015-01-01

In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0-24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate.

Processing of carbamazepine-PEG 4000 solid dispersions with supercritical carbon dioxide: preparation, characterisation, and in vitro dissolution.

PubMed

Moneghini, M; Kikic, I; Voinovich, D; Perissutti, B; Filipović-Grcić, J

2001-07-03

The purpose of this study was to apply the attractive technique of the supercritical fluid to the preparation of solvent-free solid dispersions. In particular, the gas antisolvent crystallisation technique (GAS), using supercritical carbon dioxide as processing medium, has been considered to prepare an enhanced release dosage form for of the poorly soluble carbamazepine, employing PEG 4000 as a hydrophilic carrier. The physical characterisation of the systems using laser granulometer, powder X-ray diffraction, thermal analyses, and scanning electron microscopy was carried out in order to understand the influence of this technological process on the physical status of the drug. The results of the physical characterisation attested a substantial correspondence of the solid state of the drug before and after treatment with GAS technique, whereas a pronounced change in size and morphology of the drug crystals was noticed. The dramatic reduction of the dimensions and the better crystal shape, together with the presence of the hydrophilic polymer determined a remarkable enhancement of the in vitro drug dissolution rate.

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement.

PubMed

Ponnammal, Poovizhi; Kanaujia, Parijat; Yani, Yin; Ng, Wai Kiong; Tan, Reginald B H

2018-03-16

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus ® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w / w . Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus ® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage.

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement

PubMed Central

Ponnammal, Poovizhi; Kanaujia, Parijat; Ng, Wai Kiong; Tan, Reginald B. H.

2018-01-01

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus® and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% w/w. Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form. Fourier transform Infrared (FTIR) spectroscopy results indicated formation of hydrogen bond between TAC and polymers leading to stabilization of TAC in amorphous form. The extrudates were found to be stable under accelerated storage conditions for 3 months with no re-crystallization, indicating that hot melt extrusion is suitable for producing stable amorphous solid dispersions of TAC in PVP VA64, Soluplus® and HPC. Stable solid dispersions of amorphous TAC exhibited higher dissolution rate, with the solid dispersions releasing more than 80% drug in 15 min compared to the crystalline drug giving 5% drug release in two hours. These stable solid dispersions were incorporated into orally-disintegrating tablets in which the solid dispersion retained its solubility, dissolution and stability advantage. PMID:29547585

Evaluation of polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions prepared by hot-melt extrusion.

PubMed

Feng, Jia; Xu, Lishuang; Gao, Renchao; Luo, Yanfei; Tang, Xing

2012-06-01

The aim of this study was to evaluate several polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions (SD) prepared by hot-melt extrusion (HME) and select the most appropriate polymer carrier. Solid dispersions containing bifendate in different polymers, including Plasdone(®) S-630, Eudragit(®) EPO and Kollidon(®) VA 64 were prepared by hot-melt extrusion. Differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD) and dissolution testing were used to characterize the systems. Then, the thermal degradation during the HME process and the storage stability of tablets consisting of bifendate-Kollidon(®) VA 64 SD were investigated. Finally, the oral bioavailability of bifendate dosage forms with bifendate-Plasdone(®) S-630 (1/9), bifendate-Eudragit(®) EPO (1/4) and bifendate-Kollidon(®) VA 64 (1/9) SD in beagle dogs was compared with that of commercially available benfidate pills. DSC and XDR analysis showed the dispersion of the drug in the polymer on a molecular basis or in the amorphous state. The drug release from both bifendate-Plasdone(®) S-630 SD and bifendate-Eudragit(®) EPO SD was up to more than 90% with the pH 1.2 simulated gastric fluid as the dissolution medium, while the relative bioavailability was just 87.8 ± 51.8% and 110 ± 62% compared with commercial pills, respectively. The directly compressed tablets with bifendate-Kollidon(®) VA 64 SD were found to dissolve rapidly over 95% within 30 min and the relative bioavailability was 145.0 ± 35.2%. The bioavailability of water-insoluble bifendate was markedly enhanced by dispersing the drug in the polymer carrier Kollidon(®) VA 64 employing HME technology.

Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach.

PubMed

Agrawal, Anjali; Dudhedia, Mayur; Deng, Weibin; Shepard, Kevin; Zhong, Li; Povilaitis, Edward; Zimny, Ewa

2016-02-01

The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (<15 min) and acceptable TS (≥1 MPa at 10-15% tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions.

PubMed

Dontireddy, Rakesh; Crean, Abina M

2011-10-01

Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T(g)) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T(g) from the predicted values calculated using the Couchman-Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.

Biomimetic Dissolution: A Tool to Predict Amorphous Solid Dispersion Performance.

PubMed

Puppolo, Michael M; Hughey, Justin R; Dillon, Traciann; Storey, David; Jansen-Varnum, Susan

2017-11-01

The presented study describes the development of a membrane permeation non-sink dissolution method that can provide analysis of complete drug speciation and emulate the in vivo performance of poorly water-soluble Biopharmaceutical Classification System class II compounds. The designed membrane permeation methodology permits evaluation of free/dissolved/unbound drug from amorphous solid dispersion formulations with the use of a two-cell apparatus, biorelevant dissolution media, and a biomimetic polymer membrane. It offers insight into oral drug dissolution, permeation, and absorption. Amorphous solid dispersions of felodipine were prepared by hot melt extrusion and spray drying techniques and evaluated for in vitro performance. Prior to ranking performance of extruded and spray-dried felodipine solid dispersions, optimization of the dissolution methodology was performed for parameters such as agitation rate, membrane type, and membrane pore size. The particle size and zeta potential were analyzed during dissolution experiments to understand drug/polymer speciation and supersaturation sustainment of felodipine solid dispersions. Bland-Altman analysis was performed to measure the agreement or equivalence between dissolution profiles acquired using polymer membranes and porcine intestines and to establish the biomimetic nature of the treated polymer membranes. The utility of the membrane permeation dissolution methodology is seen during the evaluation of felodipine solid dispersions produced by spray drying and hot melt extrusion. The membrane permeation dissolution methodology can suggest formulation performance and be employed as a screening tool for selection of candidates to move forward to pharmacokinetic studies. Furthermore, the presented model is a cost-effective technique.

Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process.

PubMed

Won, Dong-Han; Kim, Min-Soo; Lee, Sibeum; Park, Jeong-Sook; Hwang, Sung-Joo

2005-09-14

Solid dispersions of felodipine were formulated with HPMC and surfactants by the conventional solvent evaporation (CSE) and supercritical anti-solvent precipitation (SAS) methods. The solid dispersion particles were characterized by particle size, zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), solubility and dissolution studies. The effects of the drug/polymer ratio and surfactants on the solubility of felodipine were also studied. The mean particle size of the solid dispersions was 200-250 nm; these had a relatively regular spherical shape with a narrow size distribution. The particle size of the solid dispersions from the CSE method increased at 1 h after dispersed in distilled water. However, the particle sizes of solid dispersions from the SAS process were maintained for 6 h due to the increased solubility of felodipine. The physical state of felodipine changed from crystalline to amorphous during the CSE and SAS processes, confirmed by DSC/XRD data. The equilibrium solubility of the felodipine solid dispersion prepared by the SAS process was 1.5-20 microg/ml, while the maximum solubility was 35-110 microg/ml. Moreover, the solubility of felodipine increased with decreasing drug/polymer ratio or increasing HCO-60 content. The solid dispersions from the SAS process showed a high dissolution rate of over 90% within 2 h. The SAS process system may be used to enhance solubility or to produce oral dosage forms with high dissolution rate.

The utilization of drug-polymer interactions for improving the chemical stability of hot-melt extruded solid dispersions.

PubMed

Guo, Zhefei; Lu, Ming; Li, Yongcheng; Pang, Huishi; Lin, Ling; Liu, Xu; Wu, Chuanbin

2014-02-01

Interactions between drugs and polymers were utilized to lower the processing temperature of hot-melt extrusion (HME), and thus minimize the thermal degradation of heat-sensitive drugs during preparation of amorphous solid dispersions. Diflunisal (DIF), which would degrade upon melting, was selected as a model drug. Hydrogen bonds between DIF and polymeric carriers (PVP K30, PVP VA64, hydroxypropyl methylcellulose and Soluplus) were revealed by differential scanning calorimetry and Fourier transform infrared spectroscopy. The hot-melt extruded solid dispersion was characterized by powder X-ray diffraction (XRD), scanning electron microscopy (SEM) and high-performance liquid chromatography (HPLC). The results of hot-stage polar microscopy indicated that DIF was dissolved in molten polymers at 160°C, much lower than the melting point of DIF (215°C). At this temperature, amorphous solid dispersions were successfully produced by HME, as confirmed by XRD and SEM. The related impurities in amorphous solid dispersions detected by HPLC were lower than 0.3%, indicating that thermal degradation was effectively minimized. The dissolution of DIF from amorphous solid dispersions was significantly enhanced as compared with the pure crystalline drug. This technique based on drug-polymer interactions to prepare chemically stable amorphous solid dispersions by HME provides an attractive opportunity for development of heat-sensitive drugs. © 2013 Royal Pharmaceutical Society.

Comparison of a solid SMEDDS and solid dispersion for enhanced stability and bioavailability of clopidogrel napadisilate.

PubMed

Kim, Dong Wuk; Kwon, Min Seok; Yousaf, Abid Mehmood; Balakrishnan, Prabagar; Park, Jong Hyuck; Kim, Dong Shik; Lee, Beom-Jin; Park, Young Joon; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

2014-12-19

The intention of this study was to compare the physicochemical properties, stability and bioavailability of a clopidogrel napadisilate (CN)-loaded solid dispersion (SD) and solid self-microemulsifying drug delivery system (solid SMEDDS). SD was prepared by a surface attached method using different ratios of Cremophor RH60 (surfactant) and HPMC (polymer), optimized based on their drug solubility. Liquid SMEDDS was composed of oil (peceol), a surfactant (Cremophor RH60) and a co-surfactant (Transcutol HP). A pseudo-ternary phase diagram was constructed to identify the emulsifying domain, and the optimized liquid SMEDDS was spray dried with an inert solid carrier (silicon dioxide), producing the solid SMEDDS. The physicochemical properties, solubility, dissolution, stability and pharmacokinetics were assessed and compared to clopidogrel napadisilate (CN) and bisulfate (CB) powders. In solid SMEDDS, liquid SMEDDS was absorbed or coated inside the pores of silicon dioxide. In SD, hydrophilic polymer and surfactants were adhered onto drug surface. The drug was in crystalline and molecularly dispersed form in SD and solid SMEDDS, respectively. Solid SMEDDS and SD greatly increased the solubility of CN but gave lower drug solubility compared to CB powder. These preparations significantly improved the dissolution of CN, but the latter more increased than the former. Stability under accelerated condition showed that they were more stable compared to CB powder, and SD was more stable than solid SMEDDS. They significantly increased the oral bioavailability of CN powder. Furthermore, SD showed significantly improved oral bioavailability compared to solid SMEDDS and CB powder. Thus, SD with excellent stability and bioavailability is recommended as an alternative for the clopidogrel-based oral formulation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions.

PubMed

Adebisi, Adeola O; Kaialy, Waseem; Hussain, Tariq; Al-Hamidi, Hiba; Nokhodchi, Ali; Conway, Barbara R; Asare-Addo, Kofi

2016-10-01

This work explores the use of both spray drying and d-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging were also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5μm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (-3.8 versus 0.5nC/g for untreated material and -7.5 versus 3.1nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1-0.3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced solubility and bioavailability of sibutramine base by solid dispersion system with aqueous medium.

PubMed

Li, Dong Xun; Jang, Ki-Young; Kang, Wonku; Bae, Kyoungjin; Lee, Mann Hyung; Oh, Yu-Kyoung; Jee, Jun-Pil; Park, Young-Joon; Oh, Dong Hoon; Seo, Youn Gee; Kim, Young Ran; Kim, Jong Oh; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

2010-01-01

To develop a novel sibutramine base-loaded solid dispersion with improved solubility bioavailability, various solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction. The dissolution and pharmacokinetics in rats of solid dispersion were evaluated compared to the sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The sibutramine base-loaded solid dispersion gave two type forms. Like conventional solid dispersion system, one type appeared as a spherical shape with smooth surface, as the carriers and drug with relatively low melting point were soluble in water and formed it. The other appeared as an irregular form with relatively rough surface. Unlike conventional solid dispersion system, this type changed no crystalline form of drug. Our results suggested that this type was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting from changing the hydrophobic drug to hydrophilic form. The sibutramine-loaded solid dispersion at the weight ratio of sibutramine base/HPMC/poloxamer/citric acid of 5/3/3/0.2 gave the maximum drug solubility of about 3 mg/ml. Furthermore, it showed the similar plasma concentration, area under the curve (AUC) and C(max) of parent drug, metabolite I and II to the commercial product, indicating that it might give the similar drug efficacy compared to the sibutramine hydrochloride monohydrate-loaded commercial product in rats. Thus, this solid dispersion system would be useful to deliver poorly water-soluble sibutramine base with enhanced bioavailability.

Molecular implications of drug-polymer solubility in understanding the destabilization of solid dispersions by milling.

PubMed

Yang, Ziyi; Nollenberger, Kathrin; Albers, Jessica; Qi, Sheng

2014-07-07

The solubility of drugs in polymer matrixes has been recognized as one of the key factors governing the physical stability of solid dispersions. This study has explored the implications of drug solubility on the destabilization that occurs on milling, which is often used as an additional process for hot melt extruded (HME) solid dispersions. The theoretical drug solubility in the polymer was first predicted using various theoretical and experimental approaches. The destabilization effects of high-energy mechanical milling on the solid dispersions with drug loadings below and above the predicted solubility were then investigated using a range of thermal, microscopic, and spectroscopic techniques. Four model drug-polymer combinations were studied. The HME formulations with drug loading below the predicted solid solubility (undersaturated and true molecular dispersion) showed good stability against milling. In contrast, milling destabilized supersaturated HME dispersions via increasing molecular mobility and creating phase-separated, amorphous, drug-rich domains. However, these additional amorphous drug-rich domains created by milling show good stability under ambient conditions, though crystallization can be accelerated by additional heating. These results highlighted that the processing method used to prepare the solid dispersions may play a role in facilitating the stabilization of amorphous drug in supersaturated solid dispersions. The degree of supersaturation of the drug in the polymer showed significant impact on the destabilization behavior of milling on solid dispersions. An improved understanding of the destabilization behavior of solid dispersions upon milling can provide new insights into the processing related apparent solubility of drugs in polymers.

Impact of surfactants on the crystallization of aqueous suspensions of celecoxib amorphous solid dispersion spray dried particles.

PubMed

Chen, Jie; Ormes, James D; Higgins, John D; Taylor, Lynne S

2015-02-02

Amorphous solid dispersions are frequently prepared by spray drying. It is important that the resultant spray dried particles do not crystallize during formulation, storage, and upon administration. The goal of the current study was to evaluate the impact of surfactants on the crystallization of celecoxib amorphous solid dispersions (ASD), suspended in aqueous media. Solid dispersions of celecoxib with hydroxypropylmethylcellulose acetate succinate were manufactured by spray drying, and aqueous suspensions were prepared by adding the particles to acidified media containing various surfactants. Nucleation induction times were evaluated for celecoxib in the presence and absence of surfactants. The impact of the surfactants on drug and polymer leaching from the solid dispersion particles was also evaluated. Sodium dodecyl sulfate and Polysorbate 80 were found to promote crystallization from the ASD suspensions, while other surfactants including sodium taurocholate and Triton X100 were found to inhibit crystallization. The promotion or inhibition of crystallization was found to be related to the impact of the surfactant on the nucleation behavior of celecoxib, as well as the tendency to promote leaching of the drug from the ASD particle into the suspending medium. It was concluded that surfactant choice is critical to avoid failure of amorphous solid dispersions through crystallization of the drug.

Evaluation of crystallization behavior on the surface of nifedipine solid dispersion powder using inverse gas chromatography.

PubMed

Miyanishi, Hideo; Nemoto, Takayuki; Mizuno, Masayasu; Mimura, Hisashi; Kitamura, Satoshi; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2013-02-01

To investigate crystallization behavior on the surface of amorphous solid dispersion powder using inverse gas chromatography (IGC) and to predict the physical stability at temperatures below the glass transition temperature (T (g)). Amorphous solid dispersion powder was prepared by melt-quenching of a mixture of crystalline nifedipine and polyvinylpyrrolidon (PVP) K-30. IGC was conducted by injecting undecane (probe gas) and methane (reference gas) repeatedly to the solid dispersion at temperatures below T (g). Surface crystallization was evaluated by the retention volume change of undecane based on the observation that the surface of the solid dispersion with crystallized nifedipine gives an increased retention volume. On applying the retention volume change to the Hancock-Sharp equation, surface crystallization was found to follow a two-dimensional growth of nuclei mechanism. Estimation of the crystallization rates at temperatures far below T (g) using the Avrami-Erofeev equation and Arrhenius equation showed that, to maintain its quality for at least three years, the solid dispersion should be stored at -20°C (T (g) - 65°C). IGC can be used to evaluate crystallization behavior on the surface of a solid dispersion powder, and, unlike traditional techniques, can also predict the stability of the solid dispersion based on the surface crystallization behavior.

Development of novel fast-dissolving tacrolimus solid dispersion-loaded prolonged release tablet.

PubMed

Cho, Jung Hyun; Kim, Yong-Il; Kim, Dong-Wuk; Yousaf, Abid Mehmood; Kim, Jong Oh; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

2014-04-11

The goal of this research was to develop a novel prolonged release tablet bioequivalent to the commercial sustained release capsule. A number of tacrolimus-loaded fast-dissolving solid dispersions containing various amounts of DOSS were prepared using the spray drying technique. Their solubility, dissolution and pharmacokinetics in rats were studied. DOSS increased drug solubility and dissolution in the solid dispersions. Compared with the drug powder, the solubility, dissolution and bioavailability of tacrolimus with the fast-dissolving solid dispersion containing tacrolimus/HP-β-CD/DOSS in the weight ratio of 5:40:4 were boosted by approximately 700-, 30- and 2-fold, respectively. Several tablet formulations were accomplished with this solid dispersion in combination with various ratios of HPMC/ethylcellulose. The release behaviour and pharmacokinetic studies in beagle dogs were assessed compared with the commercial prolonged release capsule. A decrease in HPMC/ethylcellulose ratios reduced the dissolution of tacrolimus from the tablets. Particularly, the tacrolimus-loaded prolonged release tablet consisting of fast-dissolving tacrolimus solid dispersion, HPMC, ethylcellulose and talc at the weight ratio of 20:66:112:2 exhibited a dissolution profile similar to that produced by the commercial prolonged release capsule. Furthermore, there were no significant differences in the AUC, Cmax, Tmax and MRT values between them in beagle dogs. Consequently, this tacrolimus-loaded prolonged release tablet might be bioequivalent to the tacrolimus-loaded commercial capsule. Copyright © 2013 Elsevier B.V. All rights reserved.

Improvement of the dissolution rate of artemisinin by means of supercritical fluid technology and solid dispersions.

PubMed

Van Nijlen, T; Brennan, K; Van den Mooter, G; Blaton, N; Kinget, R; Augustijns, P

2003-03-26

The purpose of this study was to enhance the dissolution rate of artemisinin in order to improve the intestinal absorption characteristics. The effect of: (1) micronisation and (2) formation of solid dispersions with PVPK25 was assessed in an in vitro dissolution system [dissolution medium: water (90%), ethanol (10%) and sodium lauryl sulphate (0.1%)]. Coulter counter analysis was used to measure particle size. X-ray diffraction and DSC were used to analyse the physical state of the powders. Micronisation by means of a jet mill and supercritical fluid technology resulted in a significant decrease in particle size as compared to untreated artemisinin. All powders appeared to be crystalline. The dissolution rate of the micronised forms improved in comparison to the untreated form, but showed no difference in comparison to mechanically ground artemisinin. Solid dispersions of artemisinin with PVPK25 as a carrier were prepared by the solvent method. Both X-ray diffraction and DSC showed that the amorphous state was reached when the amount of PVPK25 was increased to 67%. The dissolution rate of solid dispersions with at least 67% of PVPK25 was significantly improved in comparison to untreated and mechanically ground artemisinin. Modulation of the dissolution rate of artemisinin was obtained by both particle size reduction and formation of solid dispersions. The effect of particle size reduction on the dissolution rate was limited. Solid dispersions could be prepared by using a relatively small amount of PVPK25. The formation of solid dispersions with PVPK25 as a carrier appears to be a promising method to improve the intestinal absorption characteristics of artemisinin. Copyright 2003 Elsevier Science B.V.

Dielectric spectroscopy for the determination of the glass transition temperature of pharmaceutical solid dispersions.

PubMed

O'Donnell, Kevin P; Woodward, W H Hunter

2015-06-01

The purpose of this study was to evaluate analytical techniques for the measurement of the glass transition temperature of HPMC and formulated solid dispersions thereof. Unmodified samples of various grades of HPMC and solid dispersions of HPMC and itraconazole produced by hot melt extrusion were analyzed by thermomechanical analysis, differential scanning calorimetry, thermally stimulated depolarization current and dielectric spectroscopy. It was found that dielectric spectroscopy offers the best accuracy and reproducibility for analysis of the base HPMC powders regardless of the substitution type or viscosity grade and that the obtained results were not frequency dependent. The results of dielectric measurements of solid dispersions prepared by hot melt extrusion were compared with predicted values of the Gordon-Taylor equation. It was found that time-temperature superposition effects and small molecule frequency dependence makes broadly applying determination of the glass transition temperature in drug dispersions by dielectric spectroscopy prohibitively difficult.

Enhanced oral bioavailability of paclitaxel by solid dispersion granulation.

PubMed

Shanmugam, Srinivasan; Im, Ho Taek; Sohn, Young Taek; Kim, Yong-Il; Park, Jae-Hyun; Park, Eun-Seok; Woo, Jong Soo

2015-01-01

The main objective of this study was to develop novel orally administrable tablets containing solid dispersion granules (SDG) of amorphous paclitaxel (PTX) prepared by fluid bed technology, and to evaluate its in vitro dissolution and in vivo pharmacokinetics (PK) in beagle dogs. The SDG were prepared using optimized composition by fluid bed technology, and characterized for solid-state properties. The release study of SDG tablet (SDG-T) in simulated gastric fluid showed a rapid release of PTX, reaching maximum dissolution within 20 min. Finally, the PK profile of SDG-T and a reference formulation Oraxol™ (oral solution formulation used in Phase I clinical study) at a dose of 60 mg orally with co-administration of P-gp inhibitor HM38101, and Taxol® at a dose of 10 mg intravenously (i.v.) was investigated in beagle dogs. The mean absolute BA% of PTX following SDG-T and Oraxol™ solution was 8.23 and 6.22% in comparison to i.v. administration of Taxol®. The relative BA% of PTX from SDG-T in comparison to Oraxol™ solution was 132.25% at a dose of 60 mg following oral administration. In conclusion, we have successfully prepared PTX tablets with solid dispersion granules (SDG) of amorphous PTX using fluid bed technology that could provide plasma PTX concentration in the range of 10-150 ng/mL for a period of 24 h following oral administration in dogs with a P-gp inhibitor. Hence, this could be a promising formulation for PTX oral delivery and could be used in our intended clinical studies following pre-clinical efficacy studies.

Formulation and Characterization of Solid Dispersion Prepared by Hot Melt Mixing: A Fast Screening Approach for Polymer Selection

PubMed Central

Enose, Arno A.; Dasan, Priya K.; Sivaramakrishnan, H.; Shah, Sanket M.

2014-01-01

Solid dispersion is molecular dispersion of drug in a polymer matrix which leads to improved solubility and hence better bioavailability. Solvent evaporation technique was employed to prepare films of different combinations of polymers, plasticizer, and a modal drug sulindac to narrow down on a few polymer-plasticizer-sulindac combinations. The sulindac-polymer-plasticizer combination that was stable with good film forming properties was processed by hot melt mixing, a technique close to hot melt extrusion, to predict its behavior in a hot melt extrusion process. Hot melt mixing is not a substitute to hot melt extrusion but is an aid in predicting the formation of molecularly dispersed form of a given set of drug-polymer-plasticizer combination in a hot melt extrusion process. The formulations were characterized by advanced techniques like optical microscopy, differential scanning calorimetry, hot stage microscopy, dynamic vapor sorption, and X-ray diffraction. Subsequently, the best drug-polymer-plasticizer combination obtained by hot melt mixing was subjected to hot melt extrusion process to validate the usefulness of hot melt mixing as a predictive tool in hot melt extrusion process. PMID:26556187

Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs.

PubMed

Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J

2016-09-01

Poor water solubility of many drugs has emerged as one of the major challenges in the pharmaceutical world. Polymer-based amorphous solid dispersions have been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. The principle drawback of this approach is that they can lack necessary stability and revert to the crystalline form on storage. Significant upfront development is, therefore, required to generate stable amorphous formulations. A thorough understanding of the processes occurring at a molecular level is imperative for the rational design of amorphous solid dispersion products. This review attempts to address the critical molecular and thermodynamic aspects governing the physicochemical properties of such systems. A brief introduction to Biopharmaceutical Classification System, solid dispersions, glass transition, and solubility advantage of amorphous drugs is provided. The objective of this review is to weigh the current understanding of solid dispersion chemistry and to critically review the theoretical, technical, and molecular aspects of solid dispersions (amorphization and crystallization) and potential advantage of polymers (stabilization and solubilization) as inert, hydrophilic, pharmaceutical carrier matrices. In addition, different preformulation tools for the rational selection of polymers, state-of-the-art techniques for preparation and characterization of polymeric amorphous solid dispersions, and drug supersaturation in gastric media are also discussed. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design.

PubMed

Djuris, Jelena; Ioannis, Nikolakakis; Ibric, Svetlana; Djuric, Zorica; Kachrimanis, Kyriakos

2014-02-01

This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate. Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate. © 2013 Royal Pharmaceutical Society.

Stabilization of a supersaturated solution of mefenamic acid from a solid dispersion with EUDRAGIT(®) EPO.

PubMed

Kojima, Taro; Higashi, Kenjirou; Suzuki, Toyofumi; Tomono, Kazuo; Moribe, Kunikazu; Yamamoto, Keiji

2012-10-01

The stabilization mechanism of a supersaturated solution of mefenamic acid (MFA) from a solid dispersion with EUDRAGIT(®) EPO (EPO) was investigated. The solid dispersions were prepared by cryogenic grinding method. Powder X-ray diffractometry, in vitro dissolution test, in vivo oral absorption study, infrared spectroscopy, and solid- and solution-state NMR spectroscopies were used to characterize the solid dispersions. Dissolution tests in acetate buffer (pH 5.5) revealed that solid dispersion showed > 200-fold higher concentration of MFA. Supersaturated solution was stable over 1 month and exhibited improved oral bioavailability of MFA in rats, with a 7.8-fold higher area under the plasma concentration-versus-time curve. Solid-state (1)H spin-lattice relaxation time (T(1)) measurement showed that MFA was almost monomolecularly dispersed in the EPO polymer matrix. Intermolecular interaction between MFA and EPO was indicated by solid-state infrared and (13)C-T(1) measurements. Solution-state (1)H-NMR measurement demonstrated that MFA existed in monomolecular state in supersaturated solution. (1)H-T(1) and difference nuclear Overhauser effect measurements indicated that cross relaxation occurred between MFA and EPO due to the small distance between them. The formation and high stability of the supersaturated solution were attributable to the specifically formed intermolecular interactions between MFA and EPO.

Crystallization of amorphous solid dispersions of resveratrol during preparation and storage-Impact of different polymers.

PubMed

Wegiel, Lindsay A; Mauer, Lisa J; Edgar, Kevin J; Taylor, Lynne S

2013-01-01

The objective of this study was to investigate intermolecular interactions between resveratrol and polymers in amorphous blends and to study the potential correlations between compound-polymer interactions, manufacturability, and stability of the amorphous system to crystallization during storage. Polymers included two grades of poly (vinylpyrrolidone) (PVP), Eudragit E100 (E100), hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMCAS), carboxymethyl cellulose acetate butyrate, and poly (acrylic acid) (PAA). Amorphous blends ("solid dispersions") were prepared by dissolving both resveratrol and polymer in a solvent followed by rotary evaporation. Crystallinity was evaluated using X-ray powder diffraction and was studied as a function of time. Mid-infrared (IR) spectroscopy was used to investigate resveratrol-polymer interactions. Polymer influence on the crystallization behavior of resveratrol varied and could be correlated to the polymer structure, whereby polymers with good hydrogen bond acceptor groups performed better as crystallization inhibitors. Resveratrol-polymer hydrogen bonding interactions could be inferred from the IR spectra. Somewhat surprisingly, E100 and resveratrol showed evidence of an acid-base reaction, in addition to intermolecular hydrogen bonding interactions. PVP K29/32 appeared to form stronger hydrogen bond interactions with resveratrol relative to HPMC, HPMCAS, and PAA, consistent with acceptor group chemistry. Long-term stability of the systems against crystallization suggested that stability is linked to the type and strength of intermolecular interactions present. whereby resveratrol blended with E100 and PVP K29/32 showed the greatest stability to crystallization. In conclusion, amorphous resveratrol is unstable and difficult to form, requiring the assistance of a polymeric crystallization inhibitor to facilitate the formation of an amorphous solid dispersion. Polymers effective at inhibiting

Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers.

PubMed

Xu, Wei-Juan; Xie, Hong-Juan; Cao, Qing-Ri; Shi, Li-Li; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

2016-01-01

This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.

Site specific solubility improvement using solid dispersions of HPMC-AS/HPC SSL--mixtures.

PubMed

Zecevic, Damir Elmar; Meier, Robin; Daniels, Rolf; Wagner, Karl-Gerhard

2014-07-01

Many upcoming drug candidates are pH-dependent poorly soluble weak bases in the pH range of the gastrointestinal tract. This often leads to a high in vivo variability and bioavailability issues. Aiming to overcome these limitations, the design of solid dispersions for site specific dissolution improvement or maintenance of a potent supersaturation over the entire gastro-intestinal pH-range, is proposed to assure a reliable drug therapy. Solid dispersions containing different ratios of Dipyridamole (DPD) or Griseofulvin (GRI) and the enteric polymer hydroxypropylmethylcellulose-acetate succinate (HPMC-AS) and the water soluble low-viscosity hydroxypropylcellulose (HPC-SSL) were prepared by hot melt extrusion (HME). The solid dispersions were evaluated for their solid state, dissolution characteristics applying a three pH-step dissolution method following an acidic to neutral pH transition and stability. The use of HPMC-AS in binary mixtures with DPD and GRI facilitated increased solubility and supersaturation at pH-controlled release of the preserved amorphous state of the dispersed drug, which even inverted the pH-dependent solubility profile of the weakly basic model drug (Dipyridamole). I.e. a potent site specific delivery system was created. With ternary solid dispersions of API, HPMC-AS and HPC-SSL, tailored release profiles with superior supersaturation over the applied pH-range could be obtained. At the same time, binary and ternary mixtures showed favorable stability properties at a temperature difference between glass transition temperature and the applied storage temperature of down to 16°C. Copyright © 2014 Elsevier B.V. All rights reserved.

New metastable form of glibenclamide prepared by redispersion from ternary solid dispersions containing polyvinylpyrrolidone-K30 and sodium lauryl sulfate.

PubMed

Thongnopkoon, Thanu; Puttipipatkhachorn, Satit

2016-01-01

Modification of polymorphic forms of poorly water-soluble drugs is one way to achieve the desirable properties. In this study, glibenclamide (GBM) particles with different polymorphic forms, including a new metastable form, were obtained from redispersion of ternary solid dispersion systems. The ternary solid dispersion systems, consisting of GBM, polyvinylpyrrolidone-K30 (PVP-K30) and sodium lauryl sulfate (SLS), were prepared by solvent evaporation method and subsequently redispersed in deionized water. The precipitated drug particles were then collected at a given time period. The drug particles with different polymorphic forms could be achieved depending on the polymer/surfactant ratio. Amorphous drug nanoparticles could be obtained by using a high polymer/surfactant ratio, whereas two different crystalline forms were obtained from the systems containing low polymer/surfactant ratios. Interestingly, a new metastable form IV of GBM with improved dissolution behavior could be obtained from the system of GBM:PVP-K30:SLS with the weight ratio of 2:2:4. This new polymorphic form IV of GBM was confirmed by differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffractometry (PXRD) and solid state 13 C nuclear magnetic resonance (NMR) spectroscopy. The molecular arrangement of the new polymorphic form IV of GBM was proposed. The GBM particles with polymorphic form IV also showed an improved dissolution behavior. In addition, it was found that the formation of the new polymorphic form IV of GBM by this process was reproducible.

Fusion processing of itraconazole solid dispersions by kinetisol dispersing: a comparative study to hot melt extrusion.

PubMed

DiNunzio, James C; Brough, Chris; Miller, Dave A; Williams, Robert O; McGinity, James W

2010-03-01

KinetiSol Dispersing (KSD) is a novel high energy manufacturing process investigated here for the production of pharmaceutical solid dispersions. Solid dispersions of itraconazole (ITZ) and hypromellose were produced by KSD and compared to identical formulations produced by hot melt extrusion (HME). Materials were characterized for solid state properties by modulated differential scanning calorimetry and X-ray diffraction. Dissolution behavior was studied under supersaturated conditions. Oral bioavailability was determined using a Sprague-Dawley rat model. Results showed that KSD was able to produce amorphous solid dispersions in under 15 s while production by HME required over 300 s. Dispersions produced by KSD exhibited single phase solid state behavior indicated by a single glass transition temperature (T(g)) whereas compositions produced by HME exhibited two T(g)s. Increased dissolution rates for compositions manufactured by KSD were also observed compared to HME processed material. Near complete supersaturation was observed for solid dispersions produced by either manufacturing processes. Oral bioavailability from both processes showed enhanced AUC compared to crystalline ITZ. Based on the results presented from this study, KSD was shown to be a viable manufacturing process for the production of pharmaceutical solid dispersions, providing benefits over conventional techniques including: enhanced mixing for improved homogeneity and reduced processing times. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Physicochemical stability, pharmacokinetic, and biodistribution evaluation of paclitaxel solid dispersion prepared using supercritical antisolvent process.

PubMed

Shanmugam, Srinivasan; Park, Jae-Hyun; Chi, Sang-Cheol; Yong, Chul Soon; Choi, Han-Gon; Woo, Jong Soo

2011-06-01

To investigate the physicochemical stability, pharmacokinetics (PK), and biodistribution of paclitaxel (PTX) from paclitaxel solid dispersion (PSD) prepared by supercritical antisolvent (SAS) process. Physicochemical stability was performed in accelerated (40°C 70 ± 5% RH) and stress (60°C) storage conditions for a period of 6 months and 4 weeks, respectively. PK and biodistribution studies were performed in rats following i.v. administration of PTX equivalent to 6 and 12 mg/kg formulations. Physical stability of PSD showed excellent stability with no recrystallization of the amorphous form. Chemical stability of PSD in terms of % PTX remaining was 98.2 ± 0.6% at 6 months and 97.9 ± 0.3% at 4 weeks of accelerated and stress conditions, respectively. The PK study showed a nonlinear increase in AUC with increasing dose, that is, 100% increase in dose (from 6 to 12 mg/kg) resulted in 405.90% increase in AUC. Unlike PK study, the organ distribution study of PTX from PSD showed linear relationship with dose escalation. The order of organ distribution of PTX from highest to lowest for both PSD and Taxol® was liver>kidney>lung>brain. This study demonstrated excellent physicochemical stability with insight information on the PK and biodistribution of PTX from PSD prepared by SAS process.

All-solid-state flexible supercapacitors based on highly dispersed polypyrrole nanowire and reduced graphene oxide composites.

PubMed

Yu, Chenfei; Ma, Peipei; Zhou, Xi; Wang, Anqi; Qian, Tao; Wu, Shishan; Chen, Qiang

2014-10-22

Highly dispersed polypyrrole nanowires are decorated on reduced graphene oxide sheets using a facile in situ synthesis route. The prepared composites exhibit high dispersibility, large effective surface area, and high electric conductivity. All-solid-state flexible supercapacitors are assembled based on the prepared composites, which show excellent electrochemical performances with a specific capacitance of 434.7 F g(-1) at a current density of 1 A g(-1). The as-fabricated supercapacitor also exhibits excellent cycling stability (88.1% capacitance retention after 5000 cycles) and exceptional mechanical flexibility. In addition, outstanding power and energy densities were obtained, demonstrating the significant potential of prepared material for flexible and portable energy storage devices.

Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol.

PubMed

Song, Im-Sook; Cha, Jin-Sun; Choi, Min-Koo

2016-10-17

The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 ( w / w / w ). The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion formulation within 10 min. After administering the formulation orally to rats, higher plasma concentrations of curcumin were observed, with increases in the maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) of 86- and 65-fold, respectively, compared with those of curcumin powder. The solid dispersion formulation effectively increased intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion formulation of curcumin with TPGS and mannitol could be a promising option for enhancing the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate, cell permeability, and P-gp modulation.

Effects of polymer type and storage relative humidity on the kinetics of felodipine crystallization from amorphous solid dispersions.

PubMed

Rumondor, Alfred C F; Stanford, Lindsay A; Taylor, Lynne S

2009-12-01

The objective of this study was to investigate the effects of polymer type and storage relative humidity (RH) on the crystallization kinetics of felodipine from amorphous solid dispersions. Crystallization of the model drug felodipine from amorphous solid dispersion samples containing poly(vinyl pyrrolidone) (PVP) and hypromellose acetate succinate (HPMCAS) were evaluated. Samples at three different drug-polymer weight ratios (10, 25, and 50 wt. % polymer) were prepared and stored at six different RHs (0%, 32%, 52% or 66%, 75%, 86%, and 93%). Periodically, the fraction of the drug that had crystallized from the samples was quantified using powder X-ray diffractometry (PXRD). Felodipine crystallization rates from PVP-containing dispersions were found to be very sensitive to changes in storage RH, while crystallization rates from HPMCAS-containing dispersions were not. PVP and HPMCAS were similar in terms of their ability to inhibit crystallization at low RH, but when the storage RH was increased to 75% or above, felodipine crystallization from PVP-containing solid dispersions proceeded much faster. It is hypothesized that this trend was caused by moisture-induced drug-polymer immiscibility in PVP-felodipine system. For PVP-containing solid dispersion samples stored at 75% RH and above, crystallization of the model drug felodipine seemed to approach a kinetic plateau, whereby a fraction of the drug still remained amorphous even after storage for 500 days or more. The physical stability of solid dispersions as a function of RH is highly dependent on the polymer used to form the solid dispersion, with PVP-containing dispersions being much less physically stable at high RH than HPMCAS-containing dispersions.

Formulation and optimization of spray-dried amlodipine solid dispersion for enhanced oral absorption.

PubMed

Jang, Dong-Jin; Sim, Taeyong; Oh, Euichaul

2013-07-01

To enhance the oral absorption of photosensitive amlodipine free base, which exhibits a slow dissolution rate and low permeability characteristics, an amorphous solid dispersion system was formulated and characterized. The solid dispersion was prepared by dispersing the amlodipine free base in excess dextrin (1:10 by weight) using a spray-drying technique in the presence of a minimum amount (0.9% w/w) of SLS as an absorption enhancer. The dextrin-based solid dispersion of amlodipine (Amlo-SD) was evaluated in term of formulation, characterization and in vivo absorption study, as well as the spray-drying process was also optimized. The Amlo-SD particles were spherical with a smooth surface and an average particle size of 12.9 μm. Amlodipine was dispersed in an amorphous state and its content remained uniform in the Amlo-SD. The physicochemical stability of the Amlo-SD was maintained at room temperature for 6 months and the photostability was considerably improved. The dissolution of the Amlo-SD was much faster than that of amlodipine at pH 1.2 and 6.8. Amlo-SD produced significantly higher plasma concentrations of amlodipine in rats than amlodipine alone. Amlo-SD with and without SLS provided 2.8- and 2.0-fold increase in AUC, respectively: the difference seems to be attributed to a permeability enhancement effect by SLS. The Amlo-SD with SLS system is a potential formulation option for amlodipine.

The Influence of Drug Physical State on the Dissolution Enhancement of Solid Dispersions Prepared Via Hot-Melt Extrusion: A Case Study Using Olanzapine

PubMed Central

Pina, Maria Fátima; Zhao, Min; Pinto, João F; Sousa, João J; Craig, Duncan Q M

2014-01-01

In this study, we examine the relationship between the physical structure and dissolution behavior of olanzapine (OLZ) prepared via hot-melt extrusion in three polymers [polyvinylpyrrolidone (PVP) K30, polyvinylpyrrolidone-co-vinyl acetate (PVPVA) 6:4, and Soluplus® (SLP)]. In particular, we examine whether full amorphicity is necessary to achieve a favorable dissolution profile. Drug–polymer miscibility was estimated using melting point depression and Hansen solubility parameters. Solid dispersions were characterized using differential scanning calorimetry, X-ray powder diffraction, and scanning electron microscopy. All the polymers were found to be miscible with OLZ in a decreasing order of PVP>PVPVA>SLP. At a lower extrusion temperature (160°C), PVP generated fully amorphous dispersions with OLZ, whereas the formulations with PVPVA and SLP contained 14%–16% crystalline OLZ. Increasing the extrusion temperature to 180°C allowed the preparation of fully amorphous systems with PVPVA and SLP. Despite these differences, the dissolution rates of these preparations were comparable, with PVP showing a lower release rate despite being fully amorphous. These findings suggested that, at least in the particular case of OLZ, the absence of crystalline material may not be critical to the dissolution performance. We suggest alternative key factors determining dissolution, particularly the dissolution behavior of the polymers themselves. PMID:24765654

[Pharmacological researches of curcumin solid dispersions in treatment of cancer].

PubMed

Mei, Xue-Ting; Xu, Dong-Hui; He, Xue-Ni; Lu, Yong-Chang

2012-10-01

To investigate the anticancer effect of curcumin Solid Dispersions (SDs). Curcumin SDs were prepared by patent technology. The anticancer effect of curcumin SDs were investigated by vivo and vitro tests of SCG-7901, BEL-7402, S-180 and Ehrlich ascites tumor models. The results showed that Curcumin SDs had markedly anticancer effect and could improve the anticancer effect of cisplatin. Curcumin SDs could be developed into one kind of adjuvant drug for anticancer, as it has markedly anticancer effect, and could improve the anticancer effects of cisplatin.

Amorphous stabilization and dissolution enhancement of amorphous ternary solid dispersions: combination of polymers showing drug-polymer interaction for synergistic effects.

PubMed

Prasad, Dev; Chauhan, Harsh; Atef, Eman

2014-11-01

The purpose of this study was to understand the combined effect of two polymers showing drug-polymer interactions on amorphous stabilization and dissolution enhancement of indomethacin (IND) in amorphous ternary solid dispersions. The mechanism responsible for the enhanced stability and dissolution of IND in amorphous ternary systems was studied by exploring the miscibility and intermolecular interactions between IND and polymers through thermal and spectroscopic analysis. Eudragit E100 and PVP K90 at low concentrations (2.5%-40%, w/w) were used to prepare amorphous binary and ternary solid dispersions by solvent evaporation. Stability results showed that amorphous ternary solid dispersions have better stability compared with amorphous binary solid dispersions. The dissolution of IND from the ternary dispersion was substantially higher than the binary dispersions as well as amorphous drug. Melting point depression of physical mixtures reveals that the drug was miscible in both the polymers; however, greater miscibility was observed in ternary physical mixtures. The IR analysis confirmed intermolecular interactions between IND and individual polymers. These interactions were found to be intact in ternary systems. These results suggest that the combination of two polymers showing drug-polymer interaction offers synergistic enhancement in amorphous stability and dissolution in ternary solid dispersions. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus.

PubMed

Lavra, Zênia Maria Maciel; Pereira de Santana, Davi; Ré, Maria Inês

2017-01-01

Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus ® ) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus ® at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40 °C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug-polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus ® , when protected from moisture.

Relationships between solid dispersion preparation process, particle size and drug release--an NMR and NMR microimaging study.

PubMed

Dahlberg, Carina; Millqvist-Fureby, Anna; Schuleit, Michael; Furó, István

2010-10-01

Solid dispersion tablets prepared by either spray drying or rotoevaporation and exhibiting different grain and pore sizes were investigated under the process of hydration-swelling-gelation. (2)H and (1)H NMR microimaging experiments were used to selectively follow water penetration and polymer mobilization kinetics, respectively, while the drug release kinetics was followed by (1)H NMR spectroscopy. The obtained data, in combination with morphological information by scanning electron microscopy (SEM), reveal a complex process that ultimately leads to release of the drug into the aqueous phase. We find that the rate of water ingress has no direct influence on release kinetics, which also renders air in the tablets a secondary factor. On the other hand, drug release is directly correlated with the polymer mobilization kinetics. Water diffusion into the originally dry polymer grains determines the rate of grain swelling and the hydration within the grains varies strongly with grain size. We propose that this sets the stage for creating homogeneous gels for small grain sizes and heterogeneous gels for large grain sizes. Fast diffusion through water-rich sections of the inhomogeneous gels that exhibit a large mesh size is the factor which yields a faster drug release from tablets prepared by rotoevaporation. Copyright © 2010. Published by Elsevier B.V.

Effect of Compression on the Molecular Arrangement of Itraconazole-Soluplus Solid Dispersions: Induction of Liquid Crystals or Exacerbation of Phase Separation?

PubMed

Singh, Abhishek; Bharati, Avanish; Frederiks, Pauline; Verkinderen, Olivier; Goderis, Bart; Cardinaels, Ruth; Moldenaers, Paula; Van Humbeeck, Jan; Van den Mooter, Guy

2016-06-06

Predensification and compression are unit operations imperative to the manufacture of tablets and capsules. Such stress-inducing steps can cause destabilization of solid dispersions which can alter their molecular arrangement and ultimately affect dissolution rate and bioavailability. In this study, itraconazole-Soluplus solid dispersions with 50% (w/w) drug loading prepared by hot-melt extrusion (HME) were investigated. Compression was performed at both pharmaceutically relevant and extreme compression pressures and dwell times. The starting materials, powder, and compressed solid dispersions were analyzed using modulated differential scanning calorimetry (MDSC), X-ray diffraction (XRD), small- and wide-angle X-ray scattering (SWAXS), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and broadband dielectric spectroscopy (BDS). MDSC analysis revealed that compression promotes phase separation of solid dispersions as indicated by an increase in glass transition width, occurrence of a peak in the nonreversing heat flow signal, and an increase in the net heat of fusion indicating crystallinity in the systems. SWAXS analysis ruled out the presence of mesophases. BDS measurements elucidated an increase in the Soluplus-rich regions of the solid dispersion upon compression. FTIR indicated changes in the spatiotemporal architecture of the solid dispersions mediated via disruption in hydrogen bonding and ultimately altered dynamics. These changes can have significant consequences on the final stability and performance of the solid dispersions.

Solid dispersion tablets of breviscapine with polyvinylpyrrolidone K30 for improved dissolution and bioavailability to commercial breviscapine tablets in beagle dogs.

PubMed

Cong, Wenjuan; Shen, Lan; Xu, Desheng; Zhao, Lijie; Ruan, Kefeng; Feng, Yi

2014-09-01

Breviscapine, one of cardiovascular drugs extracted from a Chinese herb Erigeron breviscapinus, has been frequently used to treat cardiovascular diseases such as hypertension, angina pectoris, coronary heart disease and stroke. However, its poor water solubility and low bioavailability in vivo severely restrict the clinical application. To overcome these drawbacks, breviscapine solid dispersion tablets consisting of breviscapine, polyvinylpyrrolidone K30 (PVP K30), microcrystalline cellulose and crospovidone were appropriately prepared. In vitro dissolution profiles showed that breviscapine released percentage of solid dispersion tablets reached 90 %, whereas it was only 40 % for commercial breviscapine tablets. Comparative pharmacokinetic study between solid dispersion tablets and commercial products was investigated on the normal beagle dogs after oral administration. Results showed that the bioavailability of breviscapine was greatly increased by 3.45-fold for solid dispersion tablets. The greatly improved dissolution rate and bioavailability might be attributed to intermolecular hydrogen bonding reactions between PVP K30 and scutellarin. These findings suggest that our solid dispersion tablets can greatly improve the bioavailability as well as the dissolution rate of breviscapine.

Controlled release systems containing solid dispersions: strategies and mechanisms.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

2011-10-01

In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

Solid-state characterization and dissolution properties of meloxicam-moringa coagulant-PVP ternary solid dispersions.

PubMed

Noolkar, Suhail B; Jadhav, Namdeo R; Bhende, Santosh A; Killedar, Suresh G

2013-06-01

The effect of ternary solid dispersions of poor water-soluble NSAID meloxicam with moringa coagulant (obtained by salt extraction of moringa seeds) and polyvinylpyrrolidone on the in vitro dissolution properties has been investigated. Binary (meloxicam-moringa and meloxicam-polyvinylpyrrolidone (PVP)) and ternary (meloxicam-moringa-PVP) systems were prepared by physical kneading and ball milling and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry. The in vitro dissolution behavior of meloxicam from the different products was evaluated by means of United States Pharmacopeia type II dissolution apparatus. The results of solid-state studies indicated the presence of strong interactions between meloxicam, moringa, and PVP which were of totally amorphous nature. All ternary combinations were significantly more effective than the corresponding binary systems in improving the dissolution rate of meloxicam. The best performance in this respect was given by the ternary combination employing meloxicam-moringa-PVP ratio of [1:(3:1)] prepared by ball milling, with about six times increase in percent dissolution rate, whereas meloxicam-moringa (1:3) and meloxicam-PVP (1:4) prepared by ball milling improved dissolution of meloxicam by almost 3- and 2.5-folds, respectively. The achieved excellent dissolution enhancement of meloxicam in the ternary systems was attributed to the combined effects of impartation of hydrophilic characteristic by PVP, as well as to the synergistic interaction between moringa and PVP.

Comparative study on solid self-nanoemulsifying drug delivery and solid dispersion system for enhanced solubility and bioavailability of ezetimibe

PubMed Central

Rashid, Rehmana; Kim, Dong Wuk; Yousaf, Abid Mehmood; Mustapha, Omer; Din, Fakhar ud; Park, Jong Hyuck; Yong, Chul Soon; Oh, Yu-Kyoung; Youn, Yu Seok; Kim, Jong Oh; Choi, Han-Gon

2015-01-01

Background The objective of this study was to compare the physicochemical characteristics, solubility, dissolution, and oral bioavailability of an ezetimibe-loaded solid self-nanoemulsifying drug delivery system (SNEDDS), surface modified solid dispersion (SMSD), and solvent evaporated solid dispersion (SESD) to identify the best drug delivery system with the highest oral bioavailability. Methods For the liquid SNEDDS formulation, Capryol 90, Cremophor EL, and Tween 80 were selected as the oil, surfactant, and cosurfactant, respectively. The nanoemulsion-forming region was sketched using a pseudoternary phase diagram on the basis of reduced emulsion size. The optimized liquid SNEDDS was converted to solid SNEDDS by spray drying with silicon dioxide. Furthermore, SMSDs were prepared using the spray drying technique with various amounts of hydroxypropylcellulose and Tween 80, optimized on the basis of their drug solubility. The SESD formulation was prepared with the same composition of optimized SMSD. The aqueous solubility, dissolution, physicochemical properties, and pharmacokinetics of all of the formulations were investigated and compared with the drug powder. Results The drug existed in the crystalline form in SMSD, but was changed into an amorphous form in SNEDDS and SESD, giving particle sizes of approximately 24, 6, and 11 µm, respectively. All of these formulations significantly improved the aqueous solubility and dissolution in the order of solid SNEDDS ≥ SESD > SMSD, and showed a total higher plasma concentration than did the drug powder. Moreover, SESD gave a higher area under the drug concentration time curve from zero to infinity than did SNEDDS and SMSD, even if they were not significantly different, suggesting more improved oral bioavailability. Conclusion Among the various formulations tested in this study, the SESD system would be strongly recommended as a drug delivery system for the oral administration of ezetimibe with poor water solubility

The effects of polymer carrier, hot melt extrusion process and downstream processing parameters on the moisture sorption properties of amorphous solid dispersions.

