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1.
Article in Chinese | WPRIM | ID: wpr-904797

ABSTRACT

Objective@#To explore effect on the remineralization of demineralized enamel surfaces with glycine-guided carboxymethyl chitosan (CMC)/amorphous calcium phosphate (ACP).@*Methods@# Remineralized solultion at different stages were prepared: ①reactive CMC/ACP (CMC/ACP nanoparticles treated with NaClO), ②reactive CMC/ACP+glycine; transmission electron microscopy was used to detect the morphology of the remineralized solution particles. Twenty teeth were randomly divided into two groups: group A and group B. Reactive CMC/ACP was applied to the enamel surface of group A and group B was treated with reactive CMC/ACP remineralization solution containing glycine. Scanning electron microscopy was used to detect the enamel surface morphology before and after remineralization, and nanoindentation was used to detect the mechanical strength (including nanoindentation depth, hardness and elastic modulus) of the enamel surface.@*Results@#Under a transmission electron microscope, the particles in the reactive CMC/ACP remineralization solution were smooth, and the increase in particle size was approximately 100-300 nm. After the addition of glycine, the particles in the reactive CMC/ACP remineralization solution particles showed a linear ordered arrangement, and microcrystals were formed in the solution 15 min later, with a crystal length of approximately 5-15 μm. Remineralization in group A was granular and heterogeneous. In group B, the crystal morphology of the demineralized enamel was homogeneous and ordered, similar to that of natural enamel. The nanoindentation depth of group B after remineralization was smaller than that of group A, and it was closest to that of natural enamel, there was no significant difference between group B and natural enamel in terms of the hardness and elastic modulus of the enamel surface after remineralization.@*Conclusion@# CMC/ACP nanoparticles treated with NaClO can rapidly and specifically form directional and ordered remineralization on the enamel surface of a model of glycine-guided rapid remineralization of enamel caries. The surface structure of remineralized enamel is similar to that of natural enamel in terms of nanoindentation depth, hardness and elastic modulus.

2.
Article in Chinese | WPRIM | ID: wpr-927916

ABSTRACT

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.


Subject(s)
Calorimetry, Differential Scanning , Desiccation , Drug Compounding/methods , Drug Stability , Silymarin , Solubility , Spectroscopy, Fourier Transform Infrared , Technology , X-Ray Diffraction
3.
Acta Pharmaceutica Sinica ; (12): 1312-1321, 2022.
Article in Chinese | WPRIM | ID: wpr-924761

ABSTRACT

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.

4.
Acta Pharmaceutica Sinica B ; (6): 2505-2536, 2021.
Article in English | WPRIM | ID: wpr-888870

ABSTRACT

Amorphous solid dispersions (ASDs) are popular for enhancing the solubility and bioavailability of poorly water-soluble drugs. Various approaches have been employed to produce ASDs and novel techniques are emerging. This review provides an updated overview of manufacturing techniques for preparing ASDs. As physical stability is a critical quality attribute for ASD, the impact of formulation, equipment, and process variables, together with the downstream processing on physical stability of ASDs have been discussed. Selection strategies are proposed to identify suitable manufacturing methods, which may aid in the development of ASDs with satisfactory physical stability.

5.
Acta Pharmaceutica Sinica ; (12): 1301-1313, 2021.
Article in Chinese | WPRIM | ID: wpr-887067

ABSTRACT

In recent years, the phenomenon of glass transition has been gradually applied to the field of pharmaceutics. And it exhibits important influences on multiple operating units of pharmaceutical preparations, and the properties and storage of pharmaceutical intermediates and products. At present, it has been widely used in the process of preparations such as drying, granulation, coating, tableting, holt-melt extrusion, cryogenic comminution, and so on. Meanwhile, it showed guiding significance for the process of preparation intermediates and their products, such as solid dispersion, microcapsule, liposome, particle, tablet, and other preparation intermediates and their products. Therefore, this article conducts a detailed analysis and systematic summary of the application guidance of the phenomenon of glass transition in the preparation process, and its influence on the preparation intermediates and products, so as to provide theoretical guidance for preparation production and product storage.

