Genome-Wide Identification and Transcriptome Analysis of the Hsp70 Gene Family in Monodonta labio Reveals Its Role in Response to Nanoplastics Stress.

For marine invertebrates, the disruption of organismal physiology and behavior by nanoplastics (NPs) has been extensively reported. Heat shock proteins (Hsps) are important for redundant protein breakdown, environmental changes, and intracellular protein transport. An exhaustive identification of Hsp70 genes and an experiment where different concentrations of NPs were stressed were performed to study how Hsp70 genes respond to NPs stress in Monodonta labio. Our results identified 15 members of Hsp70 within the genome of M. labio and provided insights into their responses to different concentrations of acute NP stress. Phylogenetic analyses revealed extensive amplification of the Hsp70 genes from the Hsc70 subfamily, with gene duplication events. As a result of NP stress, five of fifteen genes showed significant upregulation or downregulation. Three Hsp70 genes were highly expressed at an NP concentration of 0.1 mg/L, and no genes were downregulated. At 10 mg/L, they showed significant upregulation of two genes and significant downregulation of two genes. At 1 mg/L treatment, three genes were significantly downregulated, and no genes were significantly upregulated. Moreover, a purifying selection was revealed using a selection test conducted on duplicate gene pairs, indicating functional redundancy. This work is the first thorough examination of the Hsp70s in Archaeogastropoda. The findings improve knowledge of Hsp70s in molluscan adaptation to NP stress and intertidal living and offer essential data for the biological study of M. labio.

Chromosomal-scale genome assembly and annotation of the land slug (Meghimatium bilineatum).

Meghimatium bilineatum is a notorious pest land slug used as a medicinal resource to treat ailments in China. Although this no-model species is unique in terms of their ecological security and medicinal value, the genome resource of this slug is lacking to date. Here, we used the Illumina, PacBio, and Hi-C sequencing techniques to construct a chromosomal-level genome of M. bilineatum. With the Hi-C correction, the sequencing data from PacBio system generated a 1.61 Gb assembly with a scaffold N50 of 68.08 Mb, and anchored to 25 chromosomes. The estimated assembly completeness at 91.70% was obtained using BUSCO methods. The repeat sequence content in the assembled genome was 72.51%, which mainly comprises 34.08% long interspersed elements. We further identified 18631 protein-coding genes in the assembled genome. A total of 15569 protein-coding genes were successfully annotated. This genome assembly becomes an important resource for studying the ecological adaptation and potential medicinal molecular basis of M. bilineatum.

The Evaluation and Exploration of Piezoelectric Parameter Optimization for Droplet Ejection in Binder Jet 3D Printing Drugs.

Since the first three-dimensional (3D) printed drug was approved by the Food and Drug Administration in 2015, there has been a growing interest in using binder jet 3D printing (BJ-3DP) technology for pharmaceuticals. However, most studies are still at an exploratory stage, lacking micromechanism research, such as the droplet ejection mechanism, the effect of printhead piezoelectric parameters on inkjet smoothness and preparation formability. In this study, based on the inkjet printing and observation platform, the Epson I3200-A1 piezoelectric printhead matched to the self-developed BJ-3DP was selected to analyze the droplet ejection state of self-developed ink at the microlevel with different piezoelectric pulse parameters. The results showed that there was a stable inkjet state with an inkjet pulse width of 3.5 µs, an ink supply pulse width of 4.5 µs, and a jet frequency in the range of 5000-19,000 Hz, ensuring both better droplet pattern and print accuracy, as well as high ejection efficiency. In conclusion, we performed a systematic evaluation of the inkjet behavior under different piezoelectric pulse parameters and provided a good idea and case study for the optimization of printhead piezoelectric parameters when BJ-3DP technology was used in pharmaceuticals.

Hsp70 Gene Family in Sebastiscus marmoratus: The Genome-Wide Identification and Transcriptome Analysis under Thermal Stress.