PubMed

Feng, Xin; Vo, Anh; Patil, Hemlata; Tiwari, Roshan V; Alshetaili, Abdullah S; Pimparade, Manjeet B; Repka, Michael A

2016-05-01

The aim of this study was to evaluate the effect of polymer carrier, hot melt extrusion and downstream processing parameters on the water uptake properties of amorphous solid dispersions. Three polymers and a model drug were used to prepare amorphous solid dispersions utilizing the hot melt extrusion technology. The sorption-desorption isotherms of solid dispersions and their physical mixtures were measured by the dynamic vapour sorption system, and the effects of polymer hydrophobicity, hygroscopicity, molecular weight and the hot melt extrusion process were investigated. Fourier transform infrared (FTIR) imaging was performed to understand the phase separation driven by the moisture. Solid dispersions with polymeric carriers with lower hydrophilicity, hygroscopicity and higher molecular weight could sorb less moisture under the high relative humidity (RH) conditions. The water uptake ability of polymer-drug solid dispersion systems were decreased compared with the physical mixture after hot melt extrusion, which might be due to the decreased surface area and porosity. The FTIR imaging indicated that the homogeneity of the drug molecularly dispersed within the polymer matrix was changed after exposure to high RH. Understanding the effect of formulation and processing on the moisture sorption properties of solid dispersions is essential for the development of drug products with desired physical and chemical stability. © 2015 Royal Pharmaceutical Society.

The Effects of Polymer Carrier, Hot Melt Extrusion Process and Downstream Processing Parameters on the Moisture Sorption Properties of Amorphous Solid Dispersions

PubMed Central

Feng, Xin; Vo, Anh; Patil, Hemlata; Tiwari, Roshan V.; Alshetaili, Abdullah S.; Pimparade, Manjeet B.; Repka, Michael A.

2017-01-01

Objective The aim of this study was to evaluate the effect of polymer carrier, hot melt extrusion (HME) and downstream processing parameters on the water uptake properties of amorphous solid dispersions. Methods Three polymers and a model drug were used to prepare amorphous solid dispersions utilizing HME technology. The sorption-desorption isotherms of solid dispersions and their physical mixtures were measured by the Dynamic Vapor Sorption system, and the effect of polymer hydrophobicity, hygroscopicity, molecular weight and the HME process were investigated. FTIR imaging was performed to understand the phase separation driven by the moisture. Key findings Solid dispersions with polymeric carriers with lower hydrophilicity, hygroscopicity, and higher molecular weight could sorb less moisture under the high RH conditions. The water uptake ability of polymer-drug solid dispersion systems were decreased compared to the physical mixture after HME, which might be due to the decreased surface area and porosity. The FTIR imaging indicated the homogeneity of the drug molecularly dispersed within the polymer matrix was changed after exposure to high RH. Conclusion Understanding the effect of formulation and processing on the moisture sorption properties of solid dispersions is essential for the development of drug products with desired physical and chemical stability. PMID:26589107

Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniques.

PubMed

van Drooge, D J; Hinrichs, W L J; Visser, M R; Frijlink, H W

2006-03-09

The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)-diazepam and inulin-diazepam was studied. One glass transition temperature (T(g)), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP-diazepam solid dispersions prepared by fusion for all drug loads tested (10-80 wt.%). The T(g) of these solid dispersions gradually changed with composition and decreased from 177 degrees C for pure PVP to 46 degrees C for diazepam. These observations indicate that diazepam was dispersed in PVP on a molecular level. However, in PVP-diazepam solid dispersions prepared by freeze drying, two T(g)'s were observed for drug loads above 35 wt.% indicating phase separation. One T(g) indicated the presence of amorphous diazepam clusters, the other T(g) was attributed to a PVP-rich phase in which diazepam was dispersed on a molecular level. With both the value of the latter T(g) and the DeltaC(p) of the diazepam glass transition the concentrations of molecular dispersed diazepam could be calculated (27-35 wt.%). Both methods gave similar results. Water vapour sorption (DVS) experiments revealed that the PVP-matrix was hydrophobised by the incorporated diazepam. TMDSC and DVS results were used to estimate the size of diazepam clusters in freeze dried PVP-diazepam solid dispersions, which appeared to be in the nano-meter range. The inulin-diazepam solid dispersions prepared by spray freeze drying showed one T(g) for drug loads up to 35 wt.% indicating homogeneous distribution on a molecular level. However, this T(g) was independent of the drug load, which is unexpected because diazepam has a lower T(g) than inulin (46 and 155 degrees C, respectively). For higher drug loads, a T(g) of diazepam as well as a T(g) of the inulin-rich phase was observed, indicating the formation of amorphous diazepam clusters. From the DeltaC(p) of the diazepam glass transition the amount of molecularly dispersed

Solid dispersions of Myricetin with enhanced solubility: Formulation, characterization and crystal structure of stability-impeding Myricetin monohydrate crystals

NASA Astrophysics Data System (ADS)

Mureşan-Pop, M.; Pop, M. M.; Borodi, G.; Todea, M.; Nagy-Simon, T.; Simon, S.

2017-08-01

Three solid dispersion forms of Myricetin combined with the Polyvinylpyrrolidone were successfully prepared by spray drying method, and characterized by X-ray powder diffraction, thermal analysis, infrared spectroscopy and optical microscopy. Zeta potential measurements provided indications on solid dispersions stability in aqueous suspension related to their storage at elevated temperature and relative humidity, which depends on the Myricetin load. By increase of Myricetin load, the stability of the solid dispersion is impeded due to growth of Myricetin monohydrate crystals. The amorphous dispersions with 10% and 50% Myricetin load are stable and, compared to pure Myricetin, their aqueous solubility is enhanced by a factor of 47 and 13, respectively. The dispersion with 80% Myricetin load is unstable on storage, and this behavior acts in conjunction with the development of Myricetin monohydrate crystals. Single-crystal X-ray diffraction results obtained for Myricetin monohydrate reveal a structure of an infinite 2D network of hydrogen-bonded molecules involving all six hydroxyl groups of Myricetin. The water molecules are positioned in between the infinite chains, and contribute via H-bonds to robust crystal packing. The calculated needle-like morphology of monohydrate form is in agreement with the optical microscopy results. The study shows that the solid amorphous dispersions with up to 50% Myricetin load are a viable option for achieving substantial solubility improvement of Myricetin, and supports their potential use in pharmaceutical applications.

Both solubility and chemical stability of curcumin are enhanced by solid dispersion in cellulose derivative matrices.

PubMed

Li, Bin; Konecke, Stephanie; Wegiel, Lindsay A; Taylor, Lynne S; Edgar, Kevin J

2013-10-15

Amorphous solid dispersions (ASD) of curcumin (Cur) in cellulose derivative matrices, hydroxypropylmethylcellulose acetate succinate (HPMCAS), carboxymethylcellulose acetate butyrate (CMCAB), and cellulose acetate adipate propionate (CAAdP) were prepared in order to investigate the structure-property relationship and identify polymer properties necessary to effectively increase Cur aqueous solution concentration. XRD results indicated that all investigated solid dispersions were amorphous, even at a 9:1 Cur:polymer ratio. Both stability against crystallization and Cur solution concentration from these ASDs were significantly higher than those from physical mixtures and crystalline Cur. Remarkably, curcumin was also stabilized against chemical degradation in solution. Chemical stabilization was polymer-dependent, with stabilization in CAAdP>CMCAB>HPMCAS>PVP, while matrices enhanced solution concentration as PVP>HPMCAS>CMCAB≈CAAdP. HPMCAS/Cur dispersions have useful combinations of pH-triggered release profile, chemical stabilization, and strong enhancement of Cur solution concentration. Copyright © 2013 Elsevier Ltd. All rights reserved.

Bioavailability enhancement of a poorly water-soluble drug by solid dispersion in polyethylene glycol-polysorbate 80 mixture.

PubMed

Joshi, Hemant N; Tejwani, Ravindra W; Davidovich, Martha; Sahasrabudhe, Vaishali P; Jemal, Mohammed; Bathala, Mohinder S; Varia, Sailesh A; Serajuddin, Abu T M

2004-01-09

Oral bioavailability of a poorly water-soluble drug was greatly enhanced by using its solid dispersion in a surface-active carrier. The weakly basic drug (pK(a) approximately 5.5) had the highest solubility of 0.1mg/ml at pH 1.5, < 1 microg/ml aqueous solubility between pH 3.5 and 5.5 at 24+/-1 degrees C, and no detectable solubility (< 0.02 microg/ml) at pH greater than 5.5. Two solid dispersion formulations of the drug, one in Gelucire 44/14 and another one in a mixture of polyethylene glycol 3350 (PEG 3350) with polysorbate 80, were prepared by dissolving the drug in the molten carrier (65 degrees C) and filling the melt in hard gelatin capsules. From the two solid dispersion formulations, the PEG 3350-polysorbate 80 was selected for further development. The oral bioavailability of this formulation in dogs was compared with that of a capsule containing micronized drug blended with lactose and microcrystalline cellulose and a liquid solution in a mixture of PEG 400, polysorbate 80 and water. For intravenous administration, a solution in a mixture of propylene glycol, polysorbate 80 and water was used. Absolute oral bioavailability values from the capsule containing micronized drug, the capsule containing solid dispersion and the oral liquid were 1.7+/-1.0%, 35.8+/-5.2% and 59.6+/-21.4%, respectively. Thus, the solid dispersion provided a 21-fold increase in bioavailability of the drug as compared to the capsule containing micronized drug. A capsule formulation containing 25 mg of drug with a total fill weight of 600 mg was subsequently selected for further development. The selected solid dispersion formulation was physically and chemically stable under accelerated storage conditions for at least 6 months. It is hypothesized that polysorbate 80 ensures complete release of drug in a metastable finely dispersed state having a large surface area, which facilitates further solubilization by bile acids in the GI tract and the absorption into the enterocytes. Thus, the

Development of solid dispersions of artemisinin for transdermal delivery.

PubMed

Shahzad, Yasser; Sohail, Sadia; Arshad, Muhammad Sohail; Hussain, Talib; Shah, Syed Nisar Hussain

2013-11-30

Solid dispersions of the poorly soluble drug artemisinin were developed using polymer blends of polyvinylpyrrolidone (PVP) and polyethylene glycol (PEG) with the aim of enhancing solubility and in vitro permeation of artemisinin through skin. Formulations were characterised using a combination of molecular dynamics (MD) simulations, differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FT-IR). Solubility of artemisinin was determined in two solvents: de-ionised water and phosphate buffered saline (PBS; pH 7.4), while in vitro drug permeation studies were carried out using rabbit skin as a model membrane. MD simulations revealed miscibility between the drug and polymers. DSC confirmed the molecular dispersion of the drug in the polymer blend. Decrease in crystallinity of artemisinin with respect to polymer content and the absence of specific drug-polymer interactions were confirmed using XRD and FT-IR, respectively. The solubility of artemisinin was dramatically enhanced for the solid dispersions, as was the permeation of artemisinin from saturated solid-dispersion vehicles relative to that from saturated solutions of the pure drug. The study suggests that high energy solid forms of artemisinin could possibly enable transdermal delivery of artemisinin. Copyright © 2013 Elsevier B.V. All rights reserved.

Physiochemical Characterization and Release Rate Studies of SolidDispersions of Ketoconazole with Pluronic F127 and PVP K-30

PubMed Central

Kumar, Pankaj; Mohan, Chander; KanamSrinivasan Uma Shankar, Mara; Gulati, Monica

2011-01-01

In the present study solid dispersions of the antifungal drug Ketoconazole were prepared with Pluronic F-127 and PVP K-30 with an intention to improve its dissolution properties. Investigations of the properties of the dispersions were performed using release studies, Differential scanning calorimetery (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR). The results obtained showed that the rate of dissolution of Ketoconazole was considerably improved when formulated in solid dispersions with PVP K-30 and Pluronic F-127 as compared with pure drug and physical mixtures. The results from DSC and XRD studies showed the transition of crystalline nature of drug to amorphous form, while FTIR studies demonstrated the absence of drug-carriers interaction. PMID:24250403

Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation

PubMed Central

Feng, Xin; Ye, Xingyou; Park, Jun-Bom; Lu, Wenli; Morott, Joe; Beissner, Brad; Lian, Zhuoyang John; Pinto, Elanor; Bi, Vivian; Porter, Stu; Durig, Tom; Majumdar, Soumyajit; Repka, Michael A.

2017-01-01

The recrystallization of an amorphous drug in a solid dispersion system could lead to a loss in the drug solubility and bioavailability. The primary objective of the current research was to use an improved kinetic model to evaluate the recrystallization kinetics of amorphous structures and to further understand the factors influencing the physical stability of amorphous solid dispersions. Amorphous solid dispersions of fenofibrate with different molecular weights of hydroxypropylcellulose, HPC (Klucel™ LF, EF, ELF) were prepared utilizing hot-melt extrusion technology. Differential scanning calorimetry was utilized to quantitatively analyze the extent of recrystallization in the samples stored at different temperatures and relative humidity (RH) conditions. The experimental data were fitted into the improved kinetics model of a modified Avrami equation to calculate the recrystallization rate constants. Klucel LF, the largest molecular weight among the HPCs used, demonstrated the greatest inhibition of fenofibrate recrystallization. Additionally, the recrystallization rate (k) decreased with increasing polymer content, however exponentially increased with higher temperature. Also k increased linearly rather than exponentially over the range of RH studied. PMID:25224341

Evaluation of the recrystallization kinetics of hot-melt extruded polymeric solid dispersions using an improved Avrami equation.

PubMed

Feng, Xin; Ye, Xingyou; Park, Jun-Bom; Lu, Wenli; Morott, Joe; Beissner, Brad; Lian, Zhuoyang John; Pinto, Elanor; Bi, Vivian; Porter, Stu; Durig, Tom; Majumdar, Soumyajit; Repka, Michael A

2015-01-01

The recrystallization of an amorphous drug in a solid dispersion system could lead to a loss in the drug solubility and bioavailability. The primary objective of the current research was to use an improved kinetic model to evaluate the recrystallization kinetics of amorphous structures and to further understand the factors influencing the physical stability of amorphous solid dispersions. Amorphous solid dispersions of fenofibrate with different molecular weights of hydroxypropylcellulose, HPC (Klucel™ LF, EF, ELF) were prepared utilizing hot-melt extrusion technology. Differential scanning calorimetry was utilized to quantitatively analyze the extent of recrystallization in the samples stored at different temperatures and relative humidity (RH) conditions. The experimental data were fitted into the improved kinetics model of a modified Avrami equation to calculate the recrystallization rate constants. Klucel LF, the largest molecular weight among the HPCs used, demonstrated the greatest inhibition of fenofibrate recrystallization. Additionally, the recrystallization rate (k) decreased with increasing polymer content, however exponentially increased with higher temperature. Also k increased linearly rather than exponentially over the range of RH studied.

Physicochemical characterization of solid dispersions of carbamazepine formulated by supercritical carbon dioxide and conventional solvent evaporation method.

PubMed

Sethia, Sundeep; Squillante, Emilio

2002-09-01

Solid dispersions of carbamazepine (CBZ) were formulated by supercritical fluid processing (SCP) and conventional solvent evaporation in polyethylene glycol (PEG) 8000 with either Gelucire 44/14 or vitamin E TPGS NF (d-alpha-tocopheryl PEG 1000 succinate). Formulations were evaluated by dissolution, scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry, and excipient cytotoxicity in Caco-2 cells by MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assay. CBZ release was enhanced from supercritical fluid-treated CBZ and the CBZ/PEG 8000 (1:5), CBZ/PEG 8000/TPGS or Gelucire 44/14 (1:4:1) solid dispersions. The radically altered morphologies of SCP samples seen by scanning electron microscopy suggested polymorphic change that was confirmed by the X-ray diffraction and differential scanning calorimetry. Disappearance of the characteristic CBZ melting peak indicated that CBZ was dissolved inside the carrier system. Polymorphic change of CBZ during SCP led to faster dissolution. Therefore, SCP provides advantages over solid dispersions prepared by conventional processes. Copyright 2002 Wiley-Liss Inc.

Thermodynamic phase behavior of API/polymer solid dispersions.

PubMed

Prudic, Anke; Ji, Yuanhui; Sadowski, Gabriele

2014-07-07

To improve the bioavailability of poorly soluble active pharmaceutical ingredients (APIs), these materials are often integrated into a polymer matrix that acts as a carrier. The resulting mixture is called a solid dispersion. In this work, the phase behaviors of solid dispersions were investigated as a function of the API as well as of the type and molecular weight of the carrier polymer. Specifically, the solubility of artemisinin and indomethacin was measured in different poly(ethylene glycol)s (PEG 400, PEG 6000, and PEG 35000). The measured solubility data and the solubility of sulfonamides in poly(vinylpyrrolidone) (PVP) K10 and PEG 35000 were modeled using the perturbed-chain statistical associating fluid theory (PC-SAFT). The results show that PC-SAFT predictions are in a good accordance with the experimental data, and PC-SAFT can be used to predict the whole phase diagram of an API/polymer solid dispersion as a function of the kind of API and polymer and of the polymer's molecular weight. This remarkably simplifies the screening process for suitable API/polymer combinations.

Investigation of process temperature and screw speed on properties of a pharmaceutical solid dispersion using corotating and counter-rotating twin-screw extruders.

PubMed

Keen, Justin M; Martin, Charlie; Machado, Augie; Sandhu, Harpreet; McGinity, James W; DiNunzio, James C

2014-02-01

The use of corotating twin screw hot-melt extruders to prepare amorphous drug/polymer systems has become commonplace. As small molecule drug candidates exiting discovery pipelines trend towards higher MW and become more structurally complicated, the acceptable operating space shifts below the drug melting point. The objective of this research is to investigate the extrusion process space, which should be selected to ensure that the drug is solubilized in the polymer with minimal thermal exposure, is critical in ensuring the performance, stability and purity of the solid dispersion. The properties of a model solid dispersion were investigated using both corotating and counter-rotating hot-melt twin-screw extruders operated at various temperatures and screw speeds. The solid state and dissolution performance of the resulting solid dispersions was investigated and evaluated in context of thermodynamic predictions from Flory-Huggins Theory. In addition, the residence time distributions were measured using a tracer, modelled and characterized. The amorphous content in the resulting solid dispersions was dependent on the combination of screw speed, temperature and operating mode. The counter-rotating extruder was observed to form amorphous solid dispersions at a slightly lower temperature and with a narrower residence time distribution, which also exhibited a more desirable shape. © 2013 Royal Pharmaceutical Society.

Template-Mediated Ni(II) Dispersion in Mesoporous SiO2 for Preparation of Highly Dispersed Ni Catalysts: Influence of Template Type.

PubMed

Ning, Xin; Lu, Yiyuan; Fu, Heyun; Wan, Haiqin; Xu, Zhaoyi; Zheng, Shourong

2017-06-07

Supported Ni catalysts on three mesoporous SiO 2 supports (i.e., SBA-15, MCM-41, and HMS) were prepared using a solid-state reaction between Ni(NO 3 ) 2 and organic template-occluded mesoporous SiO 2 . For comparison, supported Ni catalysts on mesoporous SiO 2 synthesized by the conventional impregnation method were also included. The catalysts were characterized by scanning electron microscopy, X-ray diffraction, UV-vis diffuse reflectance spectroscopy, N 2 adsorption, X-ray photoelectron spectroscopy, H 2 temperature-programmed reduction, transmission electron microscopy, and transmission electron microscopy-energy-dispersive X-ray. The catalytic properties of the catalysts were evaluated using gas-phase catalytic hydrodechlorination of 1,2-dichloroethane. The results showed that upon grinding Ni(NO 3 ) 2 with template-occluded mesoporous SiO 2 , strong coordination between Ni 2+ and dodecylamine was identified in the Ni(NO 3 ) 2 -HMS system. Additionally, the results of H 2 temperature-programmed reduction revealed that NiO in calcined NiO/HMS was reduced at higher temperature than those in calcined NiO/SBA-15 and NiO/MCM-41, reflecting the presence of a strong interaction between NiO and mesoporous SiO 2 in NiO/HMS. Consistently, the average particle sizes of metallic Ni were found to be 2.7, 3.4, and 9.6 nm in H 2 -reduced Ni/HMS, Ni/SBA-15, and Ni/MCM-41, respectively, indicative of a much higher Ni dispersion in Ni/HMS. For the catalytic hydrodechlorination of 1,2-dichloroethane, Ni/MCM-41 synthesized by the solid-state reaction method exhibited a catalytic activity similar to that prepared by the impregnation method, while higher catalytic activities were observed on Ni/HMS and Ni/SBA-15 than on their counterparts prepared by the impregnation method. Furthermore, a higher conversion was identified on Ni/HMS than on Ni/SBA-15 and Ni/MCM-41, highlighting the importance of template type for the preparation of highly dispersed metal catalysts on mesoporous Si

Influence of solvent evaporation rate and formulation factors on solid dispersion physical stability.

PubMed

Wu, Jian X; Yang, Mingshi; Berg, Frans van den; Pajander, Jari; Rades, Thomas; Rantanen, Jukka

2011-12-18

New chemical entities (NCEs) often show poor water solubility necessitating solid dispersion formulation. The aim of the current study is to employ design of experiments in investigating the influence of one critical process factor (solvent evaporation rate) and two formulation factors (PVP:piroxicam ratio (PVP:PRX) and PVP molecular weight (P(MW))) on the physical stability of PRX solid dispersion prepared by the solvent evaporation method. The results showed the rank order of an increase in factors contributing to a decrease in the extent of PRX nucleation being evaporation rate>PVP:PRX>P(MW). The same rank order was found for the decrease in the extent of PRX crystal growth in PVP matrices from day 0 up to day 12. However, after 12days the rank became PVP:PRX>evaporation rate>P(MW). The effects of an increase in evaporation rate and PVP:PRX ratio in stabilizing PRX were of the same order of magnitude, while the effect from P(MW) was much smaller. The findings were confirmed by XRPD. FT-IR showed that PRX recrystallization in the PVP matrix followed Ostwald's step rule, and an increase in the three factors all led to increased hydrogen bonding interaction between PRX and PVP. The present study showed the applicability of the Quality by Design approach in solid dispersion research, and highlights the need for multifactorial analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

The effect of processing on the surface physical stability of amorphous solid dispersions.

PubMed

Yang, Ziyi; Nollenberger, Kathrin; Albers, Jessica; Moffat, Jonathan; Craig, Duncan; Qi, Sheng

2014-11-01

The focus of this study was to investigate the effect of processing on the surface crystallization of amorphous molecular dispersions and gain insight into the mechanisms underpinning this effect. The model systems, amorphous molecular dispersions of felodipine-EUDRAGIT® E PO, were processed both using spin coating (an ultra-fast solvent evaporation based method) and hot melt extrusion (HME) (a melting based method). Amorphous solid dispersions with drug loadings of 10-90% (w/w) were obtained by both processing methods. Samples were stored under 75% RH/room temperatures for up to 10months. Surface crystallization was observed shortly after preparation for the HME samples with high drug loadings (50-90%). Surface crystallization was characterized by powder X-ray diffraction (PXRD), ATR-FTIR spectroscopy and imaging techniques (SEM, AFM and localized thermal analysis). Spin coated molecular dispersions showed significantly higher surface physical stability than hot melt extruded samples. For both systems, the progress of the surface crystal growth followed zero order kinetics on aging. Drug enrichment at the surfaces of HME samples on aging was observed, which may contribute to surface crystallization of amorphous molecular dispersions. In conclusion it was found the amorphous molecular dispersions prepared by spin coating had a significantly higher surface physical stability than the corresponding HME samples, which may be attributed to the increased process-related apparent drug-polymer solubility and reduced molecular mobility due to the quenching effect caused by the rapid solvent evaporation in spin coating. Copyright © 2014 Elsevier B.V. All rights reserved.

Predicting final product properties of melt extruded solid dispersions from process parameters using Raman spectrometry.

PubMed

Vigh, Tamás; Drávavölgyi, Gábor; Sóti, Péter L; Pataki, Hajnalka; Igricz, Tamás; Wagner, István; Vajna, Balázs; Madarász, János; Marosi, György; Nagy, Zsombor K

2014-09-01

Raman spectrometry was utilized to estimate degraded drug percentage, residual drug crystallinity and glass-transition temperature in the case of melt-extruded pharmaceutical products. Tight correlation was shown between the results obtained by confocal Raman mapping and transmission Raman spectrometry, a PAT-compatible potential in-line analytical tool. Immediate-release spironolactone-Eudragit E solid dispersions were the model system, owing to the achievable amorphization and the heat-sensitivity of the drug compound. The deep investigation of the relationship between process parameters, residual drug crystallinity and degradation was performed using statistical tools and a factorial experimental design defining 54 different circumstances for the preparation of solid dispersions. From the examined factors, drug content (10, 20 and 30%), temperature (110, 130 and 150°C) and residence time (2.75, 11.00 and 24.75min) were found to have significant and considerable effect. By forming physically stable homogeneous dispersions, the originally very slow dissolution of the lipophilic and poorly water-soluble spironolactone was reasonably improved, making 3minute release possible in acidic medium. Copyright © 2014 Elsevier B.V. All rights reserved.

Dual-mechanism gastroretentive drug delivery system loaded with an amorphous solid dispersion prepared by hot-melt extrusion.

PubMed

Vo, Anh Q; Feng, Xin; Pimparade, Manjeet; Ye, Xinyou; Kim, Dong Wuk; Martin, Scott T; Repka, Michael A

2017-05-01

In the present study, we aimed to prepare a gastroretentive drug delivery system that would be both highly resistant to gastric emptying via multiple mechanisms and would also potentially induce in situ supersaturation. The bioadhesive floating pellets, loaded with an amorphous solid dispersion, were prepared in a single step of hot-melt extrusion technology. Hydroxypropyl cellulose (Klucel™ MF) and hypromellose (Benecel™ K15M) were used as matrix-forming polymers, and felodipine was used as the model drug. The foam pellets were fabricated based on the expansion of CO 2 , which was generated from sodium bicarbonate during the melt-extrusion process. A 2 n full factorial experimental design was utilized to investigate the effects of formulation compositions to the pellet properties. The melt-extrusion process transformed the crystalline felodipine into an amorphous state that was dispersed and "frozen" in the polymer matrix. All formulations showed high porosity and were able to float immediately, without lag time, on top of gastric fluid, and maintained their buoyancy over 12h. The pellet-specific floating force, which could be as high as 4800μN/g, increased significantly during the first hour, and was relatively stable until 9h. The sodium bicarbonate percentage was found to be most significantly effect to the floating force. The ex vivo bioadhesion force of the pellets to porcine stomach mucosa was approximately 5mN/pellet, which was more than five times higher than the gravitation force of the pellet saturated with water. Drug release was well controlled up to 12h in the sink condition of 0.5% sodium lauryl sulphate in 0.1N HCl. The dissolution at 1, 3, 5, and 8h were 5-12%, 25-45%, 55-80%, and ≥75% respectively for all 11 formulations. In biorelevant dissolution medium, a supersaturated solution was formed, and the concentration was maintained at around 2μg/mL, approximately 10-folds higher than that of the pure felodipine. All input factors

Preparation and evaluation of miconazole nitrate-loaded solid lipid nanoparticles for topical delivery.

PubMed

Bhalekar, Mangesh R; Pokharkar, Varsha; Madgulkar, Ashwini; Patil, Nilam; Patil, Nilkanth

2009-01-01

The purpose of this study was to prepare miconazole nitrate (MN) loaded solid lipid nanoparticles (MN-SLN) effective for topical delivery of miconazole nitrate. Compritol 888 ATO as lipid, propylene glycol (PG) to increase drug solubility in lipid, tween 80, and glyceryl monostearate were used as the surfactants to stabilize SLN dispersion in the SLN preparation using hot homogenization method. SLN dispersions exhibited average size between 244 and 766 nm. All the dispersions had high entrapment efficiency ranging from 80% to 100%. The MN-SLN dispersion which showed good stability for a period of 1 month was selected. This MN-SLN was characterized for particle size, entrapment efficiency, and X-ray diffraction. The penetration of miconazole nitrate from the gel formulated using selected MN-SLN dispersion as into cadaver skins was evaluated ex-vivo using franz diffusion cell. The results of differential scanning calorimetry (DSC) showed that MN was dispersed in SLN in an amorphous state. The MN-SLN formulations could significantly increase the accumulative uptake of MN in skin over the marketed gel and showed a significantly enhanced skin targeting effect. These results indicate that the studied MN-SLN formulation with skin targeting may be a promising carrier for topical delivery of miconazole nitrate.

Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated-Naproxen/PEG3350 Solid Dispersions

PubMed Central

Hsu, Hsin-Yun; Toth, Scott; Simpson, Garth J.; Harris, Michael T.

2016-01-01

Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API. PMID:27041744

Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated-Naproxen/PEG3350 Solid Dispersions.

PubMed

Hsu, Hsin-Yun; Toth, Scott; Simpson, Garth J; Harris, Michael T

2015-12-01

Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API.

Perspectives on Strategies Using Swellable Polymers in Solid Dispersions for Controlled Drug Release.

PubMed

Tran, Thao T D; Tran, Phuong H L

2017-01-01

Poorly water-soluble drugs, which commonly face the issue of poor absorption and low bioavailability, have been under ongoing research of many formulation scientists for the past few decades. Solid dispersion is one of the most effective strategies in concerns for improving bioavailability of poorly water-soluble drugs. Either application of solid dispersions in dissolution enhancement of poorly water-soluble drugs or the use of swellable polymers in controlled drug release has been reported in pharmaceutical designs widely. However, a review of strategies of using swellable polymers in solid dispersion to take a full advantage of these polymers as a current perspective in facilitating drug bioavailability enhancement is still missing. In this review, we aim to provide a summary of techniques used to formulate a swellable polymer in solid dispersion especially a description of a suitable fabrication method in design of a controlled release solid dispersion. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Application of ethyl cellulose, microcrystalline cellulose and octadecanol for wax based floating solid dispersion pellets.

PubMed

Yan, Hong-Xiang; Zhang, Shuang-Shuang; He, Jian-Hua; Liu, Jian-Ping

2016-09-05

The present study aimed to develop and optimize the wax based floating sustained-release dispersion pellets for a weakly acidic hydrophilic drug protocatechuic acid to achieve prolonged gastric residence time and improved bioavailability. This low-density drug delivery system consisted of octadecanol/microcrystalline cellulose mixture matrix pellet cores prepared by extrusion-spheronization technique, coated with drug/ethyl cellulose 100cp solid dispersion using single-step fluid-bed coating method. The formulation-optimized pellets could maintain excellent floating state without lag time and sustain the drug release efficiently for 12h based on non-Fickian transport mechanism. Observed by SEM, the optimized pellet was the dispersion-layered spherical structure containing a compact inner core. DSC, XRD and FTIR analysis revealed drug was uniformly dispersed in the amorphous molecule form and had no significant physicochemical interactions with the polymer dispersion carrier. The stability study of the resultant pellets further proved the rationality and integrity of the developed formulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Conjugation of Hot-Melt Extrusion with High-Pressure Homogenization: a Novel Method of Continuously Preparing Nanocrystal Solid Dispersions.

PubMed

Ye, Xingyou; Patil, Hemlata; Feng, Xin; Tiwari, Roshan V; Lu, Jiannan; Gryczke, Andreas; Kolter, Karl; Langley, Nigel; Majumdar, Soumyajit; Neupane, Dipesh; Mishra, Sanjay R; Repka, Michael A

2016-02-01

Over the past few decades, nanocrystal formulations have evolved as promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However, conventional methods of preparing nanocrystal formulations, such as spray drying and freeze drying, have some drawbacks including high cost, time and energy inefficiency, traces of residual solvent, and difficulties in continuous operation. Therefore, new techniques for the production of nanocrystal formulations are necessary. The main objective of this study was to introduce a new technique for the production of nanocrystal solid dispersions (NCSDs) by combining high-pressure homogenization (HPH) and hot-melt extrusion (HME). Efavirenz (EFZ), a Biopharmaceutics Classification System class II drug, which is used for the treatment of human immunodeficiency virus (HIV) type I, was selected as the model drug for this study. A nanosuspension (NS) was first prepared by HPH using sodium lauryl sulfate (SLS) and Kollidon® 30 as a stabilizer system. The NS was then mixed with Soluplus® in the extruder barrel, and the water was removed by evaporation. The decreased particle size and crystalline state of EFZ were confirmed by scanning electron microscopy, zeta particle size analysis, and differential scanning calorimetry. The increased dissolution rate was also determined. EFZ NCSD was found to be highly stable after storage for 6 months. In summary, the conjugation of HPH with HME technology was demonstrated to be a promising novel method for the production of NCSDs.

Preparation and characterization of progesterone dispersions using supercritical carbon dioxide.

PubMed

Falconer, James R; Wen, Jingyuan; Zargar-Shoshtari, Sara; Chen, John J; Farid, Mohammed; Tallon, Stephen J; Alany, Raid G

2014-04-01

Supercritical fluid methods offer an alternative to conventional mixing methods, particularly for heat sensitive drugs and where an organic solvent is undesirable. To design, develop and construct a unit for the particles from a gas-saturated suspension/solution (PGSS) method and form endogenous progesterone (PGN) dispersion systems using SC-CO2. The PGN dispersions were manufactured using three selected excipients: polyethylene glycol (PEG) 400/4000 (50:50), Gelucire 44/14 and D-α-tocopheryl PEG 1000 succinate (TPGS). Semisolid dispersions of PGN prepared by PGSS method were compared to the conventional methods; comelting (CM), cosolvent (CS) and physical mixing (PM). The dispersion systems made were characterized by Raman and Fourier transform infrared (FTIR) spectroscopies, X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), PGN recovery, uniformity and in vitro dissolution, analyzed by high-performance liquid chromatography (HPLC). Raman spectra revealed no changes in the crystalline structure of PGN treated with SC-CO2 compared to that of untreated PGN. XRPD and FTIR showed the presence of peaks and bands for PGN confirming that PGN has been incorporated well with each individual excipient. All PGN dispersions prepared by the PGSS method resulted in the improvement of PGN dissolution rates compared to that prepared by the conventional methods and untreated PGN after 60 min (p value < 0.05). The novel PGN dispersions prepared by the PGSS method offer the great potential to enhance PGN dissolution rate, reduce preparation time and form stable crystalline dispersion systems over those prepared by conventional methods.

Cefuroxime axetil solid dispersion with polyglycolized glycerides for improved stability and bioavailability.

PubMed

Dhumal, Ravindra S; Biradar, Shailesh V; Aher, Suyog; Paradkar, Anant R

2009-06-01

Cefuroxime axetil (CA), a poorly soluble, broad spectrum cephalosporin ester prodrug, is hydrolysed by intestinal esterase prior to absorption, leading to poor and variable bioavailability. The objective was therefore to formulate a stable amorphous solid dispersion of the drug with enhanced solubility and stability against enzymatic degradation. Spray drying was used to obtain a solid dispersion of CA with Gelucire 50/13 and Aerosil 200 (SDCAGA), and a solid dispersion of CA with polyvinyl pyrrolidone (SDCAP); amorphous CA (ACA) was obtained by spray drying CA alone. The formulations were characterized by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy and Fourier transform infrared spectroscopy studies, and compared for solubility, dissolution and bioavailability in rats. SDCAP and SDCAGA showed improved solubility and dissolution profiles owing to amorphization and formation of solid dispersions with hydrophilic carriers. The improved stability of amorphous CA in solid dispersions compared to ACA alone was attributed to hydrogen bonding interactions involving the amide of CA with the carbonyl of polyvinyl pyrrolidone in SDCAP, whereas in SDCAGA the interactions were at multiple sites involving the amide and carbonyl of CA with the carbonyl and hydroxyl of Gelucire 50/13. However, SDCAGA showed superior bioavailability compared to SDCAP, ACA and CA. Improvement in physical stability of solid dispersions was attributed to hydrogen bonding, while improvement in bioavailability of SDCAGA compared to SDCAP, in spite of comparable solubility and dissolution profile, may be attributed to Gelucire, which utilizes intestinal esterase for lipolysis, protecting the prodrug from enzymatic degradation to its non-absorbable base form.

Development and characterization of clay facial mask containing turmeric extract solid dispersion.

PubMed

Pan-On, Suchiwa; Rujivipat, Soravoot; Ounaroon, Anan; Tiyaboonchai, Waree

2018-04-01

To develop clay facial mask containing turmeric extract solid dispersion (TESD) for enhancing curcumin water solubility and permeability and to determine suitable clay based facial mask. The TESD were prepared by solvent and melting solvent method with various TE to polyvinylpyrrolidone (PVP) K30 mass ratios. The physicochemical properties, water solubility, and permeability were examined. The effects of clay types on physical stability of TESD, water adsorption, and curcumin adsorption capacity were evaluated. The TESD prepared by solvent method with a TE to PVP K30 mass ratio of 1:2 showed physically stable, dry powders, when mixed with clay. When TESD was dissolved in water, the obtained TESD micelles showed spherical shape with mean size of ∼100 nm resulting in a substantial enhancement of curcumin water solubility, ∼5 mg/ml. Bentonite (Bent) and mica (M) showed the highest water adsorption capacity. The TESD's color was altered when mixed with Bent, titanium dioxide (TiO 2 ) and zinc oxide (ZnO) indicating curcumin instability. Talcum (Talc) showed the greatest curcumin adsorption followed by M and kaolin (K), respectively. Consequently, in vitro permeation studies of the TESD mixed with Talc showed lowest curcumin permeation, while TESD mixed with M or K showed similar permeation profile as free TESD solutions. The developed TESD-based clay facial mask showed lower curcumin permeation as compared to those formulations with Tween 80. The water solubility and permeability of curcumin in clay based facial mask could be improved using solid dispersion technique and suitable clay base composed of K, M, and Talc.

A comparative study of the effect of spray drying and hot-melt extrusion on the properties of amorphous solid dispersions containing felodipine.

PubMed

Mahmah, Osama; Tabbakh, Rami; Kelly, Adrian; Paradkar, Anant

2014-02-01

To compare the properties of solid dispersions of felodipine for oral bioavailability enhancement using two different polymers, polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), by hot-melt extrusion (HME) and spray drying. Felodipine solid dispersions were prepared by HME and spray drying techniques. PVP and HPMCAS were used as polymer matrices at different drug : polymer ratios (1 : 1, 1 : 2 and 1 : 3). Detailed characterization was performed using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and in-vitro dissolution testing. Dissolution profiles were evaluated in the presence of sodium dodecyl sulphate. Stability of different solid dispersions was studied under accelerated conditions (40°C/75% RH) over 8 weeks. Spray-dried formulations were found to release felodipine faster than melt extruded formulations for both polymer matrices. Solid dispersions containing HMPCAS exhibited higher drug release rates and better wettability than those produced with a PVP matrix. No significant differences in stability were observed except with HPMCAS at a 1 : 1 ratio, where crystallization was detected in spray-dried formulations. Solid dispersions of felodipine produced by spray drying exhibited more rapid drug release than corresponding melt extruded formulations, although in some cases improved stability was observed for melt extruded formulations. © 2013 Royal Pharmaceutical Society.

Solid dispersions, part II: new strategies in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs.

PubMed

Bikiaris, Dimitrios N

2011-12-01

The absorption of poorly water-soluble drugs, when presented in the crystalline state to the gastrointestinal tract, is typically dissolution rate-limited, and according to BCS these drugs belong mainly to class II. Both dissolution kinetics and solubility are particle size dependent. Nowadays, various techniques are available to the pharmaceutical industry for dissolution rate enhancement of such drugs. Among such techniques, nanosuspensions and drug formulation in solid dispersions are those with the highest interest. This review discusses strategies undertaken over the last 10 years, which have been applied for the dissolution enhancement of poorly water-soluble drugs; such processes include melt mixing, electrospinning, microwave irradiation and the use of inorganic nanoparticles. Many problems in this field still need to be solved, mainly the use of toxic solvents, and for this reason the use of innovative new procedures and materials will increase over the coming years. Melt mixing remains extremely promising for the preparation of SDs and will probably become the most used method in the future for the preparation of solid drug dispersions.

Investigation for the amorphous state of ER-34122, a dual 5-lipoxygenase/cyclooxygenase inhibitor with poor aqueous solubility, in HPMC solid dispersion prepared by the solvent evaporation method.

PubMed

Kushida, Ikuo; Gotoda, Masaharu

2013-10-01

ER-34122, a poorly water-soluble dual 5-lipoxygenase/cyclooxygenase inhibitor, exists as a crystalline form. According to an Oak Ridge thermal ellipsoid plot drawing, carbonyl oxygen O (5) makes an intermolecular hydrogen bond with the hydrogen bonded to N (3) in the crystal structure. The FTIR and the solid-state ¹³C NMR spectra suggest that the network is spread out in the amorphous state and the hydrogen bonding gets weaker than that in the crystalline phase, because the carbonyl signals significantly shift in both spectra. When amorphous ER-34122 was heated, crystallization occurred at around 140°C. Similar crystallization happened in the solid dispersion; however, the degree of crystallization was much lower than that observed in the pure amorphous material. Also, the DSC thermogram of the solid dispersion did not show any exothermic peaks implying crystallization. The heat of fusion (ΔHf) determined in the pure amorphous material was nearly equal to that for the crystalline form, whereas the ΔHf value obtained in the solid dispersion was less than a third of them. These data prove that crystallization of the amorphous form is dramatically restrained in the solid dispersion system. The carbonyl wavenumber shifts in the FTIR spectra indicate that the average hydrogen bond in the solid dispersion is lower than that in the pure amorphous material. Therefore, HPMC will suppress formation of the intermolecular network observed in ER-34122 crystal and preserve the amorphous state, which is thermodynamically less stable, in the solid dispersed system.

Enabling thermal processing of ritonavir-polyvinyl alcohol amorphous solid dispersions by KinetiSol® Dispersing.

PubMed

LaFountaine, Justin S; Jermain, Scott V; Prasad, Leena Kumari; Brough, Chris; Miller, Dave A; Lubda, Dieter; McGinity, James W; Williams, Robert O

2016-04-01

Polyvinyl alcohol has received little attention as a matrix polymer in amorphous solid dispersions (ASDs) due to its thermal and rheological limitations in extrusion processing and limited organic solubility in spray drying applications. Additionally, in extrusion processing, the high temperatures required to process often exclude thermally labile APIs. The purpose of this study was to evaluate the feasibility of processing polyvinyl alcohol amorphous solid dispersions utilizing the model compound ritonavir with KinetiSol® Dispersing (KSD) technology. The effects of KSD rotor speed and ejection temperature on the physicochemical properties of the processed material were evaluated. Powder X-ray diffraction and modulated differential scanning calorimetry were used to confirm amorphous conversion. Liquid chromatography-mass spectroscopy was used to characterize and identify degradation pathways of ritonavir during KSD processing and (13)C nuclear magnetic resonance spectroscopy was used to investigate polymer stability. An optimal range of processing conditions was found that resulted in amorphous product and minimal to no drug and polymer degradation. Drug release of the ASD produced from the optimal processing conditions was evaluated using a non-sink, pH-shift dissolution test. The ability to process amorphous solid dispersions with polyvinyl alcohol as a matrix polymer will enable further investigations of the polymer's performance in amorphous systems for poorly water-soluble compounds. Copyright © 2016 Elsevier B.V. All rights reserved.

Extensive Diminution of Particle Size and Amorphization of a Crystalline Drug Attained by Eminent Technology of Solid Dispersion: A Comparative Study.

PubMed

Singh, Gurjeet; Sharma, Shailesh; Gupta, Ghanshyam Das

2017-07-01

The present study emphasized on the use of solid dispersion technology to triumph over the drawbacks associated with the highly effective antihypertensive drug telmisartan using different polymers (poloxamer 188 and locust bean gum) and methods (modified solvent evaporation and lyophilization). It is based on the comparison between selected polymers and methods for enhancing solubility through particle size reduction. The results showed different profiles for particle size, solubility, and dissolution of formulated amorphous systems depicting the great influence of polymer/method used. The resulting amorphous solid dispersions were characterized using x-ray diffraction (XRD), differential scanning calorimetry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and particle size analysis. The optimized solid dispersion (TEL 19) prepared with modified locust bean gum using lyophilization technique showed reduced particle size of 184.5 ± 3.7 nm and utmost solubility of 702 ± 5.47 μg/mL in water, which is quite high as compared to the pure drug (≤1 μg/mL). This study showed that the appropriate selection of carrier may lead to the development of solid dispersion formulation with desired solubility and dissolution profiles. The optimized dispersion was later formulated into fast-dissolving tablets, and further optimization was done to obtain the tablets with desired properties.

An improved kinetics approach to describe the physical stability of amorphous solid dispersions.

PubMed

Yang, Jiao; Grey, Kristin; Doney, John

2010-01-15

The recrystallization of amorphous solid dispersions may lead to a loss in the dissolution rate, and consequently reduce bioavailability. The purpose of this work is to understand factors governing the recrystallization of amorphous drug-polymer solid dispersions, and develop a kinetics model capable of accurately predicting their physical stability. Recrystallization kinetics was measured using differential scanning calorimetry for initially amorphous efavirenz-polyvinylpyrrolidone solid dispersions stored at controlled temperature and relative humidity. The experimental measurements were fitted by a new kinetic model to estimate the recrystallization rate constant and microscopic geometry of crystal growth. The new kinetics model was used to illustrate the governing factors of amorphous solid dispersions stability. Temperature was found to affect efavirenz recrystallization in an Arrhenius manner, while recrystallization rate constant was shown to increase linearly with relative humidity. Polymer content tremendously inhibited the recrystallization process by increasing the crystallization activation energy and decreasing the equilibrium crystallinity. The new kinetic model was validated by the good agreement between model fits and experiment measurements. A small increase in polyvinylpyrrolidone resulted in substantial stability enhancements of efavirenz amorphous solid dispersion. The new established kinetics model provided more accurate predictions than the Avrami equation.

The mechanisms of drug release from solid dispersions in water-soluble polymers.

PubMed

Craig, Duncan Q M

2002-01-14

Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. However, despite the publication of numerous original papers and reviews on the subject, the mechanisms underpinning the observed improvements in dissolution rate are not yet understood. In this review the current consensus with regard to the solid-state structure and dissolution properties of solid dispersions is critically assessed. In particular the theories of carrier- and drug-controlled dissolution are highlighted. A model is proposed whereby the release behaviour from the dispersions may be understood in terms of the dissolution or otherwise of the drug into the concentrated aqueous polymer layer adjacent to the solid surface, including a derivation of an expression to describe the release of intact particles from the dispersions. The implications of a deeper understanding of the dissolution mechanisms are discussed, with particular emphasis on optimising the choice of carrier and manufacturing method and the prediction of stability problems.

Investigation of phase diagrams and physical stability of drug-polymer solid dispersions.

PubMed

Lu, Jiannan; Shah, Sejal; Jo, Seongbong; Majumdar, Soumyajit; Gryczke, Andreas; Kolter, Karl; Langley, Nigel; Repka, Michael A

2015-01-01

Solid dispersion technology has been widely explored to improve the solubility and bioavailability of poorly water-soluble compounds. One of the critical drawbacks associated with this technology is the lack of physical stability, i.e. the solid dispersion would undergo recrystallization or phase separation thus limiting a product's shelf life. In the current study, the melting point depression method was utilized to construct a complete phase diagram for felodipine (FEL)-Soluplus® (SOL) and ketoconazole (KTZ)-Soluplus® (SOL) binary systems, respectively, based on the Flory-Huggins theory. The miscibility or solubility of the two compounds in SOL was also determined. The Flory-Huggins interaction parameter χ values of both systems were calculated as positive at room temperature (25 °C), indicating either compound was miscible with SOL. In addition, the glass transition temperatures of both solid dispersion systems were theoretically predicted using three empirical equations and compared with the practical values. Furthermore, the FEL-SOL solid dispersions were subjected to accelerated stability studies for up to 3 months.

Using Flory-Huggins phase diagrams as a pre-formulation tool for the production of amorphous solid dispersions: a comparison between hot-melt extrusion and spray drying.

PubMed

Tian, Yiwei; Caron, Vincent; Jones, David S; Healy, Anne-Marie; Andrews, Gavin P

2014-02-01

Amorphous drug forms provide a useful method of enhancing the dissolution performance of poorly water-soluble drugs; however, they are inherently unstable. In this article, we have used Flory-Huggins theory to predict drug solubility and miscibility in polymer candidates, and used this information to compare spray drying and melt extrusion as processes to manufacture solid dispersions. Solid dispersions were prepared using two different techniques (hot-melt extrusion and spray drying), and characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry), spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods. Spray drying permitted generation of amorphous solid dispersions across a wider drug concentration than melt extrusion. Melt extrusion provided sufficient energy for more intimate mixing to be achieved between drug and polymer, which may improve physical stability. It was also confirmed that stronger drug-polymer interactions might be generated through melt extrusion. Remixing and dissolution of recrystallised felodipine into the polymeric matrices did occur during the modulated differential scanning calorimetry analysis, but the complementary information provided from FTIR confirms that all freshly prepared spray-dried samples were amorphous with the existence of amorphous drug domains within high drug-loaded samples. Using temperature-composition phase diagrams to probe the relevance of temperature and drug composition in specific polymer candidates facilitates polymer screening for the purpose of formulating solid dispersions. © 2013 Royal Pharmaceutical Society.

Solid-State NMR Investigation of Drug-Excipient Interactions and Phase Behavior in Indomethacin-Eudragit E Amorphous Solid Dispersions.

PubMed

Lubach, Joseph W; Hau, Jonathan

2018-02-20

To investigate the nature of drug-excipient interactions between indomethacin (IMC) and methacrylate copolymer Eudragit® E (EE) in the amorphous state, and evaluate the effects on formulation and stability of these amorphous systems. Amorphous solid dispersions containing IMC and EE were spray dried with drug loadings from 20% to 90%. PXRD was used to confirm the amorphous nature of the dispersions, and DSC was used to measure glass transition temperatures (T g ). 13 C and 15 N solid-state NMR was utilized to investigate changes in local structure and protonation state, while 1 H T 1 and T 1ρ relaxation measurements were used to probe miscibility and phase behavior of the dispersions. T g values for IMC-EE solid dispersions showed significant positive deviations from predicted values in the drug loading range of 40-90%, indicating a relatively strong drug-excipient interaction. 15 N solid-state NMR exhibited a change in protonation state of the EE basic amine, with two distinct populations for the EE amine at -360.7 ppm (unprotonated) and -344.4 ppm (protonated). Additionally, 1 H relaxation measurements showed phase separation at high drug load, indicating an amorphous ionic complex and free IMC-rich phase. PXRD data showed all ASDs up to 90% drug load remained physically stable after 2 years. 15 N solid-state NMR experiments show a change in protonation state of EE, indicating that an ionic complex indeed forms between IMC and EE in amorphous solid dispersions. Phase behavior was determined to exhibit nanoscale phase separation at high drug load between the amorphous ionic complex and excess free IMC.