6.
Acta Pharmaceutica Sinica ; (12): 855-864, 2021.
Article in Chinese | WPRIM | ID: wpr-876517

ABSTRACT

Compared with crystalline drugs, their amorphous forms present long-range disordered molecular arrangements, and often exhibit higher apparent solubility and dissolution. However, several small molecule amorphous drugs may exhibit gelation phenomenon during the dissolution process, and show abnormal dissolution behavior with significantly lower dissolution than crystalline drugs. The current study aims to discover the relationship between the gelation of amorphous drugs and their abnormal dissolution, and further explore the internal gelation mechanism. Amorphous simvastatin (SIM), carvedilol (CAR), and irbesartan (IRB) were prepared by melt cooling method and characterized via X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectroscopy (FT-IR). Gel formation causes the dissolution of these three amorphous drugs to be significantly lower than their crystalline state. The formed gels were characterized as three-dimensional dense network structures by scanning electron microscope (SEM). Furthermore, amorphous SIM, CAR and IRB showed the critical gel temperature at 8-15 ℃, 25-30 ℃ and 45-50 ℃, and amorphous CAR and IRB showed the critical gel pH at 1 and 0.25. The mechanism of gel formation was proposed to be closely related to the transformation of amorphous drugs into the supercooled liquid state (as the important driving force) and the protonation induced self-assembling under acidic conditions. In addition, the wettability and properties of amorphous drugs also affect the formation of gelation.

7.
Article in Chinese | WPRIM | ID: wpr-875990

ABSTRACT

@#Dental hard tissues lack the ability to self-heal. In dentin and cementum, hydroxyapatite (HA) can exist outside and/or inside collagen fibers. It is difficult to repair or regenerate HA with a highly ordered orientation in the presence of collagen fibers. At present, the biomimetic mineralization of dentin and cementum, mainly carried out by imitating its biological formation process and its physiological structure, can be divided into those originating from the fiber mineralization mechanism and those with HA as the main component. The materials used include natural materials such as demineralized dentin matrix (DDM) and calcined bovine hydroxyapatite (BHA), and synthetic materials such as polymer-induced liquid precursor (PILP) and synthetic HA. In the future, natural materials and synthetic materials should be combined for the restoration and regeneration of dentin and cementum by means of biomimetic mineralization of calcium phosphate released by remineralization solution-HA.

8.
Article in Chinese | WPRIM | ID: wpr-847083

ABSTRACT

BACKGROUND: Based on excellent hydration ability, the materials for repairing bone defects could be fabricated by three-dimensional printing from amorphous calcium phosphate simply with pure water as adhesive solution; and more importantly, the printed products could be directly used in clinical medicine without high temperature sintering, so amorphous calcium phosphate fits well with technical features of three-dimensional printing. OBJECTIVE: To prepare bone repair materials of amorphous calcium phosphate with mechanical property and printing accuracy to meet practical application requirements by three-dimensional printing. METHODS: Amorphous calcium phosphate used as prototyping powder was prepared by coprecipitation method, and then the viscosity and surface tension of the deionized water as adhesive solution were adjusted by thickening agent and leveling agent, respectively. Afterwards, the three-dimensional printing productions for repairing bone defects were fabricated, and the effects of the viscosity and surface tension of adhesive solution on the forming of droplet, liquid-solid interaction and the mechanical property as well as printing accuracy of three-dimensional printing productions were investigated. RESULTS AND CONCLUSION: By investigating the forming of droplet and liquid-solid interaction, the optimal physicochemical parameters of the adhesive solution were obtained. The viscosity and surface tension of the optimal adhesive solution were 8.0 × 10-3 Pa•s and 40.0 × 10-3 N/m separately, and at this point, not only droplet could form stably and controllably (Z=5.06), but also it smoothly struck the powder layer during spraying (K=14.29), and then it infiltrated into the powder layer uniformly and spread in time (We=36.86). The corresponding three-dimensional printing production has good mechanical properties (compressive strength is 30.4 MPa), high printing accuracy (forming error is 0.9 mm), and a large number of pores indicating good bone conductivity, which partially meets clinical demands of repairing bone defects.

9.
Acta Pharmaceutica Sinica ; (12): 2883-2891, 2020.
Article in Chinese | WPRIM | ID: wpr-862292

ABSTRACT

The solubility/dissolution, hygroscopicity and mechanical properties of drug candidates have a profound effect on oral bioavailability, processability and stability. The physicochemical properties of crystalline drug are closely related to inner crystal structure. Crystal engineering technologies, as strategies of altering the crystal structure and tailoring physicochemical properties at molecular level, possess the potential of enhancing the pharmaceutical performance of product. The current article reviewed the modification of drug solubility/dissolution, hygroscopicity and mechanical properties by crystal engineering technologies through polymorphic selection, amorphization/co-amorphization, as well as co-crystallization, which provided a reference for the applications of pharmaceutical crystallography in improving physicochemical properties and druggability.

