Tablet Density Research Articles

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.

Powder bed fusion–laser beam (PBF-LB) three-dimensional (3D) printing: Influence of laser hatching distance on the properties of zolpidem tartrate tablets

Laser sintering, known as powder bed fusion–laser beam (PBF-LB), offers promising potential for the fabrication of patient-specific drugs. The aim of this study was to provide an insight into the PBF-LB process with regard to the process parameters, in particular the laser hatching distance, and its influence on the properties of zolpidem tartrate (ZT) tablets. PHARMACOAT® 603 was used as the polymer, while Candurin® Gold Sheen and AEROSIL® 200 were added to facilitate 3D printing. The particle size distribution of the powder blend showed that the layer height should be set to 100 µm, while the laser hatching distance was varied in five different steps (50, 100, 150, 200 and 250 µm), keeping the temperature and laser scanning speed constant. Increasing the laser hatching distance and decreasing the laser energy input led to a decrease in the colour intensity, mass, density and hardness of the ZT tablets, while the disintegration and dissolution rate were faster due to the more fragile bonds between the particles. The laser hatching distance also influenced the ZT dosage, indicating the importance of this process parameter in the production of presonalized drugs. The absence of drug-polymer interactions and the amorphization of the ZT were confirmed.

Development and Assessment of Hydroxypropyl Methylcellulose-Based Floating Tablets for Ciprofloxacin HCL Using Direct Compression Technique

The key findings and conclusions include: such as formulation approaches as aim and objective Development of floating tablets using sodium bicarbonate and HPMC aimed at enhancing gastric residence time for improved drug bioavailability. Physicochemical Compliances The formulated tablets met compliance standards for various physicochemical parameters, including dimensions, floating time, tablet density, and drug content. Method of Formulations F2, F5, and F6 displayed favorable drug release profiles, with the F7 formulation exhibiting excellent release characteristics. in the evaluation the drug release kinetics studies show Kinetic analysis revealed that F2, F5, F6, and F7 formulations followed the Korsmeyer–Peppas model, indicating non-Fickian diffusion with 'n' values ranging from 0.521 to 0.633 and the stability indicates the Optimal storage conditions for stability were determined as 2-8°C for 60 days. Formulations F2, F5, F6, and F7 demonstrated stability at room temperature, 40°C, and 2-8°C for 30 days, with refrigerated storage maintaining stability throughout the 60 days. In conclusion, the developed hydrodynamically balanced tablets of Ciprofloxacin HCl exhibit promising physicochemical characteristics, dissolution profiles, and stability. These tablets hold the potential for enhancing drug bioavailability, making them a viable option for localized drug delivery in the upper gastrointestinal tract.

Shellac‐based drug delivery system with controlled drug‐release and tunable intragastric floating‐retention properties

AbstractIntragastric floating‐retention drug delivery system (IFRDDS) could effectively prolong drug‐releasing time, achieving a good clinical efficacy of encapsulated drug. In this research, the green amphiphilic resin, shellac was adopted to fabricate a continuous network as the matrix of IFRRDS by their self‐assembly behavior triggered by H+. Meanwhile, the NaHCO3 and hydroxypropyl methyl cellulose (HPMC) acted as a forming agent and a precipitating agent to control the floating behavior, respectively, which could create a porous structure for lowering the true density of the tablet and continuously absorb water to enhance the density of tablet, respectively. Interestingly, the synergistic effect of NaHCO3 and HPMC was beneficial to the initiation of the floating of the complex tablet. By regulating tablet's constitution, we could tune the floating lag time, floating time, and drug‐release behavior of the tablet. For example, the drug‐releasing curve of the shellac‐based tablet containing 3 wt% HPMC and 10 wt% NaHCO3 presented a typical linear model, which was an ideal linear drug‐releasing system, and could float in 3 min and last for 16 h. Therefore, we successfully employed a facile strategy to fabricate a biobased IFRRDS with controlled drug‐release and tunable intragastric floating‐retention properties, which has great potential for the advanced medical industry.

Effects of Dry Granulation Operating Parameters on Forming Quality

To address the issues of the existing dry granulation process, which mostly relies on manual adjustments based on empirical experience and lacks the analysis of theoretical data, a simplified model of tablet pressing based on a modified Drucker–Prager Cap (DPC) material constitutive model was proposed to simulate and analyze the forming process of tablets, and study the impacts of the feeding speed, roller speed, friction coefficient and roller clearance on the density distribution of the pressed tablets via ABAQUS. The results show that the roller speed significantly impacts the density of tablets, and a lower roller speed and a higher friction coefficient are beneficial to the formation of tablets. As the roller clearance decreases, the average density at the clearance increases, and the unevenness of the lateral density distribution of the tablets increases, showing a distribution trend of larger density at the center and smaller density on both sides.

