Study on fluvoxamine maleate sustained-release pellets and its compression technology / 药学学报

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (24) Taguchi experiment. Using Minitab software to design a DOE experiment with 24 partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

In vitro release of paclitaxel derivative liposome by paddle membrane binding assay / 中国药科大学学报

@#The in vitro release is an important index to evaluate the quality of liposome formulation.Currently, there is no evaluation method for the in vitro release of liposome in pharmacopoeia of various countries, which leads to the lack of unified standard and safety guarantee for the quality evaluation of liposome formulation.Taking the self-made paclitaxel derivative liposomes as an example, the paddle membrane binding method established by optimizing external release conditions was used to simulate the complete release of paclitaxel derivative drugs in 12 hours under physiological conditions.The results showed that using 0.5% SDS-HEPES as the release medium and a dialysis bag with a molecular weight cutoff of 1 000 kD to release the liposome solution met the requirements and had discrimination ability, providing a reference for the development of drug-loaded liposomes release methods in vitro.

Study on release and antioxidant activity of quercetin after loaded by hot alkali hydrolysis modified UiO-66 material / 药学学报

UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.

In vitro release study on self-microemulsion of curcumin and piperine / 药学实践杂志

Objective To study the release profile of curcumin and piperine from the compound self-microemulsion. Methods The release of curcumin and piperine in vitro was investigated by dynamic dialysis under the condition of phosphate buffer of pH 4.8 and 7.5 with 0.75% Tween-80. Results The cumulative release rates of curcumin in pH 4.8 and pH 7.5 were 94.85% and 84.38% in 108 h, respectively. The cumulative release rates of piperine were 92.85% and 90.05% in 36 h, separately. Conclusion Curcumin and piperine in self-microemulsion have sustained release properties and released more in the acidic environment similar to the environment in tumors.

Preparation and in vitro evaluation of berberine hydrochloride nanoemulsion oral drug delivery systems / 药学实践杂志

Objective To prepare berberine hydrochloride nanoemulsion, optimize its formulation composition and preparation process, and investigate its in vitro characteristics. Methods BBR-NE was prepared by water drop addition and pseudo-ternary phase diagram was drawn. The formulation of NE was optimized by central composite design-response surface methodology to choose the optimal formulation composition. The particle size, potential and appearance of the prepared BBR-NE were characterized. Results The optimal prescription of BBR-NE was determined as the oil phase Capryol 90 accounted for 32.84% of the system, the surfactant Tween-80 accounted for 33.90%, the co-surfactant 1,2-propylene glycol accounted for 16.95%, and water relative system accounted for 15.25%. The prepared NE was clear and transparent in appearance, regular in shape and uniform in size, with an average particle diameter of (68.85±8) nm, polydiseperse index of (0.245±0.03) and drug loading of 0.83 mg/g. The in vitro drug release results of NE showed that the in vitro drug release behavior was passive diffusion, which had a certain slow releasing effect and met the first-order release equation. Conclusion The BBR-NE can provide a new dosage form for the clinical use of berberine.

In Vitro Pharmacokinetics and Pharmacodynamic Evaluation of Jiaojiang Cataplasms / 中国实验方剂学杂志

