Amorphous solid dispersion of a binary formulation with felodipine and HPMC for 3D printed floating tablets.

This study focuses on the combination of three-dimensional printing (3DP) and amorphous solid dispersion (ASD) technologies for the manufacturing of gastroretentive floating tablets. Employing hot melt extrusion (HME) and fused deposition modeling (FDM), the study investigates the development of drug-loaded filaments and 3D printed (3DP) tablets containing felodipine as model drug and hydroxypropyl methylcellulose (HPMC) as the polymeric carrier. Prior to fabrication, solubility parameter estimation and molecular dynamics simulations were applied to predict drug-polymer interactions, which are crucial for ASD formation. Physical bulk and surface characterization complemented the quality control of both drug-loaded filaments and 3DP tablets. The analysis confirmed a successful amorphous dispersion of felodipine within the polymeric matrix. Furthermore, the low infill percentage and enclosed design of the 3DP tablet allowed for obtaining low-density systems. This structure resulted in buoyancy during the entire drug release process until a complete dissolution of the 3DP tablets (more than 8 h) was attained. The particular design made it possible for a single polymer to achieve a zero-order controlled release of the drug, which is considered the ideal kinetics for a gastroretentive system. Accordingly, this study can be seen as an advancement in ASD formulation for 3DP technology within pharmaceutics.

Design of floating formulations and antiulcer activity of Desmostachya bipinnata.

The study aims to design and optimize the floating formulations of the aqueous extract of Desmostachya bipinnata (ADB) to treat peptic ulcers. The trial concentrations of HPMC E50, HPMC K4M, and Carbopol 940 were used as factors, and floating lag time, total floating time, and % drug release at 12 h were used as responses. The formulation underwent evaluation for different parameters: aspirin-induced ulcers in rats assessed the antiulcer activity, and X-ray studies in rabbits evaluated the gastroretentive nature. The optimized formulation has shown a floating lag time of 32 s and floated in the gastric medium for more than 9 h with a maximum drug release of 93% at the end of 12 h by following the Korsmeyer-Peppas drug release mechanism. The optimized formulation has good flow properties. The FT-IR, DSC, and XRD studies show ADB and excipients didn't show any incompatibility. The formulation has shown significant antiulcer activity against aspirin-induced ulcers in rats, with an ulcer index of 3.38 ± 0.24 and inhibition of 76.67 ± 0.56%. The in vivo X-ray imaging proved the gastric retention of the formulations for more than 8 h. The results of the formulations demonstrate the floating ability and sustained drug release of the tablet responsible for treating peptic ulcers to show a localized effect in the gastric region and to maintain the ROS levels.

Design and Evaluation of Ginkgolides Gastric Floating Controlled Release Tablets Based on Solid Supersaturated Self-nanoemulsifying.

Ginkgolides are receptor antagonist of platelet activating factor with great clinical prospect, but its application is limited by its low solubility, short half-life and poor alkaline environment stability. It is difficult to solve these problems with a single drug delivery system. In this study, supersaturated self-nanoemulsifying gastric floating tablets of ginkgolides were developed through the combination of solid supersaturated self-nanoemulsifying drug delivery system (solid S-SNEDDS) and gastric retentive floating drug delivery system (GFDDS) to solve these problems of ginkgolides. Solid S-SNEDDS was prepared by D-optimal mixture design, normalization method and single factor experiment. The properties of solid-S-SNEDDS were studied by TEM, PXRD, FT-IR, SEM and in vitro drug release profile. Then, the optimal formulation of stomach floating tablet was obtained through single factor experiment and center composite design, followed by the study of in vitro release, model and mechanism of release, in vitro buoyancy and kinetics of erosion and swelling. PXRD and FT-IR showed that the drug in solid S-SNEDDS existed in an amorphous manner and formed hydrogen bond with excipients. The results showed that the cumulative release of GA and GB in the optimal tablets was 96.12% and 92.57% higher than the simple tablets within 12 h. The release mechanism of the tablet was skeleton erosion and drug diffusion. In 12 h, the optimal tablets can float stably in vitro and release the drug at a constant rate, with a cumulative release of more than 80%. In summary, the combination of SNEDDS and GFDDS is a promising means to solve the problems of ginkgolides.

