The present study designed and prepared near-infrared responsive sinomenine hydrochloride(SIN) reservoir microneedles and evaluated the feasibility of this type of microneedles in increasing the drug loading and transdermal absorption by characterizing their mechanical properties and in vitro release characteristics.SIN was selected as the model drug, and methoxy poly(ethylene glycol) poly(caprolactone)(mPEG-PCL) copolymers and indocyanine green(ICG) were employed as amphiphilic block copolymers and light inductor to prepare near-infrared responsive nanoparticles.Based on the preparation principle of bubble microneedles, near-infrared responsive SIN reservoir microneedles were designed and prepared.The features of the near-infrared responsive SIN reservoir microneedles were characterized by measuring the morphology, length, mechanical properties, and skin penetration of microneedles.Meanwhile, the drug release performance of reservoir microneedles was evaluated by in vitro release assay.The results showed that the prepared SIN microneedles were conical, with an exposed tip height of about 650 μm.Each needle could load about 0.5 mg of drugs per square centi-meter, and this type of microneedle showed good mechanical properties and performance in skin penetration.The results of the in vitro release assay showed that the 24 h cumulative release per unit area and release rate of the microneedle were 825.61 μg·cm~(-2) and 74.3%, respectively, which indicated that its release kinetics was in line with the first-order kinetic model.This study preliminarily proved that the reservoir microneedle could effectively increase the drug loading with good mechanical properties and release perfor-mance.
Drug Delivery Systems/methods* ; Drug Liberation ; Indocyanine Green ; Morphinans ; Needles ; Polyethylene Glycols

OBJECTIVE: To explore the feasibility of preparing compound tablets for the treatment of hypertension by fused deposition modeling (FDM) 3D printing technology and to evaluate the quality of the printed compound tablets in vitro. METHODS: Polyvinyl alcohol (PVA) filaments were used as the exci-pient to prepare the shell of tablet. The ellipse-shaped tablets (the length of major axes of ellipse was 20 mm, the length of the minor axes of ellipse was 10 mm, the height of tablet was 5 mm) with two separate compartments were designed and printed using FDM 3D printer. The height of layer was 0.2 mm, and the thickness of roof or floor was 0.6 mm. The thickness of shell was 1.2 mm, and the thickness of the partition wall between the two compartments was 0.6 mm. Two cardiovascular drugs, captopril (CTP) and hydrochlorothiazide (HCT), were selected as model drugs for the printed compound tablet and filled in the two compartments of the tablet, respectively. The microscopic morphology of the tablets was observed by scanning electron microscopy (SEM). The weight variation of the tablets was investigated by electronic scale. The hardness of the tablets was measured by a single-column mechanical test system. The contents of the drugs in the tablets were determined by high performance liquid chromatography (HPLC), and the dissolution apparatus was used to measure the in vitro drug release of the tablets. RESULTS: The prepared FDM 3D printed compound tablets were all in good shape without printing defects. The average weight of the tablets was (644.3±6.55) mg. The content of CTP and HCT was separately (52.3±0.26) mg and (49.6±0.74) mg. A delayed in vitro release profile was observed for CTP and HCT, and the delayed release time for CTP and HCT in vitro was 20 min and 40 min, respectively. The time for 70% of CTP and HCT released was separately 30 min and 60 min. CONCLUSION CTP and HCT compound tablets were successfully prepared by FDM 3D printing technology, and the printed tablets were of good qualities.
Captopril ; Cytidine Triphosphate ; Drug Liberation ; Hydrochlorothiazide ; Printing, Three-Dimensional ; Tablets/chemistry* ; Technology, Pharmaceutical/methods*

OBJECTIVE: To explore the feasibility of preparing different doses of tablets for personalized treatment by fused deposition modeling (FDM) 3D printing technology, and to evaluate the in vitro quality of the FDM 3D printed tablets. METHODS: Three different sizes of hollow tablets were prepared by fused deposition modeling 3D printing technology with polyvinyl alcohol (PVA) filaments. Theophylline was chosen as the model drug. In the study, 20 mg, 50 mg and 100 mg of theophylline was filled into the cavity of the tablets, respectively. The microscopic morphology of the tablets was observed by scanning electron microscopy (SEM). The weight variation of the tablets was investigated by weighing method. The hardness of the tablets was measured by tablet hardness tester. The contents of the drugs in the tablets were determined by ultraviolet and visible spectrophotometry (UV-Vis), and the dissolution apparatus was used to assay the in vitro drug release of the tablets. RESULTS: The prepared FDM 3D printed tablets were all in good shape without printing defects. And there was no leakage phenomenon. The diameter and thickness of the tablets were consistent with the design. The layers were tightly connected, and the fine structure of the formulation could be clearly observed without printing defects by scanning electron microscopy. The average weight of the three sizes of tablets was (150.5±2.3) mg, (293.6±2.6) mg and (456.2±5.6) mg, respectively. The weight variation of the three sizes of tablets were boss less than 5%, which met the requirements; The hardness of the tablets all exceeded 200 N; The contents of theophylline in the three tablets were 98.0%, 97.2% and 97.9% of the dosage (20 mg, 50 mg and 100 mg), and the relative standard deviation (RSD) was 1.06%, 1.15% and 0.63% respectively; The time for 80% drug released from the three dosage of tablets was within 30 min. CONCLUSION Three different dosages of theophylline tablets were successfully prepared by FDM 3D printing technology in this study. The exploration may bring beneficial for the preparation of personalized dose preparations. We expect that with the development of 3D printing technology, FDM 3D printed personalized tablets can be used in the clinic as soon as possible to provide personalized treatment for patients.
Humans ; Theophylline/chemistry* ; Tablets/chemistry* ; Drug Liberation ; Printing, Three-Dimensional ; Polyvinyl Alcohol/chemistry* ; Technology, Pharmaceutical/methods*