ObjectiveTo study the in vitro kinetics of Jiaojiang cataplasms and evaluate its pharmacodynamics， so as to provide a feasible basis for the development of this preparation. MethodThe improved Franz diffusion cell was used for the in vitro release in semipermeable membrane and transdermal absorption in in vitro mouse skins. The contents of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb1 were determined by high performance liquid chromatography （HPLC）， to evaluate the in vitro release and transdermal absorption of Jiaojiang cataplasms. The mobile phase of 6-gingerol and hydroxy-α-sanshool was water-acetonitrile-methanol （2∶1∶1） with the detection wavelength of 280 nm. The mobile phase of ginsenoside Rb1 was acetonitrile-0.1% phosphoric acid aqueous solution （31∶69） with the detection wavelength of 203 nm. A mouse intestinal paralysis model was established， and mice were randomly divided into five groups， namely sham operation group， model group， domperidone group （3.9 mg·kg-1） and high- and low-dose groups of Jiaojiang cataplasms （6.2， 3.1 g·kg-1， measured by crude drug dosage）， to observe the effect of this preparation on gastrointestinal propulsion function. ResultAverage release rates of hydroxy-α-sanshool， 6-gingerol and ginsenoside Rb1 at 24 h were 16.41， 4.23， 4.15 μg∙cm-2∙h-1， the average transdermal rates of them at 24 h were 2.31， 0.64， 0.29 μg∙cm-2∙h-1， their skin retention values were 19.56， 3.59， 1.61 μg， respectively. According to the Ritger-Peppas equation， the release of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb1 was non-Fick diffusion. The high-dose group of Jiaojiang cataplasms could improve intestinal function of model mice after small intestinal friction injury， and promote intestinal peristalsis and small intestinal propulsion rate （P<0.05）. ConclusionJiaojiang cataplasms has in vitro release and transdermal properties， the in vitro release conforms to Higuchi equation， and transdermal absorption behavior conforms to zero-order kinetic equation， which can improve the postoperative function of the small intestine and the propulsion function of small intestine. It preliminarily indicates that the preparation has certain clinical development value.

Effect of Process Change on in Vitro Release and Percutaneous Penetration of Zushima Guanjie Zhitong Gao / 中国实验方剂学杂志

Objective:To investigate the effect of the production process of Zushima Guanjie Zhitong Gao from solvent method to hot-pressed method on <italic>in vitro</italic> kinetic behavior of this preparation. Method:Solvent and hot-pressed methods were used to prepare three batches of samples above pilot scale， and <italic>in vitro</italic> release and percutaneous penetration of the index components （7，8-dihydroxycoumarin and methyl salicylate） in Zushima Guanjie Zhitong Gao were investigated by modified Franz diffusing cells. Result:The contents of 7，8-dihydroxycoumarin and methyl salicylate in Zushima Guanjie Zhitong Gao prepared by solvent method were 73.72， 494.67 μg/patch， and their contents in hot-pressed method samples were 159.21， 2 638.99 μg/patch， respectively. In the solvent method samples， the average cumulative release amounts of 7，8-dihydroxycoumarin and methyl salicylate in 24 h were 2.04， 12.21 μg， and their average cumulative release amounts in 24 h of hot-pressed method samples were 2.16， 36.24 μg， respectively. In the solvent method samples， the average cumulative permeation amounts of 7，8-dihydroxycoumarin and methyl salicylate in 24 h were 0.38， 2.79 μg， and they were 0.40， 7.49 μg in hot-pressed method samples. The cumulative release and permeation amounts in 24 h of 7，8-dihydroxycoumarin in the hot-pressed method samples were basically the same as those of the solvent method samples， but the cumulative release and permeation amounts in 24 h of methyl salicylate in the hot-pressed method samples were significantly higher than those of the solvent method samples （<italic>P</italic><0.05）. Conclusion:The retention of 7，8-dihydroxycoumarin and methyl salicylate by hot-pressed method is better than that of the solvent method. The process change has no significant effect on the <italic>in vitro</italic> kinetics of 7，8-dihydroxycoumarin in Zushima Guanjie Zhitong Gao， however， after the change from the solvent method to the hot-pressed method， the methyl salicylate in this preparation has a higher cumulative release and permeation amounts.

