Evaluation of floatability characteristics of gastroretentive tablets using VIS imaging with artificial neural networks.

Gastroretentive dosage forms are recommended for several active substances because it is often necessary for the drug to be released from the carrier system into the stomach over an extended period. Among gastroretentive dosage forms, floating tablets are a very popular pharmaceutical technology. In this study, it was investigated whether a rapid, nondestructive method can be used to characterize the floating properties of a tablet. To accomplish our objective, the same composition was compressed, and varied compression forces were applied to achieve the desired tablet. In addition to physical examinations, digital microscopic images of the tablets were captured and analyzed using image analysis techniques, allowing the investigation of the floatability of the dosage form. Image processing algorithms and artificial neural networks (ANNs) were utilized to classify the samples based on their strength and floatability. The input dataset consisted solely of the acquired images. It has been shown by our research that visible imaging coupled with pattern recognition neural networks is an efficient way to categorize these samples based on their floatability. Rapid and non-destructive digital imaging of tablet surfaces is facilitated by this method, offering insights into both crushing strength and floating properties.

Design and Evaluation of New Gel-Based Floating Matrix Tablets Utilizing the Sublimation Technique for Gastroretentive Drug Delivery.

A gel-based floating matrix tablet was formulated and evaluated using the sublimation technique to enhance gastroretentive drug delivery. Anhydrous theophylline was employed as the active pharmaceutical ingredient, combined with sublimation agents and hydroxypropyl methylcellulose as the gel-forming polymer. The resulting tablets exhibited high porosity, immediate floatation, and sustained buoyancy for over 8 h. Optimization of the floating behavior and drug release profiles was achieved by adjusting the viscosity of and hydroxypropyl methylcellulose and the concentration of sublimation agents, specifically ammonium carbonate and menthol. These agents were selected for their effectiveness in creating a porous structure, thus reducing tablet density and enhancing floatation. Higher HPMC viscosity resulted in increased floating force, slower drug release, and improved swelling properties due to a slower erosion rate. A critical assessment of the balance between tablet porosity, mechanical strength, and drug release kinetics indicates that ammonium carbonate provided superior tablet hardness and lower friability compared to menthol, favoring a controlled release mechanism. The release dynamics of theophylline were best described by the anomalous (non-Fickian) diffusion model, suggesting a combined effect of diffusion and erosion. This research advances the development of gastroretentive drug delivery systems, highlighting the potential of sublimation-based floating matrix tablets for sustained drug release.

Current trends in 3D printed gastroretentive floating drug delivery systems: A comprehensive review.

Gastrointestinal (GI) environment is influenced by several factors (gender, genetics, sex, disease state, food) leading to oral drug absorption variability or to low bioavailability. In this scenario, gastroretentive drug delivery systems (GRDDS) have been developed in order to solve absorption problems, to lead to a more effective local therapy or to allow sustained drug release during a longer time period than the typical oral sustained release dosage forms. Among all GRDDS, floating systems seem to provide a promising and practical approach for achieving a long intra-gastric residence time and sustained release profile. In the last years, a novel technique is being used to manufacture this kind of systems: three-dimensional (3D) printing technology. This technique provides a versatile and easy process to manufacture personalized drug delivery systems. This work presents a systematic review of the main 3D printing based designs proposed up to date to manufacture floating systems. We have also summarized the most important parameters involved in buoyancy and sustained release of the systems, in order to facilitate the scale up of this technology to industrial level. Finally, a section discussing about the influence of materials in drug release, their biocompatibility and safety considerations have been included.

Gastroretentive Delivery Approach to Address pH-Dependent Degradation of (+)- and (-)-Phenserine.

(-)-Phenserine ("phenserine") and (+)-phenserine (posiphen; buntanetap) are longer-acting enantiomeric analogs of physostigmine with demonstrated promise in the treatment of Alzheimer's and Parkinson's diseases. Both enantiomers have short plasma half-lives, and their pharmacokinetics might be improved through the use of either once or twice-daily administration of an extended-release dosage form. Phenserine was observed to form a colored degradation product in near-neutral and alkaline pH environments, and at pH 7, the half-life of posiphen was determined to be ~ 9 h (40 °C). To limit luminal degradation which would reduce bioavailability, a gastroretentive tablet composed of a polyethylene oxide-xanthan gum matrix was developed. When placed in simulated gastric fluid (pH 1.2), approximately 70% of the phenserine was released over a 12 h period, and no degradants were detected in the release medium. In comparison, a traditional hydrophilic-matrix, extended-release tablet showed measurable amounts of phenserine degradation in a pH 7.2 medium over an 8 h release interval. These results confirm that a gastroretentive tablet can reduce the luminal degradation of phenserine or posiphen by limiting exposure to neutral pH conditions while providing sustained release of the drug over at least 12 h. Additional advantages of the gastroretentive tablet include reduced gastric and intestinal concentrations of the drug resulting from the slower release from the gastroretentive tablet which may also limit the occurrence of the dose-limiting GI side effects previously observed with immediate-release phenserine capsules.