Hydrophilic High Drug-Loaded 3D Printed Gastroretentive System with Robust Release Kinetics.

Three-dimensional printing (3DP) technology enables an important improvement in the design of new drug delivery systems, such as gastroretentive floating tablets. These systems show a better temporal and spatial control of the drug release and can be customized based on individual therapeutic needs. The aim of this work was to prepare 3DP gastroretentive floating tablets designed to provide a controlled release of the API. Metformin was used as a non-molten model drug and hydroxypropylmethyl cellulose with null or negligible toxicity was the main carrier. High drug loads were assayed. Another objective was to maintain the release kinetics as robust as possible when varying drug doses from one patient to another. Floating tablets using 10-50% w/w drug-loaded filaments were obtained by Fused Deposition Modelling (FDM) 3DP. The sealing layers of our design allowed successful buoyancy of the systems and sustained drug release for more than 8 h. Moreover, the effect of different variables on the drug release behaviour was studied. It should be highlighted that the robustness of the release kinetics was affected by varying the internal mesh size, and therefore the drug load. This could represent a step forward in the personalization of the treatments, a key advantage of 3DP technology in the pharmaceutical field.

Fabrication and In Vitro/In Vivo Appraisal of Metronidazole Intra-Gastric Buoyant Sustained-Release Tablets in Healthy Volunteers.

Helicobacter pylori is thought to be the most common cause of peptic and duodenal ulcers. Eradication of this organism is now considered one of the lines of treatment of gastric and duodenal ulcers. This can be achieved via local delivery of antibacterial agents in high concentrations. Accordingly, our objective was to fabricate and evaluate sustained release floating tablets for metronidazole to extend the gastric residence period and control the release rate of metronidazole. Floating tablets containing cellulose derivatives and Avicel were prepared using direct compression. The rate of metronidazole release from the floating tablets (K = 6.278 mg min-1/2) was significantly lower than that from conventional tablets (K = 10.666 mg min-1/2), indicating sustained drug release, according to the Higuchi model, for more than 6 h in an acidic medium of 0.1 N HCl. In vivo study in healthy volunteers revealed significantly improved bioavailability; increased Tmax, AUC, and MRT; and significantly lower absorption rate constant after a single oral dose of 150 mg metronidazole as floating tablets. In addition, the significant increase in MRT indicated an in vivo sustained drug release. The floating tablets provided several benefits, including ease of preparation, absence of effervescent ingredients, and reliance on a pH-independent gel-forming agent to deliver metronidazole in a sustained manner. In conclusion, the prepared tablets could be promising for enhancing both local and systemic metronidazole efficacy.

DDSolver Software Application for Quantitative Analysis of In vitro Drug Release Behavior of the Gastroretentive Floating Tablets Combined with Radiological Study in Rabbits.

BACKGROUND: Gastroretentive drug delivery systems (GRDDSs) are designed to release the drug in the stomach over a prolonged time; thus, they can reduce drug dosing frequency and dose size and improve patient compliance. GRDDSs are also highly effective in enhancing the bioavailability of the drug that exhibits window absorption in specific segments of the gastrointestinal (GI) tract. Famotidine (FMT), an H2 receptor antagonist, is an example of these drugs. FMT is a slightly watersoluble drug but well soluble in an acidic medium. This research aims to formulate FMT gastroretentive floating tablets (FMT-GRFTs) to improve the bioavailability and therapeutic activity of the drug and increase patients' adherence to treatment. In addition, the in vitro release behavior of the prepared FMT-GRFTs was quantitatively analyzed using the DDSolver software to assist in selecting the successful formulation that was then evaluated in vivo. METHODS: The direct compression technique prepared numerous tablet formulations and was subjected to the pre-and post-compression evaluation. Data of FMT dissolution in the simulated gastric medium was analyzed by various kinetic models built in the DDSolver program. In addition, the simulated pharmacokinetics (AUC, MDT, and MRT), R2 adjusted, AIC, MSC, correlation of the residuals, and similarity factor (f2) were also generated. RESULTS: The results revealed that FMT release from the candidate formula (FH3) fitted to the first-order kinetic model, with a high value of R2 adjusted and MSC and a low AIC. The release behavior exhibited the Fickian diffusion mechanism. The similarity factor showed no significant difference (p < 0.05) of the test sample compared to the reference product. Nevertheless, the simulated pharmacokinetic parameter, AUC, proved a two-fold enhancement in FMT bioavailability, with a significant increment in the MDT and MRT compared with the reference product.The FT-IR spectroscopy analysis indicated the absence of drug-excipients/polymer interaction.The in vivo X-ray studies on rabbits confirmed that the floating tablets showed nearly eight hours of gastric residence. CONCLUSION: DDSolver software was helpful in deciding the optimized formulation of FMT floating tablets. The radiological examination in rabbits for gastric retention was consistent with the release data analysis in vitro.