Effect of self-assembled nanoparticles from Shaoyao Gancao Decoction on release and absorption of main components of Baishao / 中国中药杂志

To study the effect of self-assembled nanoparticles from Shaoyao Gancao Decoction(SGD-SAN) on the encapsulation, in vitro release and intestinal absorption of the main components of Baishao. Particle size analysis and morphological observation were used to verify the formation of SGD-SAN in the decoction. The entrapment efficiency(EE) of SGD-SAN on the main components of Baishao was determined by ultrafiltration centrifugation. The dialysis bag method was used to study the in vitro release of the main components of Baishao with pH 6.8 phosphate buffer solution as the release media. Single-pass intestinal perfusion study was performed to investigate the effect of SGD-SAN on the absorption of the main components of Baishao. The results showed that there were nanoparticles in the SGD, and the particle sizes and PDI of SGD-SAN were about 200 nm and 0.38, respectively. SGD-SAN was irregularly spherical under transmission electron microscope(TEM). The EEs of albiflorin, paeoniflorin and benzoylpaeoniflorin in SGD-SAN were 33.78%±1.03%,33.61%±0.90%,88.53%±0.58%, respectively. The release characteristics of albiflorin, paeoniflorin and benzoylpaeoniflorin from SGD-SAN showed a slow-release effect on pH 6.8 phosphate buffer solution media. SGD-SAN could significantly enhance the absorption of albiflorin, paeoniflorin and benzoylpaeoniflorin in the ileum. The results of this study indicated that SAN could be formed during the mixed decoction of Baishao and Gancao, and SGD-SAN could encapsulate the components of Baishao, with a certain slow-release effect, and the formation of SAN facilitated the absorption of drugs in the ileum.

Optimization of the matrix formulation of Erhuang analgesic gels by central composite design-response surface methodology / 国际中医中药杂志

Objective:To optimize the matrix formulation of Erhuang analgesic gels. Methods:Central composite design-response surface methodology was adopted to optimize the best formulation of Erhuang analgesic gels by using carbomer 940, triethanolamine and glycerine as independent variables, the appearance, stability, viscosity and in vitro release of berberine hydrochloride as comprehensive evaluation indices. Results:The fitting regressing equation was Y= 82.25 + 4.95 A+ 5.19 B + 1.41 C+ 1.51 AB + 0.904 0 AC- 0.531 9 BC- 2.92 A2-1.80 B2-0.182 1 C2. P value of the model was less than 0.000 1, and the correlation coefficient r value was 0.977. The optimal formulation of Erhuang analgesic gels consisted of 1.84% carbomer 940, 1.30 times triethanolamine of carbomer 940 and 13.99 grams of glycerine. The average comprehensive scores of three verification experiments was 88.56, and the deviations from the predicted values were 2.93%, 2.85% and 1.55%. Conclusion:The formulation process by central composite design-response surface methodology was stable and the formulation of Erhuang analgesic gels has been optimized.

Research progress of in vitro-in vivo correlation of injectable polylactide-polyglycolide microspheres / 药学学报

As a depot drug delivery system, injectable polylactide-polyglycolide (PLGA) sustained-release microspheres have been successfully used to treat many diseases since the first microsphere product Lupron depot was approved for marketing in the United States in 1989. It has the ability of long-term release in the body for several days to several months, which can not only reduce the times of administration, but also reduce the drug blood concentration fluctuations, significantly improve the safety and patient compliance. In vitro-in vivo correlation (IVIVC) makes the development of microspheres more possible. It can describe the dynamic information of drug release in vivo through the in vitro release behavior of microspheres, and can reduce the workload of each stage and shorten the time span while characterizing the performance of microspheres. IVIVC can provide guidance or support for drug development, production changes, supervision and management. This article summarizes the release mechanism of injectable PLGA sustained-release microspheres, common measurement methods and theories of in vitro and in vivo release. And we also focus on the establishment and application of IVIVC, especially A level IVIVC in the field of microsphere preparations, to provide a reference for further study on in vitro-in vivo correlation of microspheres.