Ferrous ascorbate non-effervescent floating mini-caplets as an oral iron supplement.

PURPOSE: This research aimed to develop non-effervescent floating mini-caplets of Ferrous Ascorbate (FA) using low-density polymers to overcome the problems of poor bioavailability associated with immediate-release iron products. Methods: The excipients and method (melt granulation) were selected based on pre-and post-compression parameters in trial batches. The formulation was optimized by a full factorial 32 experimental design. An optimized formulation was evaluated for drug release kinetic, accelerated stability study, and in vivo study in healthy adult New Zealand female rabbits. Results: The optimized formulation F6 mini-caplets (42.5% FA, 45% Glyceryl palmitostearate as Precirol, 10% polyvinyl pyrrolidone K-30, and 2.5% lactose) were found to have instant floating and 12 h floating duration in 0.1N Hydrochloric acid (HCl) dissolution medium. In vitro drug release (diffusion mechanism) at 1 h and 5 h was 30-35% and 65-70%, respectively. It was found stable for three months under an accelerated stability study. In vivo study showed significantly increased serum iron levels and decreased unsaturated iron binding capacity (UIBC) in the test group (optimized formulation) compared to control and standard (immediate-release iron). Conclusion: Based on the in vitro and in vivo results, we conclude that non-effervescent floating FA mini-caplets have higher bioavailability compared to immediate release FA, which may be attributed to prolonged iron release at its absorption site due to their retention in the gastric region. Hence, non-effervescent floating FA mini-caplets may act as a potential approach for iron deficiency.

Fabrication of 3D printed mutable drug delivery devices: a comparative study of volumetric and digital light processing printing.

Mutable devices and dosage forms have the capacity to dynamically transform dimensionally, morphologically and mechanically upon exposure to non-mechanical external triggers. By leveraging these controllable transformations, these systems can be used as minimally invasive alternatives to implants and residence devices, foregoing the need for complex surgeries or endoscopies. 4D printing, the fabrication of 3D-printed structures that evolve their shape, properties, or functionality in response to stimuli over time, allows the production of such devices. This study explores the potential of volumetric printing, a novel vat photopolymerisation technology capable of ultra-rapid printing speeds, by comparing its performance against established digital light processing (DLP) printing in fabricating hydrogel-based drug-eluting devices. Six hydrogel formulations consisting of 2-(acryloyloxy)ethyl]trimethylammonium chloride solution, lithium phenyl-2,4,6-trimethylbenzoylphosphinate, varying molecular weights of the crosslinking monomer, poly(ethylene glycol) diacrylate, and paracetamol as a model drug were prepared for both vat photopolymerisation technologies. Comprehensive studies were conducted to investigate the swelling and water sorption profiles, drug release kinetics, and physicochemical properties of each formulation. Expandable drug-eluting 4D devices were successfully fabricated within 7.5 s using volumetric printing and were shown to display equivalent drug release kinetics to prints created using DLP printing, demonstrating drug release, swelling, and water sorption properties equivalent to or better than those of DLP-printed devices. The reported findings shed light on the advantages and limitations of each technology for creating these dynamic drug delivery systems and provides a direct comparison between the two technologies, while highlighting the promising potential of volumetric printing and further expanding the growing repertoire of pharmaceutical printing.

Exploration of moisture activated dry granulation for the development of gastroretentive tablets aided by SeDeM diagram.