Formulation, Optimization, in vitro and in-vivo evaluation of levofloxacin hemihydrate Floating Tablets

Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

Study on the quality standard of Kuipingning gastric floating tablets / 中国药房

OBJECTIVE To establish the quality standard of Kuipingning gastric floating tablets. METHODS Kuipingning gastric floating tablets were prepared and investigated in terms of property ，weight difference and friability. Crydalis yanhusuo was identified qualitatively by thin layer chromatography （TLC）method. High performance liquid chromatography method was used to determine the content of total anthraquinones in Rheum palmatum ，and set the content limit of total anthraquinones. The floating performance and release degree of the preparation were investigated ，and the release kinetic process was fitted. RESULTS Kuipingning gastric floating tablets prepared in this study were gray white to gray tablets with slight smell and bitter taste ；the weight difference and friability were all in line with relevant regulations ；the established TLC method possessed strong specificity and could accurately identify C. yanhusuo . The average content of total anthraquinones in R. palmatum was 17.95 mg/tablet，and its content limit would not be less than 14.36 mg/tablet. The initial floating time of the preparation was no more than 10 s，and the holding time was more than 8 h. The release kinetics process accorded with the Retger-Peppas release model. CONCLUSIONS The method established in this study shows good reliability ，stability and feasibility ，and can effectively control the quality of Kuipingning gastric floating tablets.

Development and Optimization of Microballoons Assisted Floating Tablets of Baclofen.

The objective of the present study was to develop microballoons aided gastro-retentive floating tablets of baclofen, a skeletal muscle relaxant with a low elimination half-life of ~ 3.5 h. Baclofen floating tablet was prepared to offer convenience by designing a tablet that would float in the stomach for a prolonged period and allow controlled drug release to enable once-a-day administration. Ethylcellulose microballoons (ECMBs) prepared by pseudo emulsion solvent diffusion method were employed as floating aid. The ECMBs were spherical with a size of 446.71 µm and a circularity index of 0.995. Buoyancy of 98.90 percent and good flowability reflected by an angle of repose of 23° suggested the feasibility of preparing floating tablets by direct compression. Directly compressed baclofen floating tablets comprised ECMBs, HPMC-K15M, and hydroxyl ethylcellulose as independent variables in the Box-Behnken design, however, performance characteristics of tablets such as in vitro drug release, floating lag time, and swelling index were selected as the dependent variables. Among the variables, ECMBs played a critical role in ensuring buoyancy. However, HPMC-K15M significantly influenced in vitro drug release. The optimized batch displayed Hickson-Crowell kinetics and exhibited a similar drug release profile as a marketed once-a-day formulation (f2, 91.03). Furthermore, optimized tablets showed a swelling index of > 300, floating lag time < 3 s, and total floating time > 24 h. Microballoons assisted floating tablets exhibited great promise for assured gastric retention of tablets.

Design and Evaluation of Losartan Potassium Effervescent Floating Matrix Tablets: In Vivo X-ray Imaging and Pharmacokinetic Studies in Albino Rabbits.