Stability and Biological Activity Evaluation of Chlorantraniliprole Solid Nanodispersions Prepared by High Pressure Homogenization

PubMed Central

Cui, Bo; Feng, Lei; Wang, Chunxin; Yang, Dongsheng; Yu, Manli; Zeng, Zhanghua; Wang, Yan; Sun, Changjiao; Zhao, Xiang; Cui, Haixin

2016-01-01

Poorly water-soluble compounds are difficult to develop as pesticide products and face great challenges in water-based and environmentally friendly formulation development. In this study, high pressure homogenization combined with lyophilization was adopted to prepare the solid nanodispersions of chlorantraniliprole with poor solubility and high melting point. The mean particle sizes of the solid nanodispersions with different pesticide contents were all less than 75 nm, even when the content was up to 91.5%. For the 2.5% chlorantraniliprole solid nanodispersion with the mean particle size of 29 nm, the suspensibility and wetting time in water were 97.32% and 13 s, respectively. The re-dispersibility and wettability were superior to those of conventional water dispersible granules. The retention on the rice leaf of 18.7 mg/cm2 was 1.5 and 3 times that of commercial aqueous suspension concentrate and pure water. The bioassay result to diamondback moths indicated that the toxicity of the solid nanodispersion was 3.3 and 2.8 times that of technical and aqueous suspension concentrate, respectively. Moreover, the solid nanodispersion has the advantages of total avoidance of organic solvents, significant reduction of surfactants and feasibility of obtaining high concentration nanoformulations. The solid nanodispersion is an attractive candidate for improving pesticide solubility and efficacy, and its application in crop production will reduce both residues in food and environmental pollution of pesticide. PMID:27500828

Dissolution and oral bioavailability enhancement of praziquantel by solid dispersions.

PubMed

Liu, Yanyan; Wang, Tianzi; Ding, Wenya; Dong, Chunliu; Wang, Xiaoting; Chen, Jianqing; Li, Yanhua

2018-06-01

The aim of the present investigation was to enhance the solubility, dissolution, and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II drug (Biopharmaceutical Classification System), using a solid dispersion (SD) technique involving hydrophilic copolymers. The SD formulations were prepared by a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000), PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG 4000/P 188. The optimized SD formulation, which had the highest solubility in distilled water, was further characterized by its surface morphology, crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at an oral dosage of 5 mg/kg PZQ, the SDs had higher C max values and areas under the curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ-loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral bioavailability of PZQ.

A novel osmotic pump-based controlled delivery system consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen: in vitro and in vivo evaluation.

PubMed

Li, Shujuan; Wang, Xiaoyu; Wang, Yingying; Zhao, Qianqian; Zhang, Lina; Yang, Xinggang; Liu, Dandan; Pan, Weisan

2015-01-01

In this study, a novel controlled release osmotic pump capsule consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen (FP) was developed to improve the solubility and oral bioavailability of FP and to minimize the fluctuation of plasma concentration. The pH-modulated solid dispersion containing FP, Kollidon® 12 PF and Na2CO3 at a weight ratio of 1/4.5/0.02 was prepared using the solvent evaporation method. The osmotic pump capsule was assembled by semi-permeable capsule shell of cellulose acetate (CA) prepared by the perfusion method. Then, the solid dispersion, penetration enhancer, and suspending agents were tableted and filled into the capsule. Central composite design-response surface methodology was used to evaluate the influence of factors on the responses. A second-order polynomial model and a multiple linear model were fitted to correlation coefficient of drug release profile and ultimate cumulative release in 12 h, respectively. The actual response values were in good accordance with the predicted ones. The optimized formulation showed a complete drug delivery and zero-order release rate. Beagle dogs were used to be conducted in the pharmacokinetic study. The in vivo study indicated that the relative bioavailability of the novel osmotic pump system was 133.99% compared with the commercial preparation. The novel controlled delivery system with combination of pH-modulated solid dispersion and osmotic pump system is not only a promising strategy to improve the solubility and oral bioavailability of poorly soluble ionizable drugs but also an effective way to reduce dosing frequency and minimize the plasma fluctuation.

Dithranol in a cream preparation: disperse or dissolve?

PubMed

Prins, M; Swinkels, O Q; Bouwhuis, S; de Gast, M J; Bouwman-Boer, Y; van der Valk, P G; van de Kerkhof, P C

2000-01-01

In the search for the ideal dithranol cream preparation for short-contact treatment of psoriasis, we investigated the clinical efficacy, side effects and patient appreciation of two dithranol cream preparations (cream A and B) in a double-blind left-right comparing study. Dithranol was dissolved at preparation in cream A and dispersed in cream B. Cream A is known to have a shelf life of 1 year, while cream B has a much shorter shelf life (several months). Ten patients with chronic plaque-type psoriasis were treated during 7 weeks in a short-contact regimen. The clinical efficacy was monitored by scoring of erythema, induration, scaling and involved area (PASI); skin irritation was scored visually, and patient appreciation was evaluated by means of a multiple-choice questionnaire. Dispersion of dithranol in a cream was associated with less irritation and less discoloration of the skin, and its efficacy was comparable with that of the cream in which the dithranol was dissolved. As the dispersed dithranol formulation is easier to be manufactured, its quality will be less depending on the pharmacist's experience and equipment, and so more reliable. Besides, it will be less expensive to prepare. We advise to use this formulation for short-contact treatment. Copyright 2000 S. Karger AG, Basel.

Exciton dispersion in molecular solids

NASA Astrophysics Data System (ADS)

Cudazzo, Pierluigi; Sottile, Francesco; Rubio, Angel; Gatti, Matteo

2015-03-01

The investigation of the exciton dispersion (i.e. the exciton energy dependence as a function of the momentum carried by the electron-hole pair) is a powerful approach to identify the exciton character, ranging from the strongly localised Frenkel to the delocalised Wannier-Mott limiting cases. We illustrate this possibility at the example of four prototypical molecular solids (picene, pentacene, tetracene and coronene) on the basis of the parameter-free solution of the many-body Bethe-Salpeter equation. We discuss the mixing between Frenkel and charge-transfer excitons and the origin of their Davydov splitting in the framework of many-body perturbation theory and establish a link with model approaches based on molecular states. Finally, we show how the interplay between the electronic band dispersion and the exchange electron-hole interaction plays a fundamental role in setting the nature of the exciton. This analysis has a general validity holding also for other systems in which the electron wavefunctions are strongly localized, as in strongly correlated insulators.

In vitro and in vivo studies on a novel solid dispersion of repaglinide using polyvinylpyrrolidone as the carrier.

PubMed

Yin, Li-Fang; Huang, Shi-Jing; Zhu, Chun-Li; Zhang, Shu-Hui; Zhang, Qiang; Chen, Xi-Jing; Liu, Qing-Wang

2012-11-01

In order to improve the dissolution and absorption of the water insoluble drug repaglinide, a solid dispersion was developed by solvent method using polyvinylpyrrolidone K30 (PVP K30) as the hydrophilic carrier for the first time. Studies indicated that both solubility and the dissolution rate of repaglinide were significantly increased in the solid dispersion system compared with that of repaglinide raw material or physical mixtures. The repaglinide solid dispersions with PVP K30 solid state was characterized by polarizing microscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FT-IR). DSC and XRD studies indicated that repaglinide existed in an amorphous form in the solid dispersion. FT-IR analysis demonstrated the presence of intermolecular hydrogen bonding between repaglinide and PVP K30 in the solid dispersion. In the in situ gastrointestinal perfusion experiment, solid dispersion was shown to remarkably enhance the absorption of repaglinide in stomach and all segments of intestine. In vivo pharmacokinetic study in rats showed that immediate and complete release of repaglinide from the solid dispersion resulted in rapid absorption that significantly increased the bioavailability and the maximum plasma concentration over repaglinide raw material. These results demonstrated PVP K30 was an appropriate carrier for solid dispersion of repaglinide, with increased dissolution and oral absorption.

Development and evaluation of gastroretentive raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions for gastric ulcer treatment.

PubMed

Kerdsakundee, Nattha; Mahattanadul, Sirima; Wiwattanapatapee, Ruedeekorn

2015-08-01

Novel raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions were developed to prolong the gastric residence time and provide for a controlled release therapy of curcumin to treat gastric ulcers. The solid dispersions of curcumin with Eudragit® EPO were prepared by the solvent evaporation method at various ratios to improve the solubility and the dissolution of curcumin. The optimum weight ratio of 1:5 for curcumin to Eudragit® EPO was used to incorporate into the raft forming systems. The raft forming formulations were composed of curcumin-Eudragit® EPO solid dispersions, sodium alginate as a gelling polymer and calcium carbonate for generating divalent Ca(2+) ions and carbon dioxide to form a floating raft. All formulations formed a gelled raft in 1min and sustained buoyancy on the 0.1N hydrochloric acid (pH 1.2) surface with a 60-85% release of curcumin within 8h. The curative effect on the acetic acid-induced chronic gastric ulcer in rats was determined. The curcumin raft forming formulations at 40mg/kg once daily showed a superior curative effect on the gastric ulcer in terms of the ulcer index and healing index than the standard antisecretory agent: lansoprazole (1mg/kg, twice daily) and a curcumin suspension (40mg/kg, twice daily). These studies demonstrated that the new raft forming systems containing curcumin solid dispersions are promising carriers for a stomach-specific delivery of poorly soluble lipophilic compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Factors Affecting the Dissolution of Indomethacin Solid Dispersions.

PubMed

Zhang, Wei; Zhang, Chen-Ning; He, Yue; Duan, Ban-Yan; Yang, Guang-Yi; Ma, Wei-Dong; Zhang, Yong-Hong

2017-11-01

The aim of this study was to investigate the influence of factors such as carrier type, drug/carrier ratio, binary carriers, and preparation method on the dissolution of an insoluble drug, indomethacin (IM), under supersaturation conditions. Using a solvent evaporation (SE) method, poloxamer 188 and PVP K30 showed better dissolution among the selected carriers. Furthermore, as the ratio of carriers increased (drug/carrier ratio from 1:0.5 to 1:2), the dissolution rate increased especially in almost two times poloxamer 188 solid dispersions (SDs), while the reverse results were observed for PVP K30 SDs. For the binary carrier SD, a lower dissolution was found. Under hot melt extrusion (HME), the dissolution of poloxamer 188 SD and PVP K30 SD was 0.83- and 0.94-folds lower than that using SE, respectively, while the binary carrier SD showed the best dissolution. For poloxamer 188 SDs, the drug's crystal form changed when using SE, while no crystal form change was observed using HME. IM was amorphous in PVP K30 SDs prepared by both methods. For binary carrier systems, amorphous and crystalline drugs coexisted in SD using SE, and negligible amorphous IM was in SD using HME. This study indicated that a higher amorphous proportion in SD did not correlate with higher dissolution rate, and other factors, such as carrier type, particle size, and density, were also critical.

Thermosensitive In Situ Gel Based on Solid Dispersion for Rectal Delivery of Ibuprofen.

PubMed

Liu, Yangdan; Wang, Xin; Liu, Youping; Di, Xin

2018-01-01

The objective of this study was to develop a thermosensitive in situ gel based on solid dispersions (SDs) for rectal delivery of ibuprofen (IBU). Thermosensitive (poloxamer 407) and mucoadhesive (hydroxypropylmethyl cellulose E5 and sodium alginate) polymers were used to prepare the in situ gel and the sol-gel transition temperature (T sol-gel ) and gel strength were optimized. The in vitro release performance and in vivo pharmacokinetic properties of the in situ gel after their rectal administration to rabbits were investigated. Compared with the solid suppository, the cumulative release of the IBU SDs loaded in situ gel was significantly increased. The in vivo pharmacokinetics indicated that in situ gel had a higher peak plasma concentration (C max ) and area under the curve (AUC (0-∞) ) in plasma than the solid suppositories. Histopathology results showed that the IBU in situ gel given at a dose of 15 mg/kg did not produce any irritation. In conclusion, this study suggested that the in situ gel could be an effective rectal formulation for IBU.

Solution behavior of PVP-VA and HPMC-AS-based amorphous solid dispersions and their bioavailability implications.

PubMed

Qian, Feng; Wang, Jennifer; Hartley, Ruiling; Tao, Jing; Haddadin, Raja; Mathias, Neil; Hussain, Munir

2012-10-01

To identify the mechanism behind the unexpected bio-performance of two amorphous solid dispersions: BMS-A/PVP-VA and BMS-A/HPMC-AS. Solubility of crystalline BMS-A in PVP-VA and HPMC-AS was measured by DSC. Drug-polymer interaction parameters were obtained by Flory-Huggins model fitting. Drug dissolution kinetics of spray-dried dispersions were studied under sink and non-sink conditions. BMS-A supersaturation was studied in the presence of pre-dissolved PVP-VA and HPMC-AS. Potency and crystallinity of undissolved solid dispersions were determined by HPLC and DSC. Polymer dissolution kinetics were obtained by mass balance calculation. Bioavailability of solid dispersions was assessed in dogs. In solid state, both polymers are miscible with BMS-A, while PVP-VA solublizes the drug better. BMS-A dissolves similarly from both solid dispersions in vitro regardless of dissolution method, while the HPMC-AS dispersion performed much better in vivo. At the same concentration, HPMC-AS is more effective in prolonging BMS-A supersaturation; this effect was negated by the slow dissolution rate of HPMC-AS. Further study revealed that fast PVP-VA dissolution resulted in elevated drug loading in undissolved dispersions and facilitated drug recrystallization before complete release. In contrast, the hydrophobicity and slower HPMC-AS dissolution prevented BMS-A recrystallization within the HPMC-AS matrix for >24 h. The lower bioavailability of PVP-VA dispersion was attributed to BMS-A recrystallization within the undissolved dispersion, due to hydrophilicity and fast PVP-VA dissolution rate. Polymer selection for solid dispersion development has significant impact on in vivo performance besides physical stability.

Sodium alginate as a potential carrier in solid dispersion formulations to enhance dissolution rate and apparent water solubility of BCS II drugs.

PubMed

Borba, Paola Aline Amarante; Pinotti, Marihá; de Campos, Carlos Eduardo Maduro; Pezzini, Bianca Ramos; Stulzer, Hellen Karine

2016-02-10

The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however it depends on a suitable carrier selection. The work explored the use of the biopolymer sodium alginate (SA) as a potential carrier in solid dispersions (SD). The data demonstrated that SA was able to improve the biopharmaceutical properties of the BCS II drug telmisartan (TEL) of low solubility even using relative small drug:polymer ratio. A solid state grinding process was used to prepare the solid dispersions (SD) during 45 min. The SD were prepared in different proportions of drug and carrier of 1:1, 1:3, 1:5, 1:7 and 1:9 (mass/mass). DSC, XRPD, FTIR and Raman confirmed the presence of molecular interactions between TEL and the carrier. FTIR supports the presence of hydrogen bonds between TEL and the carrier. SD_1:5, SD_1:7 and SD_1:9 enhanced the dissolution rate of the drug releasing more than 80% of the drug in just 30 min (83%, 84% and 87%). The the t-test results demonstrated equal dissolution efficiency values for SD_1:7 and Micardis(®), however the similarity (f2) and difference (f1) fit factors showed that the SD and Micardis(®) are statistically different. The physical stability studies demonstrated that SD using sodium alginate as a carrier remained unchanged during the period of 90 days at room temperature, showing that the sodium alginate acts as a good anti plasticizer agent, preventing the drug recrystallization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Solubilization of poorly water-soluble drugs using solid dispersions.

PubMed

Tran, Thao T-D; Tran, Phuong H-L; Khanh, Tran N; Van, Toi V; Lee, Beom-Jin

2013-08-01

Many new drugs have been discovered in pharmaceutical industry and exposed their surprised potential therapeutic effects. Unfortunately, these drugs possess low absorption and bioavailability since their solubility limitation in water. Solid dispersion (SD) is the current technique gaining so many attractions from scientists due to its effect on improving solubility and dissolution rate of poorly water-soluble drugs. A number of patents including the most recent inventions have been undertaken in this review to address various respects of this strategy in solubilization of poorly watersoluble drugs including type of carriers, preparation methods and view of technologies used to detect SD properties and mechanisms with the aim to accomplish a SD not only effective on enhanced bioavailability but also overcome difficulties associated with stability and production. Future prospects are as well discussed with an only hope that many developments and researches in this field will be successfully reached and contributed to commercial use for treatment as much as possible.

Antisolvent Recrystallization Strategy to Screen Appropriate Carriers to Stabilize Filgotinib Amorphous Solid Dispersions.

PubMed

Ren, Fuzheng; Sun, Hanjing; Cui, Lin; Si, Yike; Chen, Ning; Ren, Guobin; Jing, Qiufang

2018-06-01

Drugs in amorphous solid dispersions (ASDs) are highly dispersed in hydrophilic polymeric carriers, which also help to restrain recrystallization and stabilize the ASDs. In this study, microscopic observation after antisolvent recrystallization was developed as a rapid screening method to select appropriate polymers for the initial design filgotinib (FTN) ASDs. Using solvent evaporation, FTN ASDs with the polymers were prepared, and accelerated experimentation validated this screening method. Fourier-transform infrared spectroscopy, Raman scattering, and nuclear magnetic resonance revealed hydrogen-bonding formation in the drug-polymer binary system, which was critical for ASDs stabilization. A Flory-Huggins interaction parameter and water sorption isotherms were applied to evaluate the strength of the interaction between FTN and the polymers. The dissolution rate was also significantly improved by ASDs formulation, and the presence of the polymers exerted solubilization effects. These results suggested the efficacy of this screening method as a preliminary tool for polymer selection in ASDs design. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

An attempt to stabilize tanshinone IIA solid dispersion by the use of ternary systems with nano-CaCO3 and poloxamer 188.

PubMed

Yan, Hong-Mei; Zhang, Zhen-Hai; Jiang, Yan-Rong; Ding, Dong-Mei; Sun, E; Jia, Xiao-Bin

2014-04-01

Tanshinone IIA (TSIIA) on solid dispersions (SDs) has thermodynamical instability of amorphous drug. Ternary solid dispersions (tSDs) can extend the stability of the amorphous form of drug. Poloxamer 188 was used as a SD carrier. Nano-CaCO3 played an important role in adsorption of biomolecules and is being developed for a host of biotechnological applications. The aim of the present study was to investigate the dissolution behavior and accelerated stability of TSIIA on solid dispersions (SDs) by the use of ternary systems with nano-CaCO3 and poloxamer 188. The TSIIA tSDs were prepared by a spray-drying method. First, the effect of combination of poloxamer 188 and nano-CaCO3 on TSIIA dissolution was studied. Subsequently, a set of complementary techniques (DSC, XRPD, SEM and FTIR) was used to monitor the physical changes of TSIIA in the SDs. Finally, stability test was carried out under the conditions 40°C/75% RH for 6 months. The characterization of tSDs by differential scanning calorimetry analysis (DSC) and X-ray powder diffraction (XRPD) showed that TSIIA was present in its amorphous form. Fourier transforms infrared spectroscopy (FTIR) suggested the presence of interactions between TSIIA and carriers in tSDs. Improvement in the dissolution rate was observed for all SDs. The stability study conducted on SDs with nano-CaCO3 showed stable drug content and dissolution behavior, over the period of 6 months as compared with freshly prepared SDs. SDs preparation with nano-CaCO3 and poloxamer 188 may be a promising approach to enhance the dissolution and stability of TSIIA.

Modified sedimentation-dispersion model for solids in a three-phase slurry column

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, D.N.; Ruether, J.A.; Shah, Y.T.

1986-03-01

Solids distribution data for a three-phase, batch-fluidized slurry bubble column (SBC) are presented, using air as the gas phase, pure liquids and solutions as the liquid phase, and glass beads and carborundum catalyst powder as the solid phase. Solids distribution data for the three-phase SBC operated in a continuous mode of operation are also presented, using nitrogen as the gas phase, water as the liquid phase, and glass beads as the solid phase. A new model to provide a reasonable approach to predict solids concentration distributions for systems containing polydispersed solids is presented. The model is a modification of standardmore » sedimentation-dispersion model published earlier. Empirical correlations for prediction of hindered settling velocity and solids dispersion coefficient for systems containing polydispersed solids are presented. A new method of evaluating critical gas velocity (CGV) from concentrations of the sample withdrawn at the same port of the SBC is presented. Also presented is a new mapping for CGV which separates the two regimes in the SBC, namely, incomplete fluidization and complete fluidization.« less

Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability.

PubMed

Onoue, Satomi; Takahashi, Haruki; Kawabata, Yohei; Seto, Yoshiki; Hatanaka, Junya; Timmermann, Barbara; Yamada, Shizuo

2010-04-01

Considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders, however, the therapeutic potential of curcumin could often be limited by its poor solubility, bioavailability, and photostability. To overcome these drawbacks, efficacious formulations of curcumin, including nanocrystal solid dispersion (CSD-Cur), amorphous solid dispersion (ASD-Cur), and nanoemulsion (NE-Cur), were designed with the aim of improving physicochemical and pharmacokinetic properties. Physicochemical properties of the prepared formulations were characterized by scanning/transmission electron microscope for morphological analysis, laser diffraction, and dynamic light scattering for particle size analysis, and polarized light microscope, powder X-ray diffraction and differential scanning calorimetry for crystallinity assessment. In dissolution tests, all curcumin formulations exhibited marked improvement in the dissolution behavior when compared with crystalline curcumin. Significant improvement in pharmacokinetic behavior was observed in the newly developed formulations, as evidenced by 12- (ASD-Cur), 16- (CSD-Cur), and 9-fold (NE-Cur) increase of oral bioavailability. Upon photochemical characterization, curcumin was found to be photoreactive and photodegradable in the solution state, possibly via type 2 photochemical reaction, whereas high photochemical stability was seen in the solid formulations, especially CSD-Cur. On the basis of these observations, taken together with dissolution and pharmacokinetic behaviors, CSD strategy would be efficacious to enhance bioavailability of curcumin with high photochemical stability. 2009 Wiley-Liss, Inc. and the American Pharmacists Association

Streamlined sample cleanup using combined dispersive solid-phase extraction and in-vial filtration for analysis of pesticides and environmental pollutants in shrimp

USDA-ARS?s Scientific Manuscript database

A new method of sample preparation was developed and is reported for the first time. The approach combines in-vial filtration with dispersive solid-phase extraction (d-SPE) in a fast and convenient cleanup of QuEChERS (quick, easy, cheap, effective, rugged, and safe) extracts. The method was appli...

Solid electrolytes strengthened by metal dispersions

DOEpatents

Lauf, Robert J.; Morgan, Chester S.

1983-01-01

An improvement in solid electrolytes of advanced secondary batteries of the sodium-sulfur, sodium-halogen, and like combinations is achieved by providing said battery with a cermet electrolyte containing a metal dispersion ranging from 0.1 to 10.0 vol. % of a substantially nonreactive metal selected from the group consisting essentially of Pt, Cr, Fe, Co, Ni, Nb, their alloys, and their physical mixtures in the elemental or uncombined state, the remainder of said cermet being an ion-conductive ceramic material.

Solid electrolytes strengthened by metal dispersions

DOEpatents

Lauf, R.J.; Morgan, C.S.

1981-10-05

An improvement in solid electrolytes of advanced secondary batteries of the sodium-sulfur, sodium-halogen, and like combinations is achieved by providing said battery with a cermet electrolyte containing a metal dispersion ranging from 0.1 to 10.0 vol. % of a substantially nonreactive metal selected from the group consisting essentially of Pt, Cr, Fe, Co, Ni, Nb, their alloys, and their physical mixtures in the elemental or uncombined state, the remainder of said cermet being an ion-conductive ceramic material.

Matrix solid-phase dispersion extraction of sulfonamides from blood.

PubMed

Zhang, Yupu; Xu, Xu; Liu, He; Zhai, Yujuan; Sun, Ye; Sun, Shuo; Zhang, Hanqi; Yu, Aimin; Wang, Yinghua

2012-02-01

Matrix solid-phase dispersion extraction was applied to the extraction of sulfadiazine, sulfamerazine, and sulfamethazine from human and animal bloods. The separation and determination of the analytes were carried out by high-performance liquid chromatography. The effects of the types of the dispersion adsorbents and elution solvents were investigated, and the highest recovery was obtained when diatomaceous earth was used as the dispersion adsorbent, while acetone was used as the elution solvent. Under the optimal conditions, the linear range for determining the sulfonamides in blood samples was 0.020-10.0 µg/mL, and the average recoveries of the three sulfonamides were higher than 87.5%.

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study.

PubMed

Deshmane, Subhash; Deshmane, Snehal; Shelke, Santosh; Biyani, Kailash

2018-06-01

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD 50 ). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.

Atypical effects of incorporated surfactants on stability and dissolution properties of amorphous polymeric dispersions.

PubMed

Al-Obaidi, Hisham; Lawrence, M Jayne; Buckton, Graham

2016-11-01

To understand the impact of ionic and non-ionic surfactants on the dissolution and stability properties of amorphous polymeric dispersions using griseofulvin (GF) as a model for poorly soluble drugs. Solid dispersions of the poorly water-soluble drug, griseofulvin (GF) and the polymers, poly(vinylpyrrolidone) (PVP) and poly(2-hydroxypropyl methacrylate) (PHPMA), have been prepared by spray drying and bead milling and the effect of the ionic and non-ionic surfactants, namely sodium dodecyl sulphate (SDS) and Tween-80, on the physico-chemical properties of the solid dispersions studied. The X-ray powder diffraction data and hot-stage microscopy showed a fast re-crystallisation of GF. While dynamic vapour sorption (DVS) measurements indicated an increased water uptake, slow dissolution rates were observed for the solid dispersions incorporating surfactants. The order by which surfactants free dispersions were prepared seemed critical as indicated by DVS and thermal analysis. Dispersions prepared by milling with SDS showed significantly better stability than spray-dried dispersions (drug remained amorphous for more than 6 months) as well as improved dissolution profile. We suggest that surfactants can hinder the dissolution by promoting aggregation of polymeric chains, however that effect depends mainly on how the particles were prepared. © 2016 Royal Pharmaceutical Society.

Solid dispersions: a strategy for poorly aqueous soluble drugs and technology updates.

PubMed

Alam, Mohd Aftab; Ali, Raisuddin; Al-Jenoobi, Fahad Ibrahim; Al-Mohizea, Abdullah M

2012-11-01

Present article reviews solid dispersion (SD) technologies and other patented inventions in the area of pharmaceutical SDs, which provide stable amorphous SDs. The review briefly compiles different techniques for preparing SDs, their applications, characterization of SDs, types of SDs and also elaborates the carriers used to prepare SDs. The advantages of recently introduced SD technologies such as RightSize(™), closed-cycle spray drying (CSD), Lidose® are summarized. Stability-related issues like phase separation, re-crystallization and methods to curb these problems are also discussed. A patented carrier-screening tool for predicting physical stability of SDs on the basis of drug-carrier interaction is explained. Applications of SD technique in controlled drug delivery systems and cosmetics are explored. Review also summarizes the carriers such as Soluplus®, Neusilin®, Solumer(TM) used to prepare stable amorphous SD. Binary and ternary SDs are found to be more stable and provide better enhancement of solubility or dissolution of poorly water-soluble drugs. The use of surfactants in the carrier system of SD is a recent trend. Surfactants and polymers provide stability against re-crystallization of SDs, surfactants also improve solubility and dissolution of drug.

Magnetic dispersive solid-phase extraction based on modified magnetic nanoparticles for the detection of cocaine and cocaine metabolites in human urine by high-performance liquid chromatography-mass spectrometry.

PubMed

Yang, Feiyu; Zou, Yun; Ni, Chunfang; Wang, Rong; Wu, Min; Liang, Chen; Zhang, Jiabin; Yuan, Xiaoliang; Liu, Wenbin

2017-11-01

An easy-to-handle magnetic dispersive solid-phase extraction procedure was developed for preconcentration and extraction of cocaine and cocaine metabolites in human urine. Divinyl benzene and vinyl pyrrolidone functionalized silanized Fe 3 O 4 nanoparticles were synthesized and used as adsorbents in this procedure. Scanning electron microscopy, vibrating sample magnetometry, and infrared spectroscopy were employed to characterize the modified adsorbents. A high-performance liquid chromatography with mass spectrometry method for determination of cocaine and its metabolites in human urine sample has been developed with pretreatment of the samples by magnetic dispersive solid-phase extraction. The obtained results demonstrated the higher extraction capacity of the prepared nanoparticles with recoveries between 75.1 to 105.7% and correlation coefficients higher than 0.9971. The limits of detection for the cocaine and cocaine metabolites were 0.09-1.10 ng/mL. The proposed magnetic dispersive solid-phase extraction method provided a rapid, environmentally friendly and magnetic stuff recyclable approach and it was confirmed that the prepared adsorbents material was a kind of highly effective extraction materials for the trace cocaine and cocaine metabolites analyses in human urine. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of triazine herbicides in seaweeds: development of a sample preparation method based on Matrix Solid Phase Dispersion and Solid Phase Extraction Clean-up.

PubMed

Rodríguez-González, N; González-Castro, M J; Beceiro-González, E; Muniategui-Lorenzo, S; Prada-Rodríguez, D

2014-04-01

A method using dual process columns of Matrix Solid Phase Dispersion (MSPD) and Solid Phase Extraction (SPE) has been developed for extracting and cleaning-up of nine triazine herbicides (ametryn, atrazine, cyanazine, prometryn, propazine, simazine, simetryn, terbuthylazine and terbutryn) in seaweed samples. Under optimized conditions, samples were blended with 2g of octasilyl-derivatized silica (C8) and transferred into an SPE cartridge containing ENVI-Carb II/PSA (0.5/0.5 g) as a clean up co-sorbent. Then the dispersed sample was washed with 10 mL of n-hexane and triazines were eluted with 20 mL ethyl acetate and 5 mL acetonitrile. Finally the extract was concentrated to dryness, re-constituted with 1 mL methanol:water (1:1) and injected into the HPLC-DAD system. The linearity of the calibration curves was excellent in matrix matched standards, and yielded the coefficients of determination>0.995 for all the target analytes. The recoveries ranged from 75% to 100% with relative standard deviations lower than 7%. The achieved LOQs (<10 µg kg(-1)) for all triazines under study permits to ensure proper determination at the maximum allowed residue levels set in the European Union Legislation. Samples of three seaweeds were subjected to the procedure proving the suitability of MSPD method for the analysis of triazines in different seaweeds samples. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of physicochemical properties and in vivo efficiency of atorvastatin calcium/ezetimibe solid dispersions.

PubMed

Jahangiri, Azin; Barzegar-Jalali, Mohammad; Garjani, Alireza; Javadzadeh, Yousef; Hamishehkar, Hamed; Asadpour-Zeynali, Karim; Adibkia, Khosro

2016-01-20

Fixed-dose combination of atorvastatin calcium (ATV) and ezetimibe (EZT) provides a considerable advantage in the management of hyperlipidemia. However, both ATV and EZT suffer from the poor aqueous solubility, which can limit their oral bioavailability. The aim of the present study was to improve the in vitro performance and evaluate the in vivo efficiency of the improved (ATV/EZT) fixed-dose combination. The formulation was prepared through solid dispersion (SD)technique, using Polyvinylpyrrolidone K30 via solvent method. Solid-state analysis and the in vitro drug release of the prepared formulations were also assessed. In order to estimate the therapeutic efficiency of the prepared SDs, in vivo studies including measurement of serum lipid levels, liver index and histological analysis of the liver tissue in hyperlipidemic rats were conducted. Differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) showed that the drugs crystallinity was notably decreased during the preparation process. All SDs showed enhanced release for both drugs compared to their binary mixture, drugs: polymer physical mixtures (PMs) and marketed product. Administration of ATV/EZT SD led to a remarkable decrease (P<0.05) in the serum levels of total cholesterol (TC) and LDL-C in the high fat diet-induced hyperlipidemic rats compared to the PM. Additionally, the histopathological examination of the liver tissue revealed the improved efficiency of the SDs on the liver steatosis. According to the obtained results, ATV/EZT SD with improved physicochemical characteristics, showed favorable effects on the serum lipid levels and liver steatosis. Copyright © 2015 Elsevier B.V. All rights reserved.

Relating hydrogen-bonding interactions with the phase behavior of naproxen/PVP K 25 solid dispersions: evaluation of solution-cast and quench-cooled films.

PubMed

Paudel, Amrit; Nies, Erik; Van den Mooter, Guy

2012-11-05

In this work, we investigated the relationship between various intermolecular hydrogen-bonding (H-bonding) interactions and the miscibility of the model hydrophobic drug naproxen with the hydrophilic polymer polyvinylpyrrolidone (PVP) across an entire composition range of solid dispersions prepared by quasi-equilibrium film casting and nonequilibrium melt quench cooling. The binary phase behavior in solid dispersions exhibited substantial processing method dependence. The solid state solubility of crystalline naproxen in PVP to form amorphous solid dispersions was 35% and 70% w/w naproxen in solution-cast films and quench-cooled films, respectively. However, the presence of a single mixed phase glass transition indicated the amorphous miscibility to be 20% w/w naproxen for the films, beyond which amorphous-amorphous and/or crystalline phase separations were apparent. This was further supported by the solution state interactions data such as PVP globular size distribution and solution infrared spectral profiles. The borderline melt composition showed cooling rate dependence of amorphization. The glass transition and melting point depression profiles of the system were treated with the analytical expressions based on Flory-Huggins mixing theory to interpolate the equilibrium solid solubility. FTIR analysis and subsequent spectral deconvolution revealed composition and miscibility dependent variations in the strength of drug-polymer intermolecular H-bonding. Two types of H-bonded populations were evidenced from 25% w/w and 35% w/w naproxen in solution-cast films and quench-cooled films, respectively, with the higher fraction of strongly H-bonded population in the drug rich domains of phase separated amorphous film compositions and highly drug loaded amorphous quench-cooled dispersions.

Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation

PubMed Central

Amin, Purnima

2014-01-01

Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD) with immediate release and improved bioavailability was prepared using Soluplus (Sol) as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal) fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72) and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72) and Cmax higher than those with the commercial capsule (Noxafil). Molecular dynamic (MD) simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension. PMID:25143935

PEGylation of magnetic multi-walled carbon nanotubes for enhanced selectivity of dispersive solid phase extraction.

PubMed

Zeng, Qiong; Liu, Yi-Ming; Jia, Yan-Wei; Wan, Li-Hong; Liao, Xun

2017-02-01

Carbon nanotubes (CNTs) possess large potential as extraction absorbents in solid phase extraction. They have been widely applied in biomedicine research, while very rare application in natural product chemistry has been reported. In this work, methoxypolyethylene glycol amine (mPEG-NH 2 ) is covalently coupled to CNTs-magnetic nanoparticles (CNTs-MNP) to prepare a novel magnetic nanocomposite (PEG-CNTs-MNP) for use as dispersive solid-phase extraction (DSPE) absorbent. The average particle size was 86nm, and the saturation magnetization was 52.30emu/g. This nanocomposite exhibits excellent dispersibility in aqueous systems, high selectivity and fast binding kinetics when used for extraction of Z-ligustilide, the characteristic bioactive compound from two popular Asian herbal plants, R. chuanxiong and R. ligusticum. HPLC quantification of Z-ligustilide extracted from the standard sample solution showed a high recovery of 98.9%, and the extraction rate from the extracts of the above two herbs are both around 70.0%. To our knowledge, this is the first report on using PEG-CNTs-MNP as DSPE nanosorbents for selective extraction of natural products. This nano-material has promising application in isolation and enrichment of targeted components from complex matrices. Copyright © 2016 Elsevier B.V. All rights reserved.

White/blue-emitting, water-dispersible CdSe quantum dots prepared by counter ion-induced polymer collapse

NASA Astrophysics Data System (ADS)

Wang, Jing; Goh, Jane Betty; Goh, M. Cynthia; Giri, Neeraj Kumar; Paige, Matthew F.

2015-09-01

The synthesis and characterization of water-dispersible, luminescent CdSe/ZnS semiconductor quantum dots that exhibit nominal "white" fluorescence emission and have potential applications in solid-state lighting is described. The nanomaterials, prepared through counter ion-induced collapse and UV cross-linking of high-molecular weight polyacrylic acid in the presence of appropriate aqueous inorganic ions, were of ∼2-3 nm diameter and could be prepared in gram quantities. The quantum dots exhibited strong luminescence emission in two bands, the first in the blue-region (band edge) of the optical spectrum and the second, a broad emission in the red-region (attributed to deep trap states) of the optical spectrum. Because of the relative strength of emission of the band edge and deep trap state luminescence, it was possible to achieve visible white luminescence from the quantum dots in aqueous solution and in dried, solid films. The optical spectroscopic properties of the nanomaterials, including ensemble and single-molecule spectroscopy, was performed, with results compared to other white-emitting quantum dot systems described previously in the literature.

Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs.

PubMed

Serajuddin, A T

1999-10-01

Although there was a great interest in solid dispersion systems during the past four decades to increase dissolution rate and bioavailability of poorly water-soluble drugs, their commercial use has been very limited, primarily because of manufacturing difficulties and stability problems. Solid dispersions of drugs were generally produced by melt or solvent evaporation methods. The materials, which were usually semisolid and waxy in nature, were hardened by cooling to very low temperatures. They were then pulverized, sieved, mixed with relatively large amounts of excipients, and encapsulated into hard gelatin capsules or compressed into tablets. These operations were difficult to scale up for the manufacture of dosage forms. The situation has, however, been changing in recent years because of the availability of surface-active and self-emulsifying carriers and the development of technologies to encapsulate solid dispersions directly into hard gelatin capsules as melts. Solid plugs are formed inside the capsules when the melts are cooled to room temperature. Because of surface activity of carriers used, complete dissolution of drug from such solid dispersions can be obtained without the need for pulverization, sieving, mixing with excipients, etc. Equipment is available for large-scale manufacturing of such capsules. Some practical limitations of dosage form development might be the inadequate solubility of drugs in carriers and the instability of drugs and carriers at elevated temperatures necessary to manufacture capsules.

Physicochemical and Pharmacokinetic Characterization of Amorphous Solid Dispersion of Meloxicam with Enhanced Dissolution Property and Storage Stability.

PubMed

Ochi, Masanori; Kimura, Keisuke; Kanda, Atsushi; Kawachi, Takaki; Matsuda, Akitoshi; Yuminoki, Kayo; Hashimoto, Naofumi

2016-08-01

The aim of the present study was to develop amorphous solid dispersion (ASD) of meloxicam (MEL) for providing rapid onset of action. ASDs of MEL with polyvinylpyrrolidone (PVP) K-30 (MEL/PVP), HPC-SSL (MEL/HPC), and Eudragit EPO (MEL/EPO) were prepared. The physicochemical properties were characterized by focusing on morphology, crystallinity, dissolution properties, stability, and the interaction of MEL with coexisting polymers. MEL/EPO was physicochemically stable after storage at 40°C/75% RH for 30 days. In contrast, recrystallization of MEL was observed in MEL/PVP and MEL/HPC at 40°C/50% RH for 30 days. Infrared spectroscopic studies and (1)H NMR analyses of MEL/EPO revealed that Eudragit EPO interacted with MEL and reduced intermolecular binding between MEL molecules. Intermolecular interaction of drug molecules is necessary for the formation of crystalline. Thus, the interaction of MEL with Eudragit EPO and interruption of the formation of supramolecular interaction between MEL molecules might lead to the inhibition of crystal growth of MEL. Of all the MEL solid dispersions prepared, MEL/EPO showed the largest improvement in dissolution behavior. Oral administration of MEL/EPO to rats showed rapid and enhanced MEL exposure with a 2.4-fold increase in bioavailability compared with crystalline MEL. Based on these findings, MEL/EPO was physicochemically stable and provided a rapid onset of action and enhanced bioavailability after oral administration.

Solid lipid dispersions: potential delivery system for functional ingredients in foods.

PubMed

Asumadu-Mensah, Aboagyewa; Smith, Kevin W; Ribeiro, Henelyta S

2013-07-01

Structured solid lipid (SL) systems have the advantages of long-term physical stability, low surfactant concentrations, and may exhibit controlled release of active ingredients. In this research work, the potential use of high-melting SLs for the production of the above structured SL carrier systems was investigated. Dispersions containing either SL or blend of solid lipid and oil (SL+O) were produced by a hot melt high-pressure homogenization method. Experiments involved the use of 3 different SLs for the disperse phase: stearic acid, candelilla wax and carnauba wax. Sunflower oil was incorporated in the disperse phase for the production of the dispersions containing lipid and oil. In order to evaluate the practical aspects of structured particles, analytical techniques were used including: static light scattering to measure particle sizes, transmission electron microscopy (TEM) for investigating particle morphology and differential scanning calorimetry (DSC) to investigate the crystallization behavior of lipids in bulk and in dispersions. Results showed different mean particle sizes depending on the type of lipid used in the disperse phase. Particle sizes for the 3 lipids were: stearic acid (SL: 195 ± 2.5 nm; SL+O: 138 ± 6.0 nm); candelilla wax (SL: 178 ± 1.7 nm; SL+O: 144 ± 0.6 nm); carnauba wax (SL: 303 ± 1.5 nm; SL+O: 295 ± 5.0 nm). TEM results gave an insight into the practical morphology, showing plate-like and needle-like structures. DSC investigations also revealed that SL dispersions melted and crystallized at lower temperatures than the bulk. This decrease can be explained by the small particle sizes of the dispersion, the high-specific surface area, and the presence of a surfactant. © 2013 Institute of Food Technologists®

A comparison of the effect of temperature and moisture on the solid dispersions: aging and crystallization.

PubMed

Tian, Bin; Zhang, Ling; Pan, Zhendong; Gou, Jingxin; Zhang, Yu; Tang, Xing

2014-11-20

The purpose of this work was to compare the effect of temperature and relative humidity (RH) on the physical stability and dissolution of solid dispersions. Cinnarizine-Soluplus(®) solid dispersions (SDs) at three different drug loadings (10, 20 and 35 wt%) were prepared by hot melt extrusion and exposed to stress conditions: high temperatures (40 and 60 °C), high relative humidities (75% and 94% RH) and accelerated conditions (40 °C/75% RH) for 30 days, or stored at 25 °C for up to 5 months. Changes in solid state and dissolution of SDs were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and dissolution testing. For samples under stress conditions, the results showed a reduced dissolution and a recrystallization of the drug with an increased crystallinity in the order of 40 °C/75% RH, >60 °C/0% RH, >25 °C/94% RH, >40 °C/0% RH, >25 °C/75% RH. For samples stored at 25 °C, nonlinear physical aging was observed and the dissolution also decreased although the SDs were still amorphous. The results indicated that temperature and humidity seemed to have comparable effects on the crystallization of cinnarizine-Soluplus(®) SDs. It is not reasonable to regard recrystallization as a sign of reduced dissolution, and glass transition temperature (Tg) may be a good indicator of the changes in dissolution. Copyright © 2014 Elsevier B.V. All rights reserved.

Barrier coated drug layered particles for enhanced performance of amorphous solid dispersion dosage form.

PubMed

Puri, Vibha; Dantuluri, Ajay K; Bansal, Arvind K

2012-01-01

Amorphous solid dispersions (ASDs) may entail tailor-made dosage form design to exploit their solubility advantage. Surface phenomena dominated the performance of amorphous celecoxib solid dispersion (ACSD) comprising of amorphous celecoxib (A-CLB), polyvinylpyrrolidone, and meglumine (7:2:1, w/w). ACSD cohesive interfacial interactions hindered its capsule dosage form dissolution (Puri V, Dhantuluri AK, Bansal AK 2011. J Pharm Sci 100:2460-2468). Furthermore, ACSD underwent significant devitrification under environmental stress. In the present study, enthalpy relaxation studies revealed its free surface to contribute to molecular mobility. Based on all these observations, barrier coated amorphous CLB solid dispersion layered particles (ADLP) were developed by Wurster process, using microcrystalline cellulose as substrate and polyvinyl alcohol (PVA), inulin, and polyvinyl acetate phthalate (PVAP) as coating excipients. Capsule formulations of barrier coated-ADLP could achieve rapid dispersibility and high drug release. Evaluation under varying temperature and RH conditions suggested the crystallization inhibitory efficiency in order of inulin < PVA ≈ PVAP; however, under only temperature treatment, crystallization inhibition increased with increase in T(g) of the coating material. Simulated studies using DSC evidenced drug-polymer mixing at the interface as a potential mechanism for surface stabilization. In conclusion, surface modification yielded a fast dispersing robust high drug load ASD based dosage form. Copyright © 2011 Wiley-Liss, Inc.

Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility.

PubMed

Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Kyoung-Ho; Kim, Dong-Jin; Lee, Beom-Jin

2010-05-01

Although the solid dispersion method has been known to increase the dissolution rate of poorly water-soluble drugs by dispersing them in hydrophilic carriers, one obstacle of the solid dispersion method is its limited solubilization capacity, especially for pH-dependent soluble drugs. pH-modified solid dispersion, in which pH modifiers are incorporated, may be a useful method for increasing the dissolution rate of weakly acidic or basic drugs. Sufficient research, including the most recent reports, was undertaken in this review. How could the inclusion of the pH the pH modifiers in the solid dispersion system change drug structural behaviors, molecular interactions, microenvironmental pH, and/or release rate of pH modifiers, relating with the enhanced dissolution of weakly acidic or weakly basic drugs with poor water solubility? These questions have been investigated to determine the dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs. It is believed that step-by-step mechanistic approaches could provide the ultimate solution for solubilizing several poorly water-soluble drugs with pH-dependent solubility from a solid dispersion system, as well as provide ideas for developing future dosage systems.

Surfactant-Free Solid Dispersions of Hydrophobic Drugs in an Amorphous Sugar Matrix Dried from an Organic Solvent.

PubMed

Takeda, Koji; Gotoda, Yuto; Hirota, Daichi; Hidaka, Fumihiro; Sato, Tomo; Matsuura, Tsutashi; Imanaka, Hiroyuki; Ishida, Naoyuki; Imamura, Koreyoshi

2017-03-06

The technique for homogeneously dispersing hydrophobic drugs in a water-soluble solid matrix (solid dispersion) is a subject that has been extensively investigated in the pharmaceutical industry. Herein, a novel technique for dispersing a solid, without the need to use a surfactant, is reported. A freeze-dried amorphous sugar sample was dissolved in an organic solvent, which contained a soluble model hydrophobic component. The suspension of the sugar and the model hydrophobic component was vacuum foam dried to give a solid powder. Four types of sugars and methanol were used as representative sugars and the organic medium. Four model drugs (indomethacin, ibuprofen, gliclazide, and nifedipine) were employed. Differential scanning calorimetry analyses indicated that the sugar and model drug (100:1) did not undergo segregation during the drying process. The dissolution of the hydrophobic drugs in water from the solid dispersion was then evaluated, and the results indicated that the C max and AUC 0-60 min of the hydrophobic drug in water were increased when the surfactant-free solid dispersion was used. Palatinose and/or α-maltose were superior to the other tested carbohydrates in increasing C max and AUC 0-60 min for all tested model drugs, and the model drug with a lower water solubility tended to exhibit a greater extent of over-dissolution.

Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.

PubMed

Jung, Hyuck Jun; Ahn, Hye In; Park, Ji Yeon; Ho, Myoung Jin; Lee, Dae Ro; Cho, Ha Ra; Park, Jun Seo; Choi, Yong Seok; Kang, Myung Joo

2016-02-01

A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation of Microcapsules Containing β-Carotene with Thermo Sensitive Curdlan by Utilizing Reverse Dispersion

PubMed Central

Taguchi, Yoshinari; Ono, Fumiyasu; Tanaka, Masato

2013-01-01

We have tried to microencapsulate β-carotene with curdlan of a thermogelation type polysaccharide. Microcapsules were prepared by utilizing reverse dispersion, in which salada oil was the continuous phase (O’) and the curdlan water slurry (W) was the dispersed phase. β-carotene (O) as a core material was broken into fine oil droplets in the dispersed phase to form the (O/W) dispersion. The (O/W) dispersion was poured in the continuous phase (O’) and stirred to form the (O/W)/O’ dispersion at room temperature and then, temperature of the dispersion was raised to 80 °C to prepare curdlan-microcapusles containing β-carotene. In this microencapsulation process, the concentrations of curdlan and oil soluble surfactant and the impeller speed to form the (O/W)/O’ dispersion were mainly changed stepwise. We were able to prepare microcapsules by the microencapsulation method adopted here. The content of core material was increased with the curdlan concentration and decreased with the impeller speed and the oil soluble surfactant concentration. With the curdlan concentration, the drying rate of microcapsules was decreased and the retention ability for water was increased due to the stable preservation of β-carotene. PMID:24300565

Estimation of Crystallinity of Nifedipine-Polyvinylpyrrolidone Solid Dispersion by Usage of Terahertz Time-Domain Spectroscopy and of X-Ray Powder Diffractometer.

PubMed

Takeuchi, Issei; Shimakura, Kemmaro; Kuroda, Hideki; Nakajima, Takehisa; Goto, Satoru; Makino, Kimiko

2015-12-01

Crystalline state of pharmaceutical materials is of great importance in preparation of pharmaceutics, because their physicochemical properties affect bioavailability, quality of products, therapeutic level and manufacturing process. In this study, we have estimated time-dependent changes of nifedipine in nifedipine-polyvinylpyrrolidone (PVP) solid dispersion by measuring terahertz time-domain spectroscopy (THz-TDS) and by X-ray powder diffractometry (XRPD), and compared their correlativity. Crystallinity of nifedipine-PVP solid dispersion was changed by storing the amorphous sample at 25°C-75°C and relative humidity of over 80% for 0.25-24.00 h. To compare the results of two types of measurements, we have used a general method of linear regression analysis. Crystallinities estimated using THz-TDS were plotted on the x-axis and that of XRPD were on the y-axis. From the result of the calculation, the correlativity of them was confirmed. THz-TDS has the capability of becoming the replacement of XRPD. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Aqueous carbon black dispersions prepared with steam jet-cooked corn starch

USDA-ARS?s Scientific Manuscript database

The utilization of jet-cooked waxy and normal corn starch to prepare aqueous dispersions of hydrophobic carbon black (Vulcan XC-72R) is reported. Blending carbon black (CB) into aqueous jet-cooked dispersions of starch followed by high pressure homogenization produced stable aqueous carbon black di...

Mechanism for enhanced absorption of a solid dispersion formulation of LY2300559 using the artificial stomach duodenum model.

PubMed

Polster, Christopher S; Wu, Sy-Juen; Gueorguieva, Ivelina; Sperry, David C

2015-04-06

An artificial stomach duodenum (ASD) model has been used to demonstrate the performance difference between two formulations of LY2300559, a low-solubility acidic developmental drug. The two formulations investigated were a conventional high-shear wet granulation (HSWG) formulation and a solid dispersion formulation. A pharmacokinetic study in humans demonstrated the enhanced performance of the solid dispersion formulation relative to the HSWG formulation. The Cmax and AUC of the solid dispersion was 2.6 and 1.9 times greater, respectively, compared to the HSWG formulation. In the ASD, the solid dispersion formulation performance was characterized by three main phases: (1) rapid release in the stomach, creating a supersaturated concentration of drug, (2) precipitation in the stomach, and (3) rapid redissolution of the precipitate in the duodenum to concentration levels that are supersaturated relative to crystalline drug. A series of complementary experiments were employed to describe this performance behavior mechanistically. Imaging experiments with a pH indicating dye showed that local pH gradients from meglumine in the solid dispersion formulation were responsible for creating a high initial supersaturation concentration in the stomach. Upon dissipation of meglumine, the drug precipitated in the stomach as an amorphous solid. Because the precipitated drug is in an amorphous form, it can then rapidly redissolve as it transits to the more neutral environment of the duodenum. This unexpected sequence of physical state changes gives a mechanistic explanation for the enhanced in vivo performance of the solid dispersion formulation relative to the HSWG formulation.

Interfacial interaction track of amorphous solid dispersions established by water-soluble polymer and indometacin.

PubMed

Li, Jing; Fan, Na; Wang, Xin; Li, Chang; Sun, Mengchi; Wang, Jian; Fu, Qiang; He, Zhonggui

2017-08-30

The present work studied interfacial interactions of amorphous solid dispersions matrix of indometacin (IMC) that established using PVP K30 (PVP) and PEG 6000 (PEG) by focusing on their interaction forces and wetting process. Infrared spectroscopy (IR), raman spectroscopy, X-ray photoelectron spectra and contact angle instrument were used throughout the study. Hydrogen bond energy formed between PEG and IMC were stronger than that of PVP and IMC evidenced by molecular modeling measurement. The blue shift of raman spectroscopy confirmed that hydrogen bonding forces were formed between IMC and two polymers. The contact angle study can be used as an easy method to determine the dissolution mechanism of amorphous solid dispersions through fitting the profile of contact angle of water on a series of tablets. It is believed that the track of interfacial interactions will certainly become powerful tools to for designing and evaluating amorphous solid dispersions. Copyright © 2017 Elsevier B.V. All rights reserved.

Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy.

PubMed

Kanaujia, Parijat; Lau, Grace; Ng, Wai Kiong; Widjaja, Effendi; Schreyer, Martin; Hanefeld, Andrea; Fischbach, Matthias; Saal, Christoph; Maio, Mario; Tan, Reginald B H

2011-09-01

Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials(®) to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardless of the degree of crystallinity increase in FF, the enhanced dissolution properties were similarly diminished. Moisture uptake above 10% in KC samples also led to re-crystallization and significant decrease in dissolution rates. In conclusion, eliminating moisture sorption may not be sufficient in ensuring the stability of solid dispersions. Analytical quantification of API crystallinity is crucial in detecting subtle increase in crystallinity that can diminish the enhanced dissolution properties of solid dispersions.

Enhancement of in-vitro drug dissolution of ketoconazole for its optimal in-vivo absorption using Nanoparticles and Solid Dispersion forms of the drug

NASA Astrophysics Data System (ADS)

Syed, Mohammed Irfan

Ketoconazole is one of the most widely prescribed oral antifungal drugs for the systemic treatment of various fungal infections. However, due its hydrophobic nature and poor solubility profiles in the gastro-intestinal fluids, variations in its bioavailability have been documented. Therefore, to enhance its dissolution in the biological fluids, this study was initiated to develop and evaluate Nanoparticles and Solid Dispersion forms of the drug. Nanoparticles of ketoconazole were developed by Wet Bead Milling technique using PVP-10k as the stabilizing material at a weight ratio of (2:1). Solid dispersion powder was prepared by Hot Melt method using PEG-8000 at a weight ratio of (1:2). A commercial product containing 200mg of ketoconazole tablet and pure drug powder were used as the control for comparison purposes. The dissolution studies were carried out in SGF, SIF, USP; and SIF with 0.2% sodium lauryl sulfate using the USP-II method for a 2 hours period. Physical characterizations were carried out using SEM, DSC, XRD and FTIR studies. Wet Bead Milling method yielded nanoparticles in the particles size range of (100-300nm.). First all samples were evaluated for their in-vitro dissolution in SGF at pH=1.2. After 15 minutes, the amounts of drug dissolved were observed to be 27% from both the pure powder and commercial tablet (control), 29% from solid dispersion and 100% from the Nanoparticles dosage form. This supports the fact that Nanoparticles had a strong influence on the dissolution rate of the drug and exhibited much faster dissolution of ketoconazole. When the same formulations were studied in the SIF, USP medium, the control formulation gave 3%, solid dispersion 8% and Nanoparticles 8% drug dissolution after 2 hours period. This could be because the weakly basic ketoconazole drug remained un-dissociated in the alkaline medium. Since this medium was unable to clearly distinguish the dissolution profiles from different formulation of the drug, the SIF solution

A Molecular-Level View of the Physical Stability of Amorphous Solid Dispersions

NASA Astrophysics Data System (ADS)

Yuan, Xiaoda

Many pharmaceutical compounds being developed in recent years are poorly soluble in water. This has led to insufficient oral bioavailability of many compounds in vitro. The amorphous formulation is one of the promising techniques to increase the oral bioavailability of these poorly water-soluble compounds. However, an amorphous drug substance is inherently unstable because it is a high energy form. In order to increase the physical stability, the amorphous drug is often formulated with a suitable polymer to form an amorphous solid dispersion. Previous research has suggested that the formation of an intimately mixed drug-polymer mixture contributes to the stabilization of the amorphous drug compound. The goal of this research is to better understand the role of miscibility, molecular interactions and mobility on the physical stability of amorphous solid dispersions. Methods were developed to detect different degrees of miscibility on nanometer scale and to quantify the extent of hydrogen-bonding interactions between the drug and the polymer. Miscibility, hydrogen-bonding interactions and molecular mobility were correlated with physical stability during a six-month period using three model systems. Overall, this research provides molecular-level insights into many factors that govern the physical stability of amorphous solid dispersions which can lead to a more effective design of stable amorphous formulations.

Effect of preparation methods on dispersion stability and electrochemical performance of graphene sheets

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Li, E-mail: chenli1981@lut.cn; Li, Na; Zhang, Mingxia

Chemical exfoliation is one of the most important strategies for preparing graphene. The aggregation of graphene sheets severely prevents graphene from exhibiting excellent properties. However, there are no attempts to investigate the effect of preparation methods on the dispersity of graphene sheets. In this study, three chemical exfoliation methods, including Hummers method, modified Hummers method, and improved method, were used to prepare graphene sheets. The influence of preparation methods on the structure, dispersion stability in organic solvents, and electrochemical properties of graphene sheets were investigated. Fourier transform infrared microscopy, Raman spectra, transmission electron microscopy, and UV–vis spectrophotometry were employed tomore » analyze the structure of the as-prepared graphene sheets. The results showed that graphene prepared by improved method exhibits excellent dispersity and stability in organic solvents without any additional stabilizer or modifier, which is attributed to the completely exfoliation and regular structure. Moreover, cyclic voltammetric and electrochemical impedance spectroscopy measurements showed that graphene prepared by improved method exhibits superior electrochemical properties than that prepared by the other two methods. - Graphical abstract: Graphene oxides with different oxidation degree were obtained via three methods, and then graphene with different crystal structures were created by chemical reduction of exfoliated graphene oxides. - Highlights: • Graphene oxides with different oxidation degree were obtained via three oxidation methods. • The influence of oxidation methods on microstructure of graphene was investigated. • The effect of oxidation methods on dispersion stability of graphene was investigated. • The effect of oxidation methods on electrochemical properties of graphene was discussed.« less

Inventory of oral anticancer agents: Pharmaceutical formulation aspects with focus on the solid dispersion technique.

PubMed

Sawicki, E; Schellens, J H M; Beijnen, J H; Nuijen, B

2016-11-01

Dissolution from the pharmaceutical formulation is a prerequisite for complete and consistent absorption of any orally administered drug, including anticancer agents (oncolytics). Poor dissolution of an oncolytic can result in low oral bioavailability, high variability in blood concentrations and with that suboptimal or even failing therapy. This review discusses pharmaceutical formulation aspects and absorption pharmacokinetics of currently licensed orally administered oncolytics. In nearly half of orally dosed oncolytics poor dissolution is likely to play a major role in low and unpredictable absorption. Dissolution-limited drug absorption can be improved with a solid dispersion which is a formulation method that induces super-saturated drug dissolution and with that it enhances in vivo absorption. This review discusses formulation principles with focus on the solid dispersion technology and how it works to enhance drug absorption. There are currently three licensed orally dosed oncolytics formulated as a solid dispersion (everolimus, vemurafenib and regorafenib) and these formulations result in remarkably improved dissolution and absorption compared to what can be achieved with conventional formulations of the respective oncolytics. Because of the successful implementation of these three solid dispersion formulations, we encourage the application of this formulation method for poorly soluble oral oncolytics. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation of milk samples for immunoassay and liquid chromatographic screening using matrix solid-phase dispersion.

PubMed

Barker, S A; Long, A R

1994-01-01

The use of drugs to maintain the health and maximize the output of dairy cattle has made the monitoring of milk for such agents essential. Screening tests based on immunological, microbial inhibition, and bacterial receptor assays have been developed for the detection of violative levels of therapeutic substances. However, such assays are not infallible, and false positive or negative results can occur when contaminants bind receptors or compete for the binding of the target residues. Such effects may arise from dietary sources, diseases, or other variables. Thus, a violation by such a test is not definitive until further confirmation is obtained. Our laboratory has developed extraction procedures for several drugs used in dairy production. Our method uses matrix solid-phase dispersion (MSPD) to isolate drugs away from contaminants and to eliminate many possible interferences. MSPD can also be used to enhance the specificity of such assays by fractionating various classes of drugs that may cross-react. Similarly, such methods may be used for liquid chromatographic screening and confirmation of a suspect sample.

Increased dissolution rates of tranilast solid dispersions extruded with inorganic excipients.

PubMed

Maniruzzaman, Mohammed; Ross, Steven A; Islam, Muhammad Tariqul; Scoutaris, Nikolaos; Nair, Arun; Douroumis, Dennis

2017-06-01

The purpose of this study was to evaluate the performance of Neusilin® (NEU) a synthetic magnesium aluminometasilicate as an inorganic drug carrier co-processed with the hydrophilic surfactants Labrasol and Labrafil to develop Tranilast (TLT)-based solid dispersions using continuous melt extrusion (HME) processing. Twin-screw extrusion was optimized to develop various TLT/excipient/surfactant formulations followed by continuous capsule filling in the absence of any downstream equipment. Physicochemical characterization showed the existence of TLT in partially crystalline state in the porous network of inorganic NEU for all extruded formulations. Furthermore, in-line NIR studies revealed a possible intermolecular H-bonding formation between the drug and the carrier resulting in the increase of TLT dissolution rates. The capsules containing TLT-extruded solid dispersions showed enhanced dissolution rates and compared with the marketed Rizaben ® product.

Solubility Enhancement of a Poorly Water Soluble Drug by Forming Solid Dispersions using Mechanochemical Activation

PubMed Central

Rojas-Oviedo, I.; Retchkiman-Corona, B.; Quirino-Barreda, C. T.; Cárdenas, J.; Schabes-Retchkiman, P. S.

2012-01-01

Mechanochemical activation is a practical cogrinding operation used to obtain a solid dispersion of a poorly water soluble drug through changes in the solid state molecular aggregation of drug-carrier mixtures and the formation of noncovalent interactions (hydrogen bonds) between two crystalline solids such as a soluble carrier, lactose, and a poorly soluble drug, indomethacin, in order to improve its solubility and dissolution rate. Samples of indomethacin and a physical mixture with a weight ratio of 1:1 of indomethacin and lactose were ground using a high speed vibrating ball mill. Particle size was determined by electron microscopy, the reduction of crystallinity was determined by calorimetry and transmission electron microscopy, infrared spectroscopy was used to find evidence of any interactions between the drug and the carrier and the determination of apparent solubility allowed for the corroboration of changes in solubility. Before grinding, scanning electron microscopy showed the drug and lactose to have an average particle size of around 50 and 30 μm, respectively. After high speed grinding, indomethacin and the mixture had a reduced average particle size of around 5 and 2 μm, respectively, showing a morphological change. The ground mixture produced a solid dispersion that had a loss of crystallinity that reached 81% after 30 min of grinding while the drug solubility of indomethacin within the solid dispersion increased by 2.76 fold as compared to the pure drug. Drug activation due to hydrogen bonds between the carboxylic group of the drug and the hydroxyl group of lactose as well as the decrease in crystallinity of the solid dispersion and the reduction of the particle size led to a better water solubility of indomethacin. PMID:23798775

Comparison between hot-melt extrusion and spray-drying for manufacturing solid dispersions of the graft copolymer of ethylene glycol and vinylalcohol.

PubMed

Guns, Sandra; Dereymaker, Aswin; Kayaert, Pieterjan; Mathot, Vincent; Martens, Johan A; Van den Mooter, Guy

2011-03-01

To investigate the effect of the manufacturing method (spray-drying or hot-melt extrusion) on the kinetic miscibility of miconazole and the graft copolymer poly(ethyleneglycol-g-vinylalcohol). The effect of heat pre-treatment of solutions used for spray-drying and the use of spray-dried copolymer as excipient for hot-melt extrusion was investigated. The solid dispersions were prepared at different drug-polymer ratios and analyzed with modulated differential scanning calorimetry and X-ray powder diffraction. Miconazole either mixed with the PEG-fraction of the copolymer or crystallized in the same or a different polymorph as the starting material. The kinetic miscibility was higher for the solid dispersions obtained from solutions which were pre-heated compared to those spray-dried from solutions at ambient temperature. Hot-melt extrusion resulted in an even higher mixing capability. Here the use of the spray-dried copolymer did not show any benefit concerning the kinetic miscibility of the drug and copolymer, but it resulted in a remarkable decrease in the torque experienced by the extruder allowing extrusion at lower temperature and torque. The manufacturing method has an influence on the mixing capacity and phase behavior of solid dispersions. Heat pre-treatment of the solutions before spray-drying can result in a higher kinetic miscibility. Amorphization of the copolymer by spray-drying before using it as an excipient for hot-melt extrusion can be a manufacturing benefit.

Method of preparing a high solids content, low viscosity ceramic slurry

DOEpatents

Tiegs, Terry N.; Wittmer, Dale E.

1995-01-01

A method for producing a high solids content, low viscosity ceramic slurry composition comprises turbomilling a dispersion of a ceramic powder in a liquid to form a slurry having a viscosity less than 100 centipoise and a solids content equal to or greater than 48 volume percent.

Method of preparing a high solids content, low viscosity ceramic slurry

DOEpatents

Tiegs, T.N.; Wittmer, D.E.

1995-10-10

A method for producing a high solids content, low viscosity ceramic slurry composition comprises turbomilling a dispersion of a ceramic powder in a liquid to form a slurry having a viscosity less than 100 centipoise and a solids content equal to or greater than 48 volume percent.

Evaluate the ability of PVP to inhibit crystallization of amorphous solid dispersions by density functional theory and experimental verify.

PubMed

Wang, Bing; Wang, Dandan; Zhao, Shan; Huang, Xiaobin; Zhang, Jianbin; Lv, Yan; Liu, Xiaocen; Lv, Guojun; Ma, Xiaojun

2017-01-01

In this study, we used density functional theory (DFT) to predict polymer-drug interactions, and then evaluated the ability of poly (vinyl pyrrolidone) (PVP) to inhibit crystallization of amorphous solid dispersions by experimental-verification. Solid dispersions of PVP/resveratrol (Res) and PVP/griseofulvin (Gri) were adopted for evaluating the ability of PVP to inhibit crystallization. The density functional theory (DFT) with the B3LYP was used to calculate polymer-drug and drug-drug interactions. Fourier transform infrared spectroscopy (FTIR) was used to confirm hydrogen bonding interactions. Polymer-drug miscibility and drug crystallinity were characterized by the modulated differential scanning calorimetry (MDSC) and X-ray powder diffraction (XRD). The release profiles were studied to investigate the dissolution advantage. DFT results indicated that E PVP-Res >E Res-Res (E: represents hydrogen bonding energy). A strong interaction was formed between PVP and Res. In addition, Fourier transform infrared spectroscopy (FTIR) analysis showed hydrogen bonding formed between PVP and Res, but not between PVP and Gri. MDSC and XRD results suggested that 70-90wt% PVP/Res and PVP/Gri solid dispersions formed amorphous solid dispersions (ASDs). Under the accelerated testing condition, PVP/Res dispersions with higher miscibility quantified as 90/10wt% were more stable than PVP/Gri dispersions. The cumulative dissolution rate of 90wt% PVP/Res dispersions still kept high after 90days storage due to the strong interaction. However, the cumulative dissolution rate of PVP/Gri solid dispersions significantly dropped because of the recrystallization of Gri. Copyright © 2016 Elsevier B.V. All rights reserved.

Large-scale pesticide testing in olives by liquid chromatography-electrospray tandem mass spectrometry using two sample preparation methods based on matrix solid-phase dispersion and QuEChERS.

PubMed

Gilbert-López, Bienvenida; García-Reyes, Juan F; Lozano, Ana; Fernández-Alba, Amadeo R; Molina-Díaz, Antonio

2010-09-24

In this work we have evaluated the performance of two sample preparation methodologies for the large-scale multiresidue analysis of pesticides in olives using liquid chromatography-electrospray tandem mass spectrometry (LC-MS/MS). The tested sample treatment methodologies were: (1) liquid-liquid partitioning with acetonitrile followed by dispersive solid-phase extraction clean-up using GCB, PSA and C18 sorbents (QuEChERS method - modified for fatty vegetables) and (2) matrix solid-phase dispersion (MSPD) using aminopropyl as sorbent material and a final clean-up performed in the elution step using Florisil. An LC-MS/MS method covering 104 multiclass pesticides was developed to examine the performance of these two protocols. The separation of the compounds from the olive extracts was achieved using a short C18 column (50 mm x 4.6 mm i.d.) with 1.8 microm particle size. The identification and confirmation of the compounds was based on retention time matching along with the presence (and ratio) of two typical MRM transitions. Limits of detection obtained were lower than 10 microgkg(-1) for 89% analytes using both sample treatment protocols. Recoveries studies performed on olives samples spiked at two concentration levels (10 and 100 microgkg(-1)) yielded average recoveries in the range 70-120% for most analytes when QuEChERS procedure is employed. When MSPD was the choice for sample extraction, recoveries obtained were in the range 50-70% for most of target compounds. The proposed methods were successfully applied to the analysis of real olives samples, revealing the presence of some of the target species in the microgkg(-1) range. Besides the evaluation of the sample preparation approaches, we also discuss the use of advanced software features associated to MRM method development that overcome several limitations and drawbacks associated to MS/MS methods (time segments boundaries, tedious method development/manual scheduling and acquisition limitations). This

Improved bioavailability and antiasthmatic efficacy of poorly soluble curcumin-solid dispersion granules obtained using fluid bed granulation.

PubMed

Jang, Dong-Jin; Kim, Sung Tae; Lee, Kooyeon; Oh, Euichaul

2014-01-01

The intestinal absorption and antiasthmatic efficacy of poorly water-soluble curcumin (CUR), which has low solubility and permeability, was increased by fabricating solid dispersion granules (SDGs). The SDG containing CUR (SDG-CUR) was prepared by dispersing CUR in excess Cremophor RH40 as a solubilizer and Ryoto sugar ester L-1695 as an absorption enhancer using fluid bed granulation. We evaluated the physicochemical properties such as crystallinity and dissolution, pharmacokinetics, and antiasthmatic efficacy of SDG-CUR. Our results showed that CUR was molecularly dispersed, and the dissolution of SDG-CUR was significantly higher than that of native CUR. In addition, the blood concentration of SDG-CUR in rats was much higher than that of native CUR. Compared to CUR, SDG-CUR showed a 9.1- and 13.1-fold increase in area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax), respectively. Further, SDG-CUR effectively alleviated airway hyperresponsiveness and levels of T-helper 2 cytokines (interleukin-4, interleukin-5, and interleukin-13) in a murine model of asthma. In conclusion, our results suggest that the SDGs could be considered as a potential oral formulation to enhance the absorption and efficacy of CUR.

Analysis of a nanocrystalline polymer dispersion of ebselen using solid-state NMR, Raman microscopy, and powder X-ray diffraction.

PubMed

Vogt, Frederick G; Williams, Glenn R

2012-07-01

Nanocrystalline drug-polymer dispersions are of significant interest in pharmaceutical delivery. The purpose of this work is to demonstrate the applicability of methods based on two-dimensional (2D) and multinuclear solid-state NMR (SSNMR) to a novel nanocrystalline pharmaceutical dispersion of ebselen with polyvinylpyrrolidone-vinyl acetate (PVP-VA), after initial characterization with other techniques. A nanocrystalline dispersion of ebselen with PVP-VA was prepared and characterized by powder X-ray diffraction (PXRD), confocal Raman microscopy and mapping, and differential scanning calorimetry (DSC), and then subjected to detailed 1D and 2D SSNMR analysis involving ¹H, ¹³C, and ⁷⁷Se isotopes and ¹H spin diffusion. PXRD was used to show that dispersion contains nanocrystalline ebselen in the 35-60 nm size range. Confocal Raman microscopy and spectral mapping were able to detect regions where short-range interactions may occur between ebselen and PVP-VA. Spin diffusion effects were analyzed using 2D SSNMR experiments and are able to directly detect interactions between ebselen and the surrounding PVP-VA. The methods used here, particularly the 2D SSNMR methods based on spin diffusion, provided detailed structural information about a nanocrystalline polymer dispersion of ebselen, and should be useful in other studies of these types of materials.

One-step continuous extrusion process for the manufacturing of solid dispersions.

PubMed

Maniruzzaman, M; Nair, A; Scoutaris, N; Bradley, Michael S A; Snowden, M J; Douroumis, D

2015-12-30

The purpose of this study was to evaluate the performance of synthetic magnesium aluminometasilicate (MAS) as a novel inorganic carrier in hot melt extrusion (HME) processing of indomethacin (IND) for the development of solid dispersions. A continuous extrusion process at various IND/excipient blend ratios (20%, 30% and 40%) was performed using a twin-screw extruder. Physicochemical characterization carried out by SEM, DSC, and XRPD demonstrated the presence of IND in amorphous nature within the porous network of the inorganic material for all extruded formulations. Further, AFM and FTIR studies revealed a single-phase amorphous system and intermolecular H-bonding formation. The IND/MAS extrudates showed enhanced INM dissolution rates within 100% been released within 1h. Stability studies under accelerated conditions (40°C, RH 75%) showed that MAS retained the physical stability of the amorphous solid dispersions even at high drug loadings for 12 months. Copyright © 2015 Elsevier B.V. All rights reserved.

Extending of flat normal dispersion profile in all-solid soft glass nonlinear photonic crystal fibres

NASA Astrophysics Data System (ADS)

Siwicki, Bartłomiej; Kasztelanic, Rafał; Klimczak, Mariusz; Cimek, Jarosław; Pysz, Dariusz; Stępień, Ryszard; Buczyński, Ryszard

2016-06-01

The bandwidth of coherent supercontinuum generated in optical fibres is strongly determined by the all-normal dispersion characteristic of the fibre. We investigate all-normal dispersion limitations in all-solid oxide-based soft glass photonic crystal fibres with various relative inclusion sizes and lattice constants. The influence of material dispersion on fibre dispersion characteristics for a selected pair of glasses is also examined. A relation between the material dispersion of the glasses and the fibre dispersion has been described. We determined the parameters which limit the maximum range of flattened all-normal dispersion profile achievable for the considered pair of heavy-metal-oxide soft glasses.

Corroboration of naringin effects on the intestinal absorption and pharmacokinetic behavior of candesartan cilexetil solid dispersions using in-situ rat models.

PubMed

Surampalli, Gurunath; K Nanjwade, Basavaraj; Patil, P A

2015-01-01

The aim of this study was to corroborate the effects of naringin, a P-glycoprotein inhibitor, on the intestinal absorption and pharmacokinetics of candesartan (CDS) from candesartan cilexetil (CAN) solid dispersions using in-situ rat models. Intestinal transport and absorption studies were examined by in-situ single pass perfusion and closed-loop models. We evaluated the intestinal membrane damage in the presence of naringin by measuring the release of protein and alkaline phosphatase (ALP). We noticed 1.47-fold increase in Peff of CDS from freeze-dried CAN-loaded solid dispersions with naringin (15 mg/kg, w/w) when compared with freeze-dried solid dispersion without naringin using in-situ single pass intestinal perfusion model. However, no intestinal membrane damage was observed in the presence of naringin. Our findings from in-situ closed-loop pharmacokinetic studies showed 1.34-fold increase in AUC with elevated Cmax and shortened tmax for freeze-dried solid dispersion with naringin as compared to freeze-dried solid dispersion without naringin. This study demonstrated that increased solubilization (favored by freeze-dried solid dispersion) and efflux pump inhibition (using naringin), the relative bioavailability of CDS can be increased, suggesting an alternative potential for improving oral bioavailability of CAN.

Crystallization Kinetics of Indomethacin/Polyethylene Glycol Dispersions Containing High Drug Loadings.

PubMed

Duong, Tu Van; Van Humbeeck, Jan; Van den Mooter, Guy

2015-07-06

The reproducibility and consistency of physicochemical properties and pharmaceutical performance are major concerns during preparation of solid dispersions. The crystallization kinetics of drug/polyethylene glycol solid dispersions, an important factor that is governed by the properties of both drug and polymer has not been adequately explored, especially in systems containing high drug loadings. In this paper, by using standard and modulated differential scanning calorimetry and X-ray powder diffraction, we describe the influence of drug loading on crystallization behavior of dispersions made up of indomethacin and polyethylene glycol 6000. Higher drug loading increases the amorphicity of the polymer and inhibits the crystallization of PEG. At 52% drug loading, polyethylene glycol was completely transformed to the amorphous state. To the best of our knowledge, this is the first detailed investigation of the solubilization effect of a low molecular weight drug on a semicrystalline polymer in their dispersions. In mixtures containing up to 55% indomethacin, the dispersions exhibited distinct glass transition events resulting from amorphous-amorphous phase separation which generates polymer-rich and drug-rich domains upon the solidification of supercooled polyethylene glycol, whereas samples containing at least 60% drug showed a single amorphous phase during the period in which crystallization normally occurs. The current study demonstrates a wide range in physicochemical properties of drug/polyethylene glycol solid dispersions as a result of the complex nature in crystallization of this system, which should be taken into account during preparation and storage.

Preparation of fullerene/glass composites

DOEpatents

Mattes, Benjamin R.; McBranch, Duncan W.; Robinson, Jeanne M.; Koskelo, Aaron C.; Love, Steven P.

1995-01-01

Synthesis of fullerene/glass composites. A direct method for preparing solid solutions of C.sub.60 in silicon dioxide (SiO.sub.2) glass matrices by means of sol-gel chemistry is described. In order to produce highly concentrated fullerene-sol-gel-composites it is necessary to increase the solubility of these "guests" in a delivery solvent which is compatible with the starter sol (receiving solvent). Sonication results in aggregate disruption by treatment with high frequency sound waves, thereby accelerating the rate of hydrolysis of the alkoxide precursor, and the solution process for the C.sub.60. Depending upon the preparative procedure, C.sub.60 dispersed within the glass matrix as microcrystalline domains, or dispersed as true molecular solutions of C.sub.60 in a solid glass matrix, is generated by the present method.

Phase Behavior of Ritonavir Amorphous Solid Dispersions during Hydration and Dissolution.

PubMed

Purohit, Hitesh S; Taylor, Lynne S

2017-12-01

The aim of this research was to study the interplay of solid and solution state phase transformations during the dissolution of ritonavir (RTV) amorphous solid dispersions (ASDs). RTV ASDs with polyvinylpyrrolidone (PVP), polyvinylpyrrolidone vinyl acetate (PVPVA) and hydroxypropyl methylcellulose acetate succinate (HPMCAS) were prepared at 10-50% drug loading by solvent evaporation. The miscibility of RTV ASDs was studied before and after exposure to 97% relative humidity (RH). Non-sink dissolution studies were performed on fresh and moisture-exposed ASDs. RTV and polymer release were monitored using ultraviolet-visible spectroscopy. Techniques including fluorescence spectroscopy, confocal imaging, scanning electron microscopy (SEM), atomic force microscopy (AFM), differential scanning calorimetry (DSC) and nanoparticle tracking analysis (NTA) were utilized to monitor solid and the solution state phase transformations. All RTV-PVP and RTV-PVPVA ASDs underwent moisture-induced amorphous-amorphous phase separation (AAPS) on high RH storage whereas RTV-HPMCAS ASDs remained miscible. Non-sink dissolution of PVP- and PVPVA-based ASDs at low drug loadings led to rapid RTV and polymer release resulting in concentrations in excess of amorphous solubility, liquid-liquid phase separation (LLPS) and amorphous nanodroplet formation. High drug loading PVP- and PVPVA-based ASDs did not exhibit LLPS upon dissolution as a consequence of extensive AAPS in the hydrated ASD matrix. All RTV-HPMCAS ASDs led to LLPS upon dissolution. RTV ASD dissolution is governed by a competition between the dissolution rate and the rate of phase separation in the hydrated ASD matrix. LLPS was observed for ASDs where the drug release was polymer controlled and only ASDs that remained miscible during the initial phase of dissolution led to LLPS. Techniques such as fluorescence spectroscopy, confocal imaging and SEM were useful in understanding the phase behavior of ASDs upon hydration and dissolution

Dissolution enhancement of glibenclamide by solid dispersion: solvent evaporation versus a supercritical fluid-based solvent -antisolvent technique

PubMed Central

Tabbakhian, M.; Hasanzadeh, F.; Tavakoli, N.; Jamshidian, Z.

2014-01-01

Glibenclamide (GLIB) is a poorly soluble drug with formulation-dependent bioavailability. Therefore, we attempted in this study to improve GLIB dissolution rate by preparing drug solid dispersions by solvent evaporation (SE) and supercritical fluid solvent-antisolvent techniques (SCF-SAS). A D-optimal mixture design was used to investigate the effects of different ratios of HPMCE5 (50-100%), PEG6000 (0-40%), and Poloxamer407 (0-20%) on drug dissolution from different solid dispersion (SD) formulations prepared by SE. The ratios of carriers used in SCF-SAS method were HPMCE5 (fixed at 60%), PEG6000 (20-40%), and Poloxamer407 (0-20%). A constant drug: carrier weight ratio of 1:10 was used in all experiments. The SDs obtained were physically characterized and subjected to the dissolution study. The major GLIB bands in FTIR spectra were indicative of drug integrity. The reduced intensity and the fewer number of peaks observed in X-ray diffractograms (XRD) of GLIB formulations was the indicative of at least partial transformation of crystalline to amorphous GLIB. This change and/or dilution of drug in much higher amounts of carriers present caused disappearance of distinctive endothermic peaks in differential scanning calorimetry thermograms of GLIB formulations. The model generated according to the results of the D-optimal mixture design indicated that GLIB formulations comprising HPMC (50%-60%), PEG (34-40%), and poloxamer (6-10%) had enhanced dissolution performances. As compared to SE method, the SCF-SAS technique produced formulations of higher dissolution performances, likely due to the effects of solution and the supercritical CO2 (SC-CO2) on enhanced plasticization of polymers and thus increased diffusion of the drug into the polymer matrix. PMID:25657806

Formulation and Pharmacokinetic Evaluation of Polymeric Dispersions Containing Valsartan.

PubMed

Chella, Naveen; Daravath, Bhaskar; Kumar, Dinesh; Tadikonda, Rama Rao

2016-10-01

Valsartan exhibits poor aqueous solubility and dissolution rate limited absorption. The lower solubility in the upper part of gastrointestinal tract (pH-dependant solubility) where its absorption window exists further contributes to the low oral bioavailability of valsartan. The present work was aimed to improve the in vivo pharmacokinetics of valsartan by preparing amorphous polymeric dispersions using Eudragit E 100 as carrier. Eudragit E 100 is a cationic polymer soluble in gastric fluid up to pH 5.0 and exhibits pH-dependent release. Hence, the dispersions prepared using Eudragit E 100 rapidly dissolves at lower pH presenting drug in molecularly dispersed and soluble form at its absorption site. Polymeric solid dispersions were prepared in different drug-to-carrier ratios. The prepared dispersions were evaluated for drug-carrier interactions, solid-state transitions and drug-release properties with the help of Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and in vitro dissolution studies. The optimized formulation containing valsartan was tested in rats for bioavailability and pharmacokinetic parameters and compared with that of valsartan pure drug. The results from FTIR studies indicated no interactions between drug and excipients. DSC studies confirmed reduction in crystallinity of drug. The dissolution studies performed in 0.1 N HCl showed significant improvement (p < 0.05) in the dissolution of valsartan. In vivo pharmacokinetic studies showed 199 % relative bioavailability with significant improvement (p < 0.05) in area under the curve compared to valsartan pure drug. Eudragit E 100 can be used to improve the dissolution of drugs that show low solubility at lower pH and thereby enhancing the bioavailability.

An investigation into the use of polymer blends to improve the printability of and regulate drug release from pharmaceutical solid dispersions prepared via fused deposition modeling (FDM) 3D printing.

PubMed

Alhijjaj, Muqdad; Belton, Peter; Qi, Sheng

2016-11-01

FDM 3D printing has been recently attracted increasing research efforts towards the production of personalized solid oral formulations. However, commercially available FDM printers are extremely limited with regards to the materials that can be processed to few types of thermoplastic polymers, which often may not be pharmaceutically approved materials nor ideal for optimizing dosage form performance of poor soluble compounds. This study explored the use of polymer blends as a formulation strategy to overcome this processability issue and to provide adjustable drug release rates from the printed dispersions. Solid dispersions of felodipine, the model drug, were successfully fabricated using FDM 3D printing with polymer blends of PEG, PEO and Tween 80 with either Eudragit E PO or Soluplus. As PVA is one of most widely used polymers in FDM 3D printing, a PVA based solid dispersion was used as a benchmark to compare the polymer blend systems to in terms of processability. The polymer blends exhibited excellent printability and were suitable for processing using a commercially available FDM 3D printer. With 10% drug loading, all characterization data indicated that the model drug was molecularly dispersed in the matrices. During in vitro dissolution testing, it was clear that the disintegration behavior of the formulations significantly influenced the rates of drug release. Eudragit EPO based blend dispersions showed bulk disintegration; whereas the Soluplus based blends showed the 'peeling' style disintegration of strip-by-strip. The results indicated that interplay of the miscibility between excipients in the blends, the solubility of the materials in the dissolution media and the degree of fusion between the printed strips during FDM process can be used to manipulate the drug release rate of the dispersions. This brings new insight into the design principles of controlled release formulations using FDM 3D printing. Copyright © 2016 Elsevier B.V. All rights reserved.

Hypercrosslinked particles for the extraction of sweeteners using dispersive solid-phase extraction from environmental samples.

PubMed

Lakade, Sameer S; Zhou, Qing; Li, Aimin; Borrull, Francesc; Fontanals, Núria; Marcé, Rosa M

2018-04-01

This work presents a new extraction material, namely, Q-100, based on hypercrosslinked magnetic particles, which was tested in dispersive solid-phase extraction for a group of sweeteners from environmental samples. The hypercrosslinked Q-100 magnetic particles had the advantage of suitable pore size distribution and high surface area, and showed good retention behavior toward sweeteners. Different dispersive solid-phase extraction parameters such as amount of magnetic particles or extraction time were optimized. Under optimum conditions, Q-100 showed suitable apparent recovery, ranging in the case of river water sample from 21 to 88% for all the sweeteners, except for alitame (12%). The validated method based on dispersive solid-phase extraction using Q-100 followed by liquid chromatography with tandem mass spectrometry provided good linearity and limits of quantification between 0.01 and 0.1 μg/L. The method was applied to analyze samples from river water and effluent wastewater, and four sweeteners (acesulfame, saccharin, cyclamate, and sucralose) were found in both types of sample. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of characteristics of compounds on maintenance of an amorphous state in solid dispersion with crospovidone.

PubMed

Shibata, Yusuke; Fujii, Makiko; Kokudai, Makiko; Noda, Shinobu; Okada, Hideko; Kondoh, Masuo; Watanabe, Yoshiteru

2007-06-01

Solid dispersion (SD) of indomethacin with crospovidone (CrosPVP) shows useful characteristics for preparation of dosage forms. This study aimed to determine the types of drugs that could adopt a stable amorphous form in SD. Twenty compounds with various melting points (70-218 degrees C), molecular weights (135-504) and functional groups (amide, amino, carbonyl, hydroxyl, ketone etc.) were prepared in SD with CrosPVP. The CrosPVP SDs were prepared using a mechanical mixing and heating method. Melting point and molecular weight were found to have no influence on the ability of a compound to maintain an amorphous state in SD. All compounds containing hydrogen-bond-donor functional groups existed in an amorphous state in SD for at least 6 months. Infrared spectra suggested an interaction between the functional groups of these compounds and amide carbonyl group of CrosPVP. Compounds without hydrogen-bond-donor groups could not maintain an amorphous state and underwent recrystallization within 1 month. It was suggested that the presence of a hydrogen-bond-donor functional group in a compound is an important factor affecting the stable formation of SD with CrosPVP, which contains a hydrogen-bond acceptor.

Increased physical stability and improved dissolution properties of itraconazole, a class II drug, by solid dispersions that combine fast- and slow-dissolving polymers.

PubMed

Six, Karel; Verreck, Geert; Peeters, Jef; Brewster, Marcus; Van Den Mooter, Guy

2004-01-01

Solid dispersions were prepared of itraconazole-Eudragit E100, itraconazole-PVPVA64, and itraconazole-Eudragit E100/PVPVA64 using a corotating twin-screw hot-stage extruder. Modulated temperature differential scanning calorimetry (MTDSC) was used to evaluate the miscibility of the extrudates, and dissolution experiments were performed in simulated gastric fluid without pepsin (SGF(sp)). Itraconazole and Eudragit E100 are miscible up to 13% w/w drug loading. From that concentration on, phase separation is observed. Pharmaceutical performance of this dispersion was satisfactory because 80% of the drug dissolved after 30 min. Extrudates of itraconazole and PVPVA64 were completely miscible but the pharmaceutical performance was low, with 45% of drug dissolved after 3 h. Combination of both polymers in different ratios, with a fixed drug loading of 40% w/w, was evaluated. MTDSC results clearly indicated a two-phase system consisting of itraconazole-Eudragit E100 and itraconazole-PVPVA64 phases. In these extrudates, no free crystalline or glassy clusters of itraconazole were observed; all itraconazole was mixed with one of both polymers. The pharmaceutical performance was tested in SGF(sp) for different polymer ratios, and Eudragit E100/PVPVA64 ratios of 50/50 and 60/40 showed significant increases in dissolution rate and level. Polymer ratios of 70/30 and 80/20, on the other hand, had a release of 85% after 30 min. Precipitation of the drug was never observed. The combination of the two polymers provides a solid dispersion with good dissolution properties and improved physical stability compared with the binary solid dispersions of itraconazole. Copyright 2004 Wiley-Liss, Inc.

In Vitro and In Vivo Evaluation of Casein as a Drug Carrier for Enzymatically Triggered Dissolution Enhancement from Solid Dispersions.

PubMed

Bani-Jaber, Ahmad; Alshawabkeh, Iyad; Abdullah, Samaa; Hamdan, Imad; Ardakani, Adel; Habash, Maha

2017-07-01

Due to its unique properties, such as biodegradability, biocompatibility, high amphiphilic property, and micelle formation, casein (CS) has been increasingly studied for drug delivery. We used CS as a drug carrier in solid dispersions (SDs) and evaluated the effect of its degradation by trypsin on drug dissolution from the dispersions. SDs of CS and mefenamic acid (MA) were prepared by physical mixing, kneading, and coprecipitation methods. In comparison to pure MA, the dispersions were evaluated for drug-protein interaction, loss of drug crystalinity, and drug morphology by differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Drug dissolution from the dispersions was evaluated in simulated intestinal fluid as enzyme free and trypsin-enriched media. Furthermore, in vivo drug absorption of MA from CS-MA coprecipitate was evaluated in rats, in comparison with a reference SD of polyethylene glycol and MA (PEG-MA SD). Relative to other CS preparations, CS-MA coprecipitate showed the highest loss of drug crystallinity, drug micronization, and CS-MA interaction. CS remarkably enhanced the dissolution rate and extent of MA from the physical and kneaded mixtures. However, the highest dissolution enhancement was obtained when MA was coprecipitated with CS. Trypsin that can hydrolyze CS during dissolution resulted in further enhancement of MA dissolution from the physical and kneaded mixtures. However, a corresponding retardation effect was obtained for the coprecipitate. In correlation with in vitro drug release, CS-MA coprecipitate also showed significantly higher MA bioavailability in rats than PEG-MA SD.

Effects of tablet formulation and subsequent film coating on the supersaturated dissolution behavior of amorphous solid dispersions.

PubMed

Sakai, Toshiro; Hirai, Daiki; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-04-05

The effects of tablet preparation and subsequent film coating with amorphous solid dispersion (ASD) particles that were composed of a drug with poor water solubility and hydrophilic polymers were investigated. ASD particles were prepared with a drug and vinylpyrrolidone-vinyl acetate copolymer (PVPVA) or polyvinylpyrrolidone (PVP) at a weight ratio of 1:1 or 1:2 using a melt extrusion technique. Tablets were prepared by conventional direct compression followed by pan coating. A mathematical model based on the Noyes-Whitney equation assuming that stable crystals precipitated at the changeable surface area of the solid-liquid interface used to estimate drug dissolution kinetics in a non-sink dissolution condition. All the ASD particles showed a maximum dissolution concentration approximately ten times higher than that of the crystalline drug. The ASD particles with PVPVA showed higher precipitation rate with lower polymer ratio, while PVP did not precipitate within 960 min regardless of the polymer ratio, suggesting the ASD particles of 1:1 drug:PVPVA (ASD-1) were the most unstable among the ASD particles considered. The dissolution of a core tablet with ASD-1 showed less supersaturation and a much higher precipitation rate than those of ASD-1 particles. However, a film-coated tablet or core tablet with a trace amount of hydroxypropylmethylcellulose (HPMC) showed a similar dissolution profile to that of the ASD-1 particles, indicating HPMC had a remarkable precipitation inhibition effect. Overall, these results suggest that tablet preparation with ASD may adversely affect the maintenance of supersaturation; however, this effect can be mitigated by adding an appropriate precipitation inhibitor to the formulation. Copyright © 2018 Elsevier B.V. All rights reserved.

Initial Drug Dissolution from Amorphous Solid Dispersions Controlled by Polymer Dissolution and Drug-Polymer Interaction.

PubMed

Chen, Yuejie; Wang, Shujing; Wang, Shan; Liu, Chengyu; Su, Ching; Hageman, Michael; Hussain, Munir; Haskell, Roy; Stefanski, Kevin; Qian, Feng

2016-10-01

To identify the key formulation factors controlling the initial drug and polymer dissolution rates from an amorphous solid dispersion (ASD). Ketoconazole (KTZ) ASDs using PVP, PVP-VA, HMPC, or HPMC-AS as polymeric matrix were prepared. For each drug-polymer system, two types of formulations with the same composition were prepared: 1. Spray dried dispersion (SDD) that is homogenous at molecular level, 2. Physical blend of SDD (80% drug loading) and pure polymer (SDD-PB) that is homogenous only at powder level. Flory-Huggins interaction parameters (χ) between KTZ and the four polymers were obtained by Flory-Huggins model fitting. Solution (13)C NMR and FT-IR were conducted to investigate the specific drug-polymer interaction in the solution and solid state, respectively. Intrinsic dissolution of both the drug and the polymer from ASDs were studied using a Higuchi style intrinsic dissolution apparatus. PXRD and confocal Raman microscopy were used to confirm the absence of drug crystallinity on the tablet surface before and after dissolution study. In solid state, KTZ is completely miscible with PVP, PVP-VA, or HPMC-AS, demonstrated by the negative χ values of -0.36, -0.46, -1.68, respectively; while is poorly miscible with HPMC shown by a positive χ value of 0.23. According to solution (13)C NMR and FT-IR studies, KTZ interacts with HPMC-AS strongly through H-bonding and dipole induced interaction; with PVPs and PVP-VA moderately through dipole-induced interactions; and with HPMC weakly without detectable attractive interaction. Furthermore, the "apparent" strength of drug-polymer interaction, measured by the extent of peak shift on NMR or FT-IR spectra, increases with the increasing number of interacting drug-polymer pairs. For ASDs with the presence of considerable drug-polymer interactions, such as KTZ/PVPs, KTZ/PVP-VA, or KTZ /HPMC-AS systems, drug released at the same rate as the polymer when intimate drug-polymer mixing was ensured (i.e., the SDD systems

[Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose].

PubMed

Liao, Li; Hua, Hua; Zhao, Jun-Ning; Luo, Heng; Yang, An-Dong

2014-03-01

To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD < 15%). The precision, accuracy, recovery and applicability were found to be adequate for pharmacokinetic studies. Pharmacokinetic parameters of THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative

Preparation of fullerene/glass composites

DOEpatents

Mattes, B.R.; McBranch, D.W.; Robinson, J.M.; Koskelo, A.C.; Love, S.P.

1995-05-30

Synthesis of fullerene/glass composites is described. A direct method for preparing solid solutions of C{sub 60} in silicon dioxide (SiO{sub 2}) glass matrices by means of sol-gel chemistry is described. In order to produce highly concentrated fullerene-sol-gel-composites it is necessary to increase the solubility of these ``guests`` in a delivery solvent which is compatible with the starter sol (receiving solvent). Sonication results in aggregate disruption by treatment with high frequency sound waves, thereby accelerating the rate of hydrolysis of the alkoxide precursor, and the solution process for the C{sub 60}. Depending upon the preparative procedure, C{sub 60} dispersed within the glass matrix as microcrystalline domains, or dispersed as true molecular solutions of C{sub 60} in a solid glass matrix, is generated by the present method.

Preparation and properties of high storage stability polyester polyol dispersion for two-component waterborne polyurethane coating

NASA Astrophysics Data System (ADS)

Hao, H.; Hu, J. Q.; Wang, F.; Tu, W. P.

2017-01-01

A new type of polyester polyol dispersion with good storage stability was prepared based on a hydrophilic monomer 5-sodium sulfodimethyl isophthalate (5-SIPM), and frequently-used monomers such as neopentyl glycol (NPG), dimethyl terephthalate (DMT), dimethyl phthalate (DMP) and trimethylolpropane (TMP) by the transpolycondensation and polycondensation method. The polyester polyol dispersion was characterized by FTIR and GPC. The proper content of these monomers were determined by the performance of polyester dispersion: the content of TMP was 15wt%, the content of NPG was 7.5wt% and the hydrophilic monomer 5-SIPM content was 5wt%. Two-component waterborne polyurethane (2K-WPU) coatings were prepared by Bayhydur® XP2487/1 and polyester polyol dispersions, which were stored before and after at 40 ° for 6 weeks, the prepared films have no differences in drying time, adhesion, pencil hardness, gloss and chemical resistance, the result also reveals that the polyester polyol dispersion have excellent storage stability resistance.

Evaluation of SLS: APG mixed surfactant systems as carrier for solid dispersion.

PubMed

Patel, Ashok R; Joshi, Vishal Y

2008-01-01

The present investigation aims at studying the effect of mixed surfactant system of sodium lauryl sulphate (SLS) and alkyl polyglucosides (C(10)APG, C(12)APG and C(12/14)APG) on dissolution rate enhancement of poorly water soluble drug. Aceclofenac--a non-steroidal anti-inflammatory agent was used as a model drug as it has limited water solubility. The influence of the surfactant concentration in various blends on dissolution rate of Solid Dispersion (SD), prepared using solution method with ethanol as the solvent was studied and the advantage of mixed surfactant systems over the individual surfactants was illustrated by differences in the in-vitro dissolution profiles of SD. Physico chemical evaluation (critical micellar concentration, zeta potential and beta-parameter calculations) was carried out to study the mixed surfactant systems. Solid mixtures were characterized by Infrared spectroscopy (FT-IR); X-ray diffraction studies (XRD) and scanning electron microscopy (SEM). It was seen that the dissolution rate of aceclofenac from SD increased with the increase in the APG proportion relative to SLS with the optimum ratio of 0.2 SLS:0.8 APG showing the best effect in all cases. Results obtained from physico-chemical evaluation (the decrease in the value of critical micelle concentration and higher negative value of beta-parameters) suggested the existence of synergism between surfactants blends. The observed results in the dissolution rate enhancement could be attributed to the drug--surfactant interactions as evident from FT-IR, SEM and XRD results.

Application of melt extrusion in the development of a physically and chemically stable high-energy amorphous solid dispersion of a poorly water-soluble drug.

PubMed

Lakshman, Jay P; Cao, Yu; Kowalski, James; Serajuddin, Abu T M

2008-01-01

Formulation of active pharmaceutical ingredients (API) in high-energy amorphous forms is a common strategy to enhance solubility, dissolution rate and, consequently, oral bioavailability of poorly water-soluble drugs. Amorphous APIs are, however, susceptible to recrystallization and, therefore, there is a need to physically stabilize them as solid dispersions in polymeric carriers. Hot melt extrusion has in recent years gained wide acceptance as a method of choice for the preparation of solid dispersions. There is a potential that the API, the polymer or both may degrade if excessively high temperature is needed in the melt extrusion process, especially when the melting point of the API is high. This report details a novel method where the API was first converted to an amorphous form by solvent evaporation and then melt-extruded with a suitable polymer at a drug load of at least 20% w/w. By this means, melt extrusion could be performed much below the melting temperature of the drug substance. Since the glass transition temperature of the amorphous drug was lower than that of the polymer used, the drug substance itself served as the plasticizer for the polymer. The addition of surfactants in the matrix enhanced dispersion and subsequent dissolution of the drug in aqueous media. The amorphous melt extrusion formulations showed higher bioavailability than formulations containing the crystalline API. There was no conversion of amorphous solid to its crystalline form during accelerated stability testing of dosage forms.

Self dispersing mixed micelles forming systems for enhanced dissolution and intestinal permeability of hydrochlorothiazide.

PubMed

Sultan, Amal A; El-Gizawy, Sanaa A; Osman, Mohamed A; El Maghraby, Gamal M

2017-01-01

Mixed micelles provide promising strategy for enhancing dissolution and permeability of drugs. However, their fluid nature limited the stability of the loaded drug and hindered the development of stable oral dosage form. Accordingly, the objective was to develop solid self dispersing mixed micelle forming systems (MMFS) for enhanced dissolution and intestinal permeability of hydrochlorothiazide. Pseudoternary phase diagrams were constructed using sodium cholate, lecithin with either poloxamer 407 or PEG 4000 to determine the composition of MMFS. Both polymer free and poloxamer or PEG containing MMFS were prepared as homogenous matrices or as solid self dispersing powder. The later was developed by adsorption of MMFS on avicel-aerosil mixture. Differential scanning calorimetry provided an evidence for existence of hydrochlorothiazide as molecular dispersion in the MMFS. Dispersing polymer free, PEG 4000 or poloxamer based MMFS in aqueous medium produced micelles having size values of 119, 52.6 and 28nm, respectively. The zeta potential values were -61.8, -59.5 and -19.5mV for the same systems, respectively. Preparation of solid self dispersing MMFS enhanced the dissolution rate of hydrochlorothiazide. The intestinal absorption of hydrochlorothiazide from its aqueous solution and polymer incorporating mixed micellar systems was monitored using in situ rabbit intestinal perfusion technique. The permeability results showed a clear trend for enhanced membrane transport of the drug after being incorporated into poloxamer containing mixed micellar system. The study thus introduced a versatile easily formulated solid self dispersing system with high potential for solving the dissolution and permeability problems of class IV drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of a binary carrier system consisting polyethylene glycol 4000 - ethyl cellulose for ibuprofen solid dispersion

PubMed Central

Alagdar, Gada Sulaiman A.; Oo, May Kyaw; Sengupta, Pinaki; Mandal, Uttam Kumar; Jaffri, Julian Md.; Chatterjee, Bappaditya

2017-01-01

Background and Objective: One of the established strategies to improve solubility and dissolution rate of poorly water-soluble drugs is solid dispersion (SD). Polyethylene glycol (PEG) is used as common carrier despite its stability problem which may be overcome by the addition of hydrophobic polymer. The present research aimed to develop an SD formulation with ibuprofen, a poor water-soluble BCS Class II drug as active pharmaceutical ingredient (API) and PEG 4000-ethyl cellulose (EC) as binary carrier. Methods: Melt mixing SD method was employed using a ratio of API: binary carrier (1:3.5 w/w) (SDPE). Another SD was prepared using only PEG (SDP) as a carrier for comparative study. The developed formulation was evaluated using optical microscopy, scanning electron microscopy (SEM), determination of moisture content, differential scanning calorimetry (DSC), in vitro dissolution test, attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and flow properties. Results: SEM and DSC indicated the conversion of crystalline ibuprofen to fine partly amorphous solid dispersion, which was responsible for the increase in dissolution rate of SD than a physical mixture. The release characteristics within 1 h from the higher to the lower value were the SDPE> SDP> physical mixture. Flow property evaluation using the angle of repose showed no difference between SD and PM. However, by Carr index and Hausner ratio, the flow properties of SDPE was excellent. Conclusion: The SD formulation with the PEG 4000-EC carrier can be effective to enhance in vitro dissolution of ibuprofen immediate release dosage form. PMID:29184827

Enhanced solubility and intestinal absorption of candesartan cilexetil solid dispersions using everted rat intestinal sacs.