Moisture activated dry granulation (MADG) is an attractive granulation process. However, only a few works have explored modified drug release achieved by MADG, and to the best of the authors knowledge, none of them have explored gastroretention. The aim of this study was to explore the applicability of MADG process for developing gastroretentive placebo tablets, aided by SeDeM diagram. Floating and swelling capacities have been identified as critical quality attributes (CQAs). After a formulation screening step, the type and concentration of floating matrix formers and of binders were identified as the most relevant critical material attributes (CMAs) to investigate in ten formulations. A multiple linear regression analysis (MLRA) was applied against the factors that were varied to find the design space. An optimized product based on principal component analysis (PCA) results and MLRA was prepared and characterized. The granulate was also assessed by SeDeM. In conclusion, granulates lead to floating tablets with short floating lag time (<2 min), long floating duration (>4 h), and showing good swelling characteristics. The results obtained so far are promising enough to consider MADG as an advantageous granulation method to obtain gastroretentive tablets or even other controlled delivery systems requiring a relatively high content of absorbent materials in their composition.

Diltiazem Hydrochloride Floating Matrix Tablet: Formulation and in vitro-in vivo Evaluation.

BACKGROUND: Diltiazem hydrochloride is a calcium channel-blocker with a plasma elimination half-life of 4.4 ± 1.3 h and has a narrow absorption window. So, this work aimed to prepare a gastro-retentive floating matrix tablet. METHODS: The direct compression method was used to manufacture tablets. 32 factorial design was applied for optimization, taking Hydroxypropyl Methylcellulose K100M (HPMC K 100M) and the amount of sodium bicarbonate as independent factors and cumulative percentage release at 1 h, at 6 h, and at 12 h and floating lag time as dependent variables. RESULTS: The high amount of HPMC K100M and sodium bicarbonate shows good results. The optimized preparation was evaluated for differential scanning calorimetry, in-vivo gastric retention in male albino rabbits, kinetic modeling, and stability study. An in vivo study revealed gastric retention of tablets up to 6 h in healthy male Albino rabbits. The stability study indicated no significant change in the buoyancy and release profiles of the drug. CONCLUSION: From this study, it can be concluded that the gastro-retentive diltiazem hydrochloride floating matrix tablet was successfully prepared and retained inside the rabbit stomach for up to 6 h and was stable under accelerated stability study.

Oral co-polymeric raft-forming nano gels for targeted empagliflozin delivery against stomach cancer (SGC7901).

Empagliflozin (EMP) is known for its poor safety and efficacy profile due to its fast body distribution and poor solubility. Accordingly, an oral long-acting and floating/raft-forming nano gel was optimized to release coated EMP nanoparticles, and the released EMP nanoparticles showed enhanced dissolution compared to raw EMP particles. To repurpose EMP for cancer treatment, EMP shows anti-cancer and anti-inflammatory effects against cancer cells. EMP nanoparticles were characterized using FT-IR, PXRD, SEM, EMP encapsulation assay, and release studies. The raft-forming gel encapsulating the EMP was optimized and characterized. The EMP co-polymeric nanoparticles were studied to investigate EMP anti-cancer and anti-inflammatory activities against stomach cancer cells. The solubility of EMP nanoparticles was enhanced in 0.1 N HCl and pH 6.8 by 5 and 12 folds, respectively, compared to raw EMP powder. The particle size and zeta-potential values of improved EMP nanoparticles were 135.40 ± 18.60 nm, and -19.30 ± 0.80 mV, respectively. FT-IR, PXRD, SEM and TEM characterizations revealed polymeric coating of EMP particles. The study suggested that this optimized controlled-release raft-forming gel is a promising local oral approach against stomach cancer. The repurposing of EMP co-polymeric nanoparticles for stomach cancer and associated gastritis treatment was justified.

Cellulose ether and carbopol 971 based gastroretentive controlled release formulation design, optimization and physiologically based pharmacokinetic modeling of ondansetron hydrochloride minitablets.

This study aims to design and optimize ondansetron (OND) gastro-retentive floating minitablets for better and prolonged control of postoperative nausea and vomiting (PONV) with improved patient compliance. Minitablets were directly compressed and encapsulated in a size 2 capsule shell with an overall dose of 24 mg. Central composite design (CCD) was applied keeping one cellulose ether derivative HPMC K15M and Carbopol 971 as variable and used as swelling and rate retarding agents. The other cellulose derivative i.e. sodium carboxymethyl cellulose, along with mannitol, sodium bicarbonate, and talc, were used in fixed quantities. The floating lag time, total floating time, swelling index, in-vitro drug release, and zero-order (RSQ value), were critical quality parameters. The optimized formulation (Fpred) was evaluated for all critical parameters, along with surface morphology, thermal stability, chemical interaction, and accelerated stability. The in silico PBPK modeling was applied to compare the bioavailability of Fpred with reference OND immediate-release tablets. The numerical optimization model predicted >90 % drug release with zero-order at 12 h. In silico PBPK modeling revealed comparable relative bioavailability of Fpred with the reference formulation. The gastroretentive floating minitablets of OND were successfully designed for prolonged emesis control in patients receiving chemotherapeutic agents.