Losartan potassium (LP) is an angiotensin receptor blocker used to treat hypertension. At higher pH, it shows poor aqueous solubility, which leads to poor bioavailability and lowers its therapeutic effectiveness. The main aim of this research was to develop a direct compressed effervescent floating matrix tablet (EFMT) of LP using hydroxyl propyl methylcellulose 90SH 15,000 (HPMC-90SH 15,000), karaya gum (KG), and an effervescent agent, such as sodium bicarbonate (SB). Therefore, an EFMT has been developed to prolong the stomach residence time (GRT) of a drug to several hours and improve its bioavailability in the stomach region. The blended powder was evaluated for pre-compression characteristics, followed by post-compression characteristics, in vitro floating, water uptake studies, and in vitro studies. The optimized formulation of EFMT was investigated for in vivo buoyancy by X-ray imaging and pharmacokinetic studies in Albino rabbits. The results revealed that the parameters of pre- and post-compression were within the USP limits. All tablets showed good floating capabilities (short floating lag time <1 min and floated for >24 h), good swelling characteristics, and controlled release for over 24 h. The Fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) spectra showed drug-polymer compatibility. The optimized formulation F3 (HPMC-90SH 15,000-KG) exhibited non-Fickian diffusion and showed 100% drug release at the end of 24 h. In addition, with the optimized formulation F3, we observed that the EFMT floated continuously in the rabbit's stomach area; thus, the GRT could be extended to more than 12 h. The pharmacokinetic profiling in Albino rabbits revealed that the relative bioavailability of the optimized LP-EFMT was enhanced compared to an oral solution of LP. We conclude that this a potential method for improving the oral bioavailability of LP to treat hypertension effectively.

DoE-Based Design of a Simple but Efficient Preparation Method for a Non-Effervescent Gastro-Retentive Floating Tablet Containing Metformin HCl.

A sustained-release non-effervescent floating matrix tablet was prepared using a simple and efficient direct compression of spray-dried granules containing metformin hydrochloride and cetyl alcohol with hydroxypropyl methylcellulose K15M (HPMC K15M). The design of experiments was employed to explore the optimal composition of the tablet. The similarity factor was employed to evaluate the equivalence in dissolution profiles between the test tablets and Glucophage XR as a reference. Bootstrap analysis was used to eliminate the formulations for which the dissolution profile was potentially inequivalent to that of the reference. The optimized tablet consisting of 150 mg of cetyl alcohol and 17% HPMC K15M showed a dissolution profile comparable with that of the reference with a similarity factor of 52.41, exhibited a floating lag time of less than 3 s in buffer media, remained floating for 24 h, and reduced the tablet weight by about 20% compared to that of the reference. The current study sheds light on the potential use of non-effervescent gastro-retentive extended-release tablets for high-dose drugs using a simple and efficient direct compression method, and as a potential alternative treatment for Glucophage XR. This study also highlights the importance of a systematic approach to formulation optimization and the evaluation of the dissolution profile.

Three-dimensional printing of gastro-floating tablets using polyethylene glycol diacrylate-based photocurable printing material.

Extruded three-dimensional (3D) printing based on photocurable materials has shown good application prospects in the medical field. This has been attributed to the operational aspect that can be performed at room temperature and the high mechanical strength of the extrudate and final product. However, the commonly used photocurable polymer, polyethylene glycol diacrylate (PEGDA), has a low viscosity and exhibits a long crosslinking time. Therefore, additives are added to improve the printability of the extrudate. In this study, various hydrogels were used to improve the mixing uniformity and rheological behavior of PEGDA-based printing materials. Printing accuracy and mechanical strength were evaluated to optimize print material composition and process parameters. Hydroxypropyl methylcellulose K100M was found to improve the shear thinning and self-supporting properties of printing materials, which were essential for printability. Although the storage modulus of the photocured material proportionally increased with curing time in the range of 20-80 s, the minimal layer time of the 3D samples remained at 65 s, ensuring interlayer adhesion. Gastro-floating tablets with different infill densities were printed to illustrate the application of 3D extrusion printing in personalized medicine. The weight, crushing strength, and floating time were regulated by the infill density of the models. Overall, this study demonstrates that extrusion printing with a photocurable material is an easy way to prepare customized oral preparations with complex internal structures and tunable properties.

Formulation and evaluation of gastro-retentive floating bilayer tablet for the treatment of hypertension.

