Recent progress on dissolution and absorption of amorphous solid dispersions / 药学学报

The amorphous solid dispersion is one of the most effective formulation approaches to enhance the oral bioavailability of poorly water-soluble drugs. However, the amorphous drugs tend to crystallize during storage or dissolution due to inadequate formulations, preparation techniques, storage and dissolution conditions, thus negating their advantages. Meanwhile, it is often difficult to establish in vitro-in vivo correlation for amorphous solid dispersions owing to the difference between dissolution media and physiological environments and between the apparent concentration and membrane transport flux, the dynamic process of the in vivo absorption, which put great challenges to the development of amorphous solid dispersion products. This review covers the recent progress on the mechanistic study of the in vitro dissolution and in vivo absorption of amorphous solid dispersions, aiming to provide guidance for the formulation development of poorly soluble drugs.

Equivalencia terapéutica in vitro de tabletas de enalapril maleato 20 mg de producción nacional / In vitro therapeutic equivalence of 20 mg enalapril maleate tablets of national production

Los ensayos de equivalencia terapéutica tienen como objetivo demostrar que los medicamentos genéricos aportan la misma cantidad de principio activo en comparación con el medicamento innovador. El objetivo de la investigación fue evaluar la equivalencia terapéutica del medicamento enalapril maleato en tabletas de 20 mg, según la clasificación biofarmacéutica que le corresponde, ya que este es un medicamento representativo de la clase III, para demostrar que tienen un perfil de tolerabilidad adecuado y que son eficaces para su prescripción médica. Por otro lado, al demostrarse la equivalencia terapéutica se puede recurrir con toda seguridad al medicamento genérico y reducir los costos de los tratamientos, con lo cual la población tendrá una oferta de medicamentos confiables, seguros y a precios económicos. Se utilizó un medicamento innovador y tres de los ocho medicamentos genéricos de fabricación y comercialización nacional, a los cuales se les determinó perfiles de disolución (F2: 45.41, 92.42, 71.04), uniformidad de contenido (AV: 7.37, 2.97, 2.50) y valoración de principio activo (%: 107.14, 98.89, 101.71) para determinar la cantidad de principio activo en las muestras. Los análisis se realizaron con base en los criterios establecidos en la Farmacopea de los Estados Unidos. Se aplicó un modelo estadístico independiente, y se estableció que dos de los tres lotes analizados de los medicamentos genéricos son equivalentes terapéuticos con el lote del medicamento innovador. Con las pruebas de disolución in vitro realizadas a lo largo de este estudio, se puede concluir que los tres lotes analizados de dos medicamentos genéricos pueden ser considerados intercambiables con respecto al lote del medicamento innovador.

The therapeutic equivalence essays to demonstrate that generic medicine can provide the same amount of active ingredient compared to the innovative medicine. The objective of this research was to evaluate the therapeutic equivalence of enalapril maleate 20 mg, according to the biopharmaceutical classification, given that this is a representative class III drug. This to demonstrate that it has an acceptable tolerability profile and that it is effective for medical prescription. Once the therapeutic equivalence is stablished, the use of therapeutic bioequivalence products can reduce treatment costs, so that the general public can have access to reliable, safe and affordable medicines. For this study an innovative medicine and three of the eight generic medicines of national manufacture and commercialization were used for each medicine, the dissolucion profiles (F2: 45.41, 92.42, 71.04), the uniformity of content (AV: 7.37, 2.97, 2.50) and percentage of active ingredient (%: 107.14, 98.89, 101.71) were determined. The essays were performed based on the criteria established in The United States Pharmacopeia and were satisfactory in all the analyzed batches. An independent statistical model was carried out it was established, that two of the three analyzed batches for generic medicine are therapeutic equivalents with the batch of the innovative drug. In vitro dissolution tests obtained throughout this study, concluded that the three analyzed batches of two generic medicines can be considered interchangeable in respect to the batch of the innovative medicine.