Heat shock protein 70 kDa (Hsp70) is a highly conserved heat stress protein that is important in biotic processes and responses to abiotic stress. Hsp70 genes may be important in Sebastiscus marmoratus, for it is a kind of nearshore reef fish, and habitat temperature change is more drastic during development. However, genome-wide identification and expression analysis in the Hsp70 gene family of S. marmoratus are still lacking. Here, a total of 15 Hsp70 genes in the genome of S. marmoratus are identified, and their expression patterns were investigated using transcriptomic data from thermal stress experiments. The expansion and gene duplication events of Hsp70 genes from the Hspa4, Hspa8, and Hspa12a subfamilies in S. marmoratus are revealed by phylogenetic analysis. qRT-PCR expression patterns demonstrated that seven Hsp70 genes were significantly up-regulated and none were significantly down-regulated after heat treatment. Only the hsp70 gene was significantly up-regulated after cold treatment. The selection test further showed a purifying selection on the duplicated gene pairs, suggesting that these genes underwent subfunctionalization. Our results add novel insight to aquaculture and biological research on S. marmoratus, providing important information on how Hsp70 genes are regulated in Scorpaeniformes under thermal stress.

3D Printing Technology Based on Versatile Gelatin-Carrageenan Gel System for Drug Formulations.

Currently, there is a shortage of pediatric medicines on the market, and 3D printing technology can more flexibly produce personalized medicines to meet individual needs. The study developed a child-friendly composite gel ink (carrageenan-gelatin), created 3D models by computer-aided design technology, then produced personalized medicines using 3D printing to improve the safety and accuracy of medication for pediatric patients. An in-depth understanding of the printability of different formulations was obtained by analyzing the rheological and textural properties of different gel inks and observing the microstructure of different gel inks, which guided the formulation optimization. Through formulation optimization, the printability and thermal stability of gel ink were improved, and F6 formulation (carrageenan: 0.65%; gelatin: 12%) was selected as the 3D printing inks. Additionally, a personalized dose linear model was established with the F6 formulation for the production of 3D printed personalized tablets. Moreover, the dissolution tests showed that the 3D printed tablets were able to dissolve more than 85% within 30 min and had similar dissolution profiles to the commercially available tablets. This study demonstrates that 3D printing is an effective manufacturing technique that allows for flexible, rapid, and automated production of personalized formulations.

A Review of 3D Printing Technology in Pharmaceutics: Technology and Applications, Now and Future.

Three-dimensional printing technology, also called additive manufacturing technology, is used to prepare personalized 3D-printed drugs through computer-aided model design. In recent years, the use of 3D printing technology in the pharmaceutical field has become increasingly sophisticated. In addition to the successful commercialization of Spritam® in 2015, there has been a succession of Triastek's 3D-printed drug applications that have received investigational new drug (IND) approval from the Food and Drug Administration (FDA). Compared with traditional drug preparation processes, 3D printing technology has significant advantages in personalized drug manufacturing, allowing easy manufacturing of preparations with complex structures or drug release behaviors and rapid manufacturing of small batches of drugs. This review summaries the mechanisms of the most commonly used 3D printing technologies, describes their characteristics, advantages, disadvantages, and applications in the pharmaceutical industry, analyzes the progress of global commercialization of 3D printed drugs and their problems and challenges, reflects the development trends of the 3D printed drug industry, and guides researchers engaged in 3D printed drugs.

The Application and Challenge of Binder Jet 3D Printing Technology in Pharmaceutical Manufacturing.

Three-dimensional (3D) printing is an additive manufacturing technique that creates objects under computer control. Owing to the rapid advancement of science and technology, 3D printing technology has been widely utilized in processing and manufacturing but rarely used in the pharmaceutical field. The first commercial form of Spritam® immediate-release tablet was approved by FDA in 2015, which promoted the advancement of 3D printing technology in pharmaceutical development. Three-dimensional printing technology is able to meet individual treatment demands with customized size, shape, and release rate, which overcomes the difficulties of traditional pharmaceutical technology. This paper intends to discuss the critical process parameters of binder jet 3D printing technology, list its application in pharmaceutical manufacturing in recent years, summarize the still-open questions, and demonstrate its great potential in the pharmaceutical industry.

The Phylogenetic Relationships of the Family Sciaenidae Based on Genome-Wide Data Analysis.

