Crystallization transformation of amorphous extracts of traditional Chinese medicine and its effect on dissolution behavior — Taking total flavonoids from Pueraria lobata as an example / 中国药科大学学报

@#In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.

The relationships among Flory-Huggins specific interaction parameters, maximum amorphous capacity, and solid-state interactions of spray dried amorphous drug dispersions with conventional and novel pharmaceutical polymers / Las relaciones entre los parámetros de interacción específicos de Flry-Huggins, la capacidad amorfa máxima y las interacciones en estado sólido de las dispersiones de fármacos amorfos secados por aspersión con polímeros farmacéuticos convencionales y nuevos

This study evaluated the specific interactions between drug and polymers in amorphous spray dried dispersions (SDDs). Four Biopharmaceutics Classification System (BCS) II class drugs were evaluated. Binary and ternary SDDs were manufactured with conventional polymers and arabinogalactan. Specific interaction parameters between drug and polymer were determined using theoretical calculations and DSC data. Analytical methods were used to evaluate solid and solution state interactions. Maximum amorphous content for each formulation was calculated using DSC. Flory-Huggins Specific Interaction Parameters were calculated. Negative specific parameters were associated with solid-state interactions and improved capacity of drug in the amorphous state. Ternary SDDs containing drug, polymer, and arabinogalactan displayed similar hydrogen bonding as was observed with binary SDDs. Solution-state interactions observed in binary systems may be used in tertiary systems to improve the amorphous drug capacity and improved dissolution compared to the binary. The resultant tertiary systems are an improvement over binary drug polymer systems.

Este estudio evaluó las interacciones específicas entre el fármaco y los polímeros en dispersiones amorfas secadas por pulverización (SDD). Se evaluaron cuatro fármacos de clase II del Sistema de Clasificación Biofarmacéutica (BCS). Los SDD binarios y ternarios se fabricaron con polímeros convencionales y arabinogalactano. Los parámetros de interacción específicos entre el fármaco y el polímero se determinaron utilizando cálculos teóricos y datos de DSC. Se utilizaron métodos analíticos para evaluar las interacciones del estado sólido y de la solución. El contenido amorfo máximo para cada formulación se calculó usando DSC. Se calcularon los parámetros de interacción específicos de Flory-Huggins. Los parámetros específicos negativos se asociaron con interacciones en estado sólido y una capacidad mejorada del fármaco en el estado amorfo. Los SDD ternarios que contienen fármaco, polímero y arabinogalactano mostraron enlaces de hidrógeno similares a los observados con los SDD binarios. Las interacciones de estado de solución observadas en sistemas binarios pueden usarse en sistemas terciarios para mejorar la capacidad del fármaco amorfo y mejorar la disolución en comparación con el binario. Los sistemas terciarios resultantes son una mejora con respecto a los sistemas de polímeros de fármacos binarios.

Spray-dried co-amorphous Tadalafil ternary mixtures: a promising platform towards the enhancement of solubility and bioavailability

Abstract Tadalafil (Tad) is a poorly water-soluble drug (BCS class II) that is used for the treatment of erectile dysfunction. An enhancement of aqueous solubility is vital to accelerate its onset of action and subsequently enhance its therapeutic effect. Binary and ternary mixtures of Tad with different amino acids (histidine, valine, alanine or arginine) and other excipients (mannitol and SLS) were prepared and then spray dried. The solubilizing efficiency and physicochemical characterization of all spray dried mixtures of Tad were studied. The optimum formulation was investigated in male rats to determine the onset of erection and the pharmacokinetic parameters of Tad. In general terms, the drug solubility of spray-dried formulae was enhanced compared to the crystalline form of the drug as a result of the formation of co-amorphous structures. The final result revealed that the Tad/alanine/mannitol spray-dried mixture (F10) showed the highest solubility and an improvement in its physicochemical characteristics. Moreover, F10 showed a significantly faster erection in rats with an improvement in Tad pharmacokinetic parameters when compared to the crystalline drug. Thus, F10 is selected as a promising formulation that successfully enhanced the bioavailability and the therapeutic efficacy of Tad.