Preparation and in vitro release of ivabradine hydrochloride elementary osmotic pump tablets / 中国药科大学学报

@#In this study, ivabradine hydrochloride (IVB) was prepared as elementary osmotic pump tablets whose administration frequency was reduced to once daily. The dissolution method was developed, and effects on drug release profiles were evaluated by single factor analysis involving suspending agents, osmotic active agents and aging process. Orthogonal test was carried out at 3 levels on 3 factors including the amount of polyoxyethylene (PEO) in the core, polyethylene glycol (PEG) percentage and weight increase of controlled-release film coatings. The final formulation consisted of IVB (16.25 mg), PEO N80 (60 mg), hypromellose E5 (10 mg), lactose (111.75 mg), magnesium stearate (2 mg); and the film coatings consisted of PEG (15%), cellulose acetate (85%), with a weight increase of 7.5%. In vitro drug release behaviors were investigated. Prepared tablets exhibited similar release profiles in different pH dissolution media, with no risk of dose dumping in 40% ethanol solutions. The osmotic pressure differences inside and outside the membrane drove drug release. IVB osmotic pump tablets could reduce the frequency of administration and improve patients'' compliance, thus with better application values.

Formulation Optimization of Citalopram Hydrobromide Thermosensitive Nasal Gel and Its In Vitro Properties / 中国药学杂志

OBJECTIVE: To optimize the formulation of citalopram hydrobromide (CTH ) thermosensitive nasal gel and further evaluate its in vitro properties. METHODS: With gelling temperature and gelling time as evaluating indexes, central composite design-response surface and single factor experimental design method were used to optimize the formulation of CTH thermosensitive nasal gel by using poloxamer 407(F127) and carbomer 940 (CP940) as gel materials. Meanwhile, nasal mucosa permeation enhancer for CTH was then sieved by using Franz diffusion cell and ex vivo sheep nasal mucosa as experimental model. Finally, CTH thermosensitive nasal gel was prepared with cold method and then its in vitro properties was evaluated. In vitro cumulative erosion and cumulative release rate of the drug thermosensitive nasal gel were investigated by membrane-free dissolution method and dialysis membrane method, respectively. Moreover, the effect of temperature and pH on the viscosity of the drug nasal gel formulation was also evaluated. RESULTS: The optimal formulation of the thermosensitive nasal gel consisted of CTH 8.0%, F127 20.27%, CP940 0.17%, DM-β-CD 3.0%, ethylparaben 0.05% and distilled water. The gelling temperature, gelling time and pH of the drug thermosensitive nasal gel were found to be about 32.5 ℃,42 s and 5.0, respectively. The in vitro cumulative erosion and cumulative release percentage were both greater than 90% in 55 min and furthermore there was good linear correlation between these two parameters (r=0.998 6). Additionally, in vitro cumulative release of the drug from the gel formulation was determined to be 92% within 8 h, which conformed to Higuchi kinetic equation. Furthermore, the viscosity of the drug nasal gel was influenced by temperature as well as pH in different extent. CONCLUSION: The optimized formulation of the CTH thermosensitive nasal gel with central composite design-response surface method and single factor design method shows suitable gelling temperature, gelling time, pH value for nasal preparation and obvious in vitro drug sustained release characteristics.

Release Characteristics and Pharmacokinetic Properties of Chitosan Coated Curcumin Ethosomes / 中国药学杂志

OBJECTIVE: To investigate the release characteristics in vitro of chitosan coated curcumin ethosomes (CMETS-CS) and its pharmacokinetics in rats. METHODS: The in vitro cumulative release rate of CMETS-CS in two different media (pH 1.2 HCl and pH 6.8 PBS solution) was investigated by dynamic dialysis. The release behavior was evaluated by similar factor method. After gastrointestinal administration, the plasma drug concentration at different time point was determined by high performance liquid chromatography (HPLC), and the average plasma concentration-time curve was drawn. The pharmacokinetic parameters, bioequivalence between CMETS-CS and CM were analyzed by DAS software. RESULTS: The cumulative release rates of CMETS-CS in pH 1.2 HCl and pH 6.8 PBS solution were (70.49±0.75)%, (73.90±0.52)%, respectively. Compared with CM, the CMETS-CS significantly increase the drug release.The release behavior of CMETS-CS in the two different release media was similar. After calculation, the area under the 0-72 h curve (AUC0-72 h), mean residence time (MRT0-72 h), peak concentration (ρmax) of CMETS-CS were 11.84, 5.45, 1.55 times than those of free curcumin (CM), respectively and its relative bioavailability of CMETS-CS was 1 111.32%. The bioequivalence of AUC0-72 hAUC0-∞ and tmax and in CMETS-CS and CM were not eligible, but bioequivalence of ρmax was eligible. CONCLUSION: Compared with free curcumin, CMETS-CS can improve the release behavior in vitro, significantly improve the oral bioavailability in rats, and there is not bioequivalence between CMETS-CS and CM.