Uncertainty and controversy exist in the phylogenetic status of the Sciaenidae family because of the limited genetic data availability. In this study, a data set of 69,098 bp, covering 309 shared orthologous genes, was extracted from 18 genomes and 5 transcriptomes of 12 species belonging to the Sciaenidae family and used for phylogenetic analysis. The maximum likelihood (ML) and Bayesian approach (BA) methods were used to reconstruct the phylogenetic trees. The resolved ML and BA trees showed similar topology, thus revealing two major evolutionary lineages within the Sciaenidae family, namely, Western Atlantic (WA) and Eastern Atlantic−Indo−West Pacific (EIP). The WA group included four species belonging to four genera: Cynoscion nebulosus, Equetus punctatus, Sciaenops ocellatus, and Micropogonias undulatus. Meanwhile, the EIP group formed one monophyletic clade, harboring eight species (Argyrosomus regius, A. japonicus, Pennahia anea, Nibea albiflora, Miichthys miiuy, Collichthys lucidus, Larimichthys polyactis, and L. crocea) from six genera. Our results indicated that the Western Atlantic (WA) group was more ancient in the studied species, while the Eastern Atlantic−Indo−West Pacific (EIP) group was a younger group. Within the studied species, the genera Collichthys and Larmichthys were the youngest lineages, and we do not suggest that Collichthys and Larmichthys should be considered as one genus. However, the origin of the Sciaenidae family and problems concerning the basal genus were not resolved because of the lack of genomes. Therefore, further sampling and sequencing efforts are needed.

Semisolid Extrusion 3D Printing of Propranolol Hydrochloride Gummy Chewable Tablets: an Innovative Approach to Prepare Personalized Medicine for Pediatrics.

The demand for personalized medicine has received extensive attention, especially in pediatric preparations. An emerging technology, extrusion-based 3D printing, is highly attractive in the field of personalized medicine. In this study, we prepared propranolol hydrochloride (PR) gummy chewable tablets tailored for children by semisolid extrusion (SSE) 3D printing technology to meet personalized medicine needs in pediatrics. In this study, the effects of critical formulation variables on the rheological properties and printability of gum materials were investigated by constructing a full-factorial design. In addition, the masticatory properties, thermal stability, and disintegration time of the preparations were evaluated. Bitterness inhibitors were used to mask the bitterness of the preparations. The results of the full-factorial design showed that the amount of gelatin and carrageenan were the key factors in the formulation. Gelatin can improve printability and masticatory properties, carrageenan can improve thermal stability, and accelerate the disintegration of preparations; therefore, a reasonable combination of both could satisfactorily meet the demand for high-quality 3D printing. γ-Aminobutyric acid can reduce the bitterness of gummy chewable tablets to improve medication compliance and the determined formulation (F7) met the quality requirements. In conclusion, the gum material has excellent potential as an extrusion material for 3D printing. The dosage can be adjusted flexibly by the model shape and size. 3D printing has broad prospects in pediatric preparations.

Effect of Different Absorption Enhancers on the Nasal Absorption of Nalmefene Hydrochloride.

The purpose of this work is to explore the effects of novel absorption enhancers on the nasal absorption of nalmefene hydrochloride (NMF). First, the influence of absorption enhancers with different concentrations and types and drug concentrations on the nasal absorption of NMF was investigated in vivo in rats. The absorption enhancers studied include n-dodecyl-ß-D-maltoside (DDM), hydroxypropyl-ß-cyclodextrin (HP-ß-CD), and polyethylene glycol (15)-hydroxy Stearate (Solutol®HS15). At the same time, the in situ toad palate model and rat nasal mucosa model were used to assess the cilia toxicity. The results showed that all the absorption enhancers investigated significantly promote the nasal absorption of NMF, but with different degrees and trends. Among them, the 0.5% (w/v) DDM had the strongest enhancement effect, followed by 0.5% (w/v) Solutol®HS15, 0.25% (w/v) DDM, 0.25% (w/v) Solutol®HS15, 0.1% (w/v) Solutol®HS15, 0.1% (w/v) DDM, and 0.25% (w/v) HP-ß-CD, with absolute bioavailability of 76.49%, 72.14%, 71.00%, 69.46%, 60.41%, 59.42%, and 55.18%, respectively. All absorption enhancers exhibited good safety profiles in nasal ciliary toxicity tests. From the perspective of enhancing effect and safety, we considered DDM to be a promising nasal absorption enhancer. And in addition to DDM, Solutol®HS15 can also promote intranasal absorption of NMF, which will provide another option for the development of nalmefene hydrochloride nasal spray.

Feasibility of developing hospital preparation by semisolid extrusion 3D printing: personalized amlodipine besylate chewable tablets.