Preparation and in vitro evaluation of puerarin nanoemulsion lyophilized powder with glycyrrhizic acid as stabilizer / 中草药

Objective: Puerarin nanoemulsion lyophilized powder (Pue-NE-LP) was prepared using natural surfactant glycyrrhizic acid as stabilizer and evaluated in vitro. Methods: Pue-NE was prepared by high-speed shear and high-pressure homogenization method, and further combined with freeze-drying method to prepare Pue-NE-LP. Taking the average particle size and polydispersity index (PDI) as the evaluation indexes, the optimal prescription and process parameters of this experiment were screened out through a single factor test. The prepared Pue-NE-LP was characterized by physicochemical properties and dissolution in vitro. Results: The average particle size and PDI of Pue-NE-LP prepared with 5% glyceryl caprylate as oil phase, 2.0 mg/mL glycyrrhizic acid as stabilizer, and 7% glucose as lyophilization protectant was (215.1 ± 0.7) nm and (0.133 ± 0.024), respectively. Scanning electron microscopy showed that Pue-NE-LP was irregularly small and uniform in size; X-ray diffraction showed that Pue-NE-LP existed in an amorphous state. In vitro release results showed that the dissolution rate of Pue-NE-LP was significantly higher than the physical mixture. Conclusion: Pue-NE-LP prepared with natural surfactant glycyrrhizic acid as a stabilizer is not only simple to prepare, but also can significantly improve the solubility and bioavailability of puerarin. It provides a reference for the multiple development of Pue-NE formulations.

Formulation And Evaluation Of Liquisolid Compacts Of Lornoxicam

Objective: Objective of the present investigation was to enhance the solubility and dissolution rate of poorly water-soluble drug lornoxicam using liquisolid technique with comparative determination of in vitro release profile of liquisolid compacts and conventional formulation of lornoxicam. Methods: Formulation was prepared by a liquisolid technique using different drug concentration in a liquid vehicle and different carrier/coating ratio. Prepared liquisolid compact was evaluated for Fourier transform infrared (FTIR) spectra analysis, differential scanning calorimetry (DSC), X-ray diffraction (P-XRD), scanning electron microscopy (SEM) and in vitro dissolution study. Results: The result showed that liquisolid compacts of lornoxicam displayed significantly higher drug release rate as compared to pure drug and conventional tablet prepared. The results of both DSC and X-ray crystallography indicated loss of crystallinity of the drug upon formulated into the liquisolid compact. Conclusion: Dissolution rate of the drug from liquisolid compacts was affected by changing the drug concentration and excipient ratio. The liquisolid technique appeared to be a promising approach for improving the dissolution of poorly soluble drug lornoxicam.

Study on preparation of volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills and its protective effect on acute myocardial ischemia injury / 中国中药杂志

In this study, solid dispersion technology was used to develop volatile oil from Acorus tatarinowii self-nanoemulsion dropping pills(VOA-SNEDDS-DP) and its protective effect on acute myocardial ischemia injury was evaluated. Taking exterior quality, weight variation and the resolving time as comprehendsive evaluation indexes, the preparation process and formulation of the dropping pills were optimized by orthogonal design, and the dissolution rate in vitro of the optimized VOA-SNEDDS-DP was investigated. The rat model of acute myocardial ischemia was induced by intraperitoneal injection of isoproterenol hydrochloride and the serum levels of superoxide dismutase(SOD), malondialdehyde(MDA), creatine kinase(CK) and pathological changes of myocardial tissue were determined to evaluate therapeutic effect of the dropping pills on acute myocardial ischemia. The results showed that the optimal formulation and preparation process of VOA-SNEDDS-DP were as follows: PEG6000-PEG8000 was 1∶1, proportion of VOA-SNEDDS and matrix was l∶2.5, the temperature of drug fluids was 75 ℃, drop rate was 35 drops/min, drop distance was 5 cm, the condensing agent temperature was 2-10 ℃. The content of β-asarone in the dropping pills was 42.46 mg·g~(-1). The accumulated dissolution rate of the dropping pills reached 93.85% in 10 min. The results of pharmacodynamic experiments showed that VOA-SNEDDS-DP could significantly increase the SOD content(P<0.05), reduce the levels of MDA and CK(P<0.05) in serum, and effectively improve the pathological morphology of myocardial tissue. These results revealed that the preparation of VOA-SNEDDS-DP by solid dispersion technology was stable and feasible, and VOA-SNEDDS-DP had protective effect on acute myocardial ischemia injury.