Research progress on natural antibacterial ingredients of glass ionomer cement / 口腔疾病防治

@#Glass ionomer cement (GIC) is widely used as a common filling material in dentistry but still exhibits problems with secondary caries and fractures. Thus, the antibacterial and anti-caries performance of GIC needs to be further improved. In recent years, natural antimicrobial components have become more desirable due to their good biological properties and low drug resistance. In this review, the natural antimicrobial ingredients in GIC modification are classified, reviewed and summarized according to the different sources of antimicrobial ingredients. In terms of animal origin, chitosan and casein phosphopeptide-amorphous calcium phosphate exhibit antimicrobial properties without affecting the mechanical properties of materials; propolis and bioactive enzymes have good biocompatibility; in terms of plant origin, polyphenols help improve the antimicrobial and mechanical properties of the material; arginine has a good remineralization effect; and plant essential oils have a certain ion release effect. In terms of microbial origin, antibiotics greatly improve the antibacterial properties of materials; in addition, the combined application of natural antimicrobial ingredients also exhibited excellent performance. Despite these advantages, the optimal addition concentration and biocompatibility in vivo are questions that need to be further explored before clinical applications can be achieved.

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.

Co-amorphous technology to improve dissolution and physical stability of silybin / 中国中药杂志

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.

Study on the remineralization of demineralized enamel surfaces with glycine-guided carboxymethyl chitosan/amorphous calcium phosphate / 口腔疾病防治

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.

Effect of preconditioning the fractured coronal fragments with remineralizing agents on fracture resistance of re-attached teeth

Background: Fragment re-attachment has been considered as one of the treatment modalities for the management of fractured anterior teeth. Hydration of fractured fragments aids in inhibiting the loss of ions and maintains vitality and esthetics. Aim: The study aimed to evaluate the effect of preconditioning the fractured fragments with remineralizing agents on fracture resistance of re-attached teeth. Settings and Design: This was an in vitro study. Materials and Methods: Sixty freshly extracted noncarious human permanent maxillary central and lateral incisors were randomly allocated into three Groups of 20 each: Group 1: 2% sodium fluoride (2%NaF), Group 2: casein phosphopeptide–amorphous calcium phosphate (CPP-ACP), and Group 3: self-assembling peptide P11-4 (SAP). These were further divided into two subgroups of 10 teeth each, based on contact time with remineralizing agents, i.e., 30 min and 2 h. Fractured fragments were treated with remineralizing agents for a specified contact time and then re-attached with flowable composite resin. Force required to fracture the re-attached tooth was recorded in Newtons using universal testing machine. Statistical Analysis: Unpaired t-test, one-way analysis of variance test, and post hoc Tukey test were used for the statistical analysis. Results: A higher fracture resistance was noticed in fragments treated with 2% NaF (30 min- 215.6 N, 2 h- 188.5 N) compared to CPP-ACP (30 min- 141.3 N, 2 h- 111.1 N) and SAP (30 min- 134.8 N, 2 h- 149.5 N). At 30 min interval, it was found to be more in 2% NaF and CPP-ACP groups compared to 2 h. However, it increased with time in the SAP group. A statistically significant difference was found between the groups at both time intervals (P = 0.007 and 0.017). Conclusion: Preconditioning of fractured coronal fragments with 2% NaF showed higher fracture resistance compared to CPP-ACP and self-assembling peptide P11-4. Samples treated with SAP P11-4 exhibited good fracture resistance at 2 h contact time.

Analysis of liquid-solid interaction during three-dimensional printing of medical amorphous calcium phosphate / 中国组织工程研究

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.

Pharmaceutical amorphous solid dispersion: A review of manufacturing strategies

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.

Research progress in the application of glass transition phenomenon in pharmaceutics / 药学学报

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.

Gelation of small molecule amorphous drugs / 药学学报

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.

Biomimetic restoration and regeneration of dentin and cementum / 口腔疾病防治

@#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.

Druggability enhancement by modification of physicochemical properties of drugs via crystal engineering / 药学学报

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.

Development of Oral Solid Formulation for Insoluble Drugs Based on PASD Technology / 中国药学杂志

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.

Cardiac Calcified Amorphous Tumor Presenting as Cerebral Infarction / 日本心臓血管外科学会雑誌

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.

A Calcified Amorphous Tumor from the Aortic Valve to the Tricuspid Valve with Aortic Valve Stenosis / 日本心臓血管外科学会雑誌

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.

Biomimetic remineralization of dentin / 口腔疾病防治

@#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.

Preparation of a co-amorphous form of bexarotene-PVP-K30 and evaluation in rats / 药学学报

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.

Preparation，physicochemical properties and pharmacokinetics in rats of CHMFL-KIT-110 solid dispersions / 中国药科大学学报

@#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.