10.
Chinese Pharmaceutical Journal ; (24): 169-176, 2020.
Article in Chinese | WPRIM | ID: wpr-857780

ABSTRACT

The low aqueous solubility is the main reason that for most pharmacological active ingredients are challengeable to develop into oral solid formulation. Polymeric amorphous solid dispersion(PASD) can greatly improve the apparent solubility and dissolution rate of poorly soluble drugs, has become a common technology to improve the oral bioavailability of poorly soluble drugs. However, due to the amorphous form of the drug at a high surface free energy in PASD, crystallization would occur during storage and dissolution, thereby losing its formulation advantages. The review attempts to provide a structural development approach of PASD products from the aspects of formulation and technology, in order to guide the development of stable and commercially viable PASD formulations. And the trend analysis of marketed products and patents of PASD will be discussed to understand the prospects of PASD's application in improving the bioavailability of poorly soluble oral solid formulations.

11.
Article in Chinese | WPRIM | ID: wpr-843047

ABSTRACT

@#Solid dispersions of the insoluble compound CHMFL-KIT-110 were prepared by solvent method with polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus),Poloxamer 407,PEG 6000,Copovidone (Kollidon VA64) as carriers and SLS,Tween 80,Cremophor RH40 as solubilizers. The optimal formulation was screened and obtained with dynamic solubilities and supersaturation performances as indexes. The final product was characterized by Fourier transform infrared (FT-IR),differential thermal analysis (DTA) and X-ray powder diffraction (XRPD). The stability and pharmacokinetic behavior in rats were also investigated. Results suggested that when the weight ratio of CHMFL-KIT-110/Soluplus/SLS was 1∶4∶0.5,dynamic solubility of the solid dispersions was significantly improved with no recrystallization. In the accelerated condition (40 °C,75% RH) for 30 days,CHMFL-KIT-110 in the solid dispersions was still amorphous with no crystal observed. The results of pharmacokinetics in rats showed that the cmax and AUC0→t of CHMFL-KIT-110 solid dispersions were 373.1 times and 358.7 times higher than those of free drugs,respectively. These results help to understand the formulation development and clinical practice of CHMFL-KIT-110.

12.
Article in Japanese | WPRIM | ID: wpr-822048

ABSTRACT

We report a rare case of a hemodialysis patient with calcified amorphous tumor (CAT) originating from aortic valve cusp that continues to tricuspid valve, which may be related to aortic annular calcification and aortic valve stenosis. A 79-year-old female with chronic kidney disease on hemodialysis for 16 years was transferred to our hospital with loss of consciousness. Echocardiography revealed aortic valve stenosis and presence of tumor on the aortic valve and tricuspid valve. We suspected the presence of a cardiac tumor or vegetation. We underwent tumor resection of tricuspid valve and aortic valve replacement and coronary artery bypass grafting (SVG-RCA). Pathological findings of the tumor was CAT.

13.
Article in Chinese | WPRIM | ID: wpr-821965

ABSTRACT

@#In recent years, due to precise control of the amorphous mineral precursor in the demineralization of dentine collagen fibers in orderly deposition, forming apatite crystals similar to the natural mineralized dentin, the bottom-up remineralization approach which does not depend on the existence of seed crystallites, dentin biomimetic mineralization techniques gradually become a hotspot in the research field of restoration of demineralized dentin caused by dental caries. This paper reviews the changing concepts and practices of the remineralization of demineralized dentin, emphasizing biomimetic remineralization studies. The results of the literature review show that the traditional dentin remineralization method is usually a disordered mixture of demineralized dentin and minerals, so mineralized dentin is not comparable to natural mineralized dentin in terms of the morphological characteristics and mechanical properties. With its gradual increase in recent years, dentine biomimetic mineralization technology perfectly resembles the minerals in the dentin overlapping sequence arranged with the dentine collagen fiber structure characteristics, leading to greatly improved microstructural, physical and chemical properties. As a result, dentine biomimetic mineralization technology is expected to achieve new breakthroughs in the fields of resin-dentin bonding mixing layers and the decay of dentin. At present, the technical obstacles that need to be overcome in the clinical application of the biomimetic remineralization of dentin are how to continuously supplement all the active ingredients needed for mineralization in the process of remineralization and how to keep the mechanical properties of the parent material unchanged while slowly releasing all ingredients. Researchers have successively proposed three-step transportation of the biomimetic remineralization of raw materials, as well as the preparation of mineralization precursors stabilized by polymers in advance and the reuse of mesoporous silicon nanomaterials for the transportation of the mineralized ingredient system. The concept described above provides the preliminary in vitro experimental basis for the transformation of the biomimetic remineralization strategy of dentin in clinical applications.