PubMed

Gurunath, S; Nanjwade, Baswaraj K; Patila, P A

2014-07-01

Candesartan cilexetil (CAN) is a poor aqueous soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These key factors are responsible for its incomplete intestinal absorption. In this study, we investigated to enhance the absorption of CAN by improving its solubility and inhibiting intestinal P-gp activity. A phase solubility method was used to evaluate the aqueous solubility of CAN in PVP K30 (0.2-2%). Gibbs free energy [Formula: see text] values were all negative. Solubility was enhanced by the freeze drying technique. The in vitro dissolution was evaluated using the USP paddle method. The interaction between drug and carrier was evaluated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) studies. Naringin was selected as P-gp inhibitor. Absorption studies were performed using the everted gut sac model from rat jejunum. The drug analysis was performed by HPLC. FTIR spectra revealed no interaction between drug and PVP K30. From XRD and DSC data, CAN was in the amorphous form, which explains the cumulative release of drug from its prepared systems. We noticed an enhancement of CAN absorption by improving its solubility and inhibiting the P-gp activity. The significant results (p < 0.05) were obtained for freeze dried solid dispersions in the presence of P-gp inhibitor than without naringin (15 mg/kg) with an absorption enhancement of 8-fold. Naringin, a natural flavonoid, has no undesirable side effects. Therefore, it could be employed as an excipient in the form of solid dispersions to increase CAN intestinal absorption and its oral bioavailability.

Enhanced solubility and intestinal absorption of candesartan cilexetil solid dispersions using everted rat intestinal sacs

PubMed Central

Gurunath, S.; Nanjwade, Baswaraj K.; Patila, P.A.

2013-01-01

Objective Candesartan cilexetil (CAN) is a poor aqueous soluble compound and a P-glycoprotein (P-gp) efflux pump substrate. These key factors are responsible for its incomplete intestinal absorption. Methods In this study, we investigated to enhance the absorption of CAN by improving its solubility and inhibiting intestinal P-gp activity. A phase solubility method was used to evaluate the aqueous solubility of CAN in PVP K30 (0.2–2%). Gibbs free energy (ΔGtro) values were all negative. Solubility was enhanced by the freeze drying technique. The in vitro dissolution was evaluated using the USP paddle method. The interaction between drug and carrier was evaluated by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and Differential scanning calorimetry (DSC) studies. Naringin was selected as P-gp inhibitor. Absorption studies were performed using the everted gut sac model from rat jejunum. The drug analysis was performed by HPLC. Results FTIR spectra revealed no interaction between drug and PVP K30. From XRD and DSC data, CAN was in the amorphous form, which explains the cumulative release of drug from its prepared systems. We noticed an enhancement of CAN absorption by improving its solubility and inhibiting the P-gp activity. The significant results (p < 0.05) were obtained for freeze dried solid dispersions in the presence of P-gp inhibitor than without naringin (15 mg/kg) with an absorption enhancement of 8-fold. Conclusion Naringin, a natural flavonoid, has no undesirable side effects. Therefore, it could be employed as an excipient in the form of solid dispersions to increase CAN intestinal absorption and its oral bioavailability. PMID:25067902

Preparation of O/I1-type Emulsions and S/I1-type Dispersions Encapsulating UV-Absorbing Agents.

PubMed

Aramaki, Kenji; Kimura, Minami; Masuda, Kazuki

2015-01-01

Oil-in-cubic phase (O/I1) emulsions encapsulating the cosmetic UV absorbing agents 2-ethylhexyl 4-methoxycinnamate (EHMC), 2-ethylhexyl 2-cyano-3,3-diphenylacrylate (octocrylene, OCR) and 1-(4-tertbutylphenyl)-3-(4-methoxyphenyl)-1,3-propanedione (Avobenzone, TBMP) were prepared by vortex mixing accompanied by a heating-cooling process. A ternary phase diagram in a water/C12EO25/EHMC system at 25°C was constructed and the two-phase equilibrium of an oil phase and an I1 phase, which is necessary to prepare the O/I1-type emulsions, was confirmed. Also, the melting of the I1 phase into a fluid micellar solution phase was confirmed, allowing emulsification by a heating-cooling process. The O/I1-type emulsions were formulated in the ternary system as well as a quaternary system. The four-component system contained an additional cosolvent, isopropyl myristate (IPM). The use of the cosolvent allows the use of reduced amounts of EHMC, which is desirable because EHMC can cause temporary skin irritation. Formulation of the O/I1-type emulsions with other UV absorbing agents (OCR and TBMP) was also possible using the same emulsification method. When IPM was changed to tripalmitin, which has a melting point greater than room temperature, a solid-oil dispersion in I1 phase was formed. We have termed this a "solidin-cubic phase (S/I1) type dispersion". These novel emulsions have not been reported previously. The UV absorbability of the O/I1-type emulsions and S/I1-type dispersions that encapsulate the UV absorbing agents was confirmed by measurement of UV absorption spectra.

Formulation and process design for a solid dosage form containing a spray-dried amorphous dispersion of ibipinabant.

PubMed

Leane, Michael M; Sinclair, Wayne; Qian, Feng; Haddadin, Raja; Brown, Alan; Tobyn, Mike; Dennis, Andrew B

2013-01-01

Amorphous forms of poorly soluble drugs are more frequently being incorporated into solid dispersions for administration and extensive research has led to a reasonable understanding of how these dispersions, although still kinetically unstable, improve stability relative to the pure amorphous form. There remains however a paucity of literature describing the effects on such solid dispersions of subsequent processing into solid dosage forms such as tablets. This paper addresses this area by looking at the effects of the addition of common excipients and different manufacturing routes on the stability of a spray-dried dispersion (SDD) of the cannabinoid CB-1 antagonist, ibipinabant. A marked difference in physical stability of tablets was seen with the different fillers with microcrystalline cellulose (MCC) giving the best stability profile. It was found that minimising the number of compression steps led to improved formulation stability with a direct compression process giving the best results. Increased levels of crystallinity were seen in coated tablets most likely due to the exposure of the amorphous matrix to moisture and heat during the coating process. DSIMS analysis of the SDD particles indicated increased levels of polymer on the surface.

Improved Vemurafenib Dissolution and Pharmacokinetics as an Amorphous Solid Dispersion Produced by KinetiSol® Processing.

PubMed

Ellenberger, Daniel J; Miller, Dave A; Kucera, Sandra U; Williams, Robert O

2018-03-14

Vemurafenib is a poorly soluble, low permeability drug that has a demonstrated need for a solubility-enhanced formulation. However, conventional approaches for amorphous solid dispersion production are challenging due to the physiochemical properties of the compound. A suitable and novel method for creating an amorphous solid dispersion, known as solvent-controlled coprecipitation, was developed to make a material known as microprecipitated bulk powder (MBP). However, this approach has limitations in its processing and formulation space. In this study, it was hypothesized that vemurafenib can be processed by KinetiSol into the same amorphous formulation as MBP. The KinetiSol process utilizes high shear to rapidly process amorphous solid dispersions containing vemurafenib. Analysis of the material demonstrated that KinetiSol produced amorphous, single-phase material with acceptable chemical purity and stability. Values obtained were congruent to analysis conducted on the comparator material. However, the materials differed in particle morphology as the KinetiSol material was dense, smooth, and uniform while the MBP comparator was porous in structure and exhibited high surface area. The particles produced by KinetiSol had improved in-vitro dissolution and pharmacokinetic performance for vemurafenib compared to MBP due to slower drug nucleation and recrystallization which resulted in superior supersaturation maintenance during drug release. In the in-vivo rat pharmacokinetic study, both amorphous solid dispersions produced by KinetiSol exhibited mean AUC values at least two-fold that of MBP when dosed as a suspension. It was concluded that the KinetiSol process produced superior dosage forms containing vemurafenib with the potential for substantial reduction in patient pill burden.

Solid dispersions of the penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA): Formulation design and optimization studies

PubMed Central

Yang, Yu-Tsai; Di Pasqua, Anthony J.; Zhang, Yong; Sueda, Katsuhiko; Jay, Michael

2015-01-01

The penta-ethyl ester prodrug of diethylenetriaminepentaacetic acid (DTPA), which exists as an oily liquid, was incorporated into a solid dispersion for oral administration by the solvent evaporation method using blends of polyvinylpyrrolidone (PVP), Eudragit® RL PO and α-tocopherol. D-optimal mixture design was used to optimize the formulation. Formulations that had a high concentration of both Eudragit® RL PO and α-tocopherol exhibited low water absorption and enhanced stability of the DTPA prodrug. Physicochemical properties of the optimal formulation were evaluated using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC). In vitro release of the prodrug was evaluated using the USP Type II apparatus dissolution method. DSC studies indicated that the matrix had an amorphous structure, while FTIR spectrometry showed that DTPA penta-ethyl ester and excipients did not react with each other during formation of the solid dispersion.. Dissolution testing showed that the optimized solid dispersion exhibited a prolonged release profile, which could potentially result in a sustained delivery of DTPA penta-ethyl to enhance bioavailability. In conclusion, DTPA penta-ethyl ester was successfully incorporated into a solid matrix with high drug loading and improved stability compared to prodrug alone. PMID:24047113

Understanding the Impact of Water on the Miscibility and Microstructure of Amorphous Solid Dispersions: An AFM-LCR and TEM-EDX Study.

PubMed

Li, Na; Gilpin, Christopher J; Taylor, Lynne S

2017-05-01

Miscibility is critical for amorphous solid dispersions (ASDs). Phase-separated ASDs are more prone to crystallization, and thus can lose their solubility advantage leading to product failure. Additionally, dissolution performance can be diminished as a result of phase separation in the ASD matrix. Water is known to induce phase separation during storage for some ASDs. However, the impact of water introduced during preparation has not been as thoroughly investigated to date. The purpose of this study was to develop a mechanistic understanding of the effect of water on the phase behavior and microstructure of ASDs. Evacetrapib and two polymers were selected as the model system. Atomic force microscopy coupled with Lorentz contact resonance, and transmission electron microscopy with energy dispersive X-ray spectroscopy were employed to evaluate the microstructure and composition of phase-separated ASDs. It was found that phase separation could be induced via two routes: solution-state phase separation during ASD formation caused by water absorption during film formation by a hydrophilic solvent, or solid-phase separation following exposure to high RH during storage. Water contents of as low as 2% in the organic solvent system used to dissolve the drug and polymer were found to result in phase separation in the resultant ASD film. These findings have profound implications on lab-scale ASD preparation and potentially also for industrial production. Additionally, these high-resolution imaging techniques combined with orthogonal analyses are powerful tools to visualize structural changes in ASDs, which in turn will enable better links to be made between ASD structure and performance.

The effect of lipophilicity of spin-labeled compounds on their distribution in solid lipid nanoparticle dispersions studied by electron paramagnetic resonance.

PubMed

Pegi, Ahlin; Julijana, Kristl; Slavko, Pecar; Janez, Strancar; Marjeta, Sentjurc

2003-01-01

Solid lipid nanoparticles (SLN) constitute an attractive drug carrier system. The aim of this study was to investigate the influence of lipophilicity and structure of different model molecules on their distribution in SLN dispersions. SLN composed of glyceryl tripalmitate as lipid and soybean lecithin and poloxamer 188 as stabilizers were prepared by a melt-emulsification process. PC(10,3), MeFASL(10,3), C(14)-Tempo, and Tempol were incorporated into SLN as spin-labeled compounds. The partition of SP between triglyceride and water was determined experimentally by electron paramagnetic resonance (EPR) and compared with calculated partition coefficients. The distribution of molecules in SLN dispersions was determined from the parameters of EPR spectra, from the reduction kinetics of the spin-labeled compounds with sodium ascorbate, and by computer simulation of EPR spectral line shapes. The experimentally obtained partition coefficients increase in the order Tempol < MeFASL(10,3) < C(14)-Tempo, showing the same trend as the partition coefficients calculated according to Rekker. In SLN dispersions, it was estimated that the ratio of SP between solid lipid core, phospholipid layers (deeper in SLN layer or in liposomes and closer to the surface of SLN), and water is for Tempol 0:0:100, for C(14)-Tempo 46:54(20:34):0, for MeFASL(10,3) 34:65(38:27):1, and for PC(10,3) 10:89(26:3:60):1. Copyright 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association

Solid-phase extraction versus matrix solid-phase dispersion: Application to white grapes.

PubMed

Dopico-García, M S; Valentão, P; Jagodziñska, A; Klepczyñska, J; Guerra, L; Andrade, P B; Seabra, R M

2007-11-15

The use of matrix solid-phase dispersion (MSPD) was tested to, separately, extract phenolic compounds and organic acids from white grapes. This method was compared with a more conventional analytical method previously developed that combines solid liquid extraction (SL) to simultaneously extract phenolic compounds and organic acids followed by a solid-phase extraction (SPE) to separate the two types of compounds. Although the results were qualitatively similar for both techniques, the levels of extracted compounds were in general quite lower on using MSPD, especially for organic acids. Therefore, SL-SPE method was preferred to analyse white "Vinho Verde" grapes. Twenty samples of 10 different varieties (Alvarinho, Avesso, Asal-Branco, Batoca, Douradinha, Esganoso de Castelo Paiva, Loureiro, Pedernã, Rabigato and Trajadura) from four different locations in Minho (Portugal) were analysed in order to study the effects of variety and origin on the profile of the above mentioned compounds. Principal component analysis (PCA) was applied separately to establish the main sources of variability present in the data sets for phenolic compounds, organic acids and for the global data. PCA of phenolic compounds accounted for the highest variability (77.9%) with two PCs, enabling characterization of the varieties of samples according to their higher content in flavonol derivatives or epicatechin. Additionally, a strong effect of sample origin was observed. Stepwise linear discriminant analysis (SLDA) was used for differentiation of grapes according to the origin and variety, resulting in a correct classification of 100 and 70%, respectively.

Physical stability of API/polymer-blend amorphous solid dispersions.

PubMed

Lehmkemper, Kristin; Kyeremateng, Samuel O; Bartels, Mareike; Degenhardt, Matthias; Sadowski, Gabriele

2018-03-01

The preparation of amorphous solid dispersions (ASDs) is a well-established strategy for formulating active pharmaceutical ingredients by embedding them in excipients, usually amorphous polymers. Different polymers can be combined for designing ASDs with desired properties like an optimized dissolution behavior. One important criterion for the development of ASD compositions is the physical stability. In this work, the physical stability of API/polymer-blend ASDs was investigated by thermodynamic modeling and stability studies. Amorphous naproxen (NAP) and acetaminophen (APAP) were embedded in blends of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and either poly(vinylpyrrolidone) (PVP) or poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64). Parameters for modeling the API solubility in the blends and the glass-transition temperature curves of the water-free systems with Perturbed-Chain Statistical Associating Fluid Theory and Kwei equation, respectively, were correlated to experimental data. The phase behavior for standardized storage conditions (0%, 60% and 75% relative humidity (RH)) was predicted and compared to six months-long stability studies. According to modeling and experimental results, the physical stability was reduced with increasing HPMCAS content and increasing RH. This trend was observed for all investigated systems, with both APIs (NAP and APAP) and both polymer blends (PVP/HPMCAS and PVPVA64/HPMCAS). PC-SAFT and the Kwei equation turned out to be suitable tools for modeling and predicting the physical stability of the investigated API/polymer-blends ASDs. Copyright © 2017 Elsevier B.V. All rights reserved.

Fabrication of a novel hydrophobic/ion-exchange mixed-mode adsorbent for the dispersive solid-phase extraction of chlorophenols from environmental water samples.

PubMed

Gao, Li; Wei, Yinmao

2016-08-01

A novel mixed-mode adsorbent was prepared by functionalizing silica with tris(2-aminoethyl)amine and 3-phenoxybenzaldehyde as the main mixed-mode scaffold due to the presence of the plentiful amino groups and benzene rings in their molecules. The adsorption mechanism was probed with acidic, natural and basic compounds, and the mixed hydrophobic and ion-exchange interactions were found to be responsible for the adsorption of analytes. The suitability of dispersive solid-phase extraction was demonstrated in the determination of chlorophenols in environmental water. Several parameters, including sample pH, desorption solvent, ionic strength, adsorbent dose, and extraction time were optimized. Under the optimal extraction conditions, the proposed dispersive solid-phase extraction coupled with high-performance liquid chromatography showed good linearity range and acceptable limits of detection (0.22∽0.54 ng/mL) for five chlorophenols. Notably, the higher extraction recoveries (88.7∽109.7%) for five chlorophenols were obtained with smaller adsorbent dose (10 mg) and shorter extraction time (15 min) compared with the reported methods. The proposed method might be potentially applied in the determination of trace chlorophenols in real water samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Formation of nano/micro-dispersions with improved dissolution properties upon dispersion of ritonavir melt extrudate in aqueous media.

PubMed

Tho, Ingunn; Liepold, Bernd; Rosenberg, Joerg; Maegerlein, Markus; Brandl, Martin; Fricker, Gert

2010-04-16

The objective of the study was to characterise the aqueous dispersions of ritonavir melt extrudates. More specifically to look into the particular system formed when melt extrudate of a poorly soluble drug dissolved in a hydrophilic polymer matrix containing a surfactant is dispersed in an aqueous medium. Melt extrudates with and without ritonavir were studied. The drug containing extrudate was confirmed to be molecular dispersions of drug in a polymer/surfactant matrix. Particulate dispersions were formed in water from both drug and placebo extrudates. The dispersions were investigated with respect to mean particle size and particle size distribution (photon correlation spectroscopy and optical particle counting), surface charge (zeta potential), particle composition (ultracentrifugation), tendency to form aggregates and precipitate (turbidity), in vitro dissolution rate and drug release. It was concluded that dispersion of melt extrudates in aqueous medium give rise to nano/micro-dispersions. The stability of the nano/micro-dispersion is sensitive to anions and may be subjected to association/aggregation/flocculation as time proceeds after preparation of dispersion. Melt extrudate showed improved dissolution rate and drug release properties compared to crystalline raw material. From studies of single components and physical mixtures of the formulation composition it can be concluded that the drug delivery system itself, namely solid dispersion prepared by melt extrusion technology, plays a key role for the formation of the observed particles. 2010 Elsevier B.V. All rights reserved.

Characterization of a nonribosomal peptide antibiotic solid dispersion formulation by process analytical technologies sensors.

PubMed

Rahman, Ziyaur; Siddiqui, Akhtar; Khan, Mansoor A

2013-12-01

The focus of present investigation was to characterize and evaluate the variability of solid dispersion (SD) of amorphous vancomycin (VCM), utilizing crystalline polyethylene glycol (PEG-6000) as a carrier and subsequently, determining their percentage composition by nondestructive method of process analytical technology (PAT) sensors. The SD were prepared by heat fusion method and characterized for physicochemical and spectral properties. Enhanced dissolution was shown by the SD formulations. Decreased crystallinity of PEG-6000 was observed indicating that the drug was present as solution and dispersed form within the polymer. The SD formulations were homogenous as shown by near infrared (NIR) chemical imaging data. Principal component analysis (PCA) and partial least square (PLS) method were applied to NIR and PXRD (powder X-ray diffraction) data to develop model for quantification of drug and carrier. PLS of both data showed correlation coefficient >0.9934 with good prediction capability as revealed by smaller value of root mean square and standard error. The model based on NIR and PXRD were two folds more accurate in estimating PEG-6000 than VCM. In conclusion, the drug dissolution from the SD increased by decreasing crystallinity of PEG-6000, and the chemometric models showed usefulness of PAT sensor in estimating percentage of both VCM and PEG-600 simultaneously. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

Preparation and evaluation of lignosulfonates as a dispersant for gypsum paste from acid hydrolysis lignin.

PubMed

Matsushita, Yasuyuki; Yasuda, Seiichi

2005-03-01

In order to effectively utilize a by-product of the acid saccharification process of woody materials, the chemical conversion of guaiacyl sulfuric acid lignin (SAL), one of the acid hydrolysis lignins, into water-soluble sulfonated products with high dispersibitity was investigated. At first, SAL was phenolated (P-SAL) to enhance the solubility and reactivity. Lignosulfonates were prepared from P-SAL by three methods of hydroxymethylation followed by neutral sulfonation (two-step method), sulfomethylation (one-step method) and arylsulfonation. Surprisingly, all prepared lignosulfonates possessed 30 to 70% higher dispersibility for gypsum paste than the commercial lignosulfonate. Evaluation of the preparations for gypsum paste suggested that the higher molecular weights and sulfur contents of the preparations increased their dispersibility.

Evaluation of a molecularly imprinted polymer for determination of steroids in goat milk by matrix solid phase dispersion.

PubMed

Gañán, Judith; Morante-Zarcero, Sonia; Gallego-Picó, Alejandrina; Garcinuño, Rosa María; Fernández-Hernando, Pilar; Sierra, Isabel

2014-08-01

A molecularly imprinted polymer-matrix solid-phase dispersion methodology for simultaneous determination of five steroids in goat milk samples was proposed. Factors affecting the extraction recovery such as sample/dispersant ratio and washing and elution solvents were investigated. The molecularly imprinted polymer used as dispersant in the matrix solid-phase dispersion procedure showed high affinity to steroids, and the obtained extracts were sufficiently cleaned to be directly analyzed. Analytical separation was performed by micellar electrokinetic chromatography using a capillary electrophoresis system equipped with a diode array detector. A background electrolyte composed of borate buffer (25mM, pH 9.3), sodium dodecyl sulfate (10mM) and acetonitrile (20%) was used. The developed MIP-MSPD methodology was applied for direct determination of testosterone (T), estrone (E1), 17β-estradiol (17β-E2), 17α-ethinylestradiol (EE2) and progesterone (P) in different goat milk samples. Mean recoveries obtained ranged from 81% to 110%, with relative standard deviations (RSD)≤12%. The molecularly imprinted polymer-matrix solid-phase dispersion method is fast, selective, cost-effective and environment-friendly compared with other pretreatment methods used for extraction of steroids in milk. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigating the Dissolution Performance of Amorphous Solid Dispersions Using Magnetic Resonance Imaging and Proton NMR.

PubMed

Tres, Francesco; Coombes, Steven R; Phillips, Andrew R; Hughes, Leslie P; Wren, Stephen A C; Aylott, Jonathan W; Burley, Jonathan C

2015-09-10

We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide). A combined suite of state-of-the-art analytical techniques were employed to obtain a clear picture of the drug release, including an integrated magnetic resonance imaging UV-Vis flow cell system and 1H-NMR. Off-line 1H-NMR was used for the first time to simultaneously measure the dissolution profiles and rates of both the drug and the polymer from a solid dispersion. MRI and 1H-NMR data showed that the 5% drug loading compact erodes linearly, and that bicalutamide and Kollidon VA64 are released at approximately the same rate from the molecular dispersion. For the 30% extrudate, data indicated a slower water ingress into the compact which corresponds to a slower dissolution rate of both bicalutamide and Kollidon VA64.

Development and validation of a matrix solid-phase dispersion method to determine acrylamide in coffee and coffee substitutes.

PubMed

Soares, Cristina M Dias; Alves, Rita C; Casal, Susana; Oliveira, M Beatriz P P; Fernandes, José Oliveira

2010-04-01

The present study describes the development and validation of a new method based on a matrix solid-phase dispersion (MSPD) sample preparation procedure followed by GC-MS for determination of acrylamide levels in coffee (ground coffee and brewed coffee) and coffee substitute samples. Samples were dispersed in C(18) sorbent and the mixture was further packed into a preconditioned custom-made ISOLUTE bilayered SPE column (C(18)/Multimode; 1 g + 1 g). Acrylamide was subsequently eluted with water, and then derivatized with bromine and quantified by GC-MS in SIM mode. The MSPD/GC-MS method presented a LOD of 5 microg/kg and a LOQ of 10 microg/kg. Intra and interday precisions ranged from 2% to 4% and 4% to 10%, respectively. To evaluate the performance of the method, 11 samples of ground and brewed coffee and coffee substitutes were simultaneously analyzed by the developed method and also by a previously validated method based in a liquid-extraction (LE) procedure, and the results were compared showing a high correlation between them.

Pharmaceutical Dispersion Techniques for Dissolution and Bioavailability Enhancement of Poorly Water-Soluble Drugs.

PubMed

Zhang, Xingwang; Xing, Huijie; Zhao, Yue; Ma, Zhiguo

2018-06-23

Over the past decades, a large number of drugs as well as drug candidates with poor dissolution characteristics have been witnessed, which invokes great interest in enabling formulation of these active ingredients. Poorly water-soluble drugs, especially biopharmaceutical classification system (BCS) II ones, are preferably designed as oral dosage forms if the dissolution limit can be broken through. Minimizing a drug’s size is an effective means to increase its dissolution and hence the bioavailability, which can be achieved by specialized dispersion techniques. This article reviews the most commonly used dispersion techniques for pharmaceutical processing that can practically enhance the dissolution and bioavailability of poorly water-soluble drugs. Major interests focus on solid dispersion, lipid-based dispersion (nanoencapsulation), and liquisolid dispersion (drug solubilized in a non-volatile solvent and dispersed in suitable solid excipients for tableting or capsulizing), covering the formulation development, preparative technique and potential applications for oral drug delivery. Otherwise, some other techniques that can increase the dispersibility of a drug such as co-precipitation, concomitant crystallization and inclusion complexation are also discussed. Various dispersion techniques provide a productive platform for addressing the formulation challenge of poorly water-soluble drugs. Solid dispersion and liquisolid dispersion are most likely to be successful in developing oral dosage forms. Lipid-based dispersion represents a promising approach to surmounting the bioavailability of low-permeable drugs, though the technique needs to traverse the obstacle from liquid to solid transformation. Novel dispersion techniques are highly encouraged to develop for formulation of poorly water-soluble drugs.

Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

PubMed

Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

2017-11-01

Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

[Preparation of Oenothera biennis Oil Solid Lipid Nanoparticles Based on Microemulsion Technique].

PubMed

Piao, Lin-mei; Jin, Yong; Cui, Yan-lin; Yin, Shou-yu

2015-06-01

To study the preparation of Oenothera biennis oil solid lipid nanoparticles and its quality evaluation. The solid lipid nanoparticles were prepared by microemulsion technique. The optimum condition was performed based on the orthogonal design to examine the entrapment efficiency, the mean diameter of the particles and so on. The optimal preparation of Oenothera biennis oil solid lipid nanoparticles was as follows: Oenothera biennis dosage 300 mg, glycerol monostearate-Oenothera biennis (2: 3), Oenothera biennis -RH/40/PEG-400 (1: 2), RH-40/PEG-400 (1: 2). The resulting nanoparticles average encapsulation efficiency was (89.89 ± 0.71)%, the average particle size was 44.43 ± 0.08 nm, and the Zeta potential was 64.72 ± 1.24 mV. The preparation process is simple, stable and feasible.

Quality assessment of compost prepared with municipal solid waste

NASA Astrophysics Data System (ADS)

Jodar, J. R.; Ramos, N.; Carreira, J. A.; Pacheco, R.; Fernández-Hernández, A.

2017-11-01

One way that helps maintain the sustainability of agro-ecosystems land is the application of compost from municipal solid waste as fertilizer, because it can recover the nutrients contained in them, minimizing the negative impact on the environment. Composting as a method for preparing organic fertilizers and amendments is economically and ecologically sound and may well represent an acceptable solution for disposing of municipal solid waste. In the present work, the quality of compost is studied made from municipal solid waste; the content of mineral nutrients: potassium, calcium, magnesium, sodium, zinc, manganese, cupper, iron, nickel, chromium and lead has been investigated. The objective was to evaluate the changes in mineral nutrient concentration during the composting process. The compost was prepared in a pilot-plant using the turning-pile system. Temperature was used as a monitoring parameter to follow the composting progress, which underwent the typical trend of municipal solid waste composting mixtures. The results showed a similar evolution on the content of mineral nutrients of the mixture of municipal solid waste. This evolution originated in a mature compost (end sample) with an adequate content of mineral elements and physical-chemical characteristics for its use in agriculture. So, the use of compost of municipal solid waste represents an important tool for fertilization requirements for its use in agriculture.

Enhancement of solubility and oral bioavailability of manidipine by formation of ternary solid dispersion with d-α-tocopherol polyethylene glycol 1000 succinate and copovidone.

PubMed

Chamsai, Benchawan; Limmatvapirat, Sontaya; Sungthongjeen, Srisagul; Sriamornsak, Pornsak

2017-12-01

Low bioavailability of oral manidipine (MDP) is due to its low water solubility. The objective of this study was to increase the solubility and bioavailability of MDP by fabricating ternary solid dispersion (tSD) with d-α-tocopherol polyethyleneglycol-1000-succinate and copovidone. In this study, solid ternary phase diagram was applied in order to check the homogeneity of tSD prepared by melting and solidifying with dry ice. The physicochemical properties of different formulations were determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and hot stage microscopy. Their solubility, dissolution, stability and bioavailability were also investigated. The results demonstrated that tSD obtained from ternary phase diagram divided into homogeneous and non-homogeneous regions. In the homogenous region, the transparent characteristics of tSD was observed and considered as a glass solution, which have a higher MDP solubility than that in non-homogenous region. The hot stage microscopy, DSC and PXRD confirmed that solid dispersion was formed in which MDP was molecularly dispersed in the carriers, especially in the homogenous region of phase diagram. FTIR analysis demonstrated strong hydrogen bonding between amine groups of MDP and carbonyl groups of copovidone, which supported a higher solubility and dissolution of tSD. The pharmacokinetic study in Wistar rats showed that the tSD had the greatest effect on oral bioavailability. Immediate hypotensive effect of tSD was also observed in vivo. The improvement of stability, dissolution and oral bioavailability of MDP could be achieved by using tSD technique.

Brain-targeted intranasal zaleplon solid dispersion in hydrophilic carrier system; 23 full-factorial design and in vivo determination of GABA neurotransmitter.

PubMed

Abd-Elrasheed, Eman; Nageeb El-Helaly, Sara; El-Ashmoony, Manal M; Salah, Salwa

2018-05-01

Intranasal zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 2 3 full-factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied. The dependent variables determined from the in vitro characterization and their constraints were set as follows: minimum mean dissolution time, maximum dissolution efficiency and maximum percentage release. Numerical optimization was performed according to the constraints set based on the utilization of desirability functions. Differential scanning calorimetry, infrared spectroscopy, X-ray diffraction and scanning electron microscopy were performed. Ex vivo estimation of nasal cytotoxicity and assessment of the γ-aminobutyric acid level in plasma and brain 1 h after nasal SD administration in rabbits compared to the oral market product were conducted. The selected ZP-SD, with a desirability 0.9, composed of poloxamer 407 at drug to carrier ratio 1:2 successfully enhanced the bioavailability showing 44% increase in GABA concentration than the marketed tablets.

Thermal Dispersion Within a Porous Medium Near a Solid Wall

NASA Technical Reports Server (NTRS)

Simon, T.; McFadden, G.; Ibrahim, M.

2006-01-01

The regenerator is a key component to Stirling cycle machine efficiency. Typical regenerators are of sintered fine wires or layers of fine-wire screens. Such porous materials are contained within solid-waH casings. Thermal energy exchange between the regenerator and the casing is important to cycle performance for the matrix and casing would not have the same axial temperature profile in an actual machine. Exchange from one to the other may allow shunting of thermal energy, reducing cycle efficiency. In this paper, temperature profiles within the near-wall region of the matrix are measured and thermal energy transport, termed thermal dispersion, is inferred. The data show how the wall affects thermal transport. Transport normal to the mean flow direction is by conduction within the solid and fluid and by advective transport within the matrix. In the near-wall region, both may be interrupted from their normal in-core pattern. Solid conduction paths are broken and scales of advective transport are damped. An equation is presented which describes this change for a wire screen mesh. The near-wall layer typically acts as an insulating layer. This should be considered in design or analysis. Effective thermal conductivity within the core is uniform. In-core transverse thermal effective conductivity values are compared to direct and indirect measurements reported elsewhere and to 3D numerical simulation results, computed previously and reported elsewhere. The 3-D CFD model is composed of six cylinders in cross flow, staggered in arrangement to match the dimensions and porosity of the matrix used in the experiments. The commercial code FLUENT is used to obtain the flow and thermal fields. The thermal dispersion and effective thermal conductivities for the matrix are computed from the results.

Molecularly designed lipid microdomains for solid dispersions using a polymer/inorganic carrier matrix produced by hot-melt extrusion.

PubMed

Adler, Camille; Schönenberger, Monica; Teleki, Alexandra; Kuentz, Martin

2016-02-29

Amorphous solid dispersions have for many years been a focus in oral formulations, especially in combination with a hot-melt extrusion process. The present work targets a novel approach with a system based on a fatty acid, a polymer and an inorganic carrier. It was intended to adsorb the acidic lipid by specific molecular interactions onto the solid carrier to design disorder in the alkyl chains of the lipid. Such designed lipid microdomains (DLM) were created as a new microstructure to accommodate a compound in a solid dispersion. Vibrational spectroscopy, X-ray powder diffraction, atomic force microscopy as well as electron microscopic imaging were employed to study a system of stearic acid, hydroxypropylcellulose and aluminum magnesium silicate. β-carotene was used as a poorly water-soluble model substance that is difficult to formulate with conventional solid dispersion formulations. The results indicated that the targeted molecular excipient interactions indeed led to DLMs for specific compositions. The different methods provided complementary aspects and important insights into the created microstructure. The novel delivery system appeared to be especially promising for the formulation of oral compounds that exhibit both high crystal energy and lipophilicity. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid.

PubMed

Yuvaraja, K; Khanam, Jasmina

2014-08-05

Aim of the present work is to enhance aqueous solubility of carvedilol (CV) by solid dispersion technique using wide variety of carriers such as: β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD), tartaric acid (TA), polyvinyl pyrrolidone K-30 (PVP K-30) and poloxamer-407 (PLX-407). Various products of 'CV-solid dispersion' had been studied extensively in various pH conditions to check enhancement of solubility and dissolution characteristics of carvedilol. Any physical change upon interaction between CV and carriers was confirmed by instrumental analysis: XRD, DSC, FTIR and SEM. Negative change of Gibb's free energy and complexation constants (Kc, 75-240M(-1), for cyclodextrins and 1111-20,365M(-1), for PVP K-30 and PLX-407) were the evidence of stable nature of the binding between CV and carriers. 'Solubility enhancement factor' of ionized-CV was found high enough (340 times) with HPβCD in presence of TA. TA increases the binding efficiency of cyclodextrin and changing the pH of microenvironment in dissolution medium. In addition, ionization process was used to increase the apparent intrinsic solubility of drug. In vitro, dissolution time of CV was remarkably reduced in the solid dispersion system compared to that of pure drug. This may be attributed to increased wettability, dispersing ability and transformation of crystalline state of drug to amorphous one. Copyright © 2014 Elsevier B.V. All rights reserved.

Preparation of solid silver nanoparticles for inkjet printed flexible electronics with high conductivity.

PubMed

Shen, Wenfeng; Zhang, Xianpeng; Huang, Qijin; Xu, Qingsong; Song, Weijie

2014-01-01

Silver nanoparticles (NPs) which could be kept in solid form and were easily stored without degeneration or oxidation at room temperature for a long period of time were synthesized by a simple and environmentally friendly wet chemistry method in an aqueous phase. Highly stable dispersions of aqueous silver NP inks, sintered at room temperature, for printing highly conductive tracks (∼8.0 μΩ cm) were prepared simply by dispersing the synthesized silver NP powder in water. These inks are stable, fairly homogeneous and suitable for a wide range of patterning techniques. The inks were successfully printed on paper and polyethylene terephthalate (PET) substrates using a common color printer. Upon annealing at 180 °C, the resistivity of the printed silver patterns decreased to 3.7 μΩ cm, which is close to twice that of bulk silver. Various factors affecting the resistivity of the printed silver patterns, such as annealing temperature and the number of printing cycles, were investigated. The resulting high conductivity of the printed silver patterns reached over 20% of the bulk silver value under ambient conditions, which enabled the fabrication of flexible electronic devices, as demonstrated by the inkjet printing of conductive circuits of LED devices.

Dispersed bubble reactor for enhanced gas-liquid-solids contact and mass transfer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vimalchand, Pannalal; Liu, Guohai; Peng, WanWang

An apparatus to promote gas-liquid contact and facilitate enhanced mass transfer. The dispersed bubble reactor (DBR) operates in the dispersed bubble flow regime to selectively absorb gas phase constituents into the liquid phase. The dispersion is achieved by shearing the large inlet gas bubbles into fine bubbles with circulating liquid and additional pumped liquid solvent when necessary. The DBR is capable of handling precipitates that may form during absorption or fine catalysts that may be necessary to promote liquid phase reactions. The DBR can be configured with multistage counter current flow sections by inserting concentric cylindrical sections into the risermore » to facilitate annular flow. While the DBR can absorb CO.sub.2 in liquid solvents that may lead to precipitates at high loadings, it is equally capable of handling many different types of chemical processes involving solids (precipitates/catalysts) along with gas and liquid phases.« less

Probing hydrogen bonding in cocrystals and amorphous dispersions using (14)N-(1)H HMQC solid-state NMR.

PubMed

Tatton, Andrew S; Pham, Tran N; Vogt, Frederick G; Iuga, Dinu; Edwards, Andrew J; Brown, Steven P

2013-03-04

Cocrystals and amorphous solid dispersions have generated interest in the pharmaceutical industry as an alternative to more established solid delivery forms. The identification of intermolecular hydrogen bonding interactions in a nicotinamide palmitic acid cocrystal and a 50% w/w acetaminophen-polyvinylpyrrolidone solid dispersion are reported using advanced solid-state magic-angle spinning (MAS) NMR methods. The application of a novel (14)N-(1)H HMQC experiment, where coherence transfer is achieved via through-space couplings, is shown to identify specific hydrogen bonding motifs. Additionally, (1)H isotropic chemical shifts and (14)N electric field gradient (EFG) parameters, both accessible from (14)N-(1)H HMQC experiments, are shown to be sensitive to changes in hydrogen bonding geometry. Numerous indicators of molecular association are accessible from this experiment, including NH cross-peaks occurring from intermolecular hydrogen bonds and changes in proton chemical shifts or electric field gradient parameters. First-principles calculations using the GIPAW approach that yield accurate estimates of isotropic chemical shifts, and EFG parameters were used to assist in assignment. It is envisaged that (14)N-(1)H HMQC solid state NMR experiments could become a valuable screening technique of solid delivery forms in the pharmaceutical industry.

Encapsulation of eugenol from clove oil using casein micelle for solid preparation

NASA Astrophysics Data System (ADS)

Wijayanto, Andri; Putri, Yeshinta Risky Priasmara; Hermansyah, Heri; Sahlan, Muhamad

2017-02-01

Liquid preparation of eugenol in clove oil form is one of eugenol preparation form that is easiest to get it nowadays in many level of purity. The problem is the liquid preparation of chemical is often not easy to handle than the solid one. In this study, we observe the effectivity of cow milk casein in case of encapsulating eugenol from clove oil for creating the solid preparation of eugenol in nanoscale size. The result is 63.86% eugenol from clove oil can be encapsulated by the casein. The average particle diameter is about 377.5 nm, with loading capacity until 67.2%.

Oral bioavailability enhancement of β-lapachone, a poorly soluble fast crystallizer, by cocrystal, amorphous solid dispersion, and crystalline solid dispersion.

PubMed

Liu, Chengyu; Liu, Zhengsheng; Chen, Yuejie; Chen, Zhen; Chen, Huijun; Pui, Yipshu; Qian, Feng

2018-03-01

The aim of this paper was to compare the in vitro dissolution and in vivo bioavailability of three solubility enhancement technologies for β-lapachone (LPC), a poorly water soluble compound with extremely high crystallization propensity. LPC cocrystal was prepared by co-grinding LPC with resorcinol. LPC crystalline and amorphous solid dispersions (CSD and ASD) were obtained by spray drying with Poloxamer 188 and HPMC-AS, respectively. The cocrystal structure was solved by single crystal x-ray diffraction. All formulations were characterized by WAXRD, DSC, POM and SEM. USP II and intrinsic dissolution studies were used to compare the in vitro dissolution of these formulations, and a crossover dog pharmacokinetic study was used to compare their in vivo bioavailability. An 1:1 LPC-resorcinol cocrystal with higher solubility and faster dissolution rate was obtained, yet it converted to LPC crystal rapidly in solution. LPC/HPMC-AS ASD was confirmed to be amorphous and uniform, while the crystal and crystallite sizes of LPC in CSD were found to be ∼1-3 μm and around 40 nm, respectively. These formulations performed similarly during USP II dissolution, while demonstrated dramatically different oral bioavailability of ∼32%, ∼5%, and ∼1% in dogs, for CSD, co-crystal, and ASD, respectively. CSD showed the fastest intrinsic dissolution rate among the three. The three formulations showed poor IVIVC which could be due to rapid and unpredictable crystallization kinetics. Considering all the reasons, we conclude that for molecules with extremely high crystallization tendency that cannot be inhibited by any pharmaceutical excipients, size-reduction technologies such as CSD could be advantageous for oral bioavailability enhancement in vivo than technologies only generating transient but not sustained supersaturation. Copyright © 2018 Elsevier B.V. All rights reserved.

Determination of ibuprofen enantiomers in breast milk using vortex-assisted matrix solid-phase dispersion and direct chiral liquid chromatography.

PubMed

León-González, M E; Rosales-Conrado, N

2017-09-08

A mixture of β-cyclodextrin (β-CD) and primary and secondary amine (PSA) sorbents was employed for the extraction and quantification of ibuprofen enantiomers from human breast milk, combining a vortex-assisted matrix solid-phase dispersion method (MSPD) and direct chiral liquid chromatography (CLC) with ultraviolet detection (UV). The MSPD sample preparation procedure was optimized focusing on both the type and amount of dispersion/sorption sorbents and the nature of the elution solvent, in order to obtain acceptable recoveries and avoiding enantiomer conversion. These MSPD parameters were optimized with the aid of an experimental design approach. Hence, a factorial design was used for identification of the main variables affecting the extraction process of ibuprofen enantiomers. Under optimum selected conditions, MSPD combined with direct CLC-UV was successfully applied for ibuprofen enantiomeric determination in breast milk at enantiomer levels between 0.15 and 6.0μgg -1 . The proposed analytical method also provided good repeatability, with relative standard deviations of 6.4% and 8.3% for the intra-day and inter-day precision, respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

Increased dissolution rate and oral bioavailability of hydrophobic drug glyburide tablets produced using supercritical CO₂ silica dispersion technology.

PubMed

Guan, Jibin; Han, Jihong; Zhang, Dong; Chu, Chunxia; Liu, Hongzhuo; Sun, Jin; He, Zhonggui; Zhang, Tianhong

2014-04-01

The aim of this study was to design a silica-supported solid dispersion of a water-insoluble drug, glyburide, to increase its dissolution rate and oral absorption using supercritical fluid (SCF) technology. DSC and PXRD results indicated that the encapsulated drug in the optimal solid dispersion was in an amorphous state and the product was stable for 6 months. Glyburide was adsorbed onto the porous silica, as confirmed by the SEM images and BET analysis. Furthermore, FT-IR spectroscopy confirmed that there was no change in the chemical structure of glyburide after the application of SCF. The glyburide silica-based dispersion could also be compressed into tablet form. In vitro drug release analysis of the silica solid dispersion tablets demonstrated faster release of glyburide compared with the commercial micronized tablet. In an in vivo test, the AUC of the tablets composed of the new glyburide silica-based solid dispersion was 2.01 times greater than that of the commercial micronized glyburide tablets. In conclusion, SCF technology presents a promising approach to prepare silica-based solid dispersions of hydrophobic drugs because of its ability to increase their release and oral bioavailability. Copyright © 2013 Elsevier B.V. All rights reserved.

Amorphous solid dispersions of piroxicam and Soluplus(®): Qualitative and quantitative analysis of piroxicam recrystallization during storage.

PubMed

Lust, Andres; Strachan, Clare J; Veski, Peep; Aaltonen, Jaakko; Heinämäki, Jyrki; Yliruusi, Jouko; Kogermann, Karin

2015-01-01

The conversion of active pharmaceutical ingredient (API) from amorphous to crystalline form is the primary stability issue in formulating amorphous solid dispersions (SDs). The aim of the present study was to carry out qualitative and quantitative analysis of the physical solid-state stability of the SDs of poorly water-soluble piroxicam (PRX) and polyvinyl caprolactam-polyvinyl acetate-polyethylene-glycol graft copolymer (Soluplus(®)). The SDs were prepared by a solvent evaporation method and stored for six months at 0% RH/6 °C, 0% RH/25 °C, 40% RH/25 °C and 75% RH/25 °C. Fourier transform infrared spectroscopy equipped with attenuated total reflection accessory (ATR-FTIR) and Raman spectroscopy were used for characterizing the physical solid-state changes and drug-polymer interactions. The principal component analysis (PCA) and multivariate curve resolution alternating least squares (MCR-ALS) were used for the qualitative and quantitative analysis of Raman spectra collected during storage. When stored at 0% RH/6 °C and at 0% RH/25 °C, PRX in SDs remained in an amorphous form since no recrystallization was observed by ATR-FTIR and Raman spectroscopy. Raman spectroscopy coupled with PCA and MCR-ALS and ATR-FTIR spectroscopy enabled to detect the recrystallization of amorphous PRX in the samples stored at higher humidity. Copyright © 2015 Elsevier B.V. All rights reserved.

Combined application of mixture experimental design and artificial neural networks in the solid dispersion development.

PubMed

Medarević, Djordje P; Kleinebudde, Peter; Djuriš, Jelena; Djurić, Zorica; Ibrić, Svetlana

2016-01-01

This study for the first time demonstrates combined application of mixture experimental design and artificial neural networks (ANNs) in the solid dispersions (SDs) development. Ternary carbamazepine-Soluplus®-poloxamer 188 SDs were prepared by solvent casting method to improve carbamazepine dissolution rate. The influence of the composition of prepared SDs on carbamazepine dissolution rate was evaluated using d-optimal mixture experimental design and multilayer perceptron ANNs. Physicochemical characterization proved the presence of the most stable carbamazepine polymorph III within the SD matrix. Ternary carbamazepine-Soluplus®-poloxamer 188 SDs significantly improved carbamazepine dissolution rate compared to pure drug. Models developed by ANNs and mixture experimental design well described the relationship between proportions of SD components and percentage of carbamazepine released after 10 (Q10) and 20 (Q20) min, wherein ANN model exhibit better predictability on test data set. Proportions of carbamazepine and poloxamer 188 exhibited the highest influence on carbamazepine release rate. The highest carbamazepine release rate was observed for SDs with the lowest proportions of carbamazepine and the highest proportions of poloxamer 188. ANNs and mixture experimental design can be used as powerful data modeling tools in the systematic development of SDs. Taking into account advantages and disadvantages of both techniques, their combined application should be encouraged.

Spray drying formulation of amorphous solid dispersions.

PubMed

Singh, Abhishek; Van den Mooter, Guy

2016-05-01

Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs makes it an interesting area to explore. Numerous diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of ASDs, various formulation and process variables influencing the critical quality attributes (CQAs) of the ASDs and aspects of downstream processing. Also various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research thrust is needed. Copyright © 2015 Elsevier B.V. All rights reserved.

Preparation and characterization of fast dissolving flurbiprofen and esomeprazole solid dispersion using spray drying technique.

PubMed

Pradhan, Roshan; Tran, Tuan Hiep; Kim, Sung Yub; Woo, Kyu Bong; Choi, Yong Joo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

2016-04-11

We aimed to develop an immediate-release flurbiprofen (FLU) and esomeprazole (ESO) combination formulation with enhanced gastric aqueous solubility and dissolution rate. Aqueous solubility can be enhanced by formulating solid dispersions (SDs) with a polyvinylpyrrolidone (PVP)-K30 hydrophilic carrier, using spray-drying technique. Aqueous and gastric pH dissolution can be achieved by macro-environmental pH modulation using sodium bicarbonate (NaHCO3) and magnesium hydroxide (Mg(OH)2) as the alkaline buffer. FLU/ESO-loaded SDs (FLU/ESO-SDs) significantly improved aqueous solubility of both drugs, compared to each drug powder. Dissolution studies in gastric pH and water were compared with the microenvironmental pH modulated formulations. The optimized FLU/ESO-SD powder formulation consisted of FLU/ESO/PVP-K30/sodium carbonate (Na2CO3) in a weight ratio 1:0.22:1.5:0.3, filled in the inner capsule. The outer capsule consisted of NaHCO3 and Mg(OH)2, which created the macro-environmental pH modulation. Increased aqueous and gastric pH dissolution of FLU and ESO from the SD was attributed to the alkaline buffer effects and most importantly, to drug transformation from crystalline to amorphous SD powder, clearly revealed by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction studies. Thus, the combined FLU and ESO SD powder can be effectively delivered as an immediate-release formulation using the macro-environmental pH modulation concept. Copyright © 2016. Published by Elsevier B.V.

Facile solid-state synthesis of highly dispersed Cu nanospheres anchored on coal-based activated carbons as an efficient heterogeneous catalyst for the reduction of 4-nitrophenol

NASA Astrophysics Data System (ADS)

Wang, Shan; Gao, Shasha; Tang, Yakun; Wang, Lei; Jia, Dianzeng; Liu, Lang

2018-04-01

Coal-based activated carbons (AC) were acted as the support, Cu/AC catalysts were synthesized by a facile solid-state reaction combined with subsequent heat treatment. In Cu/AC composites, highly dispersed Cu nanospheres were anchored on AC. The catalytic activity for 4-nitrophenol (4-NP) was investigated, the effects of activation temperature and copper loading on the catalytic performance were studied. The catalysts exhibited very high catalytic activity and moderate chemical stability due to the unique characteristics of the particle-assembled nanostructures, the high surface area and the porous structure of coal-based AC and the good dispersion of metal particles. Design and preparation of non-noble metal composite catalysts provide a new direction for improving the added value of coal.

Recrystallization of nifedipine and felodipine from amorphous molecular level solid dispersions containing poly(vinylpyrrolidone) and sorbed water.

PubMed

Marsac, Patrick J; Konno, Hajime; Rumondor, Alfred C F; Taylor, Lynne S

2008-03-01

To compare the physical stability of amorphous molecular level solid dispersions of nifedipine and felodipine, in the presence of poly(vinylpyrrolidone) (PVP) and small amounts of moisture. Thin amorphous films of nifedipine and felodipine and amorphous molecular level solid dispersions with PVP were stored at various relative humidities (RH) and the nucleation rate was measured. The amount of water sorbed at each RH was measured using isothermal vapor sorption and glass transition temperatures (Tg) were determined using differential scanning calorimetry. The solubility of each compound in methyl pyrrolidone was measured as a function of water content. Nifedipine crystallizes more easily than felodipine at any given polymer concentration and in the presence of moisture. The glass transition temperatures of each compound, alone and in the presence of PVP, are statistically equivalent at any given water content. The nifedipine systems are significantly more hygroscopic than the corresponding felodipine systems. Variations in the physical stability of the two compounds could not be explained by differences in Tg. However, the relative physical stability is consistent with differences in the degree of supersaturation of each drug in the solid dispersion, treating the polymer and water as a co-solvent system for each drug compound.