The paper aimed to progress an ideal gastro retentive drug delivery system intended for directing Losartan and Hydrochlorothiazide as a fixed-dose combination for anti-hypertensive therapy. The bilayer tablets were primed through direct compression method. Losartan was formulated by means of a floating layer expending hydrophilic swellable polymer Hydroxy Propyl Methyl Cellulose K4M, ethyl cellulose (4cps) as a buoyancy enhancer, sodium bicarbonate as a gas spawning agent. The amount of polymer blends remains optimized using 23 full factorial designs. The clout of experimental factors such as swelling agent concentration, buoyancy enhancer and gas generating agent on floating lag time, total floating time, T50% and % drug release remain investigated to get optimized formulation. The responses remain analyzed using Analysis of variance, and polynomial equation stood created for every retort using Multiple linear regression analysis. Entirely preparations floated for more than 12 h. The release pattern of losartan stood fitted to diverse models based on the coefficient of correlation (r). All the formulations, except F2, showed the Korsemeyer-Peppas model as the best fit model. Formulation F2 showed the zero-order model. Diffusion exponents (n) remained indomitable designed for entirely formulations (0.45-0.89), accordingly the chief drug discharge mechanism was non-fickian (anamolous) transport. Formulation F4 containing 20% w/w Hydroxy Propyl Methyl Cellulose K4M, 15% Sodium bicarbonate and 5% ethyl cellulose (4cps) was the best formulation as per the range of drug release remain institute to be more than 95 % in 12h and floating lag time was 20.15 s. The immediate-release layer stood optimized using crospovidone and Indion 414 as a super disintegrant. Formulation A8 containing 2% Indion 414 was considered as optimized formulation as it released 99% drug within 35 min and possessed less disintegration time. Optimized formulation F4 from the controlled-release layer and A8 from immediate-release layer was used to formulate bilayer tablet. The optimized formulation was imperilled to stability reading for three months at 40○C/75% relative humidity. The stability revision exhibited no substantial alteration in the appearance of tablets, floating characteristics, drug content and in-vitro drug dissolution. Consequently, a biphasic drug release design was effectively accomplished over the formulation of floating bilayer tablets.

Exploring the Potentials of Corn Fiber Gum in Fabricating Mucoadhesive Floating Tablet of Poorly Gastro-retainable Drug.

AIM: To formulate and preliminary evaluated polysaccharide based mucoadhesive floating tablets of Cinnarizine. BACKGROUND: Gastro-retentive drug delivery systems has proved to be a successful approach to enhance the gastric residence with site specific targeting for achieving local or generalized effect. Various patents has also been filed globally employing gastro-retentive approach. OBJECTIVE: The study is designed to explore the mucoadhesive and low density characteristics of corn fibre gum (CFG) for preparation of gastro-retentive floating tablets of cinnarizine. METHODS: Floating tablets were prepared by direct compression technique using different concentrations of CFG (45, 50, 60% w/w). The formulated floating tablet batches were evaluated for their hardness, friability, drug content, floating duration/ lag time, swelling behavior, bioadhesive strength and in vitro drug release. RESULTS: Mucoadhesive strength was found to increase with an increment in the polysaccharide concentration. Swelling index was found to increase both with the increase in CFG concentration and with duration for which tablet remains in medium. The in vitro drug release studies indicated decrease in drug release (91% to 77%) with the increase in polymer concentration. The release data was further fitted to various kinetic models which revealed the drug release to be in accordance with Zero-order and Higuchi models, indicating polymer to exhibit the swellable matrix forming abilities. The value of n (between 0.458 and 0.997) from Korsemeyer Peppas model depicted the possibility of drug to follow more than one mechanism of release from the formulation i.e. diffusion and erosion. Stability studies revealed the preparations to retain their integrity and pharmaceutical characteristics at variable storage conditions. CONCLUSION: Thus from the research findings, CFG could be concluded to possess potential binder, release retardant and mucoadhesive characteristics which could be successfully employed for the formulation of gastro-retentive floating tablets.

Development of Floating Tablets of Metformin HCl by Thermoplastic Granulation. Part II: In Vitro Evaluation of the Combined Effect of Acacia Gum/HPMC on Biopharmaceutical Performances.