OBJECTIVE: To explore the feasibility of preparing gastric floating formulations by fused de-position modeling (FDM) 3D printing technology, to evaluate the in vitro properties of the prepared FDM 3D printed gastric floating formulations, and to compare the influence of different external shapes of the formulation with their in vitro properties. METHODS: Verapamil hydrochloride and polyvinyl alcohol (PVA) were used as the model drug and the excipient, respectively. The capsule-shaped and hemisphere-shaped gastric floating formulations were then prepared by FDM 3D printing. The infill percentages were 15%, the layer heights were 0.2 mm, and the roof or floor thicknesses were 0.8 mm for both the 3D printed formulations, while the number of shells was 3 and 4 for capsule-shaped and hemisphere-shaped formulation, respectively. Scanning electron microscopy (SEM) was used to observe the morpho-logy of the surface and cross section of the formulations. Gravimetric method was adopted to measure the weights of the formulations. Texture analyzer was employed to evaluate the hardness of the formulations. High performance liquid chromatography method was used to determine the drug contents of the formulations. The in vitro floating and drug release behavior of the formulations were also characterized. RESULTS: SEM showed that the appearance of the FDM 3D printed gastric floating formulations were both intact and free from defects with the filling structure which was consistent with the design. The weight variations of the two formulations were relatively low, indicating a high reproducibility of the 3D printing fabrication. Above 800.0 N of hardness was obtained in two mutually perpendicular directions for the two formulations. The drug contents of the two formulations approached to 100%, showing no drug loss during the 3D printing process. The two formulations floated in vitro without any lag time, and the in vitro floating time of the capsule-shaped and hemisphere-shaped formulation were (3.97±0.41) h and (4.48±0.21) h, respectively. The in vitro release of the two formulations was significantly slower than that of the commercially available immediate-release tablets. CONCLUSION The capsule-shaped and hemisphere-shaped verapamil hydrochloride gastric floating formulations were prepared by FDM 3D printing technology successfully. Only the floating time was found to be influenced by the external shape of the 3D printed formulations in this study.
Drug Liberation ; Excipients ; Printing, Three-Dimensional ; Reproducibility of Results ; Tablets

Immunoglobulin Y (IgY) is an effective orally administered antibody used to protect against various intestinal pathogens, but which cannot tolerate the acidic gastric environment. In this study, IgY was microencapsulated by alginate (ALG) and coated with chitooligosaccharide (COS). A response surface methodology was used to optimize the formulation, and a simulated gastrointestinal (GI) digestion (SGID) system to evaluate the controlled release of microencapsulated IgY. The microcapsule formulation was optimized as an ALG concentration of 1.56% (15.6 g/L), COS level of 0.61% (6.1 g/L), and IgY/ALG ratio of 62.44% (mass ratio). The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%, a loading capacity of 33.75%, and an average particle size of 588.75 μm. Under this optimum formulation, the coating of COS provided a less porous and more continuous microstructure by filling the cracks on the surface, and thus the GI release rate of encapsulated IgY was significantly reduced. The release of encapsulated IgY during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions, respectively. The microcapsule also allowed the IgY to retain 84.37% immune-activity after 4 h simulated GI digestion, significantly higher than that for unprotected IgY (5.33%). This approach could provide an efficient way to preserve IgY and improve its performance in the GI tract.
Alginic Acid/chemistry* ; Chitin/chemistry* ; Chitosan ; Delayed-Action Preparations ; Digestion ; Drug Compounding ; Drug Liberation ; Gastrointestinal Tract/metabolism* ; Immunoglobulins/metabolism* ; Oligosaccharides