Preparation and Properties of New Inorganic Glasses and Gel-Derived Solids

DTIC Science & Technology

1991-04-01

route were examined, including the use of SiC and diamond powder as fillers and some triphasic , solids. Many ferroelectnic thin films were prepared...use of SiC and diamond powder as fillers and some triphasic solids. Many ferroelectric thin films were prepared and their properties measured. An...Exit Filter Mmrn Holder Filter He Gas Perforated Pyrolysis Reactor 00 0 00 00 00 00 0 0 0 0 Soutolution asWe Fi.8.Shmai darm fepeiena0yses I I I ci

Silica Modified with Polyaniline as a Potential Sorbent for Matrix Solid Phase Dispersion (MSPD) and Dispersive Solid Phase Extraction (d-SPE) of Plant Samples

PubMed Central

Sowa, Ireneusz; Wójciak-Kosior, Magdalena; Strzemski, Maciej; Sawicki, Jan; Staniak, Michał; Dresler, Sławomir; Szwerc, Wojciech; Mołdoch, Jarosław; Latalski, Michał

2018-01-01

Polyaniline (PANI) is one of the best known conductive polymers with multiple applications. Recently, it was also used in separation techniques, mostly as a component of composites for solid-phase microextraction (SPME). In the present paper, sorbent obtained by in situ polymerization of aniline directly on silica gel particles (Si-PANI) was used for dispersive solid phase extraction (d-SPE) and matrix solid–phase extraction (MSPD). The efficiency of both techniques was evaluated with the use of high performance liquid chromatography with diode array detection (HPLC-DAD) quantitative analysis. The quality of the sorbent was verified by Raman spectroscopy and microscopy combined with automated procedure using computer image analysis. For extraction experiments, triterpenes were chosen as model compounds. The optimal conditions were as follows: protonated Si-PANI impregnated with water, 160/1 sorbent/analyte ratio, 3 min of extraction time, 4 min of desorption time and methanolic solution of ammonia for elution of analytes. The proposed procedure was successfully used for pretreatment of plant samples. PMID:29565297

Comparison of In Situ Polymerization and Solution-Dispersion Techniques in the Preparation of Polyimide/Montmorillonite (MMT) Nanocomposites

PubMed Central

Ahmad, Mansor Bin; Gharayebi, Yadollah; Salit, Mohd. Sapuan; Hussein, Mohd. Zobir; Shameli, Kamyar

2011-01-01

In this paper, Polyimide/Montmorillonite Nanocomposites (PI/MMT NCs), based on aromatic diamine (4-Aminophenyl sulfone) (APS) and aromatic dianhydride (3,3′,4,4′-benzophenonetetracarboxylic dianhydride) (BTDA) were prepared using in situ polymerization and solution-dispersion techniques. The prepared PI/MMT NCs films were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). The XRD results showed that at the content of 1.0 wt % Organo Montmorillonite (OMMT) for two techniques and 3.0 wt % OMMT for the in situ polymerization technique, the OMMT was well-intercalated, exfoliated and dispersed into polyimide matrix. The OMMT agglomerated when its amount exceeded 10 wt % and 3.0 wt % for solution-dispersion and in situ polymerization techniques respectively. These results were confirmed by the TEM images of the prepared PI/MMT NCs. The TGA thermograms indicated that thermal stability of prepared PI/MMT NCs were increased with the increase of loading that, the effect is higher for the samples prepared by in situ polymerization technique. PMID:22016643

Comparison of in situ polymerization and solution-dispersion techniques in the preparation of Polyimide/Montmorillonite (MMT) Nanocomposites.

PubMed

Ahmad, Mansor Bin; Gharayebi, Yadollah; Salit, Mohd Sapuan; Hussein, Mohd Zobir; Shameli, Kamyar

2011-01-01

In this paper, Polyimide/Montmorillonite Nanocomposites (PI/MMT NCs), based on aromatic diamine (4-Aminophenyl sulfone) (APS) and aromatic dianhydride (3,3',4,4'-benzophenonetetracarboxylic dianhydride) (BTDA) were prepared using in situ polymerization and solution-dispersion techniques. The prepared PI/MMT NCs films were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM) and thermogravimetric analysis (TGA). The XRD results showed that at the content of 1.0 wt % Organo Montmorillonite (OMMT) for two techniques and 3.0 wt % OMMT for the in situ polymerization technique, the OMMT was well-intercalated, exfoliated and dispersed into polyimide matrix. The OMMT agglomerated when its amount exceeded 10 wt % and 3.0 wt % for solution-dispersion and in situ polymerization techniques respectively. These results were confirmed by the TEM images of the prepared PI/MMT NCs. The TGA thermograms indicated that thermal stability of prepared PI/MMT NCs were increased with the increase of loading that, the effect is higher for the samples prepared by in situ polymerization technique.

Mixed micelle cloud point-magnetic dispersive μ-solid phase extraction of doxazosin and alfuzosin

NASA Astrophysics Data System (ADS)

Gao, Nannan; Wu, Hao; Chang, Yafen; Guo, Xiaozhen; Zhang, Lizhen; Du, Liming; Fu, Yunlong

2015-01-01

Mixed micelle cloud point extraction (MM-CPE) combined with magnetic dispersive μ-solid phase extraction (MD-μ-SPE) has been developed as a new approach for the extraction of doxazosin (DOX) and alfuzosin (ALF) prior to fluorescence analysis. The mixed micelle anionic surfactant sodium dodecyl sulfate and non-ionic polyoxyethylene(7.5)nonylphenylether was used as the extraction solvent in MM-CPE, and diatomite bonding Fe3O4 magnetic nanoparticles were used as the adsorbent in MD-μ-SPE. The method was based on MM-CPE of DOX and ALF in the surfactant-rich phase. Magnetic materials were used to retrieve the surfactant-rich phase, which easily separated from the aqueous phase under magnetic field. At optimum conditions, a linear relationship between DOX and ALF was obtained in the range of 5-300 ng mL-1, and the limits of detection were 0.21 and 0.16 ng mL-1, respectively. The proposed method was successfully applied for the determination of the drugs in pharmaceutical preparations, urine samples, and plasma samples.

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yu; Mei, Xueting; Yuan, Jingquan

2015-11-15

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions inmore » serum Zn{sup 2+} and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase{sup +} was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation

Dispersion Corrected Structural Properties and Quasiparticle Band Gaps of Several Organic Energetic Solids.

PubMed

Appalakondaiah, S; Vaitheeswaran, G; Lebègue, S

2015-06-18

We have performed ab initio calculations for a series of energetic solids to explore their structural and electronic properties. To evaluate the ground state volume of these molecular solids, different dispersion correction methods were accounted in DFT, namely the Tkatchenko-Scheffler method (with and without self-consistent screening), Grimme's methods (D2, D3(BJ)), and the vdW-DF method. Our results reveal that dispersion correction methods are essential in understanding these complex structures with van der Waals interactions and hydrogen bonding. The calculated ground state volumes and bulk moduli show that the performance of each method is not unique, and therefore a careful examination is mandatory for interpreting theoretical predictions. This work also emphasizes the importance of quasiparticle calculations in predicting the band gap, which is obtained here with the GW approximation. We find that the obtained band gaps are ranging from 4 to 7 eV for the different compounds, indicating their insulating nature. In addition, we show the essential role of quasiparticle band structure calculations to correlate the gap with the energetic properties.

All-solid-state reduced graphene oxide supercapacitor with large volumetric capacitance and ultralong stability prepared by electrophoretic deposition method.

PubMed

Wang, Mei; Duong, Le Dai; Mai, Nguyen Thi; Kim, Sanghoon; Kim, Youngjun; Seo, Heewon; Kim, Ye Chan; Jang, Woojin; Lee, Youngkwan; Suhr, Jonghwan; Nam, Jae-Do

2015-01-21

Portable energy storage devices have gained special attention due to the growing demand for portable electronics. Herein, an all-solid-state supercapacitor is successfully fabricated based on a poly(vinyl alcohol)-H3PO4 (PVA-H3PO4) polymer electrolyte and a reduced graphene oxide (RGO) membrane electrode prepared by electrophoretic deposition (EPD). The RGO electrode fabricated by EPD contains an in-plane layer-by-layer alignment and a moderate porosity that accommodate the electrolyte ions. The all-solid-state RGO supercapacitor is thoroughly tested to give high specific volumetric capacitance (108 F cm(-3)) and excellent energy and power densities (7.5 Wh cm(-3) and 2.9 W cm(-3), respectively). In addition, the all-solid-state RGO supercapacitor exhibits an ultralong lifetime for as long as 180 days (335 000 cycles), which is an ultrahigh cycling capability for a solid-state supercapacitor. The RGO is also tested for being used as a transparent supercapacitor electrode demonstrating its possible use in various transparent optoelectronic devices. Due to the facile scale-up capability of the EPD process and RGO dispersion, the developed all-solid-state supercapacitor is highly applicable to large-area portable energy storage devices.

Challenges and Strategies in Thermal Processing of Amorphous Solid Dispersions: A Review.

PubMed

LaFountaine, Justin S; McGinity, James W; Williams, Robert O

2016-02-01

Thermal processing of amorphous solid dispersions continues to gain interest in the pharmaceutical industry, as evident by several recently approved commercial products. Still, a number of pharmaceutical polymer carriers exhibit thermal or viscoelastic limitations in thermal processing, especially at smaller scales. Additionally, active pharmaceutical ingredients with high melting points and/or that are thermally labile present their own specific challenges. This review will outline a number of formulation and process-driven strategies to enable thermal processing of challenging compositions. These include the use of traditional plasticizers and surfactants, temporary plasticizers utilizing sub- or supercritical carbon dioxide, designer polymers tailored for hot-melt extrusion processing, and KinetiSol® Dispersing technology. Recent case studies of each strategy will be described along with potential benefits and limitations.

Improved chip design for integrated solid-phase microextraction in on-line proteomic sample preparation.

PubMed

Bergkvist, Jonas; Ekström, Simon; Wallman, Lars; Löfgren, Mikael; Marko-Varga, György; Nilsson, Johan; Laurell, Thomas

2002-04-01

A recently introduced silicon microextraction chip (SMEC), used for on-line proteomic sample preparation, has proved to facilitate the process of protein identification by sample clean up and enrichment of peptides. It is demonstrated that a novel grid-SMEC design improves the operating characteristics for solid-phase microextraction, by reducing dispersion effects and thereby improving the sample preparation conditions. The structures investigated in this paper are treated both numerically and experimentally. The numerical approach is based on finite element analysis of the microfluidic flow in the microchip. The analysis is accomplished by use of the computational fluid dynamics-module FLOTRAN in the ANSYS software package. The modeling and analysis of the previously reported weir-SMEC design indicates some severe drawbacks, that can be reduced by changing the microextraction chip geometry to the grid-SMEC design. The overall analytical performance was thereby improved and also verified by experimental work. Matrix-assisted laser desorption/ionization mass spectra of model peptides extracted from both the weir-SMEC and the new grid-SMEC support the numerical analysis results. Further use of numerical modeling and analysis of the SMEC structures is also discussed and suggested in this work.

Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release.

PubMed

Cao, Yizheng; Teng, Jing; Selbo, Jon

2017-11-09

Epigallocatechin gallate (EGCG) has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity) and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus ® 50:50 ( w / w ) shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma.

Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release

PubMed Central

Cao, Yizheng; Teng, Jing; Selbo, Jon

2017-01-01

Epigallocatechin gallate (EGCG) has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity) and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus® 50:50 (w/w) shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma. PMID:29120370

Use of the co-grinding method to enhance the dissolution behavior of a poorly water-soluble drug: generation of solvent-free drug-polymer solid dispersions.

PubMed

Yang, Caiqin; Xu, Xiujuan; Wang, Jing; An, Zhiqian

2012-01-01

The solid dispersion (SD) technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs. In the present work, SDs of the Ca2+ channel blocker dipfluzine (DF) with polyvinylpyrrolidone K30 (PVP) and poloxamer 188 (PLXM) were prepared by the powder solid co-grinding method under a solvent-free condition. The properties of all SDs and physical mixtures were investigated by X-ray diffraction, Fourier-transform infrared, differential scanning calorimetry, scanning electron microscopy, dissolution test, and particles size determination. Eutectic compounds were produced between the DF and PLXM matrix during the co-grinding process, whereas glass suspension formed in the SDs with PVP carrier. Hydrogen bond formation was not observed between DF and carriers and DF was microcrystalline state in the PVP and PLXM matrices. The solubility of DF in different concentration of carriers at 25, 31, and 37°C was investigated; the values obtained were used to calculate the thermodynamic parameters of interaction between DF and carriers. The Gibbs free energy (ΔrGθ) values were negative, indicating the spontaneous nature of dispersing DF into the carriers. Moreover, entropy is the drive force when DF disperses into the matrix of PVP, while, enthalpy-driven dispersing encounters in the PLXM carrier. All the SDs of DF/carriers showed a considerably higher dissolution rate than pure DF and the corresponding physical mixtures. The cumulative dissolution rate at 10 min of the SD with a 1 : 3 DF/carrier ratio increased 5.1-fold for PVP and 5.5-fold for PLXM.

Determination of sulfonamides in milk by capillary electrophoresis with PEG@MoS2 as a dispersive solid-phase extraction sorbent.

PubMed

An, Jianxin; Wang, Xuan; Ming, Meiting; Li, Jian; Ye, Nengsheng

2018-05-01

A synthetic polyethylene glycol-molybdenum disulfide (PEG@MoS 2 ) composite was prepared using a simple method, and the application of this material in dispersive solid-phase extraction (DSPE) was investigated for the enrichment of eight sulfonamides (SAs) in milk samples. The composite was characterized by energy dispersive spectroscopy, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and Brunauer-Emmett-Teller measurements. The results showed that the MoS 2 synthesized in the presence of PEG has the advantage of a larger surface area and that the adsorption effect of this MoS 2 was enhanced. After extraction, the eight SAs were separated by capillary zone electrophoresis with a good linear relationship ( R 2  > 0.9902) in the range of 0.3-30 µg ml -1 and good precision (between 0.32% and 9.83%). Additionally, good recoveries (between 60.52% and 110.91%) were obtained for the SAs in the milk samples. The developed PEG@MoS 2 -based DSPE method could be applied for the enrichment of SAs in real milk samples.

Multiscale Computational Modeling of the Nanostructure of Solid Dispersions of Hydroxypropyl Methylcellulose Acetate Succinate (HPMCAS) and Phenytoin.

PubMed

Huang, Wenjun; Mandal, Taraknath; Larson, Ronald G

2017-10-02

We recently developed coarse-grained (CG) force fields for hydroxypropyl methylcellulose acetate succinate (HPMCAS) polymers and the model drug molecule phenytoin, and a continuum transport model to study the polymer-drug nanostructures presented during a dissolution test after solvation of solid dispersion particles. We model the polymer-drug interactions that contribute to suppression of drug aggregation, release, and crystal growth during the dissolution process, and we take these as indicators of polymer effectiveness. We find that the size and the intermolecular interaction strength of the functional group and the drug loading concentration are the major factors that impact the effectiveness of the polymeric excipient. The hydroxypropyl acetyl group is the most effective functional group, followed by the acetyl group, while the deprotonated succinyl group is the least effective functional group, except that the deprotonated succinyl group at the 6-position is very effective in slowing down the phenytoin crystal growth. Our simulation results thus suggest HPMCAS with higher acetyl and lower succinyl content is more effective in promoting phenytoin solubility in dissolution media, and polymers become less effective when drug loading becomes high (i.e., 50% of the mass of the polymer/drug solid dispersion), agreeing with previous experimental studies. In addition, our transport model indicates that the drug release time from a solid dispersion particle of 2 μm diameter is less than 10 min, correlating well with the experimental time scale for a typical dissolution profile to reach maximum peak concentration. Our modeling effort, therefore, provides new avenues to understand the dissolution behavior of complex HPMCAS-phenytoin solid dispersions and offers a new design tool to optimize the formulation. Moreover, the systematic and robust approach used in our computational models can be extended to other polymeric excipients and drug candidates.

Duloxetine HCl lipid nanoparticles: preparation, characterization, and dosage form design.

PubMed

Patel, Ketan; Padhye, Sameer; Nagarsenker, Mangal

2012-03-01

Solid lipid nanoparticles (SLNs) of duloxetine hydrochloride (DLX) were prepared to circumvent the problems of DLX, which include acid labile nature, high first-pass metabolism, and high-dosing frequency. The DLX-SLNs were prepared by using two different techniques, viz. solvent diffusion method and ultrasound dispersion method, and evaluated for particle size, zeta potential, entrapment efficiency, physical characteristics, and chemical stability. Best results were obtained when SLNs were prepared by ultrasound dispersion method using glyceryl mono stearate as solid lipid and DLX in ratio of 1:20 and mixture of polysorbate 80 and poloxamer 188 as surfactant in concentration of 3%. The mean particle size of formulation and entrapment efficiency was 91.7 nm and 87%, respectively, and had excellent stability in acidic medium. Differential scanning calorimetry and X-ray diffraction data showed complete amorphization of DLX in lipid. In vitro drug release from SLNs was observed for 48 h and was in accordance with Higuchi kinetics. In vivo antidepressant activity was evaluated in mice by forced swim test. DLX-SLNs showed significant enhancement in antidepressant activity at 24 h when administered orally in comparison to drug solution. These results confirm the potential of SLNs in enhancing chemical stability and improving the efficacy of DLX via oral route. The SLN dispersion was converted into solid granules by adsorbing on colloidal silicon dioxide and characterized for particle size after redispersion, morphology, and flow properties. Results indicated that nanoparticles were successfully adsorbed on the carrier and released SLNs when dispersed in water.

Solid polymer electrolyte composite membrane comprising a porous support and a solid polymer electrolyte including a dispersed reduced noble metal or noble metal oxide

DOEpatents

Liu, Han; Mittelsteadt, Cortney K; Norman, Timothy J; Griffith, Arthur E; LaConti, Anthony B

2015-02-24

A solid polymer electrolyte composite membrane and method of manufacturing the same. According to one embodiment, the composite membrane comprises a thin, rigid, dimensionally-stable, non-electrically-conducting support, the support having a plurality of cylindrical, straight-through pores extending perpendicularly between opposing top and bottom surfaces of the support. The pores are unevenly distributed, with some or no pores located along the periphery and more pores located centrally. The pores are completely filled with a solid polymer electrolyte, the solid polymer electrolyte including a dispersed reduced noble metal or noble metal oxide. The solid polymer electrolyte may also be deposited over the top and/or bottom surfaces of the support.

Dispersive Solid Phase Extraction for the Analysis of Veterinary Drugs Applied to Food Samples: A Review

PubMed Central

Islas, Gabriela; Hernandez, Prisciliano

2017-01-01

To achieve analytical success, it is necessary to develop thorough clean-up procedures to extract analytes from the matrix. Dispersive solid phase extraction (DSPE) has been used as a pretreatment technique for the analysis of several compounds. This technique is based on the dispersion of a solid sorbent in liquid samples in the extraction isolation and clean-up of different analytes from complex matrices. DSPE has found a wide range of applications in several fields, and it is considered to be a selective, robust, and versatile technique. The applications of dispersive techniques in the analysis of veterinary drugs in different matrices involve magnetic sorbents, molecularly imprinted polymers, carbon-based nanomaterials, and the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) method. Techniques based on DSPE permit minimization of additional steps such as precipitation, centrifugation, and filtration, which decreases the manipulation of the sample. In this review, we describe the main procedures used for synthesis, characterization, and application of this pretreatment technique and how it has been applied to food analysis. PMID:29181027

Revealing facts behind spray dried solid dispersion technology used for solubility enhancement

PubMed Central

Patel, Bhavesh B.; Patel, Jayvadan K.; Chakraborty, Subhashis; Shukla, Dali

2013-01-01

Poor solubility and bioavailability of an existing or newly synthesized drug always pose challenge in the development of efficient pharmaceutical formulation. Numerous technologies can be used to improve the solubility and among them amorphous solid dispersion based spray drying technology can be successfully useful for development of product from lab scale to commercial scale with a wide range of powder characteristics. Current review deals with the importance of spray drying technology in drug delivery, basically for solubility and bioavailability enhancement. Role of additives, selection of polymer, effect of process and formulation parameters, scale up optimization, and IVIVC have been covered to gain the interest of readers about the technology. Design of experiment (DoE) to optimize the spray drying process has been covered in the review. A lot more research work is required to evaluate spray drying as a technology for screening the right polymer for solid dispersion, especially to overcome the issue related to drug re-crystallization and to achieve a stable product both in vitro and in vivo. Based on the recent FDA recommendation, the need of the hour is also to adopt Quality by Design approach in the manufacturing process to carefully optimize the spray drying technology for its smooth transfer from lab scale to commercial scale. PMID:27134535

Revealing facts behind spray dried solid dispersion technology used for solubility enhancement.

PubMed

Patel, Bhavesh B; Patel, Jayvadan K; Chakraborty, Subhashis; Shukla, Dali

2015-09-01

Poor solubility and bioavailability of an existing or newly synthesized drug always pose challenge in the development of efficient pharmaceutical formulation. Numerous technologies can be used to improve the solubility and among them amorphous solid dispersion based spray drying technology can be successfully useful for development of product from lab scale to commercial scale with a wide range of powder characteristics. Current review deals with the importance of spray drying technology in drug delivery, basically for solubility and bioavailability enhancement. Role of additives, selection of polymer, effect of process and formulation parameters, scale up optimization, and IVIVC have been covered to gain the interest of readers about the technology. Design of experiment (DoE) to optimize the spray drying process has been covered in the review. A lot more research work is required to evaluate spray drying as a technology for screening the right polymer for solid dispersion, especially to overcome the issue related to drug re-crystallization and to achieve a stable product both in vitro and in vivo. Based on the recent FDA recommendation, the need of the hour is also to adopt Quality by Design approach in the manufacturing process to carefully optimize the spray drying technology for its smooth transfer from lab scale to commercial scale.

Determination of sulfonamides in livers using matrix solid-phase dispersion extraction high-performance liquid chromatography.

PubMed

Zhang, Yupu; Xu, Xu; Qi, Xiao; Gao, Wenquan; Sun, Shuo; Li, Xiaotian; Jiang, Chengfei; Yu, Aimin; Zhang, Hanqi; Yu, Yong

2012-01-01

The matrix solid-phase dispersion (MSPD) was applied for extracting seven sulfonamides (SAs) in liver samples. The separation and determination were carried out by high-performance liquid chromatography. The analytes were derivated with fluorescamine and detected with fluorescence detector. The types of dispersion adsorbents for MSPD were examined and the highest recovery was obtained when the diatomaceous earth was used as the dispersion adsorbent and the mass ratio of dispersion adsorbent to sample was 3:1. The acetone was used as the elution solvent. Under the optimal conditions, the linear range for determining the SAs in liver samples was 5.0-1000.0 ng/g. The porcine, chicken and cattle liver samples were analyzed and the average recoveries of seven SAs were higher than 84.6%. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Developing dissolution testing methodologies for extended-release oral dosage forms with supersaturating properties. Case example: Solid dispersion matrix of indomethacin.

PubMed

Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Mimura, Hisahi; Ozaki, Yukihiro; Reppas, Christos; Kitamura, Satoshi

2015-07-25

The objective of this study was to develop an in vitro dissolution test method with discrimination ability for an extended-release solid dispersion matrix of a lipophilic drug using the United States Pharmacopeia (USP) Apparatus 4, flow-through cell apparatus. In the open-loop configuration, the sink condition was maintained by manipulating the flow rate of the dissolution medium. To evaluate the testing conditions, the drug release mechanism from an extended-release solid dispersion matrix containing hydrophobic and hydrophilic polymers was investigated. As the hydroxypropyl methylcellulose (HPMC) maintained concentrations of indomethacin higher than the solubility in a dissolution medium, the release of HPMC into the dissolution medium was also quantified using size-exclusion chromatography. We concluded that the USP Apparatus 4 is suitable for application to an in vitro dissolution method for orally administered extended-release solid dispersion matrix formulations containing poorly water-soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Characterization of solid polymer dispersions of active pharmaceutical ingredients by 19F MAS NMR and factor analysis

NASA Astrophysics Data System (ADS)

Urbanova, Martina; Brus, Jiri; Sedenkova, Ivana; Policianova, Olivia; Kobera, Libor

In this contribution the ability of 19F MAS NMR spectroscopy to probe structural variability of poorly water-soluble drugs formulated as solid dispersions in polymer matrices is discussed. The application potentiality of the proposed approach is demonstrated on a moderately sized active pharmaceutical ingredient (API, Atorvastatin) exhibiting extensive polymorphism. In this respect, a range of model systems with the API incorporated in the matrix of polvinylpyrrolidone (PVP) was prepared. The extent of mixing of both components was determined by T1(1H) and T1ρ(1H) relaxation experiments, and it was found that the API forms nanosized domains. Subsequently it was found out that the polymer matrix induces two kinds of changes in 19F MAS NMR spectra. At first, this is a high-frequency shift reaching 2-3 ppm which is independent on molecular structure of the API and which results from the long-range polarization of the electron cloud around 19F nucleus induced by electrostatic fields of the polymer matrix. At second, this is broadening of the signals and formation of shoulders reflecting changes in molecular arrangement of the API. To avoid misleading in the interpretation of the recorded 19F MAS NMR spectra, because both the contributions act simultaneously, we applied chemometric approach based on multivariate analysis. It is demonstrated that factor analysis of the recorded spectra can separate both these spectral contributions, and the subtle structural differences in the molecular arrangement of the API in the nanosized domains can be traced. In this way 19F MAS NMR spectra of both pure APIs and APIs in solid dispersions can be directly compared. The proposed strategy thus provides a powerful tool for the analysis of new formulations of fluorinated pharmaceutical substances in polymer matrices.

Solubility enhancement of BCS Class II drug by solid phospholipid dispersions: Spray drying versus freeze-drying.

PubMed

Fong, Sophia Yui Kau; Ibisogly, Asiye; Bauer-Brandl, Annette

2015-12-30

The poor aqueous solubility of BCS Class II drugs represents a major challenge for oral dosage form development. Using celecoxib (CXB) as model drug, the current study adopted a novel solid phospholipid nanoparticle (SPLN) approach and compared the effect of two commonly used industrial manufacturing methods, spray- and freeze-drying, on the solubility and dissolution enhancement of CXB. CXB was formulated with Phospholipoid E80 (PL) and trehalose at different CXB:PL:trehalose ratios, of which 1:10:16 was the optimal formulation. Spherical amorphous SPLNs with average diameters <1μm were produced by spray-drying; while amorphous 'matrix'-like structures of solid PL dispersion with larger particle sizes were prepared by freeze-drying. Formulations from both methods significantly enhanced the dissolution rates, apparent solubility, and molecularly dissolved concentration of CXB in phosphate buffer (PBS, pH 6.5) and in biorelevant fasted state simulated intestinal fluid (FaSSIF, pH 6.5) (p<0.05). While similar dissolution rates were found, the spray-dried SPLNs had a larger enhancement in apparent solubility (29- to 132-fold) as well as molecular solubility (18-fold) of CXB at equilibrium (p<0.05). The strong capability of the spray-dried SPLNs to attain 'true' supersaturation state makes them a promising approach for bioavailability enhancement of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Optimization of the emulsification and solvent displacement method for the preparation of solid lipid nanoparticles.

PubMed

Noriega-Peláez, Eddy Kei; Mendoza-Muñoz, Néstor; Ganem-Quintanar, Adriana; Quintanar-Guerrero, David

2011-02-01

The essential aim of this article is to prepare solid lipid nanoparticles (SLNs) by emulsification and solvent displacement method and to determine the best process conditions to obtain submicron particles. The emulsification and solvent displacement method is a modification of the well-known emulsification-diffusion method, but without dilution of the system. The extraction of the partially water-miscible solvent from the emulsion globules is carried out under reduced pressure, which causes the diffusion of the solvent toward the external phase, with subsequent lipid aggregation in particles whose size will depend on the process conditions. The critical variables affecting the process, such as stirring rate, the proportion of phases in the emulsion, and the amount of stabilizer and lipid, were evaluated and optimized. By this method, it was possible to obtain a high yield of solids in the dispersion for the lipids evaluated (Compritol(®) ATO 888, Geleol(®), Gelucire(®) 44/14, and stearic acid). SLNs of up to ∼20 mg/mL were obtained for all lipids evaluated. A marked reduction in size, between 500 and 2500 rpm, was seen, and a transition from micro- to nanometric size was observed. The smaller particle sizes obtained were 113 nm for Compritol(®) ATO 888, 70 nm for Gelucire(®) 44/14, 210 nm for Geleol(®), and 527 nm for stearic acid, using a rotor-stator homogenizer (Ultra-Turrax(®)) at 16,000 rpm. The best phase ratio (organic/aqueous) was 1 : 2. The process proposed in this study is a new alternative to prepare SLNs with technological potential.

Enhanced chemoprophylactic and clinical efficacy of albendazole formulated as solid dispersions in experimental cystic echinococcosis.

PubMed

Pensel, Patricia E; Castro, Silvina; Allemandi, Daniel; Bruni, Sergio Sánchez; Palma, Santiago D; Elissondo, María Celina

2014-06-16

Cystic echinococcosis is a chronic, complex, and still neglected disease. Although albendazole has demonstrated efficacy, only about one-third of patients experience complete remission or cure and 30-50% of treated patients develop some evidence of a therapeutic response. Different strategies have been developed in order to improve the albendazole water solubility and dissolution rate. The aim of the current work was to investigate the chemoprophylactic and clinical efficacy of an albendazole:poloxamer 188 solid dispersion formulation on mice infected with Echinococcus granulosus metacestodes. Albendazole formulated as solid dispersion had greater chemoprophylactic and clinical efficacy than albendazole alone. The improved in therapeutic efficacy could be a consequence of the increase in the systemic availability of albendazole sulfoxide. The work reported here demonstrates that in vivo treatment with albendazole:poloxamer 188 impairs the development of the hydatid cysts. This new pharmacotechnically based strategy could be a suitable alternative for treating cystic echinococcosis in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

Amorphous solid dispersion of cyclosporine A prepared with fine droplet drying process: Physicochemical and pharmacokinetic characterization.

PubMed

Suzuki, Hiroki; Moritani, Tatsuru; Morinaga, Tadahiko; Seto, Yoshiki; Sato, Hideyuki; Onoue, Satomi

2017-03-15

The present study aimed to develop an amorphous solid dispersion (ASD) of cyclosporine A (CsA) by a fine droplet drying (FDD) process for improvement in oral absorption of CsA. CsA and hydroxypropyl cellulose-SSL were dissolved in 1,4-dioxane, and the solution was powdered by the FDD process to obtain the ASD formulation of CsA (ASD/CsA). The ASD/CsA was characterized in terms of morphology, particle size distribution, crystallinity, dissolution behavior, physicochemical stability, and pharmacokinetic behavior in rats. The ASD/CsA was obtained in the form of uniform spherical particles, and the span factor was calculated to be ca. 0.4. CsA in the formulation existed in an amorphous state. The ASD/CsA exhibited a higher dissolution behavior of CsA than amorphous CsA, whereas storage of the ASD/CsA under accelerated conditions led to impairment in the dissolution behavior. The constant release of CsA from non-aged ASD/CsA was observed during dissolution testing. After oral administration of CsA samples (10mg-CsA/kg) in rats, the ASD/CsA showed a high and sustained plasma concentration of CsA as evidenced by a 18-fold increase in the oral bioavailability of CsA compared with amorphous CsA. From these findings, the FDD process might be an efficacious option for the ASD formulation of CsA with enhanced biopharmaceutics properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhancing the bioavailability of mebendazole by integrating the principles solid dispersion and nanocrystal techniques, for safe and effective management of human echinococcosis.

PubMed

Chaudhary, Sushant; Garg, Tarun; Rath, Goutam; Murthy, Rs Rayasa; Goyal, Amit K

2016-05-01

The method based on integrating the principles of solid dispersion and nanocrystal techniques was developed to prepare polymer crystals (PCs) of mebendazole (MBZ) and polyethylene glycol (PEG). Powder X-Ray diffraction (PXRD) of the PC crystals shows the required integrated crystalline and amorphous regions. The in vitro solubility studies showed a 32-fold increase in the solubility of the drug. Tests of dissolution of the PCs showed that the crystals have an enhanced dissolution rate in comparison to those in the MF. The results of the pharmacokinetic study showed a 2.12-fold increase in the bioavailability of the drug. Thus, the present study has proved the potential in enhancing solubility, dissolution, and bioavailability of the drug.

Effect of storage conditions on the recrystallization of drugs in solid dispersions with crospovidone.

PubMed

Shibata, Yusuke; Fujii, Makiko; Suzuki, Ayako; Koizumi, Naoya; Kanada, Ken; Yamada, Masaki; Watanabe, Yoshiteru

2014-06-01

The physical stability of amorphous solid dispersions (SDs) is influenced by their storage conditions. The goal of this work was to investigate the factors affecting the recrystallization of drugs in SDs after storage under conditions of high temperature and high humidity. SDs of three drugs (dipyridamole, nifedipine and indomethacin) with different functional groups (amino, carbonyl and hydroxyl) and onset times for crystallization of the amorphous state were prepared using crospovidone (CrosPVP). All of the drugs in the SDs remained in an amorphous state at 25 °C/50% relative humidity (RH) in closed glass bottles for at least six months. Under conditions of high temperature (40 °C/75%RH/closed and 60 °C/open), differences in interactions between the hydrogen bond donors of the drugs and the amide carbonyl group of CrosPVP are essential factors for recrystallization of the drugs in the SDs. On the other hand, under condition of high humidity (40 °C/75%RH/open), in addition to the difference in the interaction between the drug and CrosPVP, the rate of increase in moisture content affects their recrystallization in SDs.

Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

PubMed

Barea, Silvana A; Mattos, Cristiane B; Cruz, Ariadne C C; Chaves, Vitor C; Pereira, Rafael N; Simões, Claudia M O; Kratz, Jadel M; Koester, Letícia S

2017-03-01

Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire ® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor ® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.

Role of the Strength of Drug-Polymer Interactions on the Molecular Mobility and Crystallization Inhibition in Ketoconazole Solid Dispersions.

PubMed

Mistry, Pinal; Mohapatra, Sarat; Gopinath, Tata; Vogt, Frederick G; Suryanarayanan, Raj

2015-09-08

The effects of specific drug-polymer interactions (ionic or hydrogen-bonding) on the molecular mobility of model amorphous solid dispersions (ASDs) were investigated. ASDs of ketoconazole (KTZ), a weakly basic drug, with each of poly(acrylic acid) (PAA), poly(2-hydroxyethyl methacrylate) (PHEMA), and polyvinylpyrrolidone (PVP) were prepared. Drug-polymer interactions in the ASDs were evaluated by infrared and solid-state NMR, the molecular mobility quantified by dielectric spectroscopy, and crystallization onset monitored by differential scanning calorimetry (DSC) and variable temperature X-ray diffractometry (VTXRD). KTZ likely exhibited ionic interactions with PAA, hydrogen-bonding with PHEMA, and weaker dipole-dipole interactions with PVP. On the basis of dielectric spectroscopy, the α-relaxation times of the ASDs followed the order: PAA > PHEMA > PVP. In addition, the presence of ionic interactions also translated to a dramatic and disproportionate decrease in mobility as a function of polymer concentration. On the basis of both DSC and VTXRD, an increase in strength of interaction translated to higher crystallization onset temperature and a decrease in extent of crystallization. Stronger drug-polymer interactions, by reducing the molecular mobility, can potentially delay the crystallization onset temperature as well as crystallization extent.

Matrix solid-phase dispersion coupled with homogeneous ionic liquid microextraction for the determination of sulfonamides in animal tissues using high-performance liquid chromatography.

PubMed

Wang, Zhibing; He, Mengyu; Jiang, Chunzhu; Zhang, Fengqing; Du, Shanshan; Feng, Wennan; Zhang, Hanqi

2015-12-01

Matrix solid-phase dispersion coupled with homogeneous ionic liquid microextraction was developed and applied to the extraction of some sulfonamides, including sulfamerazine, sulfamethazine, sulfathiazole, sulfachloropyridazine, sulfadoxine, sulfisoxazole, and sulfaphenazole, in animal tissues. High-performance liquid chromatography was applied to the separation and determination of the target analytes. The solid sample was directly treated by matrix solid-phase dispersion and the eluate obtained was treated by homogeneous ionic liquid microextraction. The ionic liquid was used as the extraction solvent in this method, which may result in the improvement of the recoveries of the target analytes. To avoid using organic solvent and reduce environmental pollution, water was used as the elution solvent of matrix solid-phase dispersion. The effects of the experimental parameters on recoveries, including the type and volume of ionic liquid, type of dispersant, ratio of sample to dispersant, pH value of elution solvent, volume of elution solvent, amount of salt in eluate, amount of ion-pairing agent (NH4 PF6 ), and centrifuging time, were evaluated. When the present method was applied to the analysis of animal tissues, the recoveries of the analytes ranged from 85.4 to 118.0%, and the relative standard deviations were lower than 9.30%. The detection limits for the analytes were 4.3-13.4 μg/kg. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of five pyrethroids in tea drinks by dispersive solid phase extraction with polyaniline-coated magnetic particles.

PubMed

Wang, Yuanpeng; Sun, Ying; Gao, Yan; Xu, Bo; Wu, Qiong; Zhang, Hanqi; Song, Daqian

2014-02-01

The polyaniline-coated magnetic particles with bowl-shaped morphology (Fe3O4/C/PANI microbowls) were successfully prepared and characterized by scanning electron microscopy, transmission electron microscopy and vibrating sample magnetometry. The prepared microbowls were used as the magnetic adsorbent in dispersive solid phase extraction of five pyrethroids, including cyhalothrin, beta-cypermethrin, esfenvalerate, permethrin and bifenthrin in plain tea drinks. The effects of experiment factors, including amount of Fe3O4/C/PANI microbowls, pH value, ultrasound extraction time and desorption conditions, were investigated. The extraction recoveries obtained with 8 mg of magnetic microbowls were satisfactory, and the microbowls can be reused after easy washing. Thus, a simple, selective and effective method for the determination of the pyrethroids was established successfully. The results showed that the method had good linearity (r=0.9992-0.9998), and the limits of detections (LODs) were from 0.025 to 0.032 ng mL(-1). The intra-day and inter-day relative standard deviations (RSDs) were in the range of 2.4-6.1% and 3.5-8.8%, respectively. Recoveries obtained by analyzing the real tea drinks were in the range of 72.1-118.4%. © 2013 Published by Elsevier B.V.

Plasmon dispersion in a multilayer solid torus in terms of three-term vector recurrence relations and matrix continued fractions

DOE PAGES

Garapati, K. V.; Bagherian, M.; Passian, A.; ...

2018-01-03

Toroidal confinement, which has played a crucial role in magnetized plasmas and Tokamak physics, is emerging as an effective means to obtain useful electronic and optical response in solids. In particular, excitation of surface plasmons in metal nanorings by photons or electrons finds important applications due to the engendered field distribution and electromagnetic energy confinement. However, in contrast to the case of a plasma, often the solid nanorings are multilayered and/or embedded in a medium. The non-simply connected geometry of the torus results in surface modes that are not linearly independent. A three-term difference equation was recently shown to arisemore » when seeking the nonretarded plasmon dispersion relations for a stratified solid torus (Garapati et al 2017 Phys. Rev. B 95 165422). The reported generalized plasmon dispersion relations are here investigated in terms of the involved matrix continued fractions and their convergence properties including the determinant forms of the dispersion relations obtained for computing the plasmon eigenmodes. We also present the intricacies of the derivation and properties of the Green's function employed to solve the three term amplitude equation that determines the response of the toroidal structure to arbitrary external excitations.« less

Plasmon dispersion in a multilayer solid torus in terms of three-term vector recurrence relations and matrix continued fractions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garapati, K. V.; Bagherian, M.; Passian, A.

Toroidal confinement, which has played a crucial role in magnetized plasmas and Tokamak physics, is emerging as an effective means to obtain useful electronic and optical response in solids. In particular, excitation of surface plasmons in metal nanorings by photons or electrons finds important applications due to the engendered field distribution and electromagnetic energy confinement. However, in contrast to the case of a plasma, often the solid nanorings are multilayered and/or embedded in a medium. The non-simply connected geometry of the torus results in surface modes that are not linearly independent. A three-term difference equation was recently shown to arisemore » when seeking the nonretarded plasmon dispersion relations for a stratified solid torus (Garapati et al 2017 Phys. Rev. B 95 165422). The reported generalized plasmon dispersion relations are here investigated in terms of the involved matrix continued fractions and their convergence properties including the determinant forms of the dispersion relations obtained for computing the plasmon eigenmodes. We also present the intricacies of the derivation and properties of the Green's function employed to solve the three term amplitude equation that determines the response of the toroidal structure to arbitrary external excitations.« less

Synergic effect of SDBS and GA to prepare stable dispersion of CNT in water for industrial heat transfer applications

NASA Astrophysics Data System (ADS)

Babita; Sharma, S. K.; Mital Gupta, Shipra

2018-05-01

Dispersion of hydrophobic carbon nanotubes in water is challenging. Herein, efforts have been made to study the dispersive effect of surface active agents on multi-walled carbon nanotubes (MWCNT). A method was developed to prepare a stable dispersion of MWCNT using sodium dodecyl benzene sulfonate (SDBS) and gum arabic (GA). Effect of ultrasonication time and surfactant concentration was also investigated. Compared to pure SDBS and GA based dispersion, their mixture was found to be effective to obtain a better dispersion of MWCNT, reflecting a synergistic effect of this mixture due to electrostatic and steric hindrance mechanism of surfactants. Rheology of CNT nanofluids showed the Newtonian behavior as viscosity was independent of shear rate. The viscosity of CNT nanofluids was higher than that of water. The thermal conductivity of dispersion was much higher than that of base fluid. This study provides the bases for using mixed surfactant system to disperse MWCNT in the polar base fluid to prepare nanofluids having enhanced thermal conductivity which can be used for heat transfer applications.

Sensitive determination of three aconitum alkaloids and their metabolites in human plasma by matrix solid-phase dispersion with vortex-assisted dispersive liquid-liquid microextraction and HPLC with diode array detection.

PubMed

Wang, Xiaozhong; Li, Xuwen; Li, Lanjie; Li, Min; Liu, Ying; Wu, Qian; Li, Peng; Jin, Yongri

2016-05-01

A simple and sensitive method for determination of three aconitum alkaloids and their metabolites in human plasma was developed using matrix solid-phase dispersion combined with vortex-assisted dispersive liquid-liquid microextraction and high-performance liquid chromatography with diode array detection. The plasma sample was directly purified by matrix solid-phase dispersion and the eluate obtained was concentrated and further clarified by vortex-assisted dispersive liquid-liquid microextraction. Some important parameters affecting the extraction efficiency, such as type and amount of dispersing sorbent, type and volume of elution solvent, type and volume of extraction solvent, salt concentration as well as sample solution pH, were investigated in detail. Under optimal conditions, the proposed method has good repeatability and reproducibility with intraday and interday relative standard deviations lower than 5.44 and 5.75%, respectively. The recoveries of the aconitum alkaloids ranged from 73.81 to 101.82%, and the detection limits were achieved within the range of 1.6-2.1 ng/mL. The proposed method offered the advantages of good applicability, sensitivity, simplicity, and feasibility, which makes it suitable for the determination of trace amounts of aconitum alkaloids in human plasma samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A solid state actuator based on polypyrrole (PPy) and a solid electrolyte NBR working in air

NASA Astrophysics Data System (ADS)

Cho, Misuk; Nam, Jaedo; Choi, Hyouk Ryeol; Koo, Jachoon; Lee, Youngkwan

2005-05-01

The solid polymer electrolyte based conducting polymer actuator was presented. In the preparation of acutuator module, an ionic liquid impregnated a synthetic rubber (NBR) and PPy were used as a solid polymer electrolyte and conducting polymer, respectively. An ionic liquid, 1-butyl-3-methylimidazolium bis (trifluoromethyl sulfonyl)imide (BMITFSI) is gradually dispersed into the NBR film and the conducting polymer, PPy was synthesized on the surface of NBR. The ionic conductivity of new type solid polymer electrolyte as a function of the immersion time was investigated. The cyclic voltammetry responsed and the redox switching dynamics of PEDOT in NBR matrix were studied. The displacement of the actuator was measured by laser beam.

Preparation and characterization of citral-loaded solid lipid nanoparticles.

PubMed

Tian, Huaixiang; Lu, Zhuoyan; Li, Danfeng; Hu, Jing

2018-05-15

Citral-loaded solid lipid nanoparticles (citral-SLNs) were prepared via a high-pressure homogenization method, using glyceryl monostearate (GMS) as the solid lipid and a mixture of Tween 80 (T-80) and Span 80 (S-80) at a weight ratio of 1:1 as the surfactant. The microstructure and properties of the citral-SLNs were characterized by dynamic light scattering (DLS), scanning electron microscopy (SEM), differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and thermal gravimetric analysis (TGA). The chemical stability of citral in the citral-SLNs was analyzed by solid-phase microextraction gas chromatography (SPME-GC). The GC results showed that 67.0% of the citral remained in the citral-SLN suspensions after 12 days, while only 8.22% remained in the control. Therefore, the encapsulation of citral in the solid lipid can enhance its stability in acidic surroundings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization and evaluation of 5-fluorouracil-loaded solid lipid nanoparticles prepared via a temperature-modulated solidification technique.

PubMed

Patel, Meghavi N; Lakkadwala, Sushant; Majrad, Mohamed S; Injeti, Elisha R; Gollmer, Steven M; Shah, Zahoor A; Boddu, Sai Hanuman Sagar; Nesamony, Jerry

2014-12-01

The aim of this research was to advance solid lipid nanoparticle (SLN) preparation methodology by preparing glyceryl monostearate (GMS) nanoparticles using a temperature-modulated solidification process. The technique was reproducible and prepared nanoparticles without the need of organic solvents. An anticancer agent, 5-fluorouracil (5-FU), was incorporated in the SLNs. The SLNs were characterized by particle size analysis, zeta potential analysis, differential scanning calorimetry (DSC), infrared spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM), drug encapsulation efficiency, in vitro drug release, and in vitro cell viability studies. Particle size of the SLN dispersion was below 100 nm, and that of redispersed lyophilizates was ~500 nm. DSC and infrared spectroscopy suggested that the degree of crystallinity did not decrease appreciably when compared to GMS. TEM and AFM images showed well-defined spherical to oval particles. The drug encapsulation efficiency was found to be approximately 46%. In vitro drug release studies showed that 80% of the encapsulated drug was released within 1 h. In vitro cell cultures were biocompatible with blank SLNs but demonstrated concentration-dependent changes in cell viability to 5-FU-loaded SLNs. The 5-FU-loaded SLNs can potentially be utilized in an anticancer drug delivery system.

Improved intestinal absorption of a poorly water-soluble oral drug using mannitol microparticles containing a nanosolid drug dispersion.

PubMed

Nishino, Yukiko; Kubota, Aya; Kanazawa, Takanori; Takashima, Yuuki; Ozeki, Tetsuya; Okada, Hiroaki

2012-11-01

A nozzle for a spray dryer that can prepare microparticles of water-soluble carriers containing various nanoparticles in a single step was previously developed in our laboratory. To enhance the solubility and intestinal absorption of poorly water-soluble drugs, we used probucol (PBL) as a poorly water-soluble drug, mannitol (MAN) as a water-soluble carrier for the microparticles, and EUDRAGIT (EUD) as a polymer vehicle for the solid dispersion. PBL-EUD-acetone-methanol and aqueous MAN solutions were simultaneously supplied through different liquid passages of the spray nozzle and dried together. PBL-EUD solid dispersion was nanoprecipitated in the MAN solution using an antisolvent mechanism and rapidly dried by surrounding it with MAN. PBL in the dispersion vehicle was amorphous and had higher physical stability according to powder X-ray diffraction and differential scanning calorimetry analysis. The bioavailability of PBL in PBL-EUD S-100-MAN microparticles after oral administration in rats was markedly higher (14- and 6.2-fold, respectively) than that of the original PBL powder and PBL-MAN microparticles. These results demonstrate that the composite microparticles containing a nanosized solid dispersion of a poorly water-soluble drug prepared using the spray nozzle developed by us should be useful to increase the solubility and bioavailability of drugs after oral administration. Copyright © 2012 Wiley Periodicals, Inc.

Extraction of acetanilides in rice using ionic liquid-based matrix solid phase dispersion-solvent flotation.

PubMed

Zhang, Liyuan; Wang, Changyuan; Li, Zuotong; Zhao, Changjiang; Zhang, Hanqi; Zhang, Dongjie

2018-04-15

Ionic liquid-based matrix solid phase dispersion-solvent flotation coupled with high performance liquid chromatography was developed for the determination of the acetanilide herbicides, including metazachlor, propanil, alachlor, propisochlor, pretilachlor, and butachlor in rice samples. Some experimental parameters, including the type of dispersant, the mass ratio of dispersant to sample, pH of sample solution, the type of extraction solvent, the type of ionic liquid, flotation time, and flow rate of N 2 were optimized. The average recoveries of the acetanilide herbicides at spiked concentrations of 50, 125, and 250 µg/kg ranged from 89.4% to 108.7%, and relative standard deviations were equal to or lower than 7.1%, the limits of quantification were in the range of 38.0 to 84.7 µg/kg. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of Phase Mixing in Amorphous Solid Dispersions of AMG 517 in HPMC-AS Using DSC, Solid-State NMR, and Solution Calorimetry.

PubMed

Calahan, Julie L; Azali, Stephanie C; Munson, Eric J; Nagapudi, Karthik

2015-11-02

Intimate phase mixing between the drug and the polymer is considered a prerequisite to achieve good physical stability for amorphous solid dispersions. In this article, spray dried amorphous dispersions (ASDs) of AMG 517 and HPMC-as were studied by differential scanning calorimetry (DSC), solid-state NMR (SSNMR), and solution calorimetry. DSC analysis showed a weakly asymmetric (ΔTg ≈ 13.5) system with a single glass transition for blends of different compositions indicating phase mixing. The Tg-composition data was modeled using the BKCV equation to accommodate the observed negative deviation from ideality. Proton spin-lattice relaxation times in the laboratory and rotating frames ((1)H T1 and T1ρ), as measured by SSNMR, were consistent with the observation that the components of the dispersion were in intimate contact over a 10-20 nm length scale. Based on the heat of mixing calculated from solution calorimetry and the entropy of mixing calculated from the Flory-Huggins theory, the free energy of mixing was calculated. The free energy of mixing was found to be positive for all ASDs, indicating that the drug and polymer are thermodynamically predisposed to phase separation at 25 °C. This suggests that miscibility measured by DSC and SSNMR is achieved kinetically as the result of intimate mixing between drug and polymer during the spray drying process. This kinetic phase mixing is responsible for the physical stability of the ASD.

Type of oral solid medication packaging and medication preparation time in nursing homes: A direct observation study.

PubMed

Cready, C M; Hudson, C; Dreyer, K

2017-12-01

Medication administration is a substantial portion of the workday in nursing homes, with the medication preparation step being the most time-consuming. However, little is known about how medication preparation time is affected by the type of packaging used for oral solid medications (ie, tablets/capsules). We examined the effects of two types of packaging. As fewer steps are associated with strip packaging compared to bingo card packaging, we hypothesized that the increase in medication preparation seconds per resident with each additional oral solid medication would be smaller when strip packaging was used. A total of 430 medication preparations conducted by eight nurses during the regularly scheduled morning medication administration period in two nursing homes-using strip packaging and bingo card packaging, respectively-were observed. Each medication preparation observation was matched to its corresponding medication administration record and observations averaged across resident. Using the resident sample (N=149), we estimated three regression models (adjusting the standard errors for the clustering of resident by nurse). The first model regressed medication preparation seconds on the number of oral solid medications. The second model added the type of packaging used and the control variables (type of unit [long-term care, post-acute care], the number of one-half pills and the dosage form diversity in the preparation). To test our hypothesis, the third model added an interaction term between the number of oral solid medications and the type of packaging used. As hypothesized, all else equal, the number of oral solid medications tended to increase medication preparation time per resident in both nursing homes, but the increase was smaller in the strip packaging nursing home (P<.05). Each additional oral solid medication in the bingo card packaging nursing home increased medication preparation by an average of 13 seconds (b=13.077), whereas each oral solid

Water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) amorphous solid dispersions: Insights with confocal fluorescence microscopy.