14.
Acta Pharmaceutica Sinica ; (12): 1015-1021, 2020.
Article in Chinese | WPRIM | ID: wpr-821680

ABSTRACT

Bexarotene is a synthetic analogue of retinoic acid and exerts protective effects on the nervous system. However, low bioavailability and poor solubility of the crystal type I form severely limits the application of bexarotene in the clinic. A co-amorphous sample of bexarotene-PVP-K30 was prepared and the structure was characterized by X-ray diffraction and infrared spectroscopy. To determine the pharmacokinetics and tissue distribution of bexarotene, an LC-MS method was established to profile and quantify bexarotene in plasma and tissues of SD rats. In vitro dissolution indicated that the co-amorphous form improved the dissolution of bexarotene in pure water 4.17-fold. After rats were orally administered bexarotene or bexarotene-PVP-K30 co-amorphous (equivalent to 30 mg·kg-1 bexarotene) the AUC of bexarotene was 7 034.89 and 10 174.03 μg·L-1·h respectively, the peak time was advanced from 7.33 h to 0.9 h with the amorphous form, and Cmax was enhanced from 627.76 to 3 011.88 μg·L-1. The co-amorphous form yielded higher concentrations of bexarotene in various tissues, especially brain, liver and kidney. Animal welfare and experimental procedures complied with the rules of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. The results indicate that bexarotene-PVP-K30 co-amorphous improves the pharmacokinetic characteristics of bexarotene and provides preclinical data in support of bexarotene-PVP-K30 for the treatment of brain diseases.

15.
Article in Japanese | WPRIM | ID: wpr-781942

ABSTRACT

We report the case of a 62-year-old man who was admitted for acute cerebral infarction linked to a cardiac calcified amorphous tumor (CAT). The patient, who had been on hemodialysis for about 10 years, was referred to our hospital with dysarthria, and left hemiplegia. Brain magnetic resonance imaging (MRI) showed acute cerebral infarction in right parietal lobe of the cortex, and transthoracic echocardiography revealed moderate aortic valve stenosis and a mobile mass measuring 8 mm×5 mm in diameter attached to the aortic valve. The mobile structure was thought to be related to the cerebral infarction. Aortic valve replacement was performed. On the basis of the pathological examination, a cardiac calcified amorphous tumor was diagnosed. The patient was discharged from our hospital without any complication.

16.
Rev. Fac. Odontol. Univ. Antioq ; 30(2): 248-262, Jan.-June 2019. tab, graf
Article in English | LILACS | ID: biblio-1092028

ABSTRACT

ABSTRACT Saliva and external agents containing different concentrations of sodium fluoride (NaF) promote the dental remineralization process. However, these resources may not be sufficient to counteract the multiple factors involved in the process of dental caries, especially in high-risk patients. There are alternatives that have been extensively researched, such as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) which provides essential ions, like phosphate and calcium, acting as an adjuvant in the remineralization process. Manufacturers of CPP-ACP-based products also suggest that it can produce desensitizing effects. This nanocomplex has been used experimentally with some dental cements and adhesive systems, but it is important to clarify the effects of this procedure, and the remineralizing/desensitizing advantages it offers. The objective of this topic review was to present the state of the art on CPP-ACP nanocomplex. In terms of dental caries prevention, this remineralizing option is not better than NaF. CPP-ACP provides a dental desensitizing action, but it is temporary, similar or less effective than other alternatives such as potassium nitrate or NaF. The experimental incorporation of CPP-ACP into dental cements should be controlled for not to compromise the physico-chemical properties of the material. The use of dental products based on this nanocomplex as dental surface pretreatment may decrease the bond strength of adhesive materials, but this effect is material dependent.