Preparation and in vitro release study of ligustrazine pamoate sustained-release nanosuspension / 中草药

Objective: To prepare ligustrazine pamoate (Lig-PAM) sustained-release nanosuspension (Lig-PAM-NSps) and determine its in vitro release characteristics. Methods: Lig-PAM was prepared by hydrophobic salt formation method and its physicochemical properties were characterized. Then, Lig-PAM-NSps was prepared by miniaturized medium grinding method. The prescription and preparation process of Lig-PAM-NSps were optimized by the single factor and orthogonal experiment with average particle size, polydispersity index (PDI) and stability coefficient (SI) as indicators. Lig-PAM-NSps was characterized, and its stability and in vitro release was also investigated. Results: The compound ratio of Lig-PAM prepared by Lig and PAM in the amount of 1:1 was (97.48 ± 0.04)%. Compared with Lig, the solubilities of Lig-PAM in water and simulated body fluids were decreased by 95.50% and 77.39%, respectively. Fourier transform infrared spectroscopy (FT-IR) and X-ray powder diffraction (XRD) showed that the Lig and PAM formed Lig-PAM. The optimum prescription size of Lig-PAM-NSps was (585 ± 5) nm, PDI was (0.328 ± 0.015) and SI was (0.928 ± 0.012). The scanning electron microscopy (SEM) showed that Lig-PAM-NSps was spherical with uniform size distribution, and the particle size was about 600 nm and its physical stability was good within 60 d. The results of in vitro release showed that Lig-PAM-NSps had obvious sustained-release effect compared with Lig solution within 48 h, and showed the first-order release characteristics [ln(1-Q) = 0.153 67 t + 80.458 14, r = 0.998 26]. Conclusion: The preparation progress of Lig-PAM-NSps is stable and can release Lig slowly in vitro.

Preparation of Lonicerae Japonicae Flos extract supramolecular hydrogel and its release behavior in vitro / 中草药

Objective: To prepare the Lonicerae Japonicae Flos (LJF) extract supramolecular hydrogel and investigate its properties and release behavior in vitro. Methods: The LJF was extracted with 40% ethanol. Taking the content of phenolic acids as the quantitative index, N-(9-fluorenylmethoxycarbonyl)-L-phenylalanine was selected as the gelator to prepare LJF extract supramolecular hydrogels. The release behavior was studied by in vitro release experiment. Results: The addition of LJF extract not only did not affect the formation of supramolecular hydrogel, but also improved the stability of supramolecular hydrogel. The release behavior of LJF extract was related to its loading and pH value of release medium. When the drug loading of LJF extract was 0.5 mg/mL, the cumulative release rate was the highest. Moreover, the cumulative release rate increased with the pH value of the release medium, showing obvious controlled release characteristics. Conclusion: Supramolecular hydrogels as the release carrier for LJF extract have an obvious sustained and controlled release, which provides a new idea for the development and application of LJF in medicine.