In this paper, a real time release testing(RTRT) model for predicting the disintegration time of Tianshu tablets was established on the basis of the concept of quality by design(QbD), in order to improve the quality controllability of the production process. First, 49 batches of raw materials and intermediates were collected. Afterwards, the physical quality attributes of all materials were comprehensively characterized. The partial least square(PLS) regression model was established with the 72 physical quality attributes of raw materials and intermediates as input and the disintegration time(DT) of uncoated tablets as output. Then, the variable screening was carried out based on the variable importance in the projection(VIP) indexes. Moisture content of raw materials(%HR), tapped density of wet masses(D_c), hygroscopicity of dry granules(%H), moisture content of milling granules(%HR) and Carr's index of mixed granules(IC) were determined as the potential critical material attributes(pCMAs). According to the effects of interactions of pCMAs on the performance of the prediction model, it was finally determined that the wet masses' D_c and the dry granules'%H were critical material attributes(CMAs). A RTRT model of the disintegration time prediction was established as DT=34.09+2×D_c+3.59×%H-5.29×%H×D_c,with R~2 equaling to 0.901 7 and the adjusted R~2 equaling to 0.893 3. The average relative prediction error of validation set for the RTRT model was 3.69%. The control limits of the CMAs were determined as 0.55 g·cm~(-3) Drug Compounding ; Drug Liberation ; Drugs, Chinese Herbal/chemistry* ; Least-Squares Analysis ; Solubility ; Tablets

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.
Administration, Cutaneous ; Animals ; Drug Liberation ; Emulsions ; Gels ; Glycyrrhiza ; Mice ; Skin Absorption

L_9(3~4) orthogonal experiment design was used to optimize the preparation of the patches,and investigate its affecting factors and skin irritation. Eugenol was taken as the index component to study the release behavior in vitro and percutaneous penetration of Cangai oil transfersomes patches by HPLC.The results showed that the optimal prescription for preparing Cangai oil transfersomes patches were Eudragit E100 0.6 g, succinic acid 0.08 g,triethyl citrate 0.25 g,glycerol 0.2 g.Patches prepared by the preferred preparation had a flat appearance without obvious bubbles.The initial adhesion was 18.33±2.52, the stickiness was(30.01±2.45) min,and the peel strength was(5.62±0.95) kN·m~(-1).The results of affecting factors experiment showed the order of factors affecting its adhesion was humidity>temperature>lighting,and the skin irritation test results showed no significant skin irritation after 24 h of single administration. The results of drug release behavior in vitro showed that the release and the percutaneous penetration of both Cangai oil patches and Cangai oil transfersomes patches conformed to the Higuchi equation.The release amount of eugenol were 80.66% and 82.25% at 72 h, with no significant difference. The cumulative permeation area of eugenol per unit area reached(0.195 6±0.065 9),(0.131 0±0.045 5) mg·cm~(-2) at 72 h, with significant differences(P<0.05).The experiment results proved that the preparation process of Cangai oil transfersomes patches was stable,and the prepared patches had a good adhesion. At the same time,the preparation of transfersomes patches could alleviate and control the release of the drug to a certain extent, and provide a certain experimental basis for clinical pediatric drug safety.
Administration, Cutaneous ; Drug Carriers ; Drug Liberation ; Humans ; Plant Oils/pharmacology* ; Polymethacrylic Acids ; Skin/drug effects* ; Skin Absorption ; Transdermal Patch

Silk fibroin/xanthan composite was investigated as a suitable biomedical material for controlled drug delivery, and blending ratios of silk fibroin and xanthan were optimized by response surface methodology (RSM) and artificial neural network (ANN) approach. A non-linear ANN model was developed to predict the effect of blending ratios, percentage swelling and porosity of composite material on cumulative percentage release. The efficiency of RSM was assessed against ANN and it was found that ANN is better in optimizing and modeling studies for the fabrication of the composite material. In-vitro release studies of the loaded drug chloramphenicol showed that the optimum composite scaffold was able to minimize burst release of drug and was followed by controlled release for 5 days. Mechanistic study of release revealed that the drug release process is diffusion controlled. Moreover, during tissue engineering application, investigation of release pattern of incorporated bioactive agent is beneficial to predict, control and monitor cellular response of growing tissues. This work also presented a novel insight into usage of various drug release model to predict material properties. Based on the goodness of fit of the model, Korsmeyer–Peppas was found to agree well with experimental drug release profile, which indicated that the fabricated material has swellable nature. The chloramphenicol (CHL) loaded scaffold showed better efficacy against gram positive and gram negative bacteria. CHL loaded SFX55 (50:50) scaffold shows promising biocomposite for drug delivery and tissue engineering applications.
Chloramphenicol ; Diffusion ; Drug Liberation ; Fibroins ; Gram-Negative Bacteria ; Porosity ; Silk ; Tissue Engineering

Drug eluting stents are one of the main devices of coronary intervention, which play a therapeutic role through the combination of medical devices. Drug is an important part of the drug eluting stents. The loading method, the type of carrier, drug and carrier interaction and the preparation process of the drug directly affect the drugs release kinetics characteristics of the device and the final treatment. According to the characteristics of the drug coating, drug coated stents can be divided into non-degradable polymers drug coated stents, biodegradable polymers drug coated stents and polymer-free drug eluting stents. This article discussed the stent coating process and drug release kinetics of the three types of drug eluting stent.
Drug Liberation ; Drug-Eluting Stents ; Kinetics ; Polymers ; Stents