RESUMEN La saliva y agentes externos que contienen diferentes concentraciones de fluoruro de sodio (NaF) favorecen el proceso de remineralización dental. No obstante, estos recursos podrían no ser suficientes para contrarrestar los múltiples factores involucrados en el proceso de caries dental, especialmente en pacientes con alto riesgo. Existen alternativas que han sido ampliamente investigadas, como el fosfopéptido de caseína-fosfato de calcio amorfo (CPP-ACP) que aporta iones esenciales como fosfato y calcio, actuando como coadyuvante en el proceso de remineralización. Los fabricantes de productos basados en CPP-ACP también sugieren que este es capaz de generar efectos desensibilizantes. Este nanocomplejo ha sido utilizado de forma experimental con algunos cementos dentales y sistemas adhesivos, pero es importante esclarecer los efectos de dicha incorporación y las ventajas remineralizantes/desensibilizantes que ofrece esta alternativa. El objetivo del presente artículo de revisión de tema consistió en presentar el estado del arte sobre el nanocomplejo CPP-ACP. En términos de prevención de caries dental, esta opción remineralizante no es superior al NaF. El nanocomplejo ejerce acción desensibilizante dental, pero esta es transitoria, similar o inferior a otras alternativas como nitrato de potasio o NaF. La incorporación experimental de CPP-ACP en cementos dentales debe ser controlada para no comprometer las propiedades fisicoquímicas del material. La utilización de productos dentales a base de este nanocomplejo como pretratamiento de la superficie dental puede disminuir la resistencia de unión de materiales adhesivos, pero este efecto es material-dependiente.


Subject(s)
Tooth Demineralization , Phosphopeptides , Dental Caries
17.
Article | IMSEAR | ID: sea-192226

ABSTRACT

Background: Although fluoride enables remineralization, presence of calcium and phosphate ions is necessary to promote the process. So, various nonfluoridated remineralizing agents have been emerging to treat the noncavitated carious lesions. Aim: The aim of this systematic review was to assess the clinical effectiveness of nonfluoridated remineralizing agents on initial enamel carious lesions. Methods: Seven electronic databases were searched using the key words. In total, 158 human clinical trials were retrieved in the search from January 1950 to October 2016. Seventy-one repeated articles were excluded. Among the 87 articles obtained, 53 articles were eliminated after reading the title and abstracts. After assessing the full text, 28 articles were excluded. Three more studies were included from the cross references of the articles chosen. Results: All the nine trials included assessed the clinical effectiveness of casein phosphopeptide amorphous calcium phosphate (CPP ACP). They showed a positive effect of CPP ACP on the remineralization of white spot lesions. Conclusion: The use of CPP ACP resulted in significant reduction of the white spot lesion size measured using visual examination methods. This systematic review indicated a lack of reliable evidence supporting the clinical effectiveness of other commercially available nonfluoridated remineralizing agents.

18.
Braz. J. Pharm. Sci. (Online) ; 55: e18295, 2019. tab, graf, ilus
Article in English | LILACS | ID: biblio-1011644

ABSTRACT

Inorganic and carbon based nanomaterials are widely used against several diseases, such as cancer, autoimmune diseases as well as fungi and bacteria colonization. In this work, Santa Barbara Amorphous mesoporous silica (SBA), Halloysite Nanotubes (HNTs) and Multiwalled Carbon Nanotubes (CNTs) were loaded with fluoroquinolone Levofloxacin (LVF) to be applied as antimicrobial agents. The prepared via adsorption nanocarriers were characterized by Fourier-Transformed Spectroscopy, Scanning Electron Microscopy as well as High Pressure liquid Chromatography. In vitro release studies were carried out using Simulated Body Fluid at 37oC and data analyzed by various kinetic models showing slow dissolution over 12-24 hours. Antimicrobial studies showed improved antibacterial activity against Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Staphylococcus aureus, and Staphylococcus epidermidis compared to neat nanomaterials. CNTs were found to be the most promising candidates for LVF delivery and they were chosen to be further studied for their acute oral toxicity and histopathological examination using C57/Black mice. Histological examination depicted that drug loading did not affect mice organs morphology as well as hepatocyte degeneration, central vein degeneration and parenchymal necrosis scores. To conclude, the prepared nanomaterials present significant characteristics and can act as antimicrobial drug carriers; CNTs found to be safe candidates when orally fed to mice.


Subject(s)
Nanotubes/adverse effects , Nanostructures/analysis , Projects , Toxicity , Levofloxacin/agonists , In Vitro Techniques/classification , Anti-Infective Agents
19.
China Pharmacy ; (12): 2348-2354, 2019.
Article in Chinese | WPRIM | ID: wpr-817138