A phase 4 randomized active-controlled clinical study to compare the efficacy and safety of sustained-release pregabalin with immediate-release pregabalin in type 2 diabetic patients with peripheral neuropathic pain.

AIMS: The objective of this study was to demonstrate that sustained-release (SR) pregabalin is non-inferior to immediate-release (IR) pregabalin in attenuating diabetic peripheral neuropathic (DPN) pain along with patient satisfaction and compliance. METHODS: This was an 8-week, randomized, active-controlled, open-label, phase 4 study. Eligible subjects who had been on IR pregabalin for 4 weeks were randomized to 1:1 ratio to either continue with twice-daily IR pregabalin (75 mg), or to switch to once-daily SR pregabalin (150 mg). Primary efficacy endpoint was the change in visual analogue scale (VAS) scores after 8 weeks of treatment compared to baseline in both SR and IR pregabalin groups. RESULTS: Among 130 randomized subjects, 125 patients were included in full analysis set. For the change in VAS pain score, the least squares (LS) mean were -17.95 (SR pregabalin) and -18.74 (IR pregabalin) and the LS mean difference between both groups was 0.79, with the upper limit of the 95 % confidence interval [-5.99, 7.58] below the pre-specified non-inferiority margin of 9.2 mm. CONCLUSIONS: This study demonstrates that the new once-daily SR pregabalin formulation is not different to the twice-daily IR pregabalin in alleviating DPN pain, indicating its potential as a promising treatment for DPN pain with a comparable safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05624853.

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 3: Theoretical models of drug concentration in blood.

In this part, drug concentration in blood after ingesting slow-release gastroretentive fibrous dosage forms and immediate-release particulate forms is modeled. The tyrosine kinase inhibitor nilotinib, which is slightly soluble in low-pH gastric fluid but practically insoluble in pH-neutral intestinal fluid is used as drug. The models suggest that upon ingestion, the fibrous dosage form expands, is retained in the stomach for prolonged time, and releases drug into the gastric fluid at a constant rate. The released drug molecules flow into the duodenum with the gastric fluid, and are absorbed by the blood. The drug is eliminated from the blood by the liver at a rate proportional to its concentration. Eventually, the elimination and absorption rates will be equal, and the drug concentration in blood plateaus out. After the gastric residence time drug absorption stops, and the drug concentration in blood drops to zero. By contrast, after administering an immediate-release particulate dosage form the drug particles are swept out of the stomach rapidly, and drug absorption stops much earlier. The drug concentration in blood rises and falls without attaining steady state. The gastroretentive fibrous dosage forms enable a constant drug concentration in blood for drugs that are insoluble in intestinal fluids.

Expanding the Manufacturing Approaches for Gastroretentive Drug Delivery Systems with 3D Printing Technology.

Gastroretentive drug delivery systems (GRDDSs) have gained substantial attention in the last 20 years due to their ability to retain the drug in the stomach for an extended time, thus promoting an extended release and high bioavailability for a broad range of active pharmaceutical ingredients (APIs) that are pH-sensitive and/or have a narrow absorption window. The currently existing GRDDSs include floating, expanding, mucoadhesive, magnetic, raft-forming, ion-exchanging, and high-density systems. Although there are seven types of systems, the main focus is on floating, expanding, and mucoadhesive systems produced by various techniques, 3D printing being one of the most revolutionary and currently studied ones. This review assesses the newest production technologies and briefly describes the in vitro and in vivo evaluation methods, with the aim of providing a better overall understanding of GRDDSs as a novel emerging strategy for targeted drug delivery.

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 2: Experimental validation of the models of expansion, post-expansion mechanical strength, and drug release.

In Part 1, we have introduced expandable gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. The expansion rate, post-expansion mechanical strength, and drug release rate were modeled for a dosage form containing 200 mg nilotinib. In the present part, the dosage form was prepared and tested in vitro to validate the models. Upon immersing in a dissolution fluid, the fibrous dosage form expanded at a constant rate to a normalized radial expansion of 0.5 by 4 h, and then formed an expanded viscoelastic mass of high strength. The drug was released at a constant rate over a day. For comparison, a particle-filled gelatin capsule with the same amount of nilotinib disintegrated almost immediately, and released eighty percent of the drug content in just 10 min. The experimental data validate the theoretical models of Part 1 reasonably.