Semisolid extrusion (SSE) 3D printing is an emerging technology in personalized medicine. To address clinical multi-dose requirements, SSE has been explored to manufacture new preparations. In this study, amlodipine besylate (AMB) was the model drug, and SSE was the pharmaceutical strategy. We developed semisolids suitable for SSE and AMB chewable tablets with six strengths (1.5-5 mg) to meet the needs of 2-16-year-old patients. First, the semisolid extrudability was evaluated by texture analyzer, and then the amounts of carboxymethyl cellulose sodium, sodium starch glycolate, and glycerin were optimized by full factorial design. Then, rheological tests were performed to evaluate the properties of the semisolid and the effect of starch sodium glycolate on printability. Finally, the amount of corrigents was optimized using the electronic tongue. Laboratory amplified semisolids and 3D printed tablets can be stored for a few months, and the whole SSE process had no effect on crystal type. This study validated the feasibility of SSE 3D printing, and tablets with appropriate taste and cartoon appearance can meet or even exceed the traditional preparations. Our study provides a new strategy for multi-dose solid preparations and effectively meet the need for personalized amlodipine medicine.

Study on the Complexation and Release Mechanism of Methylphenidate Hydrochloride Ion Exchange Resin Complex.

Since the advent of ion exchange resin, it has been widely used in many fields, including drug delivery systems. The drug binds to the resin through an exchange reaction to form a drug-resin complex, which can gradually release drugs through the exchange of physiological ions in the gastrointestinal tract, to realize functions such as taste masking and regulating release. In this study, the complexes of methylphenidate hydrochloride and Amberlite IRP69 were prepared and evaluated to explore the mechanism of complexation, influencing factors and release mechanism at a molecular level. Firstly, with the properties of the selected complexes, molecular dynamics simulation was innovatively used to find that the intermolecular interaction between drug molecules and ion exchange resin molecules is mainly caused by the stacking effect of π and salt bridges. Secondly, with the drug loading status as an indicator, the factors affecting the compounding process of the drug and resin were explored. Finally, the release mechanism of the drug-resin complex was studied by mathematical model fitting. In summary, a variety of methods were used to study the mechanism of complexation and release between drug and resin, providing a theoretical basis for promoting the marketing of ion-exchange resin-mediated oral preparations.

Optimization of Personalized Amlodipine Dosing Strategies for Children Based on Pharmacokinetic Data from Chinese Male Adults and PBPK Modeling.

For children, a special population who are continuously developing, a reasonable dosing strategy is the key to clinical therapy. Accurate dose predictions can help maximize efficacy and minimize pain in pediatrics. Methods: This study collected amlodipine pharmacokinetics (PK) data from 236 Chinese male adults and established a physiological pharmacokinetic (PBPK) model for adults using GastroPlus™. A PBPK model of pediatrics is constructed based on hepatic-to-body size and enzyme metabolism, used similar to the AUC0-∞ to deduce the optimal dosage of amlodipine for children aged 1-16 years. A curve of continuous administration for 2-, 6-, 12-, 16-, and 25-year-olds and a personalized administration program for 6-year-olds were developed. Results: The results show that children could not establish uniform allometric amplification rules. The optimal doses were 0.10 mg·kg-1 for ages 2-6 years and -0.0028 × Age + 0.1148 (mg/kg) for ages 7-16 years, r = 0.9941. The trend for continuous administration was consistent among different groups. In a 6-year-old child, a maintenance dose of 2.30 mg was used to increase the initial dose by 2.00 mg and the treatment dose by 1.00 mg to maintain stable plasma concentrations. Conclusions: A PBPK model based on enzyme metabolism can accurately predict the changes in the pharmacokinetic parameters of amlodipine in pediatrics. It can be used to support the optimization of clinical treatment plans in pediatrics.

Binder Jet 3D Printing of Compound LEV-PN Dispersible Tablets: An Innovative Approach for Fabricating Drug Systems with Multicompartmental Structures.

Three-dimensional (3D) printing is an emerging technology that has high application potential for individualized medicines and complex solid dosage forms. This study is designed to explore binder jet 3D printing (BJ-3DP) for the development of high-precision and repeatable compound levetiracetam-pyridoxine hydrochloride (LEV-PN) multicompartmental structure dispersible tablets. PN was dissolved in printing ink directly and accurately jetted into the middle, nested layer of the tablet, and precise control of the drug dose was achieved through the design of printing layers. With modification of the drying method, the "coffee ring" effect caused by drug migration during the curing and molding of the tablets was overcome. Furthermore, 3D topography showed that the tablets have a promising surface morphology. Scanning electron microscopy and porosity results indicated that the tablets have a loose interior and tight exterior, which would ensure good mechanical properties while enabling the tablet to disintegrate quickly in the mouth and achieve rapid release of the two drugs. This study used BJ-3DP technology to prepare personalized multicompartmental structures of drug systems and provides a basis for the development of complex preparations.