Effect of HPMCAS/curcumin amorphous solid dispersion in enhancing dissolution and chemical stability of curcumin / 中国中药杂志

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.

Comparison of in Vitro Dissolution of Active Ingredients in Gastrodiae Rhizoma Powder with Different Particle Size / 中国实验方剂学杂志

Objective: To compare in vitro dissolution behaviors of active ingredients (gastrodin,parishin A,p-hydroxybenzyl alcohol,parishin B and parishin C) in Gastrodiae Rhizoma powder with different particle size.Method: In vitro dissolution of Gastrodiae Rhizoma powder in different dissolution media (water,artificial gastric juice and artificial intestinal juice) were detected by stirring paddle method.Dissolution of these five components in Gastrodiae Rhizoma powder with different particle size was determined by HPLC,mobile phase was acetonitrile-0.1% phosphoric acid solution for gradient elution,column temperature was set at 40℃ and detection wavelength was 220 nm.Result: In water and artificial intestinal juice,the dissolution rates of five active components in three kinds of Gastrodiae Rhizoma ultrafine powders were higher than that of the fine powder and the finest powder;in artificial gastric juice,the dissolution rates of gastrodin and p-hydroxybenzyl alcohol in Gastrodiae Rhizoma ultrafine powders were higher than that of the other powders,and the dissolution rate of parishin A in Gastrodiae Rhizoma ultrafine powders was lower than that of the other powders.Conclusion: An appropriate degree of superfine grinding can promote the dissolution of active ingredients in Gastrodiae Rhizoma,but not as fine as possible.The dissolution medium has an obvious influence on the dissolution behaviors of active components,which provides a reference for screening optical particle size of Gastrodiae Rhizoma powder in clinical application.

Preparation and quality evaluation of licorice flavonoids self-microemulsifying drug delivery system / 中草药

Objective: To study the prescription and preparation technology of licorice flavonoids self-microemulsifying drug delivery system (LF-SMEDDS) and evaluate its quality. Methods: The optimal formulation of LF-SMEDDS was screened by test of solubility, compatibility of oil and emulsifier, and pseudo-ternary phase diagram. Simplex lattice method was applied to optimize formulation with average particle size, polydispersity index and drug loading as evaluation indexes, the physicochemical characteristics, in vitro dissolution and stability were also determined. Results: The optimal prescription composition of LF-SMEDDS was 10% of Cinnamomi Cortex oil, 55% of RH-40, and 35% of 1,2-propanediol. The LF-SMEDDS exhibited uniform and transparent appearance, with the average particle size of (16.30 ± 0.22) nm, polydispersity index of 0.155 ± 0.008, Zeta pontential of (-20.11 ± 0.50) mV and drug loading of (86.03 ± 0.37) mg/g. The results of in vitro dissolution test indicated that the accumulative dissolution of LF was 90.65% at 30 min. The stability experiment showed that LF-SMEDDS was affected by high temperature and illumination, indicating that it should be stored at low temperature and protected from light. Conclusion: The LF-SMEDDS is simple in preparation and stable in quality, significantly increasing the solubility of LF and improving its oral bioavailability, which can provide reference for further research and development about the related preparations of the active fraction.