Purpose: The aim of this study was to evaluate the combined effect, acacia gum(AG)/ hydroxypropylmethylcellulose (HPMC), on biopharmaceutical performances of floating tablets of metformin hydrochloride (MTH) prepared by thermoplastic granulation using stearic acid. Methods: We have prepared the matrixes using AG/HPMC as a polymer combination. This combination of polymers which represents 15% of the total mass of tablet was used at various ratios 3:1, 1:1, 1:3, with two viscosity grade of HPMC (k15M and k100M). The developed matrixes have been evaluated for their pharmacotechnical and biopharmaceutical properties. Results: In addition to the satisfactory physical characteristics of matrixes, it was revealed that the Fc3 and Fc6 formulations with AG/HPMC k15M and AG/HPMC k100M respectively, at ratio, 1:3 were considered the most performance. These formulations have shown swelling, fast flotation, 360 and 480 seconds respectively, and remained floating on the surface of the medium for more than 24 hours, with the matrix integrity, while F1, containing only AG, did not show swelling and did not float. In addition, extendedin vitro release (>8 hours) with decreased dissolved MTH rates was demonstrated for Fc3 and Fc6 matrixes, 95% and 91% respectively, compared to F1 where MTH dissolution was complete after 2 hours. The drug release from the highest-performance matrixes (Fc3 and Fc6) was found to follow Korsmeyer-Peppas's model. The mechanism drug release was controlled by diffusion and erosion. Conclusion: The AG/HPMC combination was suitable as a polymer matrix to improve the in vitro biopharmaceutical properties of MTH compared to AG.

Preparation and evaluation of captopril loaded gastro-retentive zein based porous floating tablets.

In this study, gastro-retentive porous floating tablets of captopril based on zein are reported using l-menthol as a porogen. Tablets were prepared by the direct compression method. Removing of l-menthol through sublimation process generated pores in tablets, which decreased the density to promote floating over gastric fluid. Prepared tablets showed no floating lag time and prolong total floating time (>24 h). Drug release was found dependent upon porosity of tablets, an increase in porosity of tablets resulted in increased drug release, so it can be tuned by varying concentration of l-menthol. In addition to floating and sustained release properties, porous tablets showed robust mechanical behavior in wet conditions, which can enable them to withstand real gastric environment stress. In vivo studies using New Zealand rabbits also confirmed the prolonged gastric retention (24 h) and plasma drug concentration-time profile showed sustained release of captopril with higher Tmax and MRT as compared to marketed immediate-release tablets. Overall, it was concluded that effective gastric retention can be achieved using porous zein tablets using l-menthol as a porogen.

A Controlled Release Theophylline Delivery System Based on a Bilayer Floating System.

OBJECTIVES: Bilayer floating drug delivery is an approach that helps to overcome the shortcomings of single-layered tablets. There is little or no fluctuation of the drug in the blood stream or tissue, while control is enabled over the time and site of drug release. In the current study, bilayer theophylline matrix tablets were formulated by double compression and evaluated using granules produced by polymeric granulation and simple coacervation techniques. MATERIALS AND METHODS: Bilayer floating theophylline tablets containing an immediate release layer (IRL) and a sustained release layer (SRL) were prepared. Granules for the IRL section were produced by wet granulation, while those for the SRL section were produced by polymeric granulation and simple coacervation techniques using Eudragit RL100 and carboxymethyl cellulose (CMC) as binder. The resulting granules were characterized for flowability and packing properties. Granules with adequate flow were compressed into flat-faced tablets 12 mm in diameter using a single punch tableting machine at an arbitrary load of 28 kgF on a load scale. The tablets were evaluated for hardness, weight variability, disintegration, friability, swelling index, floating time, and in vitro drug release. RESULTS: The angle of repose and Hausner ratio were 29.07±0.330 to 40.08±0.660 and 1.07±0.01 to 1.28±0.01, respectively. Tablets hardness values ranged from 4.74±0.36 to 9.84±0.49 kgF, while percentage friability ranged from 0.5% to 1.51%. Floating lag time was between 1±0.41 and 9±0.71 min, while the total floating time was between 1 min and 9 h. Over 50% of the drug was released within 7 h. CONCLUSION: Drug release from the tablets showed a prompt release phase and an extended release phase. Therefore, appropriate combination of Eudragit and CMC and the right reagent can produce well retarded bilayer floating tablets.