Innovative color jet 3D printing of levetiracetam personalized paediatric preparations.

3D printing is a promising technology used in the fabrication of complex oral dosage delivery pharmaceuticals. This study first reports an innovative color jet 3D printing (CJ-3DP) technology to produce colorful cartoon levetiracetam pediatric preparations with high accuracy and reproducibility. For this study, the ideal printing ink consisted of 40% (v/v) isopropanol aqueous solution containing 0.05% (w/w) polyvinylpyrrolidone and 4% (w/w) glycerin, which was satisfied with scale-up of the production. The external and internal spatial structures of the tablets were designed to control the appearance and release, and cartoon tablets with admirable appearances and immediate release characteristics were printed. The dosage model showed a good linear relationship between the model volume and the tablet strength (r > 0.999), which proved the potential of personalized administration. The surface roughness indicated that the appearance of the CJ-3DP tablets was significantly better than the first listed 3D printed drug (SpritamⓇ). Moreover, the scanning electron microscopy and porosity results further showed that the tablets have a structure of loose interior and tight exterior, which could ensure good mechanical properties and rapid dispersion characteristics simultaneously. In conclusion, the innovative CJ-3DP technology can be used to fabricate personalized pediatric preparations for improved compliance. Due to the stable formulation and fabrication process, this technology has the potential in scale-up production.

Taste Masking Study Based on an Electronic Tongue: the Formulation Design of 3D Printed Levetiracetam Instant-Dissolving Tablets.

PURPOSE: Proper taste-masking formulation design is a critical issue for instant-dissolving tablets (IDTs). The purpose of this study is to use the electronic tongue to design the additives of the 3D printed IDTs to improve palatability. METHODS: A binder jet 3D printer was used to prepare IDTs of levetiracetam. A texture analyzer and dissolution apparatus were used to predict the oral dispersion time and in vitro drug release of IDTs, respectively. The palatability of different formulations was investigated using the ASTREE electronic tongue in combination with the design of experiment and a model for masking bitter taste. Human gustatory sensation tests were conducted to further evaluate the credibility of the results. RESULTS: The 3D printed tablets exhibited rapid dispersion (<30 s) and drug release (2.5 min > 90%). The electronic tongue had an excellent ability of taste discrimination, and levetiracetam had a good linear sensing performance based on a partial least square regression analysis. The principal component analysis was used to analyze the signal intensities of different formulations and showed that 2% sucralose and 0.5% spearmint flavoring masked the bitterness well and resembled the taste of corresponding placebo. The results of human gustatory sensation test were consistent with the trend of the electronic tongue evaluation. CONCLUSIONS: Owing to its objectivity and reproducibility, this technique is suitable for the design and evaluation of palatability in 3D printed IDT development.

Development and in vivo evaluation of intranasal formulations of parathyroid hormone (1-34).

For efficient intranasal transport of parathyroid hormone (1-34) [PTH(1-34)], there is a great medical need to investigate permeation enhancers for intranasal formulations. In this study, the development of PTH(1-34) intranasal formulations was conducted. Based on conformation and chemical stability studies, the most preferable aqueous environment was determined to be 0.008 M acetate buffer solution (ABS). Subsequently, citric acid and Kolliphor® HS·15 were compared as permeation enhancers. The mechanisms of action of citric acid and Kolliphor® HS·15 were investigated using an in vitro model of nasal mucosa, and Kolliphor® HS·15 led to higher permeability of fluorescein isothiocyanate-labeled PTH(1-34) (FITC-PTH) by enhancing both the transcellular and paracellular routes. Moreover, citric acid showed severe mucosal toxicity resulting in cilia shedding, while Kolliphor® HS·15 did not cause obvious mucosa damage. Finally, Kolliphor® HS·15 was studied as a permeation enhancer using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The results showed that 5% and 10% Kolliphor® HS·15 increased the bioavailability of PTH(1-34) to 14.76% and 30.87%, respectively. In conclusion, an effective and biosafe PTH(1-34) intranasal formulation was developed by using 10% Kolliphor® HS·15 as a permeation enhancer. Intranasal formulations with higher concentrations of Kolliphor® HS·15 for higher bioavailability of PTH(1-34) could be further researched.

Lyophilization Serves as an Effective Strategy for Drug Development of the α9α10 Nicotinic Acetylcholine Receptor Antagonist α-Conotoxin GeXIVA[1,2].