Preparation and bioavailability of magnolol solid dispersions / 中草药

Objective: Hot-melt extrusion technique was applied to prepare magnolol solid dispersions, which can improve the in vitro solubility of magnolol and the in vivo bioavailability in rats. Methods: Four kinds of excipients, such as PS-630, HPC, EPO, and Soluplus, which were compatible with magnolol were used to prepare solid dispersions of different drug loadings by solubility parameter calculation. The prepared solid dispersion was characterized by differential scanning calorimetry (DSC), X-ray diffraction analysis (XRPD) and infrared spectroscopy (IR) using in vitro dissolution as an indicator; UPLC-MS/MS was used to evaluate the pharmacokinetic behavior of rats after oral administration of magnolol solid dispersion. Results: The in vitro dissolution test showed that the solid dispersion prepared by the 1:6 drug loading of PS-630, HPC, and EPO can significantly improve the dissolution of magnolol, and the drug was dispersed in the carrier in an amorphous state. The in vivo bioavailability test showed that the Cmax of magnolol in the solid dispersion prepared by PS-630 and HPC was about five times and 2.3 times that of the monomer, respectively, and the AUC0-t was increased about 37.22% and 70.88%, respectively. There was no increase in the EPO system. Conclusion: Hot melt extrusion technology can be successfully applied to improve the in vitro dissolution and in vivo bioavailability of the poorly soluble drug magnolol.

Dissolution kinetics of Compound Danshen Tablets based on cell bioelectrical sensing effect / 中草药

Objective: Establishing the model of cell bioelectrical sensing effect of Compound Danshen Tablets to study its dissolution kinetics. Methods: By means of real-time cell-based assay, the in vitro dissolution of Compound Danshen Tablets can be investigated, and then the dissolution kinetics model can also be established. In addition, the result was compared and verified by UV-Vis. Results: The cell line with specific dependence on Compound Danshen Tablets was screened by CCK-8 experiment and RTCA experiment. The dissolution kinetics model of Compound Danshen Tablets based on RTCA technology was established, and the best fitting model was obtained: Weibull model ln{ln[1/(1-Q)] =1.071 4 lnt-3.736 7; Establish a dissolution kinetic model of Compound Danshen Tablets based on UV spectrophotometry to obtain the best fitting model, Weibull model ln{ln[1/(1-Q)]}=1.080 4 lnt-3.723 4; Comparing the two Weibull models, the RTCA fitted model worked better. Conclusion: The application of RTCA in the dissolution kinetics of traditional Chinese medicine compound solid preparations is feasible, Which provides new ideas for traditional Chinese medicines and the quality evaluation of traditional Chinese medicine compunds.

Preparation and characterization of SiO2 solid dispersions of Curcumae longae Rhizoma extract / 中成药

AIM To prepare and characterize SiO2 solid dispersions of Curcumae longae Rhizoma extract.METHODS For the solid dispersions prepared by solvent evaporation method,its ratio of extract to carrier (SiO2) was screened by in vitro dissolution test,and the characterization was achieved by determination of particle size,specific surface area,porosity,micromorphology observation,infrared spectroscopy and X-ray.RESULTS When the ratio of extract to carfer was 1:8,three main components (bisdemethoxycurcumin,demethoxycurcumin and curcumin) in the extract reached the highest accumulative dissolution rates.Compared with physical mixture,the solid dispersions demonstrated lower particle size,specific surface area and porosity.Extract was dispensed in the carrier in an amorphous state.CONCLUSION SiO2 solid dispersions can obviously improve the dissolution rates of the main components in Curcumae longae Rhizoma extract.

Influence of Different Particle Size on the Quality of Nifedipine Sustained Release Tablets / 中国药师