ABSTRACT

OBJECTIVE:To prepare Co-amorphous curcumin (CUR)-tryptophan (TRY) (Co-amorphous CUR-TRY), and to study its pharmacokinetic characteristics in rats. METHODS: Co-amorphous CUR-TRY was prepared by ball milling method. differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD) were used to characterize Co-amorphous CUR-TRY. The in vitro dissolution rate (dissolution) of Co-amorphous CUR-TRY, CUR and CUR-TRY physical mixture were compared under sink condition and non-sink condition. 18 SD rats were selected and randomly divided into Co-amorphous CUR-TRY group (155.43 mg/kg), CUR raw material group (100 mg/kg), CUR-TRY physical mixture group (155.43 mg/kg), with 6 rats in each group. They were given relevant medicine intragastrically once. Each blood samples 0.3 mL were collected from orbital venous plexus 0.167, 0.33, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 h after medication. UPLC-MS/MS was used to determine plasma concentration of CUR in rats. The pharmacokinetic study was performed by using DAS 3.0 software. RESULTS: DSC and XRD showed that Co-amorphous CUR-TRY was successfully prepared. Under sink condition (120 min), compared with CUR raw material [cumulative dissolution rate of CUR is (36.79±3.79)%] and CUR-TRY physical mixture [cumulative dissolution rate of CUR is (33.12±0.68)%], cumulative dissolution rate of CUR in Co-amorphous CUR-TRY (90.37±2.52)% was improved significantly (P<0.01). Under non-sink condition, compared with CUR raw material and CUR-TRY physical mixture, CUR of Co-amorphous CUR-TRY exhibited  dissolution and maintained supersaturation for a long time. Pharmacokinetic study showed that compared with CUR raw material group and CUR-TRY physical mixture group, cmax, AUC0-24 h and AUC0-∞ were increased significantly in Co-amorphous CUR-TRY group (P<0.01); Relative bioavailability of CUR  was improved by 2.14 and 1.86 fold (P<0.01). CONCLUSIONS:Prepared Co-amorphous CUR-TRY can effectively improve in vitro dissolution and in vivo bioavailability in rats of CUR.

20.
China Pharmacy ; (12): 458-463, 2019.
Article in Chinese | WPRIM | ID: wpr-817087

ABSTRACT

OBJECTIVE: To investigate the effects of crystal form on in vivo and in vitro behavior of Astilbin nanosuspensions (AT-NS). METHODS: AT-NS1 and AT-NS2 were prepared by precipitation method and miniaturized media milling method respectively. The particle size and polydispersity index (PDI) were determined by laser particle size analyzer. X-ray diffraction (XRD), scanning electron microscopy (SEM), HPLC and paddle method were used to analyze and compare the structure characteristics, appearance morphology and in vitro dissolution of AT raw material, AT-NS1 and AT-NS2. Totally 15 healthy male SD rats were randomly divided into AT raw material, AT-NS1 and AT-NS2 group, with 5 rats in each group. They were given relevant medicine suspension 120 mg/kg (using water as solvent) intragastrically; blood samples  were collected from orbit before medication (0 min) and 5, 10, 20, 30, 60, 120, 240, 480 min after medication. Using rutin as internal standard, HPLC method was used to determine plasma concentration of AT in rats. Pharmacokinetic parameters were calculated by using DAS 2.0 software and then compared. RESULTS: The particle sizes of AT-NS1 and AT-NS2 were (212.48±0.32) nm and (226.36±2.29) nm, respectively; PDI were 0.129 3±0.026 3 and 0.254 7±0.012 4. XRD analysis showed AT-NS1 was amorphous, and AT-NS2 was crystalline. Diffraction peaks of both were different from those of AT raw material. SEM analysis showed that AT-NS1 and AT-NS2 were similar in morphology, and they were spherical and uniform in size; AT raw material was lump with large particle size and different sizes. Results of dissolution tests showed that accumulative dissolution of AT raw material, AT-NS1 and AT-NS2 were 4.54%, 35.01%, 12.22% at 1 h; accumulative dissolution of them were 24.01%, 81.14%, 64.69% at 12 h; accumulative dissolution of them were 36.04%, 84.47%, 85.86% at 24 h, respectively. Results of pharmacokinetic study showed, compared with AT raw material group, cmax and AUC0-∞ of AT-NS1 and AT-NS2 groups as well as t1/2z of AT-NS1 group were increased significantly, while tmax of AT-NS1 group was significantly reduced significantly (P<0.05). Compared with AT-NS2 goup, cmax, AUC0-∞ and t1/2z of AT-NS1 group were increased significantly, while tmax was reduced significantly (P<0.05). CONCLUSIONS: When AT is prepared into NS, dissolution in vitro and oral absorption in vivo of AT are increased significantly. In a short time, the dissolution/absorption of amorphous NS is faster than crystalline NS.

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