Optimization of puerarin nanoemulsion based on glycyrrhizic acid by central composite design-response surface method and its in vitro release studies / 中草药

Objective: Puerarin nanoemulsion (Pue-NE) was prepared with glycyrrhizic acid as a natural stabilizer, and its release characteristics in vitro were investigated. Methods: Data processing was performed using particle size and polydispersity index (PDI) as independent variables, and using the overall desirability (OD) as the evaluation index. The central composite design-response surface method was used to optimize the prescription, and the physical and chemical properties and release characteristics of Pue-NE prepared by the optimal prescription were investigated. Results: The best prescription for Pue-NE is puerarin at a concentration of 5.0 mg/mL, glycyrrhizic acid at a concentration of 1.75 mg/mL, and caprylic glyceride in an amount of 3.5 mL. The average particle size of the nanoemulsion is (184.5 ± 0.8) nm, the PDI is 0.088 ± 0.002, the zeta potential is (10.56 ± 0.35) mv, the conductivity is (98.3 ± 0.4) μs/cm, pH is 6.750 ± 0.005, solubility (4.970 ± 0.008) mg/mL, drug loading is (99.4 ± 0.2)%, turbidity (24.3 ± 1.0) cm-1 (n = 3). It was identified as O/W emulsion by dyeing method. TEM scanning results show that the droplets are spherical and uniform in size and the stability results showed that Pue-NE has good storage stability at 25 ℃. In vitro release results showed that Pue-NE has the greatest release in phosphate buffered pH 6.8 within 24 hours. Conclusion: The preparation of Pue-NE with glycyrrhizic acid as a natural stabilizer is not only simple and convenient, but also can effectively replace the use of traditional chemical synthetic stabilizers and improve the solubility of puerarin.

Optimization of formulation of paeonol lipid microspheres by central composite design-response surface method and its drug release mechanism in vitro / 中草药

Objective: To optimize the formulation of paeonol lipid microspheres (Pae-LM) through central composite design- response surface method and determine its in vitro release characteristics. Methods: Using the mean particle size and centrifugal stability constant (Ke) as evaluation indexes, the oil phase type and the ratio of composite oil, the amount of phospholipid and stearic acid, the type of emulsifier, the type and amount of stabilizer, the quality of PC and CH, the high-speed shear temperature and time, the homogenization pressure and time was screened in prescription process. Effects of dosage of paeonol and high pressure homogenizing pressure on the properties of Pae-LM preparation were investigated by central composite design-response surface method. The binomial model and multivariate linear regression model were used to establish the mathematical relationship between the indexes and the factors. According to the best mathematical model of evaluation index, the response surface was depicted and the best prescription was analyzed by the response surface method. According to the optimized formulation Pae-LM, the in vitro drug release characteristics were investigated. Results: The best prescription of Pae-LM was basically round, with mean particle size of (149.32 ± 0.57) nm, Zeta potential of (-36.01 ± 3.09) mV, encapsulation rate of (98.24 ± 0.32)% and drug-loading rate of (11.94 ± 0.04)%. There was a credible quantitative relationship between Ke and the two factors, and the binomialmodel was more reliable than the multivariate linear model. The cumulative release of paeonol drug substance at 12, 24 and 36 h were 71.84%, 85.21% and 95.07%, while the cumulative release of Pae-LM was only 57.21%, 59.66%, and 63.91% at 12, 24 and 36 h, respectively. The drug release was in accordance with the Ritger-peppas model. Conclusion: Central composite design-response surface method can be applied to optimize prescription of lipid emulsion microspheres. The optimized particle size of Pae-LM was suitable with a higher encapsulation rate, which can provide a reference for the development of paeonol cardiovascular delivery system.