Objective: To establish a method for the determination of the particle size of nifedipine and study the effect of particle size on the in vitro dissolution behaviors of nifedipine sustained release tablets. Methods: Light scattering was used to study the parti-cle size of nifedipine API. Nifedipine APIs with different particle sizes were prepared by a portable high-speed grinder. The in vitro dis-solution curve of nifedipine sustained released tablets (Ⅰ) was determined by HPLC. The similarity was evaluated using the similarity factor ( f2) with the original drug (trade name: Adalat-L, specification: 10mg) as the reference preparation. Results: The granulo-metric conditions were as follows: the pump speed of laser size analyzer was 1 800 r·min-1, the shading rate was 8%-20% , the bal-ance time was 0 s, the media was 0. 3% Tween 80, and the ultrasonic time was 1 min. The in vitro dissolution of nifedipine sustained released tablets (Ⅰ) showed that the smaller particle size of nifedipine API, the better the dissolution was. As the Dv90 ( the particle size accounting for 90% of the total particle quantity) was reduced from 118. 781 μm to 3. 471 μm, the cumulative dissolution in 0. 25 h of nifedipine sustained released tablets (Ⅰ) increased from 11. 2% to 44. 0% , the similarity factor ( f2) compared with the dis-solution cruve of the original drug increased firstly and then decreased, and f2value was 77 when the Dv90 was 29. 823 μm. Conclu-sion: The in vitro dissolution of nifedipine sustained released tablets is improved remarkably by micronization technology. In order to produce nifedipine sustained released tablets (Ⅰ) with the same bioavailability as the original drug preparation, the particle size of nife-dipine API should be controlled within the range of 15 μm≤Dv90≤45 μm.

Preparation and in vitro Dissolution of Febuxostat Nanosuspension Sustained-release Pellets / 中国药师

Objective:To prepare febuxostat nanosuspension and prepare sustained-release pellets,and investigate the in vitro dis-solution.Methods: Febuxostat nanosuspension was prepared by a high pressure homogenization method. Febuxostat nanosuspension pellets were prepared by fluidized bed coating technique. Eudragit RL30D and Eudragit RS30D were used to prepare the sustained-re-lease pellets. The dissolution mechanism of febuxostat nanosuspension sustained-release pellets was evaluated. Results: The average particle size of the prepared febuxostat nanosuspension was (212.5 ± 36.3) nm, PdI was (0.193 ± 0.018), zeta potential was ( -12.4 ± 0.3) mV,and the scanning electron microscopy showed that the particle size distribution of febuxostat nanosuspension was narrow. The in vitro dissolution of febuxostat nanosuspension sustained-release pellets was more stable and conformed to the first-order release model. Conclusion: The in vitro dissolution of febuxostat nanosuspension sustained-release pellets is more stable, and the preparation provides a new choice for febuxostat clinical application.

Study on the Preparation of Lansoprazole Enteric-coated Pellets Orally Disintegrating Tablets / 中国药师

Objective:To prepare lansoprazole enteric-coated pellets and compress them into orally disintegrating tablets , and e-valuate the acid resistance in the acid stage and the in vitro dissolution in the buffer stage .Methods:Lansoprazole enteric-coated pel-lets were prepared by fluid bed coating technology , and the effects of the ratio of methacrylic acid copolymer dispersion to ethyl acrylate–methyl methacrylate copolymer dispersion , the concentration of triethyl citrate and the main pressure on the acid resistance in the acid stage and the in vitro dissolution in the buffer stage were evaluated .The similarity of the self-prepared orally disintegrating tablets and the reference preparation was evaluated by using f 2 similarity factor method .Results:The average particle size of microcrystalline cellulose core was 150-180 μm, the ratio of methacrylic acid copolymer dispersion to ethyl acrylate –methyl methacrylate copolymer dispersion was adjusted to 8:2, the enteric-coated weight was 30％, 20％triethyl citrate was used and the main pressure was controlled within the range of 10-16 kN.Lansoprazole enteric-coated pellets had sufficiently flexibility and stability against the compression force . The enteric coating did not break , showing good acid resistance .The dissolution similarity factor of the self-prepared orally disintegra-ting tablets and the reference preparation was greater than 50.Conclusion: Lansoprazole enteric-coated pellets orally disintegrating tablets have good acid resistance and high similarity for the in vitro dissolution, which can be further amplified .