α-Conotoxin GeXIVA[1,2] is a highly potent and selective antagonist of the α9α10 nicotinic acetylcholine receptor (nAChR) subtype. It has the advantages of strong efficacy, no tolerance, and no effect on motor function, which has been expected help patients with neuropathic pain. However, drug development for clinical use is severely limited owing to its instability. Lyophilization is applied as the most preferred method to solve this problem. The prepared lyophilized powder is characterized by differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and Fourier transform infrared spectroscopy (FTIR). Molecular simulation is also used to explore the internal distribution and forces formed in the system. The analgesic effect on paclitaxel-induced neuropathic pain following single and 14-day repeated administrations are evaluated by the von Frey test and the tail-flick test. Trehalose combined with mannitol in a ratio of 1:1 is employed as the excipients in the determined formulation, where trehalose acts as the stabilizer and mannitol acts as the bulking agent, according to the results of DSC, PXRD, and FTIR. Both GeXIVA[1,2] (API) and GeXIVA[1,2] lyophilized powder (formulation) could produce stable analgesic effect. These results indicated that GeXIVA[1,2] lyophilized powder could improve the stability and provide an effective strategy to push it into clinical use as a new analgesic drug.

A novel cyanoacrylate-based matrix excipient in HPMCP capsules forms a sustained intestinal delivery system for orally administered drugs with enhanced absorption efficiency.

Patients prefer oral drug delivery due to its convenience and noninvasiveness. Nevertheless, a multitude of potentially clinically important drugs will not reach the market or achieve their full potential, due to their low bioavailability and instability in gastric acid. In this study, a novel oral drug delivery system based on poly-cyanoacrylate [a polymer of 2-(2-methoxyethoxy)ethyl-2-cyanoacrylate (MECA)] and hydroxypropyl methylcellulose phthalate (HPMCP) was developed and shown to permit intestinal targeting and sustained drug release. Aspirin [acetylsalicylic acid (ASA)] was selected as a model drug for atherosclerosis treatment. It was physically dissolved in liquid MECA, and the ASA-MECA matrix was then polymerized into a solid drug-loading depot in an HPMCP shell. The delivery of the drug depot in the intestine was achieved with the HPMCP shell; then the polymerized MECA (polyMECA) provided sustained drug release. The polyMECA excipient was not absorbed by the intestine due to its high molecular weight; a fluorescein-labeled assay indicated that it was excreted completely in feces after drug release. The formulation, ASA-polyMECA-HPMCP, showed good intestinal targeting and sustained drug release in vitro and in vivo. Pharmacokinetic studies indicated that this formulation improved the bioavailability of ASA relative to commercially available controls. ASA-polyMECA-HPMCP showed desirable anti-atherosclerosis efficacy in a rabbit model, with significant enhancement of atheromatous lesion stability. Biosafety tests proved the low toxicity of ASA-polyMECA-HPMCP and the polyMECA matrix. We believe that this work has provided a practical and biocompatible system for sustained intestinal drug delivery that can be applied broadly with various drugs for specific therapeutic aims.

In Vitro and In Vivo Bioequivalence Study of 3D-Printed Instant-Dissolving Levetiracetam Tablets and Subsequent Personalized Dosing for Chinese Children Based on Physiological Pharmacokinetic Modeling.

Recently, the development of Binder Jet 3D printing technology has promoted the research and application of personalized formulations, which are especially useful for children's medications. Additionally, physiological pharmacokinetic (PBPK) modeling can be used to guide drug development and drug dose selection. Multiple technologies can be used in combination to increase the safety and effectiveness of drug administration. In this study, we performed in vivo pharmacokinetic experiments in dogs with preprepared 3D-printed levetiracetam instant-dissolving tablets (LEV-IDTs). Bioequivalence analysis showed that the tablets were bioequivalent to commercially available preparations (Spritam®) for dogs. Additionally, we evaluated the bioequivalence of 3D-printed LEV-IDTs with Spritam® by a population-based simulation based on the established PBPK model of levetiracetam for Chinese adults. Finally, we established a PBPK model of oral levetiracetam in Chinese children by combining the physiological parameters of children, and we simulated the PK (pharmacokinetics) curves of Chinese children aged 4 and 6 years that were administered the drug to provide precise guidance on adjusting the dose according to the effective dose range of the drug. Briefly, utilizing both Binder jet 3D printing technology and PBPK models is a promising route for personalized drug delivery with various age groups.