Preparation of acetaminophen tablets by 3D printing technology / 国际药学研究杂志

Objective: To prepare acetaminophen tablets by hot-melt extrusion 3D printing technique. Methods:The acetaminophen tablets were prepared by the direct combination of hot-melt extrusion technology and 3D printing. Soluplus was used as hot-melt matrix and PEG6000 as plasticizer. The physical properties and molecular structure of the materials in the tablets were investigated, and in vitro release of the tablets was studied. Results:The printing of acetaminophen tablets was completed successfully, and the size, internal structure and shape of the tablets could be changed by 3D printing technology. The thermogravimetric analysis showed that all materials could maintain thermal stability at printing temperature. The results of crystal form study showed that all materials solidified in a amorphous form after the hot-melt 3D printing. The IR, Raman, MS and 1 H NMR data showed that the molecular structure of acetaminophen kept unchanged after the 3D printing. The in vitro release studies showed that the release of printed tablets could achieve over 80% within 24 h in the pH 6.8 phosphate buffer medium, by adding the disintegrating agent, kolidon cl-F, and changing the path spacing and shell numbers in the printing process. Conclusion:The acetaminophen tablets could be prepared by the hot-melt extrusion 3D printing technology, and the release of the tablets could be adjusted by the change of printing-related parameters.

In vitro release and in vivo pharmacokinetics in Beagle dogs of pregabalin sustained-release tablets / 国际药学研究杂志

Objective: To evaluate the in vitro release degree, release mechanism and dose dumping of test tablet and reference tablet Lyrica® CR. The in vivo pharmacokinetics of the test tablet and the reference tablet were further investigated using the Beagle dog as a model. Methods: With Pfizer's pregabalin sustained-release tablets(Lyrica® CR)as the reference listed drug, the in vitro release behavior was evaluated using an automatic dissolution apparatus, and similarity factor(f2)method was used to analyze the in vitro release similarity between the reference tablet and the test tablet. The in vitro release equation was fitted to evaluate the drug release mechanism. Study was conducted on dose dumping of preparations based on the relevant guiding principles of the United States, Europe and China. Finally, the pharmacokinetic parameters of the test tablet and the reference tablet in Beagle dogs were compared. Results: The f2 of the test tablet and the reference tablet were more than 80 in all five release media, and there was no sudden release in the release medium containing ethanol. The pharmacokinetic parameters of the reference tablet and the test tablet were as follows: The Tmax was(6.00±2.19)and(4.00±2.19)h, the Cmax was(19.35±11.43)and(17.25±7.77)μg/ml, and the AUC0-t was(340.37± 220.66)and(281.65 ± 196.25)h•μg/ml for the reference tablet and the test tablet, respectively. Conclusion: In this study, the release curve of the test tablet was similar to that of the reference tablet in the five media. The drug was released slowly without sudden release, and the release mechanism in vitro was similar. There was no significant difference in pharmacokinetic parameters between the test tablet and the reference tablet in beagle dogs, and the relative bioavailability was more than 80%.

Preparation of compound liquorice microemulsion gel and its pharmacodynamics evaluation / 中国中药杂志

Based on the previous study of compound liquorice microemulsion, this paper aims to prepare the compound liquorice microemulsion gel and investigate its pharmacodynamics of chronic eczema. The type, dosage and adding method of gel matrix, and formula dosage of humectant were optimized by single factor method to obtain the formula and preparation technique of the gel. With glycyrrhizic acid, glycyrrhetin and oxymatrine used as evaluation indexes, the Franz diffusion cell method was adopted to monitor the in vitro release profile of the gel. Eczema model of delayed-type hypersensitivity in mice was chosen to detect the ear swelling rate, degree of inflammatory cell infiltration of ear pieces, and pathological changes of ear pieces, so as to investigate the therapeutic effect of the microemulsion gel. The preparation process of the compound liquorice microemulsion gel was stable. The release of glycyrrhizin and oxymatrine was most consistent with the Hixcon-Crowell kinetic model, while the release of glycyrrhizic acid was most consistent with the Ritger-Peppas kinetic model. The pharmacodynamics studies proved that compound liquorice microemulsion gel could significantly reduce the ear swelling rate in mice, with good anti-inflammatory effect as well as the ability to resist the pathological changes of chronic eczema and inhibit the infiltration of dermal inflammatory cells. Therefore, the preparation process of compound liquorice microemulsion gel is feasible, with stable drug release and a significant therapeutic effect on chronic eczema.