Optimization of Meloxicam Nanosuspensions Fast Dissolving Sublingual Films (MLX-NS-Fdsfs) by Box-Behnken Response Surface Methodology / 中国药学杂志

OBJECTIVE: To prepare and optimize meloxicam nanosuspensions fast dissolving sublingual films (MLX-NS-FDSFs) and to evaluate its in vitro dissolution characteristics. METHODS: Meloxicam nanosuspensions (MLX-NS) were prepared by pH-dependent dissolving-precipitating/high speed shearing method and then transformed into fast dissolving sublingual films (FDSFs). The formulations of MLX-NS-FDSFs were optimized by employing Box-Behnken design-response surface methodology with the amount of HPMC-E30, PEG-400 and MLX-NS as investigation factors, and particle size of reconstituted nanoparticles from MLX-NS-FDSFs, disintegration time and stretch length as indexes. The morphology, content uniformity and in vitro dissolution of the optimal formulation were also evaluated. RESULTS: The MLX-NS-FDSFs prepared by optimized formulation (35 mg·mL-1 HPMC-E30, 40 mg·mL-1 PEG-400, 10 mL MLX-NS) could fast disintegrate in (26.08±1.76) s, the tensile length was (1.51±0.13) mm, and the particle size of reconstituted nanoparticles from MLX-NS-FDSFs was (186.4±6.3) nm. There was a little deviation between the theoretically predicted value and the measured value. It showed that this model had a good prediction. Morphological analysis showed that well-dispersed MLX nanoparticles embedded in MLX-NS-FDSFs. The conformity of drug content was up to standard. MLX could be released in vitro as much as (91.75±8.05)% within five minutes. CONCLUSION: Using Box-Behnken design and response surface method to optimize MLX-NS-FDSFs is effective and feasible. MLX-NS-FDSFs can significantly increase the cumulative dissolution of MLX.

Preparation and characterization of solid dispersion in vitro from extract of Tripterygium wilfordii based on multi-component evaluation / 中草药

Objective To improve the dissolution in vitro, thereby to prepare the solid dispersion (SD) from the extract of Tripterygium wilfordii (ETW). Methods Polyethylene glycol 6000 (PEG 6000) and poloxamer 188 (F68) were used as carrier to prepare ETW-SD by solvent-melting method. The triptolide, triptonide, wilforine, tripterine and wilforlide were used as the evaluation indexes to characterize the optimal prescription of ETW-SD by dissolution in vitro, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), and X-ray diffraction (XRD). Results The optimal formulation for ETW-SD composed of ETW-PEG 6000-F68 (1∶2∶1). Compared with the raw materials, the dissolution of triptonide, triptolide and wilforine increased by a factor of 3.32, and wilforine by 2 times, while the dissolution of tripterine and wilforlide reached more than 83% within 60 min.

Optimization of preparation process and dissolution test of tetrandrine dropping pills / 中草药

Objective: To optimize the preparation process of tetrandrine dropping pills (TDP) and investigate the in vitro dissolution rate. Methods: Plackett-Burman experimental design was used to screen the critical factors in the preparation process of TDP from the ratio of matrix, ratio of matrix to drug, dropping temperature, dropping rate, dropping distance, and condensate temperature. The forming rate and weight variation of TDP were used as the evaluation index, the parameters in the preparation process of TDP were optimized by using the Box-Behnken response surface method. Moreover, the in vitro dissolution rate of TDP was compared with tetrandrine tablets by rotating basket method. Results: The Plackett-Burman experimental design results showed that the ratio of matrix, dropping temperature and condensate temperature had a significant effect on the forming rate of TDP. The optimum preparation parameters by Box-Behnken response surface method were as follows: the ratio of matrix was 2.6∶1, dropping temperature was 82.4 ℃ and condensation temperature was 7.5 ℃ with high forming rate, good roundness, stable weight, and fast drug dissolution rate of TDP. Conclusion: The quality of TDP by experimental design method can meet the requirements and can be further amplified.