PubMed

Saboo, Sugandha; Taylor, Lynne S

2017-08-30

The aim of this study was to evaluate the utility of confocal fluorescence microscopy (CFM) to study the water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) (mico-PVPVA) amorphous solid dispersions (ASDs), induced during preparation, upon storage at high relative humidity (RH) and during dissolution. Different fluorescent dyes were added to drug-polymer films and the location of the dyes was evaluated using CFM. Orthogonal techniques, in particular atomic force microscopy (AFM) coupled with nanoscale infrared spectroscopy (AFM-nanoIR), were used to provide additional analysis of the drug-polymer blends. The initial miscibility of mico-PVPVA ASDs prepared under low humidity conditions was confirmed by AFM-nanoIR. CFM enabled rapid identification of drug-rich and polymer-rich phases in phase separated films prepared under high humidity conditions. The identity of drug- and polymer-rich domains was confirmed using AFM-nanoIR imaging and localized IR spectroscopy, together with Lorentz contact resonance (LCR) measurements. The CFM technique was then utilized successfully to further investigate phase separation in mico-PVPVA films exposed to high RH storage and to visualize phase separation dynamics following film immersion in buffer. CFM is thus a promising new approach to study the phase behavior of ASDs, utilizing drug and polymer specific dyes to visualize the evolution of heterogeneity in films exposed to water. Copyright © 2017 Elsevier B.V. All rights reserved.

Dissolution enhancement of a drug exhibiting thermal and acidic decomposition characteristics by fusion processing: a comparative study of hot melt extrusion and KinetiSol dispersing.

PubMed

Hughey, Justin R; DiNunzio, James C; Bennett, Ryan C; Brough, Chris; Miller, Dave A; Ma, Hua; Williams, Robert O; McGinity, James W

2010-06-01

In this study, hot melt extrusion (HME) and KinetiSol Dispersing (KSD) were utilized to prepare dissolution-enhanced solid dispersions of Roche Research Compound A (ROA), a BCS class II drug. Preformulation characterization studies showed that ROA was chemically unstable at elevated temperatures and acidic pH values. Eudragit L100-55 and AQOAT LF (HPMCAS) were evaluated as carrier polymers. Dispersions were characterized for ROA recovery, crystallinity, homogeneity, and non-sink dissolution. Eudragit L100-55 dispersions prepared by HME required the use of micronized ROA and reduced residence times in order to become substantially amorphous. Compositions containing HPMCAS were also prepared by HME, but an amorphous dispersion could not be obtained. All HME compositions contained ROA-related impurities. KSD was investigated as a method to reduce the decomposition of ROA while rendering compositions amorphous. Substantially amorphous, plasticizer free compositions were processed successfully by KSD with significantly higher ROA recovery values and amorphous character than those achieved by HME. A near-infrared chemical imaging analysis was conducted on the solid dispersions as a measure of homogeneity. A statistical analysis showed similar levels of homogeneity in compositions containing Eudragit L100-55, while differences were observed in those containing HMPCAS. Non-sink dissolution analysis of all compositions showed rapid supersaturation after pH adjustment to approximately two to three times the equilibrium solubility of ROA, which was maintained for at least 24 h. The results of the study demonstrated that KSD is an effective method of forming dissolution-enhanced amorphous solid solutions in cases where HME is not a feasible technique.

Preparation of CNC-dispersed Fe3O4 nanoparticles and their application in conductive paper.

PubMed

Liu, Kai; Nasrallah, Joseph; Chen, Lihui; Huang, Liulian; Ni, Yonghao

2015-08-01

Well-dispersed Fe3O4 nanoparticles (NPs) were synthesized by a co-precipitation method in the presence of cellulose nano-crystals (CNC) as the template. The thus prepared Fe3O4 NPs were then used as a coating agent for the preparation of conductive paper. Fourier transform infrared spectroscopy (FTIR) results revealed that the Fe3O4 NPs were immobilized on the CNC through interactions between the hydroxyl groups of CNC and Fe3O4. Scanning transmission electron microscopy (STEM) images showed that the Fe3O4 NPs prepared in the presence of CNC can be dispersed in the CNC network, while the Fe3O4 NPs prepared in the absence of CNC tended to aggregate in aqueous solutions. The conductivity of the Fe3O4 NPs coated paper can reach to 0.0269 S/m at the coating amount of 14.75 g/m(2) Fe3O4/CNC nanocomposites. Therefore, the thus obtained coated paper can be potentially used as anti-static packaging material in the packaging field. Copyright © 2015 Elsevier Ltd. All rights reserved.

One-Step Extraction and Hydrolysis of Flavonoid Glycosides in Rape Bee Pollen Based on Soxhlet-Assisted Matrix Solid Phase Dispersion.

PubMed

Tu, Xijuan; Ma, Shuangqin; Gao, Zhaosheng; Wang, Jing; Huang, Shaokang; Chen, Wenbin

2017-11-01

Flavonoids are frequently found as glycosylated derivatives in plant materials. To determine contents of flavonoid aglycones in these matrices, procedures for the extraction and hydrolysis of flavonoid glycosides are required. The current sample preparation method is both labour and time consuming. Develop a modified matrix solid phase dispersion (MSPD) procedure as an alternative methodology for the one-step extraction and hydrolysis of flavonoid glycosides. HPLC-DAD was applied for demonstrating the one-step extraction and hydrolysis of flavonoids in rape bee pollen. The obtained contents of flavonoid aglycones (quercetin, kaempferol, isorhamnetin) were used for the optimisation and validation of the method. The extraction and hydrolysis were accomplished in one step. The procedure completes in 2 h with silica gel as dispersant, a 1:2 ratio of sample to dispersant, and 60% aqueous ethanol with 0.3 M hydrochloric acid as the extraction solution. The relative standard deviations (RSDs) of repeatability were less than 5%, and the recoveries at two fortified levels were between 88.3 and 104.8%. The proposed methodology is simple and highly efficient, with good repeatability and recovery. Compared with currently available methods, the present work has advantages of using less time and labour, higher extraction efficiency, and less consumption of the acid catalyst. This method may have applications for the one-step extraction and hydrolysis of bioactive compounds from plant materials. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Amorphization of thiamine chloride hydrochloride: A study of the crystallization inhibitor properties of different polymers in thiamine chloride hydrochloride amorphous solid dispersions.

PubMed

Arioglu-Tuncil, Seda; Bhardwaj, Vivekanand; Taylor, Lynne S; Mauer, Lisa J

2017-09-01

Amorphous solid dispersions of thiamine chloride hydrochloride (THCl) were created using a variety of polymers with different physicochemical properties in order to investigate how effective the various polymers were as THCl crystallization inhibitors. THCl:polymer dispersions were prepared by lyophilizing solutions of THCl and amorphous polymers (guar gum, pectin, κ-carrageenan, gelatin, and polyvinylpyrrolidone (PVP)). These dispersions were stored at select temperature (25 and 40°C) and relative humidity (0, 23, 32, 54, 75, and 85% RH) conditions and monitored at different time points using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Moisture sorption isotherms of all samples were also obtained. Initially amorphous THCl was produced in the presence of ≥40% w/w pectin, κ-carrageenan, gelatin, and guar gum or ≥60% w/w PVP. Trends in polymer THCl crystallization inhibition (pectin≥κ-carrageenan>gelatin>guar gum≫PVP) were primarily based on the ability of the polymer to interact with THCl via hydrogen bonding and/or ionic interactions. The onset of THCl crystallization from the amorphous dispersions was also related to storage conditions. THCl remained amorphous at low RH conditions (0 and 23% RH) in all 1:1 dispersions except THCl:PVP. THCl crystallized in some dispersions below the glass transition temperature (T g ) but remained amorphous in others at T~T g . At high RHs (75 and 85% RH), THCl crystallized within one day in all samples. Given the ease of THCl amorphization in the presence of a variety of polymers, even at higher vitamin concentrations than would be found in foods, it is likely that THCl is amorphous in many low moisture foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effect of particle size of drug on conversion of crystals to an amorphous state in a solid dispersion with crospovidone.

PubMed

Sugamura, Yuka; Fujii, Makiko; Nakanishi, Sayaka; Suzuki, Ayako; Shibata, Yusuke; Koizumi, Naoya; Watanabe, Yoshiteru

2011-01-01

The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1 µm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds. © 2011 Pharmaceutical Society of Japan

Iron oxide functionalized graphene nano-composite for dispersive solid phase extraction of chemical warfare agents from aqueous samples.

PubMed

Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Goud, D Raghavender; Dubey, D K; Pardasani, Deepak

2015-05-15

Present study deals with the preparation and evaluation of graphene based magnetic nano-composite for dispersive solid phase extraction of Chemical Weapons Convention (CWC) relevant chemicals from aqueous samples. Nano-composite, Fe3O4@SiO2-G was synthesized by covalently bonding silica coated Fe3O4 onto the graphene sheets. Nerve agents (NA), Sulfur mustard (SM) and their non-toxic environmental markers were the target analytes. Extraction parameters like amount of sorbent, extraction time and desorption conditions were optimized. Dispersion of 20 milligram of sorbent in 200mL of water sample for 20min. followed by methanol/chloroform extraction produced average to good recoveries (27-94%) of targeted analytes. Recoveries of real agents exhibited great dependency upon sample pH and ionic strength. Sarin produced maximum recovery under mild acidic conditions (56% at pH 5) while VX demanded alkaline media (83% at pH 9). Salts presence in the aqueous samples was found to be advantageous, raising the recoveries to as high as 94% for SM. Excellent limits of detection (LOD) for sulphur mustard and VX (0.11ngmL(-1) and 0.19ngmL(-1) respectively) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals. Copyright © 2015 Elsevier B.V. All rights reserved.

A matrix solid-phase dispersion method for the extraction of seven pesticides from mango and papaya.

PubMed

Navickiene, Sandro; Aquino, Adriano; Bezerra, Débora Santos Silva

2010-10-01

A simple and effective extraction method based on matrix solid-phase dispersion was developed to determine trichlorfon, pyrimethanil, methyl parathion, tetraconazole, thiabendazole, imazalil, and tebuconazole in papaya and mango using gas chromatography-mass spectrometry with selected ion monitoring. Different parameters of the method were evaluated, such as type of solid-phase (silica-gel, neutral alumina, and Florisil), the amount of solid-phase, and eluent [dichloromethane, ethyl acetate-dichloromethane (4:1, 1:4, 1:1, 2:3, v/v)]. The best results were obtained using 2.0 g of mango or papaya, 3.0 g of silica as dispersant sorbent, and ethyl acetate-dichloromethane (1:1, v/v) as eluting solvent. The method was validated using mango and papaya samples fortified with pesticides at different concentration levels (0.05, 0.10, and 1.0 mg/kg). Average recoveries (4 replicates) ranged from 80% to 146%, with relative standard deviations between 1.0% and 28%. Detection and quantification limits for mango and papaya ranged from 0.01 to 0.03 mg/kg and 0.05 to 0.10 mg/kg, respectively. The proposed method was applied to the analysis of these compounds in commercial fruit samples from a local market (Aracaju/SE, Brazil), and residues of the pesticides were not detected on the samples.

Current trends in sample preparation for cosmetic analysis.

PubMed

Zhong, Zhixiong; Li, Gongke

2017-01-01

The widespread applications of cosmetics in modern life make their analysis particularly important from a safety point of view. There is a wide variety of restricted ingredients and prohibited substances that primarily influence the safety of cosmetics. Sample preparation for cosmetic analysis is a crucial step as the complex matrices may seriously interfere with the determination of target analytes. In this review, some new developments (2010-2016) in sample preparation techniques for cosmetic analysis, including liquid-phase microextraction, solid-phase microextraction, matrix solid-phase dispersion, pressurized liquid extraction, cloud point extraction, ultrasound-assisted extraction, and microwave digestion, are presented. Furthermore, the research and progress in sample preparation techniques and their applications in the separation and purification of allowed ingredients and prohibited substances are reviewed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simultaneous determination of fumonisins B1 and B2 in different types of maize by matrix solid phase dispersion and HPLC-MS/MS.

PubMed

de Oliveira, Gabriel Barros; de Castro Gomes Vieira, Carolyne Menezes; Orlando, Ricardo Mathias; Faria, Adriana Ferreira

2017-10-15

This work involved the optimization and validation of a method, according to Directive 2002/657/EC and the Analytical Quality Assurance Manual of Ministério da Agricultura, Pecuária e Abastecimento, Brazil, for simultaneous extraction and determination of fumonisins B1 and B2 in maize. The extraction procedure was based on a matrix solid phase dispersion approach, the optimization of which employed a sequence of different factorial designs. A liquid chromatography-tandem mass spectrometry method was developed for determining these analytes using the selected reaction monitoring mode. The optimized method employed only 1g of silica gel for dispersion and elution with 70% ammonium formate aqueous buffer (50mmolL -1 , pH 9), representing a simple, cheap and chemically friendly sample preparation method. Trueness (recoveries: 86-106%), precision (RSD ≤19%), decision limits, detection capabilities and measurement uncertainties were calculated for the validated method. The method scope was expanded to popcorn kernels, white maize kernels and yellow maize grits. Copyright © 2017 Elsevier Ltd. All rights reserved.

Electrostatic stabilization of multi-walled carbon nanotubes dispersed in nonaqueous media.

PubMed

Damasceno, João Paulo V; Zarbin, Aldo J G

2018-06-04

Dispersing carbon nanotubes is an easy and low-cost way to manipulate these solids and allows the preparation of more complex materials or devices, so it is fundamental for further uses that these dispersions have controlled properties and high colloidal stability. In this work we report the spontaneous electrical charge build-up in pristine multi-walled carbon nanotubes dispersed in common organic solvents such as chloroform and tetrahydrofuran and the achievement of dispersions stable for long periods without adding passivant agents or functional groups on nanotubes surface. Results from electrokinetics, homo- and heterocoagulation provided macroscopic evidences that carbon nanotubes acquire electric charges after dispersion in some organic liquids and we confirmed this process by measuring in situ Raman spectra of the nanotubes dispersions with higher surface electric potentials. We also show that the signal of electric potential of the dispersions can be predicted by the acid-base behaviour of the dispersing medium, corroborating previously reports for other dispersions of carbon nanomaterials. Copyright © 2018 Elsevier Inc. All rights reserved.

Preparation of surfactant-free nanoparticles of methacrylic acid copolymers used for film coating.

PubMed

Nguyen, Cung An; Konan-Kouakou, Yvette Niamien; Allémann, Eric; Doelker, Eric; Quintanar-Guerrero, David; Fessi, Hatem; Gurny, Robert

2006-07-28

The aim of the present study was to prepare surfactant-free pseudolatexes of various methacrylic acid copolymers. These aqueous colloidal dispersions of polymeric materials for oral administration are intended for film coating of solid dosage forms or for direct manufacturing of nanoparticles. Nanoparticulate dispersions were produced by an emulsification-diffusion method involving the use of partially water-miscible solvents and the mutual saturation of the aqueous and organic phases prior to the emulsification in order to reduce the initial thermodynamic instability of the emulsion. Because of the self-emulsifying properties of the methacrylic acid copolymers, it was possible to prepare aqueous dispersions of colloidal size containing up to 30% wt/vol of Eudragit RL, RS, and E using 2-butanone or methyl acetate as partially water-miscible solvents, but without any surfactant. However, in the case of the cationic Eudragit E, protonation of the tertiary amine groups by acidification of the aqueous phase was necessary to improve the emulsion stability in the absence of surfactant and subsequently to prevent droplet coalescence during evaporation. In addition, a pseudolatex of Eudragit E was used to validate the coating properties of the formulation for solid dosage forms. Film-coated tablets of quinidine sulfate showed a transparent glossy continuous film that was firmly attached to the tablet. The dissolution profile of quinidine sulfate from the tablets coated with the Eudragit E pseudolatex was comparable to that of tablets coated with an acetonic solution of Eudragit E. Furthermore, both types of coating ensured similar taste masking. The emulsification-evaporation method used was shown to be appropriate for the preparation of surfactant-free colloidal dispersions of the 3 types of preformed methacrylic acid copolymers; the dispersions can subsequently be used for film coating of solid dosage forms.

Lubricant-Induced Crystallization of Itraconazole From Tablets Made of Electrospun Amorphous Solid Dispersion.

PubMed

Démuth, Balázs; Farkas, Attila; Balogh, Attila; Bartosiewicz, Karolina; Kállai-Szabó, Barnabás; Bertels, Johny; Vigh, Tamás; Mensch, Jurgen; Verreck, Geert; Van Assche, Ivo; Marosi, György; Nagy, Zsombor K

2016-09-01

Investigation of downstream processing of nanofibrous amorphous solid dispersions to generate tablet formulation is in a quite early phase. Development of high speed electrospinning opened up the possibility to study tableting of electrospun solid dispersions (containing polyvinylpyrrolidone-vinyl acetate and itraconazole [ITR] in this case). This work was conducted to investigate the influence of excipients on dissolution properties and the feasibility of scaled-up rotary press tableting. The dissolution rates from tablets proved to be mainly composition dependent. Magnesium stearate acted as a nucleation promoting agent (providing an active hydrophobic environment for crystallization of ITR) hindering the total dissolution of ITR. This crystallization process proved to be temperature dependent as well. However, the extent of dissolution of more than 95% was realizable when a less hydrophobic lubricant, sodium stearyl fumarate (soluble in the medium), was applied. Magnesium stearate induced crystallization even if it was put in the dissolution medium next to proper tablets. After optimization of the composition, scaled-up tableting on a rotary press was carried out. Appropriate dissolution of ITR from tablets was maintained for 3 months at 25°C/60% relative humidity. HPLC measurements confirmed that ITR was chemically stable both in the course of downstream processing and storage. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Characterization and enhanced nonlinear optical limiting response in carbon nanodots dispersed in solid-state hybrid organically modified silica gel glasses

NASA Astrophysics Data System (ADS)

Huang, Li; Zheng, Chan; Guo, Qiaohang; Huang, Dongdong; Wu, Xiukai; Chen, Ling

2018-02-01

Freely dispersed carbon nanodots (CNDs) were introduced into a 3-glycidoxy-propyltrimethoxysilane modified silicate gel glass (i.e. an organically modified silica or ORMOSIL) by a highly efficient and simple sol-gel process, which could be easily extended to prepare functional molecules/nanoparticles solid state optoelectronic devices. Scanning electron microscope imaging, Fourier transform infrared spectroscopy, pore structure measurements, ultraviolet-visible spectroscopy, and fluorescence spectroscopy were used to investigate the surface characteristics, structure, texture, and linear optical properties of the CND/SiO2 ORMOSIL gel glasses. Images and UV/Vis spectra confirmed the successful dispersion of CNDs in the ORMOSIL gel glass. The surface characteristics and pore structure of the host SiO2 matrix were markedly changed through the introduction of the CNDs. The linear optical properties of the guest CNDs were also affected by the sol-gel procedure. The nonlinear optical (NLO) properties of the CNDs were investigated by a nanosecond open-aperture Z-scan technique at 532 nm both in liquid and solid matrices. We found that the NLO response of the CNDs was considerably improved after their incorporation into the ORMOSIL gel glasses. Possible enhancement mechanisms were also explored. The nonlinear extinction coefficient gradually increased while the optical limiting (OL) threshold decreased as the CND doping level was increased. This result suggests that the NLO and OL properties of the composite gel glasses can be optimized by tuning the concentration of CNDs in the gel glass matrix. Our findings show that CND/SiO2 ORMOSIL gel glasses are promising candidates for optical limiters to protect sensitive instruments and human eyes from damage caused by high power lasers.

Development of micro-fibrous solid dispersions of poorly water-soluble drugs in sucrose using temperature-controlled centrifugal spinning.

PubMed

Marano, Stefania; Barker, Susan Anne; Raimi-Abraham, Bahijja Tolulope; Missaghi, Shahrzad; Rajabi-Siahboomi, Ali; Craig, Duncan Q M

2016-06-01

Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug-sucrose interaction assessment were measured. Scanning electron microscopy revealed that bead-free drug-loaded microfibers with homogenous morphology and diameter in the range of a few micrometers were prepared using our process. Differential scanning calorimetric and X-ray diffraction analyses showed that both drug and carrier were present in the amorphous state in the microfibers, although in the case of piroxicam-loaded microfibers, the presence of small amounts of crystalline drug was observed under polarized light microscopy and in Fourier transform infrared spectra. Drug dissolution performance was evaluated under both sink and non-sink conditions and was found to be significantly enhanced compared to the corresponding crystalline physical mixtures and pure drugs, with evidence of supersaturation behavior noted under non-sink conditions. This study has demonstrated that microfiber-based dispersions may be manufactured by the centrifugal spinning process and may possess characteristics that are favorable for the enhanced dissolution and oral absorption of drugs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Variation in Supersaturation and Phase Behavior of Ezetimibe Amorphous Solid Dispersions upon Dissolution in Different Biorelevant Media.

PubMed

Elkhabaz, Ahmed; Sarkar, Sreya; Dinh, Janny K; Simpson, Garth J; Taylor, Lynne S

2018-01-02

The delivery of poorly water-soluble drugs using amorphous solid dispersions (ASDs) has been widely acknowledged as a promising strategy for enhancing oral bioavailability. Upon dissolution, ASDs have accelerated dissolution rates and yield supersaturated solutions leading to higher apparent solubilities. Understanding the complex phase behavior of ASDs during dissolution is crucial for developing an effective formulation. Since the absorption of a lipophilic, high permeability drug is determined primarily by the intraluminal dissolution process and the final concentration achieved, there is a need for evaluation in biorelevant dissolution media that simulate both fasting and fed gastrointestinal states. In this study, using ezetimibe as a model drug, three different ASDs were prepared using poly(acrylic acid) (PAA), polyvinylpyrrolidone (PVP), and hydroxypropyl methylcellulose acetyl succinate (HPMC-AS). Dissolution of ASDs was carried out in sodium phosphate buffer, fed-state simulated intestinal fluid (FeSSIF), and Ensure Plus to evaluate the impact of different dissolution media on release profile, supersaturation, and phase behavior. The supersaturation level and crystallization kinetics varied among the dispersions and were found to be highly dependent on the medium employed. The presence of solubilizing additives in biorelevant media greatly affected the generation and stabilization of supersaturated solutions. Second harmonic generation microscopy was found to enable the detection of crystals in all media including the highly turbid Ensure Plus system. In conclusion, it is important to evaluate the impact of complex biorelevant media on the dissolution performance of ASDs to better design supersaturating formulations for oral delivery.

Functionalized metal-organic framework nanocomposites for dispersive solid phase extraction and enantioselective capture of chiral drug intermediates.

PubMed

Ma, Xue; Zhou, Xiaohua; Yu, Ajuan; Zhao, Wuduo; Zhang, Wenfen; Zhang, Shusheng; Wei, Linlin; Cook, Debra J; Roy, Anirban

2018-02-16

The facile preparation, characterization and application of a novel magnetic graphene oxide- metal organic framework [Zn 2 (d-Cam) 2 (4, 4'-bpy)] n (MGO-ZnCB) as a sorbent for fast, simple and enantioselective capture of chiral drug intermediates are presented in this paper. The MGO-ZnCB nanocomposite, developed by encapsulating MGO nanoparticles into the homochiral metal organic framework of ZnCB, can integrate the advantages from each component endowing the hybrids with improved synergystic effects. The enantioselective performance of MGO-ZnCB was evaluated by dispersive magnetic nanoparticle solid phase extraction (d-MNSPE) of 1, 1'-bi-2-naphthol (BN) and 2, 2'-furoin (Furoin) racemic solutions. Due to the excellent dispersive capability, high stability, relatively larger saturation magnetization and distinct enrichment capacity of MGO-ZnCB, the d-MNSPE method provids good enantioselective separation of these compounds with enantiomeric excess (ee) values as high as 74.8% and 57.4%, respectively. The entire process with BN or Furoin can be completed within 3 min or less. After washing with methanol, the host MGO-ZnCB can be easily recycled and reused six times without any apparent loss of performance. Furthermore, the adsorbed BN and Furoin in nanodomains of the MGO-ZnCB composite were directly investigated for the first time by atomic force microscopy-infrared (AFM-IR) technique. Copyright © 2017 Elsevier B.V. All rights reserved.

Novel strategies for sample preparation in forensic toxicology.

PubMed

Samanidou, Victoria; Kovatsi, Leda; Fragou, Domniki; Rentifis, Konstantinos

2011-09-01

This paper provides a review of novel strategies for sample preparation in forensic toxicology. The review initially outlines the principle of each technique, followed by sections addressing each class of abused drugs separately. The novel strategies currently reviewed focus on the preparation of various biological samples for the subsequent determination of opiates, benzodiazepines, amphetamines, cocaine, hallucinogens, tricyclic antidepressants, antipsychotics and cannabinoids. According to our experience, these analytes are the most frequently responsible for intoxications in Greece. The applications of techniques such as disposable pipette extraction, microextraction by packed sorbent, matrix solid-phase dispersion, solid-phase microextraction, polymer monolith microextraction, stir bar sorptive extraction and others, which are rapidly gaining acceptance in the field of toxicology, are currently reviewed.

Simultaneous determination and qualitative analysis of six types of components in Naoxintong capsule by miniaturized matrix solid-phase dispersion extraction coupled with ultra high-performance liquid chromatography with photodiode array detection and quadrupole time-of-flight mass spectrometry.

PubMed

Wang, Huilin; Jiang, Yan; Ding, Mingya; Li, Jin; Hao, Jia; He, Jun; Wang, Hui; Gao, Xiu-Mei; Chang, Yan-Xu

2018-02-03

A simple and effective sample preparation process based on miniaturized matrix solid-phase dispersion was developed for simultaneous determination of phenolic acids (gallic acid, chlorogenic acid, ferulic acid, 3,5-dicaffeoylqunic acid, 1,5-dicaffeoylqunic acid, rosmarinic acid, lithospermic acid, and salvianolic acid B), flavonoids (kaempferol-3-O-rutinoside, calycosin, and formononetin), lactones (ligustilide and butyllidephthalide), monoterpenoids (paeoniflorin), phenanthraquinones (cryptotanshinone), and furans (5-hydroxymethylfurfural) in Naoxintong capsule by ultra high-performance liquid chromatography. The optimized condition was that 25 mg Naoxintong powder was blended homogeneously with 100 mg Florisil PR for 4 min. One milliliter of methanol/water (75:25, v/v) acidified by 0.05% formic acid was selected to elute all components. It was found that the recoveries of the six types of components ranged from 61.36 to 96.94%. The proposed miniaturized matrix solid-phase dispersion coupled with ultra high-performance liquid chromatography was successfully applied to simultaneous determination of the six types of components in Naoxintong capsules. The results demonstrated that the proposed miniaturized matrix solid-phase dispersion coupled with ultra high-performance liquid chromatography could be used as an environmentally friendly tool for the extraction and determination of multiple bioactive components in natural products. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of selected UV filters in indoor dust by matrix solid-phase dispersion and gas chromatography-tandem mass spectrometry.

PubMed

Negreira, N; Rodríguez, I; Rubí, E; Cela, R

2009-07-31

A simple, inexpensive sample preparation procedure, based on the matrix solid-phase dispersion (MSPD) technique, for the determination of six UV filters: 2-ethylhexyl salicylate (EHS), 3,3,5-trimethylcyclohexyl salicylate (Homosalate, HMS), 3-(4-methylbenzylidene) camphor (4-MBC), isoamyl-p-methoxycinnamate (IAMC), 2-ethylhexyl-p-methoxycinnamate (EHMC) and octocrylene (OCR), in dust from indoor environments is presented and the influence of several operational parameters on the extraction performance discussed. Under the final working conditions, sieved samples (0.5 g) were mixed with the same amount of anhydrous sodium sulphate and dispersed with 2 g of octadecyl bonded silica (C18) in a mortar with a pestle. This blend was transferred to a polypropylene solid-phase extraction cartridge containing 2 g of activated silica, as the clean-up co-sorbent. The cartridge was first rinsed with 5 mL of n-hexane and the analytes were then recovered with 4 mL of acetonitrile. This extract was adjusted to 1 mL, filtered and the compounds were determined by gas chromatography combined with tandem mass spectrometry (GC-MS/MS). Recoveries for samples spiked at two different concentrations ranged between 77% and 99%, and the limits of quantification (LOQs) of the method between 10 and 40 ng g(-1). Analysis of settled dust from different indoor areas, including private flats, public buildings and vehicle cabins, showed that EHMC and OCR were ubiquitous in this matrix, with maximum concentrations of 15 and 41 microg g(-1), respectively. Both UV filters were also quantified in dust reference material SRM 2585 for first time. EHS, 4-MBC and IAMC were detected in some of the analyzed samples, although at lower concentrations than EHMC and OCR.

Microstructure of Pharmaceutical Semicrystalline Dispersions: The Significance of Polymer Conformation.

PubMed

Van Duong, Tu; Goderis, Bart; Van Humbeeck, Jan; Van den Mooter, Guy

2018-02-05

The microstructure of pharmaceutical semicrystalline solid dispersions has attracted extensive attention due to its complexity that might result in the diversity in physical stability, dissolution behavior, and pharmaceutical performance of the systems. Numerous factors have been reported that dictate the microstructure of semicrystalline dispersions. Nevertheless, the importance of the complicated conformation of the polymer has never been elucidated. In this study, we investigate the microstructure of dispersions of polyethylene glycol and active pharmaceutical ingredients by small-angle X-ray scattering and high performance differential scanning calorimetry. Polyethylene glycol with molecular weight of 2000 g/mol (PEG2000) and 6000 g/mol (PEG6000) exhibited remarkable discrepancy in the lamellar periodicity in dispersions with APIs which was attributed to the differences in their folding behavior. The long period of PEG2000 always decreased upon aging-induced exclusion of APIs from the interlamellar region of extended chain crystals whereas the periodicity of PEG6000 may decrease or increase during storage as a consequence of the competition between the drug segregation and the lamellar thickening from nonintegral-folded into integral-folded chain crystals. These processes were in turn significantly influenced by the crystallization tendency of the pharmaceutical compounds, drug-polymer interactions, as well as the dispersion composition and crystallization temperature. This study highlights the significance of the polymer conformation on the microstructure of semicrystalline systems that is critical for the preparation of solid dispersions with consistent and reproducible quality.

Effect of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of amorphous solid dispersions.

PubMed

Sun, Weiwei; Pan, Baoliang

2017-06-15

This study investigates the effects of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of micro-environment pH modifying solid dispersions (pH M -SD) for the poorly water-soluble model drug Toltrazuril (TOL). Various pH M -SDs were prepared using Ca(OH) 2 as a pH-modifier in hydrophilic polymers, including polyethylene glycol 6000 (PEG6000), polyvinylpyrrolidone k30 (PVPk30) and hydroxypropyl methylcellulose (HPMC). Based on the results of physicochemical characterizations and in-vitro dissolution testing, the representative ternary (Ca(OH) 2 :TOL:PEG6000/HPMC/PVPk30=1:8:24, w/w/w) and binary (TOL:PVPk30=1:3, w/w) solid dispersions were selected and optimized to perform in-vivo pharmacokinetic study. The micro-environment pH modification improved the in-vitro water-solubility and in-vivo bioavailability of parent drug TOL. Furthermore, the addition of alkalizers not only enhanced the release and absorption of prototype drug, but also promoted the generation of active metabolites, including toltrazuril sulfoxide (TOLSO) and toltrazuril sulfone (TOLSO 2 ). The in-vitro dissolution profiles and in-vivo absorption, distribution and metabolism behaviors of the pH M -SDs varied with polymer type. Moreover, in-vivo bioavailability of three active pharmaceutical ingredients increased with an increase in in-vitro dissolution rates of the drug from the pH M -SDs prepared with various polymers. Therefore, a non-sink in-vitro dissolution method can be used to predict the in-vivo performance of pH M -SDs formulated with various polymers with trend consistency. In-vitro and in-vivo screening procedures revealed that the pH M -SD composed of Ca(OH) 2 , TOL and PVPk30 at a weight ratio of 1:8:24, of which the safety was adequately proved via histopathological examination, may be a promising candidate for providing better clinical outcomes. Copyright © 2017. Published by Elsevier B.V.

Stirring-controlled solidified floating solid-liquid drop microextraction as a new solid phase-enhanced liquid-phase microextraction method by exploiting magnetic carbon nanotube-nickel hybrid.

PubMed

Ghazaghi, Mehri; Mousavi, Hassan Zavvar; Shirkhanloo, Hamid; Rashidi, Alimorad

2017-01-25

A specific technique is introduced to overcome limitations of classical solidification of floating organic drop microextraction, such as tedious and time-consuming centrifuge step and using disperser solvent, by facile and efficient participation of solid and liquid phases. In this proposed method of stirring-controlled solidified floating solid-liquid drop microextraction (SC-SF-SLDME), magnetic carbon nanotube-nickel hybrid (MNi-CNT) as a solid part of the extractors are dispersed ultrasonically in sample solution, and the procedure followed by dispersion of liquid phase (1-undecanol) through high-rate stirring and easily recollection of MNi-CNT in organic solvent droplets through hydrophobic force. With the reduction in speed of stirring, one solid-liquid drop is formed on top of the solution. MNi-CNT acts as both extractor and the coalescence helper between organic droplets for a facile recollection. MNi-CNT was prepared by spray pyrolysis of nickel oleate/toluene mixture at 1000 °C. Four tyrosine kinase inhibitors were selected as model analytes and the effecting parameters were investigated. The results confirmed that magnetic nanoadsorbent has an important role in the procedure and complete collection of dispersed solvent is not achieved in the absence of the solid phase. Also, short extraction time exhibited success of the proposed method and effect of dispersed solid/liquid phases. The limits of quantification (LOQs) for imatinib, sunitinib, erlotinib, and nilotinib were determined to be as low as 0.7, 1.7, 0.6, and 1.0 μg L -1 , respectively. The intra-day precisions (RSDs) were lower than 4.5%. Method performance was investigated by determination of mentioned tyrosine kinase inhibitors (TKIs) in human serum and cerebrospinal fluid samples with good recoveries in the range of 93-98%. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanism of drug release from polymethacrylate-based extrudates and milled strands prepared by hot-melt extrusion.

PubMed

Albers, Jessica; Alles, Rainer; Matthée, Karin; Knop, Klaus; Nahrup, Julia Schulze; Kleinebudde, Peter

2009-02-01

The aim of the study was the formulation of solid dispersions of the poorly water-soluble drug celecoxib and a polymethacrylate carrier by hot-melt extrusion. The objectives were to elucidate the mechanism of drug release from obtained extrudates and milled strands addicted to the solid-state properties of the solid dispersions and to examine and eliminate stability problems occurring under storage, exposure of mechanical stress, and in vitro dissolution. Transparent extrudates containing up to 60% drug could be prepared with a temperature setting below the melting point of celecoxib. XRPD and DSC measurements indicated the formation of a glassy solid solution, where the drug is molecularly dispersed in the carrier. The amorphous state of the glassy solid solution could be maintained during the exposure of mechanical stress in a milling process, and was stable under storage for at least 6 months. Solid-state properties and SEM images of extrudates after dissolution indicated a carrier-controlled dissolution, whereby the drug is molecularly dispersed within the concentrated carrier layer. The glassy solid solution showed a 58-fold supersaturation in 0.1 N HCl within the first 10 min, which was followed by a recrystallization process. Recrystallization could be inhibited by an external addition of HPMC.

Sustained-release solid dispersion of pelubiprofen using the blended mixture of aminoclay and pH independent polymers: preparation and in vitro/in vivo characterization.

PubMed

Lee, Yeo-Song; Song, Jae Guen; Lee, Sang Hoon; Han, Hyo-Kyung

2017-11-01

The present study aimed to develop the sustained-release oral dosage form of pelubiprofen (PEL) by using the blended mixture of 3-aminopropyl functionalized-magnesium phyllosilicate (aminoclay) and pH-independent polymers. The sustained-release solid dispersion (SRSD) was prepared by the solvent evaporation method and the optimal composition of SRSD was determined as the weight ratio of drug: Eudragit® RL PO: Eudragit® RS PO of 1:1:2 in the presence of 1% of aminoclay (SRSD(F6)). The dissolution profiles of SRSD(F6) were examined at different pHs and in the simulated intestinal fluids. The drug release from SRSD(F6) was limited at pH 1.2 and gradually increased at pH 6.8, resulting in the best fit to Higuchi equation. The sustained drug release from SRSD(F6) was also maintained in simulated intestinal fluid at fasted-state (FaSSIF) and fed-state (FeSSIF). The structural characteristics of SRSD(F6) were examined by using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR), indicating the change of drug crystallinity to an amorphous form. After oral administration in rats, SRSD(F6) exhibited the prolonged drug exposure in plasma. For both PEL and PEL-transOH (active metabolite), once a day dosing of SRSD(F6) achieved oral exposure (AUC) comparable to those from the multiple dosing (3 times a day) of untreated drug. In addition, the in vivo absorption of SRSD(F6) was well-correlated with the in vitro dissolution data, establishing a good level A in vitro/in vivo correlation. These results suggest that SRSD(F6) should be promising for the sustained-release of PEL, thereby reducing the dosing frequency.

Manufacturing Amorphous Solid Dispersions with a Tailored Amount of Crystallized API for Biopharmaceutical Testing.

PubMed

Theil, Frank; Milsmann, Johanna; Anantharaman, Sankaran; van Lishaut, Holger

2018-05-07

The preparation of an amorphous solid dispersion (ASD) by dissolving a poorly water-soluble active pharmaceutical ingredient (API) in a polymer matrix can improve the bioavailability by orders of magnitude. Crystallization of the API in the ASD, though, is an inherent threat for bioavailability. Commonly, the impact of crystalline API on the drug release of the dosage form is studied with samples containing spiked crystallinity. These spiked samples possess implicit differences compared to native crystalline samples, regarding size and spatial distribution of the crystals as well as their molecular environment. In this study, we demonstrate that it is possible to grow defined amounts of crystalline API in solid dosage forms, which enables us to study the biopharmaceutical impact of actual crystallization. For this purpose, we studied the crystal growth in fenofibrate tablets over time under an elevated moisture using transmission Raman spectroscopy (TRS). As a nondestructive method to assess API crystallinity in ASD formulations, TRS enables the monitoring of crystal growth in individual dosage forms. Once the kinetic trace of the crystal growth for a certain environmental condition is determined, this method can be used to produce samples with defined amounts of crystallized API. To investigate the biopharmaceutical impact of crystallized API, non-QC dissolution methods were used, designed to identify differences between the various amounts of crystalline materials present. The drug release in the samples manufactured in this fashion was compared to that of samples with spiked crystallinity. In this study, we present for the first time a method for targeted crystallization of amorphous tablets to simulate crystallized ASDs. This methodology is a valuable tool to generate model systems for biopharmaceutical studies on the impact of crystallinity on the bioavailability.

Preparation of a deuterated polymer: Simulating to produce a solid tritium radioactive source

NASA Astrophysics Data System (ADS)

Hu, Rui; Kan, Wentao; Xiong, Xiaoling; Wei, Hongyuan

2017-08-01

The preparation of a deuterated polymer was performed in order to simulate the production of the corresponding tritiated polymer as a solid tritium radioactive source. Substitution and addition reaction were used to introduce deuterium into the polymer. Proton nuclear magnetic resonance and FT-IR spectroscopy were used to investigate the extent and location of deuterium in the polymer, indicating an effectively deuterated polymer was produced. The thermal analysis showed that the final polymer product could tolerate the environmental temperature below 125 °C in its application. This research provides a prosperous method to prepare solid tritium radioactive source.

Trace determination of five triazole fungicide residues in traditional Chinese medicine samples by dispersive solid-phase extraction combined with ultrasound-assisted dispersive liquid-liquid microextraction and UHPLC-MS/MS.

PubMed

Ma, Shuping; Yuan, Xucan; Zhao, Pengfei; Sun, Hong; Ye, Xiu; Liang, Ning; Zhao, Longshan

2017-08-01

A novel and reliable method for determination of five triazole fungicide residues (triadimenol, tebuconazole, diniconazole, flutriafol, and hexaconazol) in traditional Chinese medicine samples was developed using dispersive solid-phase extraction combined with ultrasound-assisted dispersive liquid-liquid microextraction before ultra-high performance liquid chromatography with tandem mass spectrometry. The clean up of the extract was conducted using dispersive solid-phase extraction by directly adding sorbents into the extraction solution, followed by shaking and centrifugation. After that, a mixture of 400 μL trichloromethane (extraction solvent) and 0.5 mL of the above supernatant was injected rapidly into water for the dispersive liquid-liquid microextraction procedure. The factors affecting the extraction efficiency were optimized. Under the optimum conditions, the calibration curves showed good linearity in the range of 2.0-400 (tebuconazole, diniconazole, and hexaconazole) and 4.0-800 ng/g (triadimenol and flutriafol) with the regression coefficients higher than 0.9958. The limit of detection and limit of quantification for the present method were 0.5-1.1 and 1.8-4.0 ng/g, respectively. The recoveries of the target analytes ranged from 80.2 to 103.2%. The proposed method has been successfully applied to the analysis of five triazole fungicides in traditional Chinese medicine samples, and satisfactory results were obtained. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of phenolic acids and flavonoids in raw propolis by silica-supported ionic liquid-based matrix solid phase dispersion extraction high performance liquid chromatography-diode array detection.

PubMed

Wang, Zhibing; Sun, Rui; Wang, Yuanpeng; Li, Na; Lei, Lei; Yang, Xiao; Yu, Aimin; Qiu, Fangping; Zhang, Hanqi

2014-10-15

The silica-supported ionic liquid (S-SIL) was prepared by impregnation and used as the dispersion adsorbent of matrix solid phase dispersion (MSPD) for the simultaneous extraction of eight phenolic acids and flavonoids, including caffeic acid, ferulic acid, morin, luteolin, quercetin, apigenin, chrysin, and kaempferide in raw propolis. High performance liquid chromatography with a Zorbax SB-C18 column (150mm×4.6mm, 3.5μm) was used for separation of the analytes. The mobile phase consisted of 0.2% phosphoric acid aqueous solution and acetonitrile and the flow rate of the mobile phase was 0.5mL/min. The experimental conditions for silica-supported ionic liquid-based matrix solid phase dispersion (S-SIL-based MSPD) were optimized. S-SIL containing 10% [C6MIM]Cl was used as dispersant, 20mL of n-hexane as washing solvent and 15mL of methanol as elution solvent. The ratio of S-SIL to sample was selected to be 4:1. The standard curves showed good linear relationship (r>0.9995). The limits of detection and quantification were in the range of 5.8-22.2ngmL(-1) and 19.2-74.0ngmL(-1), respectively. The relative standard deviations (RSDs) of intra-day and inter-day determination were lower than 8.80% and 11.19%, respectively. The recoveries were between 65.51% and 92.32% with RSDs lower than 8.95%. Compared with ultrasound-assisted extraction (UAE) and soxhlet extraction, the present method consumed less sample, organic solvent, and extraction time, although the extraction yields obtained by S-SIL-based MSPD are slightly lower than those obtained by UAE. Copyright © 2014 Elsevier B.V. All rights reserved.

Simultaneous determination of phenolic compounds in Equisetum palustre L. by ultra high performance liquid chromatography with tandem mass spectrometry combined with matrix solid-phase dispersion extraction.

PubMed

Wei, Zuofu; Pan, Youzhi; Li, Lu; Huang, Yuyang; Qi, Xiaolin; Luo, Meng; Zu, Yuangang; Fu, Yujie

2014-11-01

A method based on matrix solid-phase dispersion extraction followed by ultra high performance liquid chromatography with tandem mass spectrometry is presented for the extraction and determination of phenolic compounds in Equisetum palustre. This method combines the high efficiency of matrix solid-phase dispersion extraction and the rapidity, sensitivity, and accuracy of ultra high performance liquid chromatography with tandem mass spectrometry. The influential parameters of the matrix solid-phase dispersion extraction were investigated and optimized. The optimized conditions were as follows: silica gel was selected as dispersing sorbent, the ratio of silica gel to sample was selected to be 2:1 (400/200 mg), and 8 mL of 80% methanol was used as elution solvent. Furthermore, a fast and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the determination of nine phenolic compounds in E. palustre. This method was carried out within <6 min, and exhibited satisfactory linearity, precision, and recovery. Compared with ultrasound-assisted extraction, the proposed matrix solid-phase dispersion procedure possessed higher extraction efficiency, and was more convenient and time saving with reduced requirements on sample and solvent amounts. All these results suggest that the developed method represents an excellent alternative for the extraction and determination of active components in plant matrices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterization and evaluation of avermectin solid nanodispersion prepared by microprecipitation and lyophilisation techniques

PubMed Central

Wang, Chunxin; Zhao, Xiang; Yao, Junwei; Zeng, Zhanghua; Wang, Yan; Sun, Changjiao; Liu, Guoqiang; Cui, Haixin

2018-01-01

Poorly water-soluble and photosensitive pesticide compounds are difficult to formulate as solvent-free nanoformulations with high efficacy. A avermectin solid nanodispersion with a mean particle size of 188 nm was developed by microprecipitation and lyophilisation techniques. The suspensibility and wetting time of the solid nanodispersion in water were 99.8% and 13 s, respectively, superior to those of conventional water dispersible granules and wettable powders. The anti-photolysis performance of the nanoformulation was twice that of the technical material, and the biological activity against diamondback moths was more than 1.5 times that of the conventional solid formulations while taking LC 50 as the evaluation index. Moreover, the formulation composition substantially decreased the surfactant content and avoided organic solvents. Microprecipitation combined with lyophilisation is an easy and promising method to construct solid nanoformulations for pesticides with poor water solubility and environmental sensitivity. The application of the highly effective solid nanodispersion in crop production will have a great potential in reducing chemical residues and environmental pollution. PMID:29360866

Solid lipid microparticles containing loratadine prepared using a Micromixer.

PubMed

Milak, Spomenka; Medlicott, Natalie; Tucker, Ian G

2006-12-01

Solid lipid microparticles were investigated as a taste-masking approach for a lipophilic weak base in a suspension. The idea was that the drug concentration in the aqueous phase of a suspension might be reduced by its partitioning into the solid lipid particles. Loratadine, as a model drug, was used to prepare Precirol ATO 5 microparticles by a Micromixer. The effects of three process variables: drug loading, PVA concentration and water/lipid ratio on the microparticle size, encapsulation efficiency, surface appearance, in-vitro release and drug partitioning in a suspension were studied. Loratadine release was slow in simulated saliva and very fast at the pH of stomach. In suspension of loratadine lipid microparticles, drug was released into the aqueous phase to the same concentration as in a drug suspension. Therefore, the usefulness of these microparticles for taste-masking in liquids is limited. However, they might be useful for taste-masking in solid dosage forms.

Structural Elucidation of Poloxamer 237 and Poloxamer 237/Praziquantel Solid Dispersions: Impact of Poly(Vinylpyrrolidone) over Drug Recrystallization and Dissolution.

PubMed

Orlandi, Silvina; Priotti, Josefina; Diogo, Hermínio P; Leonardi, Dario; Salomon, Claudio J; Nunes, Teresa G

2018-04-01

Praziquantel (PZQ) is the recommended, effective, and safe treatment against all forms of schistosomiasis. Solid dispersions (SDs) in water-soluble polymers have been reported to increase solubility and bioavailability of poorly water-soluble drugs like PZQ, generally due to the amorphous form stabilization. In this work, poloxamer (PLX) 237 and poly(vinylpyrrolidone) (PVP) K30 were evaluated as potential carriers to revert PZQ crystallization. Binary and ternary SDs were prepared by the solvent evaporation method. PZQ solubility increased similarly with PLX either as binary physical mixtures or SDs. Such unpredicted data correlated well with crystalline PZQ and PLX as detected by solid-state NMR (ssNMR) and differential scanning calorimetry in those samples. Ternary PVP/PLX/PZQ SDs showed both ssNMR broad and narrow superimposed signals, thus revealing the presence of amorphous and crystalline PZQ, respectively, and exhibited the highest PZQ dissolution efficiency (up to 82% at 180 min). SDs with PVP provided a promising way to enhance solubility and dissolution rate of PZQ since PLX alone did not prevent recrystallization of amorphous PZQ. Based on ssNMR data, novel evidences on PLX structure and molecular dynamics were also obtained. As shown for the first time using ssNMR, propylene glycol and ethylene glycol constitute the PLX amorphous and crystalline components, respectively.

Can matrix solid phase dispersion (MSPD) be more simplified? Application of solventless MSPD sample preparation method for GC-MS and GC-FID analysis of plant essential oil components.

PubMed

Wianowska, Dorota; Dawidowicz, Andrzej L

2016-05-01

This paper proposes and shows the analytical capabilities of a new variant of matrix solid phase dispersion (MSPD) with the solventless blending step in the chromatographic analysis of plant volatiles. The obtained results prove that the use of a solvent is redundant as the sorption ability of the octadecyl brush is sufficient for quantitative retention of volatiles from 9 plants differing in their essential oil composition. The extraction efficiency of the proposed simplified MSPD method is equivalent to the efficiency of the commonly applied variant of MSPD with the organic dispersing liquid and pressurized liquid extraction, which is a much more complex, technically advanced and highly efficient technique of plant extraction. The equivalency of these methods is confirmed by the variance analysis. The proposed solventless MSPD method is precise, accurate, and reproducible. The recovery of essential oil components estimated by the MSPD method exceeds 98%, which is satisfactory for analytical purposes. Copyright © 2016 Elsevier B.V. All rights reserved.

Nonlinear Dispersive Elastic Waves in Solids: Exact, Approximate, and Numerical Solutions

NASA Astrophysics Data System (ADS)

Khajehtourian, Romik

Wave motion lies at the heart of many disciplines in the physical sciences and engineering. For example, problems and applications involving light, sound, heat, or fluid flow are all likely to involve wave dynamics at some level. A particular class of problems is concerned with the propagation of elastic waves in a solid medium, such as a fiber-reinforced composite material responding to vibratory excitations, or soil and rock admitting seismic waves moments after the onset of an earthquake, or phonon transport in a semiconducting crystal like silicon. Regardless of the type of wave, the dispersion relation provides a fundamental characterization of the elastodynamic properties of the medium. The first part of the dissertation examines the propagation of a large-amplitude elastic wave in a one-dimensional homogeneous medium with a focus on the effects of inherent nonlinearities on the dispersion relation. Considering a thin rod, where the thickness is small compared to the wavelength, an exact, closed-form formulation is presented for the treatment of two types of nonlinearity in the strain-displacement gradient relation: Green-Lagrange and Hencky. The derived relation is then verified by direct time-domain simulations, examining both instantaneous dispersion (by direct observation) and short-term, pre-breaking dispersion (by Fourier transformation). A high-order perturbation analysis is also conducted yielding an explicit analytical space-time solution, which is shown to be spectrally accurate. The results establish a perfect match between theory and simulation and reveal that regardless of the strength of the nonlinearity, the dispersion relation fully embodies all information pertaining to the nonlinear harmonic generation mechanism that unfolds as an arbitrary-profiled wave evolves in the medium. In the second part of the dissertation, the analysis is extended to a continuous periodic thin rod exhibiting multiple phases or embedded local resonators. The

Optimization of the Büchi B-90 spray drying process using central composite design for preparation of solid dispersions.

PubMed

Gu, Bing; Linehan, Brian; Tseng, Yin-Chao

2015-08-01

A central composite design approach was applied to study the effect of polymer concentration, inlet temperature and air flow rate on the spray drying process of the Büchi B-90 nano spray dryer (B-90). Hypromellose acetate succinate-LF was used for the Design of Experiment (DoE) study. Statistically significant models to predict the yield, spray rate, and drying efficiency were generated from the study. The spray drying conditions were optimized according to the models to maximize the yield and efficiency of the process. The models were further validated using a poorly water-soluble investigational compound (BI064) from Boehringer Ingelheim Pharmaceuticals. The polymer/drug ratio ranged from 1/1 to 3/1w/w. The spray dried formulations were amorphous determined by differential scanning calorimetry and X-ray powder diffraction. The particle size of the spray dried formulations was 2-10 μm under polarized light microscopy. All the formulations were physically stable for at least 3h when suspended in an aqueous vehicle composed of 1% methyl cellulose. This study demonstrates that DoE is a useful tool to optimize the spray drying process, and the B-90 can be used to efficiently produce amorphous solid dispersions with a limited quantity of drug substance available during drug discovery stages. Copyright © 2015 Elsevier B.V. All rights reserved.