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 1: Dosage form design, and models of expansion, post-expansion mechanical strength, and drug release.

At present, the efficacy and safety of many sparingly-soluble tyrosine kinase inhibitors (TKIs) delivered by the prevalent oral dosage forms are compromised by excessive fluctuations in the drug concentration in blood. To mitigate this limitation, in this four-part study gastroretentive fibrous dosage forms that deliver drug into the gastric fluid (and into the blood) at a controlled rate for prolonged time are presented. The dosage form comprises a cross-ply structure of expandable, water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC)-based fibers coated with a strengthening, enteric excipient. The intervening spaces between the coated fibers are solid annuli of drug particles, and low-molecular-weight HPMC and enteric excipients. The central regions of the annuli are open channels. In this part, models are developed for dosage form expansion, post-expansion mechanical strength, and drug release. The models suggest that upon immersing in a dissolution fluid, the fluid percolates the open channels, diffuses into the annuli and the coated fibers, and the dosage form expands. The expansion rate is inversely proportional, and the post-expansion mechanical strength proportional to the thickness of the strengthening coating. Drug particles are released from the annuli as the surrounding excipient dissolves. The drug release rate is proportional to the concentration of low-molecular-weight HPMC at the annulus/dissolution fluid interface. The dosage forms can be readily designed for expansion in a few hours, formation of a high-strength viscoelastic mass, and drug release at a constant rate over a day.

Gastroretentive fibrous dosage forms for prolonged delivery of sparingly-soluble tyrosine kinase inhibitors. Part 4: Experimental validation of the models of drug concentration in blood.

In this final part, the models of drug concentration in blood developed in Part 3 are validated on dogs. Both slow-release gastroretentive fibrous and immediate-release particulate dosage forms containing 200 mg nilotinib were tested. After administering, the fibrous dosage form expanded linearly with time in the stomach, to about 1.5 times the initial radius by 4 h. The expanded dosage form fractured after 10 h, and then passed into the intestines. The drug concentration in blood exhibited a broad peak with a maximum of 0.51 µg/ml and a width at half-height of 10.2 h. By contrast, after administering the immediate-release capsule the drug concentration in blood exhibited a sharp peak with a maximum of 0.68 µg/ml and a width at half-height of just 3.6 h. The experimental data validate the theoretical models reasonably. The gastroretentive fibrous dosage forms designed in this study enable a steady drug concentration in blood for increasing the efficacy and mitigating side effects of drug therapies.

Design and fabrication of 3D-printed gastric floating tablets of captopril: effect of geometry and thermal crosslinking of polymer on floating behavior and drug release.

The present study aims to investigate the potential of the 3D printing technique to design gastroretentive floating tablets (GFTs) for modifying the drug release profile of an immediate-release tablet. A 3D-printed floating shell enclosing a captopril tablet was designed having varying number of drug-release windows. The impact of geometrical changes in the design of delivery system and thermal cross-linking of polymers were evaluated to observe the influence on floating ability and drug release. Water uptake, water insolubilization, Differential Scanning Calorimetry (DSC), and Attenuated Total Reflection-Fourier Transform Infrared Spectroscopy (ATR-FTIR) were performed to assess the degree of thermal cross-linking of polyvinyl alcohol (PVA) filament. The 3D-printed GFT9 was considered the optimized gastric floating tablet that exhibited >12 h of total floating time with zero floating lag time and successfully accomplished modified-drug release by exhibiting >80% of drug release in 8 h. The zero-order release model, with an r2 value of 0.9923, best fitted the drug release kinetic data of the GFT9, which followed a super case II drug transport mechanism with an n value of 0.95. The optimized gastric floating device (GFT9) also exhibited the highest MDT values (238.55), representing slow drug release from the system due to thermal crosslinking and the presence of a single drug-releasing window in the device.

Simultaneous Delivery of Curcumin and Resveratrol via In Situ Gelling, Raft-Forming, Gastroretentive Formulations.