In vitro dissolution and anti-vitiligo activity of isopsoralen nanostructured lipid carriers / 中草药

Objective To evaluate the in vitro dissolution characteristic of IPRN-NLC and to study its effects on B16F10 cells proliferation, melanin synthesis, and tyrosinase activity. Methods The dynamic dialysis was employed to compare the in vitro dissolution of IPRN and IPRN-NLC; MTT assay was used to detect the proliferation of B16F10; The tyrosinase activity was determined by L-DOPA-oxidation; The melain content was determined by GENMED Cell Melanin Quantitative Assay Kit. Results The accumulation dissolution of IPRN-NLC was 67.31% within 72 h, which showed sustained release; While the dissolution of IPRN-suspension, IPRN-physical mixture, and IPRN-DMSO were 53.34%, 90.30%, and 98.67%, respectively. The IPRN-NLC could significantly promote the proliferation, tyrosinase activity and melanin content compared with IPRN DMSO groups (P < 0.05) at the same concentration. Conclusion IPRN-NLC could increase the solubility of the drug with sustained release, and showed good cell biology intermiscibility, which could significantly increase the effects on B16F10 cells.

Extraction, separation, and in vitro dissolution of HgS micro & nano-particles from Mongolian medicine Menken Usu / 中草药

Objective To study the extraction, separation, and in vitro dissolution method of HgS micro & nano-particles from Mongolian medicine Menken Usu. Methods The Soxhlet extraction method was used to investigate the sulfur from Menken Usu effectively, and the optimum time of extraction was determined by investigating the influence of different extraction time on the extraction rate of sulfur in the Menken Usu. Then, the mercuric sulfide particles were separated by differential centrifugation. The mercuric sulfide micro & nano-particles with different particle sizes can be obtained by controlling the concentration of PVP, molar ratio, centrifuge speed, and other factors. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were used to analyze the morphology and composition of the particles. Using dithizone colorimetric method to determine and compare the dissolution of HgS particles with different sizes, Menken Usu original herbs, and Menken Usu-18 in simulated human gastric and small intestinal. Results The SEM results showed that the obtained six mercuric sulfide particle samples have a uniform size distribution: Uniform size were 2 000-4 000, 800-2 000, 200-800, 80-200, 50-80, and 20-50 nm. The main components in the extracted samples were α-HgS and β-HgS. As the particle size of HgS gradually became smaller, the dissolution of mercury was increased, which indicated that the size of HgS particle was inversely related to the dissolution of mercury. At the same time, the dissolution of mercury is also affected by sulfur, pH, and compounds. Conclusion This is a simple and efficient method for the separation of mercuric sulfide particles, and provides the basis for the pharmacokinetics and pharmacological study of mercuric sulfide nanoparticles with different particle size.

Preparation of mesoporous silica nanoparticles in different pore size and its use in the solidification of sirolimus loaded self-microemulsifying drug delivery system / 药学学报

The mesoporous silica nanoparticles (MSN) in different pore size and sirolimus (SRL) loaded self-microemulsifying drug delivery system (SMEDDS) were prepared. The results in morphology were collected by scanning electron microscope, transmission electron microscope, small-angle X-ray diffraction, and N2 adsorption-desorption. The results showed that the prepared MSN has ordered nanochannels with a pore size of 6.3, 8.1, 10.8 nm, respectively. The particle size of SRL-SMEDDS were measured by particle sizing system, which was 20.6±1.3 nm. The stirring method was developed to prepare SRL-SMEDDS-MSN. It was found that the optimal ratio of SRL-SMEDDS to MSN was 2:1, while the drug loading rate was near 0.83%, and the flow properties of SRL-SMEDDS-MSN were of good condition. The differential scanning calorimetry results proving a molecular or amorphous dispersed state of SRL in MSN while the suspension experiment has shown great reconstitution properties of SRL-SMEDDS-MSN. There is no significant influence on maximum drug release rate of different pore size of SRL-SMEDDS-MSN in 250 mL water within 2 h, while the results of the first 40 min have an obvious difference. Above all, MSN might provide a new strategy for the solidification of SMEDDS.