Preparation and Quality Evaluation of Gastric Floating Tablets of Schisandra chinensis Total Lignans / 中国药房

OBJECTIVE：To study the prepar ation technology of gastric floating tablets of Schisandra chinensis total lignans （SCTL），and evaluate the quality of prepared tablets. METHODS ：Based on single factor test ，the orthogonal experiment was conducted to optimize the formulation of SCTL gastric floating tablets with the contents of hydroxypropylmethylcellulose （HPMC） K15M，NaHCO3 and microcrystalline cellulose as the factors ，using starting time ，holding time and cumulative release rate of gastric floating tablets as evaluation indexes. The properties ，weight difference ，floatability and accumulative release rate of the prepared SCTL gastric floating tablets were determined. The gastric floating tablets were qualitatively identified by TLC ，and the contents of schisandrin A and total lignans were determined by HPLC and UV spectrophotometry. RESULTS ：The optimal formulation of SCTL gastric floating tablets was made up of 23％ SCTL extract ，20％ HPMC K 15M，40％ microcrystalline cellulose，15％ sodium bicarbonate ，1％ octadecyl alcohol and 1％ polyvinylpyrrolidone. The results of detection of this preparation were in line with the related provisions of “0101 tablet”stated in 2015 edition of Chinese Pharmacopoeia （part Ⅳ）. TLC indicated that the chromatogram of the test sample showed the main spots of same color as the corresponding positions of the chromatogram of schizandrol A control ，Schisandra chinensis reference substance and raw material ，while the negative control has no interference. Content determination results shows that the average content of schizandrol A and total lignans in SCTL gastric floating tablets is 3.187，19.617 mg. It was preliminarily formulated that the content limitation of schizandrol A in one tablet should not be less than 2.50 mg，and the content of total lignans （calculated by schizandrol A ）should not be less than 15.50 mg. CONCLUSIONS：The preparation technology of SCTL gastric floating tablets is stable ，feasible and controllable in quality.

Preparation and In vitro Evaluation of FDM 3D-Printed Ellipsoid-Shaped Gastric Floating Tablets with Low Infill Percentages.

The aim of the study is to investigate the feasibility of fabricating FDM 3D-printed gastric floating tablets with low infill percentages and the effect of infill percentage on the properties of gastric floating tablets in vitro. Propranolol hydrochloride was selected as a model drug, and drug-loaded polyvinyl alcohol (PVA) filaments were produced by hot melt extrusion (HME). Ellipsoid-shaped gastric floating tablets with low infill percentage of 15% and 25% (namely E-15 and E-25) were then prepared respectively by feeding the extruded filaments to FDM 3D printer. Thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) were employed to characterize the filaments and 3D-printed tablets, and a series of evaluations were performed to the 3D-printed tablets, including the weight variation, drug content, hardness, in vitro floating behavior, and drug release of the tablets. The SEM results showed that the drug-loaded filaments and 3D-printed tablets appeared intact without defects, and the printed tablets were composed of filaments deposited uniformly layer by layer. The model drug and the excipients were thermally stable under the process temperature of extruding and printing, with a small amount of drug crystals dispersing in the drug-loaded filaments and 3D-printed tablets. Both E-15 and E-25 could float on artificial gastric fluids without any lag time and released in a sustained manner. Compared with E-15, the E-25 presented less weight variation, higher tablet hardness, shorter floating time, and longer drug release time.

Flexibility of 3D Extruded Printing for a Novel Controlled-Release Puerarin Gastric Floating Tablet: Design of Internal Structure.

The objective of this study was to investigate the development of a novel puerarin gastric floating system with a concentric annular internal pattern by a 3D extrusion-based printing technique and to explore the flexibility of turning the release behavior through the design of the internal structure. The composition consisted of the conventional sustained-release pharmaceutical excipients without addition of foaming agent or light materials. First, the proper alcohol/water proportion was selected for the binding agent. The desired drug release behaviors and good floating properties were obtained either through modification of the formulation composition or adjustment of the internal structure. In vitro, the printed tablets were evaluated for drug release, mechanical properties, lag time, and floating duration time. The in vivo behaviors of the formulations were noted at certain time intervals through assessment of the radiographic pictures of healthy volunteers. The gastric retention time in the 3D-printed tablet was approximately 6 h in vivo. Results indicated these puerarin gastric floating 3D-printed tablets had great potential to achieve good gastric residence time and controlled release. Therefore, 3D extrusion-based printing appears to be appropriate for the production of oral administration systems, owing to its flexibility and the great floating ability and controlled-release capacity of its products.