Curcumin and resveratrol are polyphenolic compounds that have been shown to exhibit synergistic therapeutic properties including anti-inflammatory, anticancer, and antiulcer activities, which may be exploited for the treatment of gastric diseases. However, both compounds have poor aqueous solubility and rapid metabolism, resulting in a low oral bioavailability. In situ gelling, liquid formulations were developed to produce a gastroretentive, raft-forming delivery vehicle to improve bioavailability. Solid dispersions containing a mixture of curcumin and resveratrol with Eudragit® EPO (Cur/Res-SD) were first prepared using solvent evaporation, to improve the solubility and dissolution of the compounds. Solid dispersions of a weight ratio of 1:10 curcumin/resveratrol to Eudragit® EPO were subsequently incorporated into in situ gelling, liquid formulations based on the gelling polymers, sodium alginate (low viscosity and medium viscosity), pectin, and gellan gum, respectively. Calcium carbonate and sodium bicarbonate were included to produce carbon dioxide bubbles in the gel matrix, on exposure to gastric fluid, and to achieve flotation. Moreover, the calcium ions acted as a crosslinking agent for the hydrogels. Optimized formulations floated rapidly (<60 s) in simulated gastric fluid (pH = 1.2) and remained buoyant, resulting in the gradual release of more than 80% of the curcumin and resveratrol content within 8 h. The optimized formulation based on medium-viscosity sodium alginate exhibited enhanced cytotoxic activity toward human gastric adenocarcinoma cell lines (AGS), compared with unformulated curcumin and resveratrol compounds, and increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate that in situ gelling, liquid formulations, loaded with a combination of curcumin and resveratrol in the form of solid dispersions, show potential as gastroretentive delivery systems for local and systemic effects.

Improved gastric residence time of famotidine by raft-forming drug delivery system using DOE.

OBJECTIVE: This study investigated the raft-forming suspension of famotidine as an anti-reflux formulation to improve the oral bioavailability of narrow absorption window drugs by enhancing gastric residence time (GRT) and preventing gastro-esophageal reflux disease (GERD). METHOD: Various combinations of raft-forming agents, such as Tragacanth gum (TG), guar gum (GG), and xanthan gum (XG), were evaluated alongside sodium alginate (SA) to develop an effective raft. Preformulation studies and preliminary screening were conducted to identify the most suitable raft-forming agent, and GG was chosen due to its mucilaginous properties. The formulation was optimized using a 32 full factorial design, with the quantities of GG and SA as independent factors and apparent viscosity and in-vitro drug release (%) as dependent factors. The in vivo floating behavior study was performed for optimized and stabilized formulation. RESULTS: Among the tested batches, F6 was selected as the optimized formulation. It exhibited desirable characteristics such as adequate raft weight for extended floating in gastric fluid, improved apparent viscosity, and a significant percentage of drug release at 12 h. A mathematical model was applied to the in-vitro data to gain insights into the drug release mechanism of the formulation. The stability of the suspension was assessed under accelerated conditions, and it demonstrated satisfactory stability. The formulation remains floating in the Rabbit stomach for more than 12 h. CONCLUSION: It concludes that the developed formulation has enhanced bioavailability in the combination of GG and SA. The floating layer of the raft prevents acid reflux, and the famotidine is retained for an extended period of time in the gastric region, preventing excess acid secretion. The developed formulations are effective for stomach ulcers and GERD, with the effect of reducing acid secretion by H2 receptor antagonists.

3D printing of multi-unit gastro-retentive tablets for the pulsatile release of artesunate.

Pulsatile drug delivery is hardly achieved by conventional gastro-retentive dosage forms. Artesunate as a typical anti-malaria medicine needs oral pulsatile release. Here, artesunate-loaded pulsatile-release multi-unit gastro-retentive tablets (APGTs) were prepared with a semi-solid extrusion three-dimensional (3D) printing method. An APGT was composed of three units: artesunate-loaded immediate and delayed release units and a block unit. The matrix of the immediate/delayed release units consisted of polyvinylpyrrolidone (PVP) K30 and croscarmellose sodium, which improved the rapid release of artesunate when contacting water. The block unit consisted of octadecanol, hydroxypropyl methyl cellulose K15M, PVP K30, and poloxamer F68. APGTs showed multi-phase release in simulated gastric liquids (SGLs). The first immediate release phase continued for 1 h followed by a long block phase for 7 h. The second rapid release phase was initiated when the eroded holes in the block unit extended to the inner delayed release unit, and this phase continued for about 14 h. Low-density APGTs could ensure their long-term floating in the stomach. Oral APGTs remained in the rabbit stomach for about 20 h. 3D printing provides a new strategy for the preparation of oral pulsatile-release tablets.