Solid-state NMR study of geopolymer prepared by sol-gel chemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tsai, Yi-Ling; Hanna, John V.; Lee, Yuan-Ling, E-mail: yuanlinglee@ntu.edu.t

2010-12-15

Geopolymers are a new class of materials formed by the condensation of aluminosilicates and silicates obtained from natural minerals or industrial wastes. In this work, the sol-gel method is used to synthesize precursor materials for the preparation of geopolymers. The geopolymer samples prepared by our synthetic route have been characterized by a series of physical techniques, including Fourier-transform infrared, X-ray diffraction, and multinuclear solid-state NMR. The results are very similar to those obtained for the geopolymers prepared from natural kaolinite. We believe that our synthetic approach can offer a good opportunity for the medical applications of geopolymer. -- Graphical abstract:more » Geopolymer prepared by the sol-gel route has the same spectroscopic properties as the sample prepared from the natural kaolinite. Display Omitted« less

Electrosprayed core-shell solid dispersions of acyclovir fabricated using an epoxy-coated concentric spray head.

PubMed

Liu, Zhe-Peng; Cui, Lei; Yu, Deng-Guang; Zhao, Zhuan-Xia; Chen, Lan

2014-01-01

A novel structural solid dispersion (SD) taking the form of core-shell microparticles for poorly water-soluble drugs is reported for the first time. Using polyvinylpyrrolidone (PVP) as a hydrophilic polymer matrix, the SDs were fabricated using coaxial electrospraying (characterized by an epoxy-coated concentric spray head), although the core fluids were unprocessable using one-fluid electrospraying. Through manipulating the flow rates of the core drug-loaded solutions, two types of core-shell microparticles with tunable drug contents were prepared. They had average diameters of 1.36±0.67 and 1.74±0.58 μm, and were essentially a combination of nanocomposites with the active ingredient acyclovir (ACY) distributed in the inner core, and the sweeter sucralose and transmembrane enhancer sodium dodecyl sulfate localized in the outer shell. Differential scanning calorimetry and X-ray diffraction results demonstrated that ACY, sodium dodecyl sulfate, and sucralose were well distributed in the PVP matrix in an amorphous state because of favorable second-order interactions. In vitro dissolution and permeation studies showed that the core-shell microparticle SDs rapidly freed ACY within 1 minute and promoted nearly eightfold increases in permeation rate across the sublingual mucosa compared with raw ACY powders.

Electrosprayed core–shell solid dispersions of acyclovir fabricated using an epoxy-coated concentric spray head

PubMed Central

Liu, Zhe-Peng; Cui, Lei; Yu, Deng-Guang; Zhao, Zhuan-Xia; Chen, Lan

2014-01-01

A novel structural solid dispersion (SD) taking the form of core–shell microparticles for poorly water-soluble drugs is reported for the first time. Using polyvinylpyrrolidone (PVP) as a hydrophilic polymer matrix, the SDs were fabricated using coaxial electrospraying (characterized by an epoxy-coated concentric spray head), although the core fluids were unprocessable using one-fluid electrospraying. Through manipulating the flow rates of the core drug-loaded solutions, two types of core–shell microparticles with tunable drug contents were prepared. They had average diameters of 1.36±0.67 and 1.74±0.58 μm, and were essentially a combination of nanocomposites with the active ingredient acyclovir (ACY) distributed in the inner core, and the sweeter sucralose and transmembrane enhancer sodium dodecyl sulfate localized in the outer shell. Differential scanning calorimetry and X-ray diffraction results demonstrated that ACY, sodium dodecyl sulfate, and sucralose were well distributed in the PVP matrix in an amorphous state because of favorable second-order interactions. In vitro dissolution and permeation studies showed that the core–shell microparticle SDs rapidly freed ACY within 1 minute and promoted nearly eightfold increases in permeation rate across the sublingual mucosa compared with raw ACY powders. PMID:24790437

Dispersive solid-phase extraction followed by vortex-assisted dispersive liquid-liquid microextraction based on the solidification of a floating organic droplet for the determination of benzoylurea insecticides in soil and sewage sludge.

PubMed

Peng, Guilong; He, Qiang; Mmereki, Daniel; Lu, Ying; Zhong, Zhihui; Liu, Hanyang; Pan, Weiliang; Zhou, Guangming; Chen, Junhua

2016-04-01

A novel dispersive solid-phase extraction combined with vortex-assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet was developed for the determination of eight benzoylurea insecticides in soil and sewage sludge samples before high-performance liquid chromatography with ultraviolet detection. The analytes were first extracted from the soil and sludge samples into acetone under optimized pretreatment conditions. Clean-up of the extract was conducted by dispersive solid-phase extraction using activated carbon as the sorbent. The vortex-assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet procedure was performed by using 1-undecanol with lower density than water as the extraction solvent, and the acetone contained in the solution also acted as dispersive solvent. Under the optimum conditions, the linearity of the method was in the range 2-500 ng/g with correlation coefficients (r) of 0.9993-0.9999. The limits of detection were in the range of 0.08-0.56 ng/g. The relative standard deviations varied from 2.16 to 6.26% (n = 5). The enrichment factors ranged from 104 to 118. The extraction recoveries ranged from 81.05 to 97.82% for all of the analytes. The good performance has demonstrated that the proposed methodology has a strong potential for application in the multiresidue analysis of complex matrices. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Solid dispersions, part I: recent evolutions and future opportunities in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs.

PubMed

Bikiaris, Dimitrios N

2011-11-01

In recent years, the number of active pharmaceutical ingredients with high therapeutic impact, but very low water solubility, has increased significantly. Thus, a great challenge for pharmaceutical technology is to create new formulations and efficient drug-delivery systems to overcome these dissolution problems. Drug formulation in solid dispersions (SDs) is one of the most commonly used techniques for the dissolution rate enhancement of poorly water-soluble drugs. Generally, SDs can be defined as a dispersion of active ingredients in molecular, amorphous and/or microcrystalline forms into an inert carrier. This review covers literature which states that the dissolution enhancement of SDs is based on the fact that drugs in the nanoscale range, or in amorphous phase, dissolve faster and to a greater extent than micronized drug particles. This is in accordance to the Noyes-Whitney equation, while the wetting properties of the used polymer may also play an important role. The main factors why SD-based pharmaceutical products on the market are steadily increasing over the last few years are: the recent progress in various methods used for the preparation of SDs, the effect of evolved interactions in physical state of the drug and formulation stability during storage, the characterization of the physical state of the drug and the mechanism of dissolution rate enhancement.

Analysis of malachite green in aquatic products by carbon nanotube-based molecularly imprinted - matrix solid phase dispersion.

PubMed

Wang, Yu; Chen, Ligang

2015-10-01

A simple method based on matrix solid phase dispersion (MSPD) using molecularly imprinted polymers (MIPs) as sorbents for selective extraction of malachite green (MG) from aquatic products was developed. The MIPs were prepared by using carbon nanotube as support, MG as template, methacrylic acid as functional monomer, ethyleneglycol dimethacrylate as crosslinker and methylene chloride as solvent. The MIPs were characterized by Fourier transform infrared spectrometry and transmission electron microscopy. The isothermal adsorption, kinetics absorption and selective adsorption experiments were carried out. We optimized the extraction conditions as follows: the ratio of MIPs to sample was 2:3, the dispersion time was 15min, washing solvent was 4mL 50% aqueous methanol and elution solvent was 3mL methanol-acetic acid (98: 2, v/v). Once the MSPD process was completed, the MG extracted from aquatic products was determined by high performance liquid chromatography. The detection limit of MG was 0.7μgkg(-1). The relative standard deviations of intra-day and inter-day were obtained in the range of 0.9%-4.7% and 3.4%-9.8%, respectively. In order to evaluate the applicability and reliability of the proposed method, it was applied to determine MG in different aquatic products samples including fish, shrimp, squid and crabs. The satisfied recoveries were in the range of 89.2%-104.6%. The results showed that this method is faster, simpler and makes extraction and purification in the same system. Copyright © 2015 Elsevier B.V. All rights reserved.

Evaluation and modeling of the eutectic composition of various drug-polyethylene glycol solid dispersions.

PubMed

Baird, Jared A; Taylor, Lynne S

2011-06-01

The purpose of this study was to gain a better understanding of which factors contribute to the eutectic composition of drug-polyethylene glycol (PEG) blends and to compare experimental values with predictions from the semi-empirical model developed by Lacoulonche et al. Eutectic compositions of various drug-PEG 3350 solid dispersions were predicted, assuming athermal mixing, and compared to experimentally determined eutectic points. The presence or absence of specific interactions between the drug and PEG 3350 were investigated using Fourier transform infrared (FT-IR) spectroscopy. The eutectic composition for haloperidol-PEG and loratadine-PEG solid dispersions was accurately predicted using the model, while predictions for aceclofenac-PEG and chlorpropamide-PEG were very different from those experimentally observed. Deviations in the model prediction from ideal behavior for the systems evaluated were confirmed to be due to the presence of specific interactions between the drug and polymer, as demonstrated by IR spectroscopy. Detailed analysis showed that the eutectic composition prediction from the model is interdependent on the crystal lattice energy of the drug compound (evaluated from the melting temperature and the heat of fusion) as well as the nature of the drug-polymer interactions. In conclusion, for compounds with melting points less than 200°C, the model is ideally suited for predicting the eutectic composition of systems where there is an absence of drug-polymer interactions.

Preparative isolation of flavonoid glycosides from Sphaerophysa salsula using hydrophilic interaction solid-phase extraction coupled with two-dimensional preparative liquid chromatography.

PubMed

Jiao, Lijin; Tao, Yanduo; Wang, Weidong; Shao, Yun; Mei, Lijuan; Wang, Qilan; Dang, Jun

2017-10-01

An offline preparative two-dimensional reversed-phase liquid chromatography/hydrophilic interaction liquid chromatography coupled with hydrophilic interaction solid-phase extraction method was developed for the preparative isolation of flavonoid glycosides from a crude sample of Sphaerophysa salsula. First, the non-flavonoids were removed using an XAmide solid-phase extraction cartridge. Based on the separation results of three different chromatographic stationary phases, the first-dimensional preparation was performed on an XAqua C18 prep column, and 15 fractions were obtained from the 5.2 g target sample. Then, three representative fractions were selected for additional purification on an XAmide preparative column to further isolate the flavonoid glycosides. In all, eight flavonoid glycosides were isolated in purities over 97%. The results demonstrated that the two-dimensional liquid chromatography method used in this study was effective for the preparative separation of flavonoid glycosides from Sphaerophysa salsula. Additionally, this method showed great potential for the separation of flavonoid glycosides from other plant materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Composition and method of preparation of solid state dye laser rods

DOEpatents

Hermes, Robert E.

1992-01-01

The present invention includes solid polymeric-host laser rods prepared using bulk polymerization of acrylic acid ester comonomers which, when admixed with dye(s) capable of supporting laser oscillation and polymerized with a free radical initiator under mild thermal conditions, produce a solid product having the preferred properties for efficient lasing. Unsaturated polymerizable laser dyes can also be employed as one of the comonomers. Additionally, a method is disclosed which alleviates induced optical stress without having to anneal the polymers at elevated temperatures (>85.degree. C.).

Water nanodroplet thermodynamics: quasi-solid phase-boundary dispersivity.

PubMed

Zhang, Xi; Sun, Peng; Huang, Yongli; Ma, Zengsheng; Liu, Xinjuan; Zhou, Ji; Zheng, Weitao; Sun, Chang Q

2015-04-23

It has long been puzzling that water nanodroplets undergo simultaneously "supercooling" at freezing and "superheating" at melting. Recent progress (Sun et al. J. Phys. Chem. Lett. 2013, 4, 2565, 3238) enables us to resolve this anomaly from the perspective of hydrogen bond (O:H-O) specific heat disparity. A superposition of the specific heat ηx(T) curves for the H-O bond (x = H) and the O:H nonbond (x = L) defines two intersecting temperatures that form the ice/quasi-solid/liquid phase boundaries. Molecular undercoordination (with fewer than four nearest neighbors in the bulk) stretches the ηH(T) curve by raising the Debye temperature ΘDH through H-O bond shortening and phonon stiffening. The ηH(T) stretching is coupled with the ηL(T) depressing because of the Coulomb repulsion between electron pairs on oxygen ions. The extent of dispersion varies with the size of a droplet that prefers a core-shell structure configuration-the bulk interior and the skin. Understandings may open an effective way of dealing with the thermodynamic behavior of water droplets and bubbles from the perspective of O:H-O bond cooperativity.

Preparation of almost dispersant-free colloidal silica with superb dispersiblility in organic solvents and monomers

NASA Astrophysics Data System (ADS)

Huang, Feng-Hsi; Chang, Chao-Ching; Oyang, Tai-Yueh; Chen, Ching-Chung; Cheng, Liao-Ping

2011-09-01

Surface modification of silica nanoparticles synthesized by the sol-gel process was performed using coupling agents, 3-(trimethoxysilyl) propyl methacrylate (MSMA) and/or trimethyethoxylsilane (TMES). The chemical structures of the formed particles were analyzed by means of Fourier Transform Infrared Spectroscopy (FTIR) and solid-state Si-Nuclear Magnetic Resonance (Si-NMR), and the particle sizes were determined by Transmission Electron Microscopy (TEM) imaging. The latter results indicate that such surface modifications can effectively lessen the serious aggregation being common to pure silica nanoparticles. In some cases, separate particles of ca. 5-10 nm dia. could be obtained, when both MSMA and TMES were employed during the modification process. Dynamic light scattering method was adopted to examine the stability of the prepared silica sols during a long-term storage. It was found that the aggregation phenomenon can essentially be eliminated in case that the surface of silica contained sufficient amount of TMES moiety. Vacuum distillation was used to remove the volatile components such as methanol, ethanol, and water from the silica sol. The condensed product, containing 2 wt% residual solvent, appeared as a uniform transparent paste-like material, which can be dispersed in common organic solvents and monomers within a few seconds.

Synthesis of acrylic polymer beads for solid-supported proline-derived organocatalysts.

PubMed

Kristensen, Tor E; Vestli, Kristian; Fredriksen, Kim A; Hansen, Finn K; Hansen, Tore

2009-07-16

A completely non-chromatographic and highly large-scale adaptable synthesis of acrylic polymer beads containing proline and prolineamides has been developed. Novel monomeric proline (meth)acrylates are prepared from hydroxyproline in only one step. Free-radical copolymerization then gives solid-supported proline organocatalysts directly in as little as two steps overall, without using any prefabricated solid supports, by using either droplet or dispersion polymerization. These affordable acrylic beads have highly favorable and adjustable swelling characteristics and are excellent reusable catalysts for organocatalytic reactions.

Preparation of LuAG Powders with Single Phase and Good Dispersion for Transparent Ceramics Using Co-Precipitation Method

PubMed Central

Pan, Liangjie; Jiang, Benxue; Fan, Jintai; Yang, Qiuhong; Zhou, Chunlin; Zhang, Pande; Mao, Xiaojian; Zhang, Long

2015-01-01

The synthesis of pure and well dispersed lutetium aluminum garnet (LuAG) powder is crucial and important for the preparation of LuAG transparent ceramics. In this paper, high purity and well dispersed LuAG powders have been synthesized via co-precipitation method with lutetium nitrate and aluminum nitrate as raw materials. Ammonium hydrogen carbonate (AHC) was used as the precipitant. The influence of aging time, pH value, and dripping speed on the prepared LuAG powders were investigated. It showed that long aging duration (>15 h) with high terminal pH value (>7.80) resulted in segregation of rhombus Lu precipitate and Al precipitate. By decreasing the initial pH value or accelerating the dripping speed, rhombus Lu precipitate was eliminated and pure LuAG nano powders were synthesized. High quality LuAG transparent ceramics with transmission >75% at 1064 nm were fabricated using these well dispersed nano LuAG powders. PMID:28793510

Preparation of LuAG Powders with Single Phase and Good Dispersion for Transparent Ceramics Using Co-Precipitation Method.

PubMed

Pan, Liangjie; Jiang, Benxue; Fan, Jintai; Yang, Qiuhong; Zhou, Chunlin; Zhang, Pande; Mao, Xiaojian; Zhang, Long

2015-08-19

The synthesis of pure and well dispersed lutetium aluminum garnet (LuAG) powder is crucial and important for the preparation of LuAG transparent ceramics. In this paper, high purity and well dispersed LuAG powders have been synthesized via co-precipitation method with lutetium nitrate and aluminum nitrate as raw materials. Ammonium hydrogen carbonate (AHC) was used as the precipitant. The influence of aging time, pH value, and dripping speed on the prepared LuAG powders were investigated. It showed that long aging duration (>15 h) with high terminal pH value (>7.80) resulted in segregation of rhombus Lu precipitate and Al precipitate. By decreasing the initial pH value or accelerating the dripping speed, rhombus Lu precipitate was eliminated and pure LuAG nano powders were synthesized. High quality LuAG transparent ceramics with transmission >75% at 1064 nm were fabricated using these well dispersed nano LuAG powders.

Acoustic and Seismic Dispersion in Complex Fluids and Solids

NASA Astrophysics Data System (ADS)

Goddard, Joe

2017-04-01

The first part of the present paper is the continuation of a previous work [3] on the effects of higher spatial gradients and temporal relaxation on stress and heat flux in complex fluids. In particular, the general linear theory is applied to acoustic dispersion, extending a simpler model proposed by Davis and Brenner [2]. The theory is applied to a linearized version of the Chapman-Enskog fluid [1] valid to terms of Burnett order and including Maxwell-Cataneo relaxation of stress and heat flux on relaxation time scales τ. For this model, the dispersion relation k(ω) giving spatial wave number k as function of temporal frequency ω is a cubic in k2, in contrast to the quadratic in k2 given by the classical model and the recently proposed modification [2]. The cubic terms are shown to be important only for ωτ = O(1) where Maxwell-Cataneo relaxation is also important. As a second part of the present work, it is shown how the above model can also be applied to isotropic solids, where both shear and pressure waves are important. Finally, consideration is given to hyperstress in micro- polar continua, including both graded and micro-morphic varieties. [1]S. Chapman and T. Cowling. The mathematical theory of non-uniform gases. Cambridge University Press, [Cambridge, UK], 1960. [2]A. M.J. Davis and H. Brenner. Thermal and viscous effects on sound waves: revised classical theory. J. Acoust. Soc. Am., 132(5):2963-9, 2012. [3] J.D. Goddard. On material velocities and non-locality in the thermo-mechanics of continua. Int. J. Eng. Sci., 48(11):1279-88, 2010.

A stable solid acid material: Sulfated ZrO2 dispersed on alumina nanotubes

NASA Astrophysics Data System (ADS)

Feng, Yu; Jiaqi, Chen; Xu, Wang; Rui-Feng, Li

2017-02-01

A tubular solid acid catalyst was designed by loading sulfated zirconia into γ-Al2O3 nanotubes using the method of stepwise deposition. The XRD, N2 adsorption-desorption characterization demonstrated that introducing alumina nanotube and SO4 2- anions have played an important role in stabilizing the metastable tetragonal ZrO2 phase, and the sulfated zirconia on the surface of the γ-Al2O3 nanotube has high dispersion and stability. The catalyst reused repeatedly possesses large amounts of acid sites and good acidity, exhibiting high catalytic activity and stability for isopropylbenzene cracking.

A study of the oxide dispersion and recrystallization in NiCrAl prepared from preoxidized powder

NASA Technical Reports Server (NTRS)

Glasgow, T. K.

1975-01-01

The SAP technique of dispersion strengthening (formation of an oxide dispersion by preoxidation of metal powders) was applied to atomized powder of the alloy Ni-17Cr-5Al-0.2 Y. SAP-NiCrAl was worked by extrusion and rod rolling at 1205 C and by swaging at 760 C. A variety of annealing treatments were applied after working to determine the recrystallization response. NiCrAlY, similarly prepared from atomized powder, but without a preoxidation treatment, was examined for comparison. The SAP-NiCrAl of this study exhibited oxide particle size and spacing much larger than that usually observed in oxide dispersion strengthened alloys; nonetheless, it was possible to achieve abnormal (secondary) recrystallization in the SAP-NiCrAl as has been reported for other oxide dispersion strengthened alloys. In contrast, unoxidized NiCrAlY exhibited only primary recrystallization.

Preparation and application of conducting polymer/Ag/clay composite nanoparticles formed by in situ UV-induced dispersion polymerization

PubMed Central

Zang, Limin; Qiu, Jianhui; Yang, Chao; Sakai, Eiichi

2016-01-01

In this work, composite nanoparticles containing polypyrrole, silver and attapulgite (PPy/Ag/ATP) were prepared via UV-induced dispersion polymerization of pyrrole using ATP clay as a templet and silver nitrate as photoinitiator. The effects of ATP concentration on morphology, structure and electrical conductivity were studied. The obtained composite nanoparticles with an interesting beads-on-a-string morphology can be obtained in a short time (10 min), which indicates the preparation method is facile and feasible. To explore the potential applications of the prepared PPy/Ag/ATP composite nanoparticles, they were served as multifunctional filler and blended with poly(butylene succinate) (PBS) matrix to prepare biodegradable composite material. The distribution of fillers in polymer matrix and the interfacial interaction between fillers and PBS were confirmed by scanning electron microscope, elemental mapping and dynamic mechanical analysis. The well dispersed fillers in PBS matrix impart outstanding antibacterial property to the biodegradable composite material as well as enhanced storage modulus due to Ag nanoparticles and ATP clay. The biodegradable composite material also possesses modest surface resistivity (106 ~ 109 Ω/◻). PMID:26839126

Preparation and application of conducting polymer/Ag/clay composite nanoparticles formed by in situ UV-induced dispersion polymerization.

PubMed

Zang, Limin; Qiu, Jianhui; Yang, Chao; Sakai, Eiichi

2016-02-03

In this work, composite nanoparticles containing polypyrrole, silver and attapulgite (PPy/Ag/ATP) were prepared via UV-induced dispersion polymerization of pyrrole using ATP clay as a templet and silver nitrate as photoinitiator. The effects of ATP concentration on morphology, structure and electrical conductivity were studied. The obtained composite nanoparticles with an interesting beads-on-a-string morphology can be obtained in a short time (10 min), which indicates the preparation method is facile and feasible. To explore the potential applications of the prepared PPy/Ag/ATP composite nanoparticles, they were served as multifunctional filler and blended with poly(butylene succinate) (PBS) matrix to prepare biodegradable composite material. The distribution of fillers in polymer matrix and the interfacial interaction between fillers and PBS were confirmed by scanning electron microscope, elemental mapping and dynamic mechanical analysis. The well dispersed fillers in PBS matrix impart outstanding antibacterial property to the biodegradable composite material as well as enhanced storage modulus due to Ag nanoparticles and ATP clay. The biodegradable composite material also possesses modest surface resistivity (10(6)~ 10(9) Ω/◻).

Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

PubMed

Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

2015-11-15

The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (P<0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P<0.01). qBase(+) was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P<0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. Copyright © 2015 Elsevier Inc

A study of preparation techniques and properties of bulk nanocomposites based on aqueous albumin dispersion

NASA Astrophysics Data System (ADS)

Gerasimenko, A. Yu.; Dedkova, A. A.; Ichkitidze, L. P.; Podgaetskii, V. M.; Selishchev, S. V.

2013-08-01

Bulk nanocomposites prepared from an aqueous albumin dispersion with carbon nanotubes by removing the liquid component from the dispersion have been investigated. The composites were obtained by thermostating and exposure to LED and IR diode laser radiation. The nanocomposites obtained under laser irradiation retain their shape and properties for several years, in contrast to the composites fabricated in different ways (which decompose into small fragments immediately after preparation). The low density of the composites under study (˜1200 kg/m3), which is close to the density of water, is due to their high porosity. The hardness of stable nanocomposites (˜300 MPa) was found to be at the same level as the hardness of polymethylmethacrylate, aluminum, and iron and close to the hardness of human bone tissue. The cluster quasiordering of the inner structure of nanocomposites revealed by atomic force microscopy indicates the possibility of forming a bulk nanotube framework in them, which can be caused by the effect of the electric field of laser radiation and ensure their stability and hardness. The presence of a framework in nanocomposites provides conditions for self-assembly of biological tissues and makes it possible to apply laser-prepared nanocomposites as a component of surgical implants.

Diesel exhaust particulate material expression of in vitro genotoxic activities when dispersed into a phospholipid component of lung surfactant

NASA Astrophysics Data System (ADS)

Shi, X. C.; Keane, M. J.; Ong, T. M.; Harrison, J. C.; Slaven, J. E.; Bugarski, A. D.; Gautam, M.; Wallace, W. E.

2009-02-01

Bacterial mutagenicity and mammalian cell chromosomal and DNA damage in vitro assays were performed on a diesel exhaust particulate material (DPM) standard in two preparations: as an organic solvent extract, and as an aqueous dispersion in a simulated pulmonary surfactant. U.S. National Institute for Standards and Technology DPM SRM 2975 expressed mutagenic activity in the Salmonella reversion assay, and for in vitro genotoxicity to mammalian cells as micronucleus induction and as DNA damage in both preparations: as an acetone extract of the DPM mixed into dimethylsulfoxide, and as a mixture of whole DPM in a dispersion of dipalmitoyl phosphatidyl choline. Dispersion in surfactant was used to model the conditioning of DPM depositing on the deep respiratory airways of the lung. DPM solid residue after acetone extraction was inactive when assayed as a surfactant dispersion in the micronucleus induction assay, as was surfactant dispersion of a respirable particulate carbon black. In general, a given mass of the DPM in surfactant dispersion expressed greater activity than the solvent extract of an equal mass of DPM.

Two- and three-body interatomic dispersion energy contributions to binding in molecules and solids

NASA Astrophysics Data System (ADS)

Anatole von Lilienfeld, O.; Tkatchenko, Alexandre

2010-06-01

We present numerical estimates of the leading two- and three-body dispersion energy terms in van der Waals interactions for a broad variety of molecules and solids. The calculations are based on London and Axilrod-Teller-Muto expressions where the required interatomic dispersion energy coefficients, C6 and C9, are computed "on the fly" from the electron density. Inter- and intramolecular energy contributions are obtained using the Tang-Toennies (TT) damping function for short interatomic distances. The TT range parameters are equally extracted on the fly from the electron density using their linear relationship to van der Waals radii. This relationship is empiricially determined for all the combinations of He-Xe rare gas dimers, as well as for the He and Ar trimers. The investigated systems include the S22 database of noncovalent interactions, Ar, benzene and ice crystals, bilayer graphene, C60 dimer, a peptide (Ala10), an intercalated drug-DNA model [ellipticine-d(CG)2], 42 DNA base pairs, a protein (DHFR, 2616 atoms), double stranded DNA (1905 atoms), and 12 molecular crystal polymorphs from crystal structure prediction blind test studies. The two- and three-body interatomic dispersion energies are found to contribute significantly to binding and cohesive energies, for bilayer graphene the latter reaches 50% of experimentally derived binding energy. These results suggest that interatomic three-body dispersion potentials should be accounted for in atomistic simulations when modeling bulky molecules or condensed phase systems.

Application of Solid-State NMR Relaxometry for Characterization and Formulation Optimization of Grinding-Induced Drug Nanoparticle.

PubMed

Ueda, Keisuke; Higashi, Kenjirou; Moribe, Kunikazu

2016-03-07

The formation mechanism of drug nanoparticles was investigated using solid-state nuclear magnetic resonance (NMR) techniques for the efficient discovery of an optimized nanoparticle formulation. The cogrinding of nifedipine (NIF) with polymers, including hydroxypropyl methylcellulose (HPMC) and polyvinylpyrrolidone (PVP), and sodium dodecyl sulfate (SDS) was performed to prepare the NIF nanoparticle formulations. Then, solid-state NMR relaxometry was used for the nanometer-order characterization of NIF in the polymer matrix. Solid-state NMR measurements revealed that the crystal size of NIF was reduced to several tens of nanometers with amorphization of NIF by cogrinding with HPMC and SDS for 100 min. Similarly, the size of the NIF crystal was reduced to less than 90 nm in the 40 min ground mixture of NIF/PVP/SDS. Furthermore, 100 min grinding of NIF/PVP/SDS induced amorphization of almost all the NIF crystals followed by nanosizing. The hydrogen bond between NIF and PVP led to the efficient amorphization of NIF in the NIF/PVP/SDS system compared with NIF/HPMC/SDS system. The efficient nanosizing of the NIF crystal in the solid state, revealed by the solid-state NMR relaxation time measurements, enabled the formation of large amounts of NIF nanoparticles in water followed by the polymer dissolution. In contrast, excess amorphization of the NIF crystals failed to efficiently prepare the NIF nanoparticles. The solid-state characterization of the crystalline NIF revealed good correlation with the NIF nanoparticles formation during aqueous dispersion. Furthermore, the solid-state NMR measurements including relaxometry successfully elucidated the nanometer-order dispersion state of NIF in polymer matrix, leading to the discovery of optimized conditions for the preparation of suitable drug nanoparticles.

Preparation of oridonin-loaded solid lipid nanoparticles and studies on them in vitro and in vivo

NASA Astrophysics Data System (ADS)

Zhang, Dianrui; Tan, Tianwei; Gao, Lei

2006-12-01

Oridonin, a lipophilic Chinese medicine, has very low oral bioavailability due to its poor solubility. Solid lipid nanoparticle (SLN) delivery systems of oridonin have been formed using stearic acid, soybean lecithin and pluronic F68 in our studies to overcome this problem. Emulsion evaporation-solidification at low temperature was used to prepare SLN dispersions. The particle size and morphology were examined by transmission electron microscopy (TEM), and the zeta potential was measured by a television micro-electrophoresis apparatus. Process and formulation variables have been studied and optimized on the basis of entrapment efficiency. Differential scanning calorimetry (DSC) and powder x-ray diffraction (PXRD) studies were performed to characterize the state of the drug. In vitro release studies were performed in phosphate-buffer solution (PBS) (pH 7.4). The tissue distribution in mice and the pharmacokinetics in rabbits were studied to evaluate the tissue targeted property of SLNs. Stable SLN formulations of oridonin having a mean size range of 15-35 nm and mean zeta potential -45.07 mV were developed. More than 40% oridonin was entrapped in SLNs. DSC and PXRD analysis showed that oridonin is dispersed in SLNs in an amorphous state. The release pattern of the drug was analysed and found to follow the Higuchi equations. In vivo studies demonstrated that oridonin-loaded SLNs obviously increased the concentration of oridonin in liver, lung and spleen, while its distribution in heart and kidney decreased.

Understanding the generation and maintenance of supersaturation during the dissolution of amorphous solid dispersions using modulated DSC and 1H NMR.

PubMed

Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J

2018-01-30

In this study, the dissolution behaviour of dipyridamole (DPM) and cinnarizine (CNZ) spray-dried amorphous solid dispersions (ASDs) using polyvinyl pyrrolidone (PVP) and polyacrylic acid (PAA) as a carrier matrix were evaluated and compared. The drug concentrations achieved from the dissolution of PVP and PAA solid dispersions were significantly greater than the equilibrium solubility of crystalline DPM and CNZ in phosphate buffer pH 6.8 (PBS 6.8). The maximum drug concentration achieved by dissolution of PVP and PAA solid dispersions did not exceed the theoretically calculated apparent solubility of amorphous DPM and CNZ. However, the degree of supersaturation of DPM and CNZ increased considerably as the polymer weight fraction within the solid dispersion increased. In addition, the supersaturation profile of DPM and CNZ were studied in the presence and absence of the polymers. PAA was found to maintain a higher level of supersaturation compared to PVP. The enhanced drug solution concentration following dissolution of ASDs can be attributed to the reduced crystal growth rates of DPM and CNZ at an equivalent supersaturation. We have also shown that, for drugs having high crystallization tendency and weak drug-polymer interaction, the feasible way to increase dissolution might be increase the polymer weight fraction in the ASD. Solution 1 H NMR spectra were used to understand dissolution mechanism and to identify drug-polymer interaction. The change in electron densities of proton attached to different groups in DPM and CNZ suggested drug-polymer interaction in solution. The relative intensities of peak shift and nature of interaction between drug and polymer in different systems are different. These different effects suggest that DPM and CNZ interacts in a different way with PVP and PAA in solution which goes some way towards explaining the different polymeric effect, particularly in terms of inhibition of drug recrystallization and dissolution of DPM and CNZ ASDs

Interactions between carbamazepine and polyethylene glycol (PEG) 6000: characterisations of the physical, solid dispersed and eutectic mixtures.

PubMed

Naima, Z; Siro, T; Juan-Manuel, G D; Chantal, C; René, C; Jerome, D

2001-02-01

The influence of a hydrophilic carrier (PEG 6000) on the polymorphism of carbamazepine, an antiepileptic drug, was investigated in binary physical mixtures and solid dispersions by means of differential scanning calorimetry (DSC), thermal gravimetry, hot-stage microscopy (HSM), and X-ray diffractometry, respectively. This study provides also an attempt to develop a method to calculate more precisely the eutectic composition. In rather ideal physical mixtures, carbamazepine was found as monoclinic Form III. In solid dispersions, the drug was found to crystallize as trigonal Form II; a eutectic invariant in the PEG 6000-rich composition domain (6% of carbamazepine mass) was evidenced by DSC experiments and confirmed by HSM observations. In the binary phase diagram the ideal carbamazepine liquidus curve was located at temperatures higher than the respective experimental ones. This suggests that drug can be maintained in the liquid state in the temperature-mass fraction (T--x) region between the two carbamazepine liquidus curves. This indicates in turn that attractive interactions occur between carbamazepine and PEG 6000-chains. These interactions have been also claimed to prevent carbamazepine from degradation into iminostilbene (a compound resulting from the chemical degradation of carbamazepine which is postulated to be responsible for the idiosyncratic toxicity of the drug) and thought to lead to the crystallization of metastable Carbamazepine II from melt. The negative excess entropy for eutectic mixtures indicated that the drug crystals are finely dispersed in the bulk of polymer chains.

Polypyrrole-magnetite dispersive micro-solid-phase extraction combined with ultraviolet-visible spectrophotometry for the determination of rhodamine 6G and crystal violet in textile wastewater.

PubMed

Kamaruddin, Amirah Farhan; Sanagi, Mohd Marsin; Wan Ibrahim, Wan Aini; Md Shukri, Dyia S; Abdul Keyon, Aemi S

2017-11-01

Polypyrrole-magnetite dispersive micro-solid-phase extraction method combined with ultraviolet-visible spectrophotometry was developed for the determination of selected cationic dyes in textile wastewater. Polypyrrole-magnetite was used as adsorbent due to its thermal stability, magnetic properties, and ability to adsorb Rhodamine 6G and crystal violet. Dispersive micro-solid-phase extraction parameters were optimized, including sample pH, adsorbent amount, extraction time, and desorption solvent. The optimum polypyrrole-magnetite dispersive micro-solid phase-extraction conditions were sample pH 8, 60 mg polypyrrole-magnetite adsorbent, 5 min of extraction time, and acetonitrile as the desorption solvent. Under the optimized conditions, the polypyrrole-magnetite dispersive micro-solid-phase extraction with ultraviolet-visible method showed good linearity in the range of 0.05-7 mg/L (R 2  > 0.9980). The method also showed a good limit of detection for the dyes (0.05 mg/L) and good analyte recoveries (97.4-111.3%) with relative standard deviations < 10%. The method was successfully applied to the analysis of dyes in textile wastewater samples where the concentration found was 1.03 mg (RSD ±7.9%) and 1.13 mg/L (RSD ± 4.6%) for Rhodamine 6G and crystal violet, respectively. It can be concluded that this method can be adopted for the rapid extraction and determination of dyes at trace concentration levels. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A study of the oxide dispersion and recrystallization in NiCrAl prepared from preoxidized powder

NASA Technical Reports Server (NTRS)

Glasgow, T. K.

1975-01-01

The sintered aluminum powder (SAP) technique of dispersion strengthening (formation of an oxide dispersion by preoxidation of metal powders) was applied to atomized powder of a nickel alloy containing, by weight, 17% Cr, 5% Al, and 0.2% Y. The SAP-NiCrAl alloy (without the ytterbium removed by oxdation) was worked by extrusion and rod rolling at 1205 C and by swaging at 760 C. Annealing treatments were applied after working to determine the recrystallization response. The NiCrAlY alloy, similarly prepared from atomized powder, but without a preoxidation treatment, was examined for comparison. The SAP-NiCrAl alloy exhibited oxide particle size and spacing much larger than that usually observed in oxide dispersion strengthened alloys; nonetheless, it was possible to achieve abnormal (secondary) recrystallization in the SAP-NiCrAl alloy as has been reported for other oxide dispersion strengthened alloys. In contrast, the unoxidized NiCrAlY alloy exhibited only primary recrystallization.

Preparation of In2S3 nanopraricle by ultrasonic dispersion and its tribology property.

PubMed

Li, Zhiwei; Tao, Xiaojun; Wu, Zhishen; Zhang, Pingyu; Zhang, Zhijun

2009-02-01

In this paper, we describe a facile and rapid method for preparing In2S3 nanoparticles via ultrasound dispersion. This method allows us to prepare In2S3 nanoparticles from bulk indium and sulfur with ease and without using expensive agents and in a short time. The possible growing mechanism of the In2S3 nanoparticles was presented. In addition, we provide detailed characterizations including TEM, XRD, TG-DTA, and XPS to study the shape, composition and structure of In2S3 nanoparticles. We also studied the tribology property of In2S3 nanoparticles made using this novel recipe.

Methods for the preparation and analysis of solids and suspended solids for total mercury

USGS Publications Warehouse

Olund, Shane D.; DeWild, John F.; Olson, Mark L.; Tate, Michael T.

2004-01-01

The methods documented in this report are utilized by the Wisconsin District Mercury Lab for analysis of total mercury in solids (soils and sediments) and suspended solids (isolated on filters). Separate procedures are required for the different sample types. For solids, samples are prepared by room-temperature acid digestion and oxidation with aqua regia. The samples are brought up to volume with a 5 percent bromine monochloride solution to ensure complete oxidation and heated at 50?C in an oven overnight. Samples are then analyzed with an automated flow injection system incorporating a cold vapor atomic fluorescence spectrometer. A method detection limit of 0.3 ng of mercury per digestion bomb was established using multiple analyses of an environmental sample. Based on the range of masses processed, the minimum sample reporting limit varies from 0.6 ng/g to 6 ng/g. Suspended solids samples are oxidized with a 5 percent bromine monochloride solution and held at 50?C in an oven for 5 days. The samples are then analyzed with an automated flow injection system incorporating a cold vapor atomic fluorescence spectrometer. Using a certified reference material as a surrogate for an environmental sample, a method detection limit of 0.059 ng of mercury per filter was established. The minimum sample reporting limit varies from 0.059 ng/L to 1.18 ng/L, depending on the volume of water filtered.

Determination of oral bioavailability of curcuminoid dispersions and nanoemulsions prepared from Curcuma longa Linnaeus.

PubMed

Lu, Pei Shan; Inbaraj, Baskaran Stephen; Chen, Bing Huei

2018-01-01

Curcuminoid from Curcuma longa Linnaeus has been demonstrated to be effective in anti-cancer and anti-inflammation. The objectives of the present study were to prepare curcuminoid dispersion and nanoemulsion from C. longa and determine their oral bioavailabilities in rats. After curcuminoid extraction using 99.5% ethanol, bisdemethoxycurcumin (BDMC), demethoxycurcumin (DMC) and curcumin were separated within 10 min by high-performance liquid chromatography using an Eclipse XDB-C18 column (Agilent, Palo Alto, CA, USA) and a gradient mobile phase of 0.1% aqueous formic acid and acetonitrile, with a flow rate of 1 mL min -1 , column temperature of 35 °C and detection wavelength of 425 nm. Curcuminoid nanoemulsion at a particle size of 12.1 nm and encapsulation efficiency 98.8% was prepared using lecithin, Tween 80 and water. A pharmacokinetic study in rats revealed that the parameters including T max , C max , t 1/2 and the area under the curve were higher for curcuminoid nanoemulsions than for curcuminoid dispersion at the same dose employed for gavage administration, whereas, for intravenous injection, an opposite trend was shown. The oral bioavailabilities of BDMC, DMC, curcumin and total curcuminoids in nanoemulsion and dispersion were 34.39 and 4.65%, 39.93 and 5.49%, 47.82 and 9.38%, and 46 and 8.7%, respectively. The results of the present study demonstrate a higher oral bioavailability after incorporation of curcuminoid into nanoemulsion, facilitating its application as a botanic drug. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

Development, Characterization and Evaluation of Solid Lipid Nanoparticles as a potential Anticancer Drug Delivery System

NASA Astrophysics Data System (ADS)

Patel, Meghavi

Solid lipid nanoparticles (SLNs) consist of spherical solid lipid particles in the nanometer size range, which are dispersed in water or in an aqueous surfactant solution. SLN technology represents a promising new approach to deliver hydrophilic as well as lipophilic drugs. The commercialization of SLN technology remains limited despite numerous efforts from researchers. The purpose of this research was to advance SLN preparation methodology by investigating the feasibility of preparing glyceryl monostearate (GMS) nanoparticles by using three preparation methods namely microemulsion technique, magnetic stirring technique and temperature modulated solidification technique of which the latter two were developed in our laboratory. An anticancer drug 5-fluorouracil was incorporated in the SLNs prepared via the temperature modulated solidification process. Optimization of the magnetic stirring process was performed to evaluate how the physicochemical properties of the SLN was influenced by systematically varying process parameters including concentration of the lipid, concentration of the surfactant, type of surfactant, time of stirring and temperature of storage. The results demonstrated 1:2 GMS to tween 80 ratio, 150 ml dispersion medium and 45 min stirring at 4000 RPM speed provided an optimum formulation via the temperature modulated solidification process. SLN dispersions were lyophilized to stabilize the solid lipid nanoparticles and the lyophilizates exhibited good redispersibility. The SLNs were characterized by particle size analysis via dynamic light scattering (DLS), zeta potential, transmission electron microscopy (TEM), differential scanning calorimetry (DSC), drug encapsulation efficiency and in vitro drug release studies. Particle size of SLN dispersion prepared via the three preparation techniques was approximately 66 nm and that of redispersed lyophilizates was below 500 nm. TEM images showed spherical to oval particles that were less dense in the core

Polymorphic transition of solid-fats dispersed systems — its characterization by a novel method and scanning electron microscopy observation

NASA Astrophysics Data System (ADS)

Hirokawa, Norio; Ueda, Masahiro; Harano, Yoshio

1994-08-01

Solid-fats dispersed systems, such as margarine, butter and cacao-butter, were characterized by a novel method based on liquid permeation under pressure, for the simultaneous measurement of a solid-content ɛ p and an average diameter dp of solid particles (fats crystals) in them. Further, micro-structures of these systems were observed by a scanning electron microscope (SEM). As the result, it has been clarified that the spherical fats crystals of several μm in size appeared in the initial solid-fats products are agglomerates of fine particles of ca. 0.1 μm and that these fine particles are uniformly redispersed during an annealing treatment accompanying the reduction of ɛ p and dp. It is strongly suggested that this phenomenon is caused by a transition of fat crystals into a more stable polymorph.

Micro-matrix solid-phase dispersion coupled with MEEKC for quantitative analysis of lignans in Schisandrae Chinensis Fructus using molecular sieve TS-1 as a sorbent.

PubMed

Chu, Chu; Wei, Mengmeng; Wang, Shan; Zheng, Liqiong; He, Zheng; Cao, Jun; Yan, Jizhong

2017-09-15

A simple and effective method was developed for determining lignans in Schisandrae Chinensis Fructus by using a micro-matrix solid phase dispersion (MSPD) technique coupled with microemulsion electrokinetic chromatography (MEEKC). Molecular sieve, TS-1, was applied as a solid supporting material in micro MSPD extraction for the first time. Parameters that affect extraction efficiency, such as type of dispersant, mass ratio of the sample to the dispersant, grinding time, elution solvent and volume were optimized. The optimal extraction conditions involve dispersing 25mg of powdered Schisandrae samples with 50mg of TS-1 by a mortar and pestle. A grinding time of 150s was adopted. The blend was then transferred to a solid-phase extraction cartridge and the target analytes were eluted with 500μL of methanol. Moreover, several parameters affecting MEEKC separation were studied, including the type of oil, SDS concentration, type and concentration of cosurfactant, and concentration of organic modifier. A satisfactory linearity (R>0.9998) was obtained, and the calculated limits of quantitation were less than 2.77μg/mL. Finally, the micro MSPD-MEEKC method was successfully applied to the analysis of lignans in complex Schisandrae fructus samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation of graphite dispersed copper composite on copper plate with CO2 laser

NASA Astrophysics Data System (ADS)

Yokoyama, S.; Ishikawa, Y.; Muizz, M. N. A.; Hisyamudin, M. N. N.; Nishiyama, K.; Sasano, J.; Izaki, M.

2018-01-01

It was tried in this work to prepare the graphite dispersed copper composite locally on a copper plate with a CO2 laser. The objectives of this study were to clear whether copper graphite composite was prepared on a copper plate and how the composite was prepared. The carbon content at the laser spot decreased with the laser irradiation time. This mainly resulted from the elimination by the laser trapping. The carbon content at the outside of the laser spot increased with time. Both the laser ablation and the laser trapping did not act on the graphite particles at the outside of the laser spot. Because the copper at the outside of the laser spot melted by the heat conduction from the laser spot, the particles were fixed by the wetting. However, the graphite particles were half-floated on the copper plate. The Vickers hardness decreased with an increase with laser irradiation time because of annealing.

Trace matrix solid phase dispersion using a molecular sieve as the sorbent for the determination of flavonoids in fruit peels by ultra-performance liquid chromatography.

PubMed

Cao, Wan; Hu, Shuai-Shuai; Ye, Li-Hong; Cao, Jun; Pang, Xiao-Qing; Xu, Jing-Jing

2016-01-01

A simple, rapid, and highly selective trace matrix solid phase dispersion (MSPD) technique, coupled with ultra-performance liquid chromatography-ultraviolet detection, was proposed for extracting flavonoids from orange fruit peel matrices. Molecular sieve SBA-15 was applied for the first time as a solid support in trace MSPD. Parameters, such as the type of dispersant, mass ratio of the sample to the dispersant, grinding time, and elution pH, were optimized in detail. The optimal extraction conditions involved dispersing a powdered fruit peel sample (25 mg) into 25mg of SBA-15 and then eluting the target analytes with 500 μL of methanol. A satisfactory linearity (r(2) > 0.9990) was obtained, and the calculated limits of detection reached 0.02-0.03 μg/mL for the compounds. The results showed that the method developed was successfully applied to determine the content of flavonoids in complex fruit peel matrices. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transport of temperature-velocity covariance in gas-solid flow and its relation to the axial dispersion coefficient

NASA Astrophysics Data System (ADS)

Subramaniam, Shankar; Sun, Bo

2015-11-01

The presence of solid particles in a steady laminar flow generates velocity fluctuations with respect to the mean fluid velocity that are termed pseudo-turbulence. The level of these pseudo-turbulent velocity fluctuations has been characterized in statistically homogeneous fixed particle assemblies and freely evolving suspensions using particle-resolved direct numerical simulation (PR-DNS) by Mehrabadi et al. (JFM, 2015), and it is found to be a significant contribution to the total kinetic energy associated with the flow. The correlation of these velocity fluctuations with temperature (or a passive scalar) generates a flux term that appears in the transport equation for the average fluid temperature (or average scalar concentration). The magnitude of this transport of temperature-velocity covariance is quantified using PR-DNS of thermally fully developed flow past a statistically homogeneous fixed assembly of particles, and the budget of the average fluid temperature equation is presented. The relation of this transport term to the axial dispersion coefficient (Brenner, Phil. Trans. Roy. Soc. A, 1980) is established. The simulation results are then interpreted in the context of our understanding of axial dispersion in gas-solid flow. NSF CBET 1336941.

Two and three-body interatomic dispersion energy contributions to binding in molecules and solids.

DOE Office of Scientific and Technical Information (OSTI.GOV)

von Lilienfeld-Toal, Otto Anatole; Tkatchenko, Alexandre

We present numerical estimates of the leading two- and three-body dispersion energy terms in van der Waals interactions for a broad variety of molecules and solids. The calculations are based on London and Axilrod-Teller-Muto expressions where the required interatomic dispersion energy coefficients, C{sub 6} and C{sub 9}, are computed 'on the fly' from the electron density. Inter- and intramolecular energy contributions are obtained using the Tang-Toennies (TT) damping function for short interatomic distances. The TT range parameters are equally extracted on the fly from the electron density using their linear relationship to van der Waals radii. This relationship is empiriciallymore » determined for all the combinations of He-Xe rare gas dimers, as well as for the He and Ar trimers. The investigated systems include the S22 database of noncovalent interactions, Ar, benzene and ice crystals, bilayer graphene, C{sub 60} dimer, a peptide (Ala{sub 10}), an intercalated drug-DNA model [ellipticine-d(CG){sub 2}], 42 DNA base pairs, a protein (DHFR, 2616 atoms), double stranded DNA (1905 atoms), and 12 molecular crystal polymorphs from crystal structure prediction blind test studies. The two- and three-body interatomic dispersion energies are found to contribute significantly to binding and cohesive energies, for bilayer graphene the latter reaches 50% of experimentally derived binding energy. These results suggest that interatomic three-body dispersion potentials should be accounted for in atomistic simulations when modeling bulky molecules or condensed phase systems.« less

Determination of six pesticides in the medicinal herb Cordia salicifolia by matrix solid-phase dispersion and gas chromatography/mass spectrometry.

PubMed

de Carvalho, Pedro Henrique Viana; Prata, Vanessa de Menezes; Alves, Péricles Barreto; Navickiene, Sandro

2009-01-01

A simple and effective extraction method based on matrix solid-phase dispersion was developed for acephate, chlorpropham, pyrimicarb, bifenthrin, tetradifon, and phosalone in leaves of the medicinal plant Cordia salicifolia, whose extracts are commercialized in Brazil as diuretic, appetite suppressant, and weight loss products. The determination method was GC/MS with selected-ion monitoring. Different parameters of the method were evaluated, such as type of solid phase (C18, alumina, silica gel, and Florisil) and the amount of solid phase and eluent (dichloromethane, ethyl acetate, chloroform, and cyclohexane). The best results were obtained using 0.5 g herb sample, 0.5 g neutral alumina as the dispersant sorbent, 0.5 g C18 as the cleanup sorbent, and cyclohexane-dichloromethane (3 + 1, v/v) as the eluting solvent. The method was validated using herb samples fortified with pesticides at different concentration levels (0.3, 0.5, and 1.0 mg/kg). Average recoveries (seven replicates) ranged from 67.7 to 129.9%, with relative standard deviations between 6.3 and 26%. Detection and quantitation limits for the herb ranged from 0.10 to 0.15 and 0.15 to 0.25 mg/kg, respectively.

Crosslinked hydrogels-a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs.

PubMed

Sun, Dajun D; Lee, Ping I

2014-02-01

Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

Crosslinked hydrogels—a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

PubMed Central

Sun, Dajun D.; Lee, Ping I.

2014-01-01

Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs. PMID:26579361

Cellulose nanocrystal/polyolefin biocomposites prepared by solid-state shear pulverization: Superior dispersion leading to synergistic property enhancements

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Krishnan A. Iyer; Gregory T. Schueneman; John M. Torkelson

2015-01-01

Cellulose nanocrystals (CNCs), a class of renewable bionanomaterials with excellent mechanical properties, have gained major interest as filler for polymers. However, challenges associated with effective CNC dispersion have hindered the production of composites with desired property enhancements. Here, composites of polypropylene (PP) and low density polyethylene (LDPE...