Evaluation of alternative methods to derive particle density from compression data

The determination of particle density is a critical part of material characterization regarding compression analyses. Helium pycnometry as the most commonly used method is criticized for different aspects. Most prominent is the susceptibility to errors when measuring water-containing powders. Alternative methods for determining particle density using compression data have already been described. However, a systematic investigation and evaluation is still missing. In this study, the methods by Sun and Krumme were investigated in detail regarding their robustness against variations in tableting settings. Twelve pharmaceutical excipients were tableted at five different settings to verify the applicability and sensitivity to changes in the experimental set-up. Both methods were found to be robust against influencing parameters from the experiments. A sufficiently high compression pressure to approach a constant density value of the corresponding material during tableting was considered to be an essential requirement for the performance of the methods. Brittle materials with high yield pressure were found to be unsuitable for the application of both methods. The method of Krumme gave small deviations to measurements of helium pycnometry for water-free materials. By using the tablet density after in-die elastic recovery, Krumme's method could be used for water-containing materials as well. The method of Sun was found to give significantly smaller values for particle density due to inclusion of slow elastic recovery.

Terahertz frequency-domain sensing combined with quantitative multivariate analysis for pharmaceutical tablet inspection

Near infrared (NIR) and Raman spectroscopy combined with multivariate analysis are established techniques for the identification and quantification of chemical properties of pharmaceutical tablets like the concentration of active pharmaceutical ingredients (API). However, these techniques suffer from a high sensitivity to particle size variations and are not ideal for the characterization of physical properties of tablets such as tablet density. In this work, we have explored the feasibility of terahertz frequency-domain spectroscopy, with the advantage of low scattering effects, combined with multivariate analysis to quantify API concentration and tablet density. We studied 33 tablets, consisting of Ibuprofen, Mannitol, and a lubricant with API concentration and filler particle size as the design factors. The terahertz signal was measured in transmission mode across the frequency range 750 GHz to 1.5 THz using a vector network analyzer, frequency extenders, horn antennas, and four off-axis parabolic mirrors. The attenuation spectral data were pre-processed and orthogonal partial least square (OPLS) regression was applied to the spectral data to obtain quantitative prediction models for API concentration and tablet density. The performance of the models was assessed using test sets. While a fair model was obtained for API concentration, a high-quality model was demonstrated for tablet density. The coefficient of determination (R2) for the calibration set was 0.97 for tablet density and 0.98 for API concentration, while the relative prediction errors for the test set were 0.7% and 6% for tablet density and API concentration models, respectively. In conclusion, terahertz spectroscopy demonstrated to be a complementary technique to Raman and NIR spectroscopy, which enables the characterization of physical properties of tablets like tablet density, and the characterization of API concentration with the advantage of low scattering effects.

Releasing fast and slow: Non-destructive prediction of density and drug release from SLS 3D printed tablets using NIR spectroscopy

Selective laser sintering (SLS) 3D printing is a revolutionary 3D printing technology that has been found capable of creating drug products with varied release profiles by changing the laser scanning speed. Here, SLS 3D printed formulations (printlets) loaded with a narrow therapeutic index drug (theophylline) were produced using SLS 3D printing at varying laser scanning speeds (100–180 mm/s). The use of reflectance Fourier Transform – Near Infrared (FT-NIR) spectroscopy was evaluated as a non-destructive approach to predicting 3D printed tablet density and drug release at 2 h and 4 h. The printed drug products formulated with a higher laser speed exhibited an accelerated drug release and reduced density compared with the slower laser scanning speeds. Univariate calibration models were developed based on a baseline shift in the spectra in the third overtone region upon changing physical properties. For density prediction, the developed univariate model had high linearity (R2 value = 0.9335) and accuracy (error < 0.029 mg/mm3). For drug release prediction at 2 h and 4 h, the developed univariate models demonstrated a linear correlation (R2 values of 0.9383 and 0.9167, respectively) and accuracy (error < 4.4%). The predicted vs. actual dissolution profiles were found to be statistically similar (f2 > 50) for all of the test printlets. Overall, this article demonstrates the feasibility of SLS 3D printing to produce drug products containing a narrow therapeutic index drug across a range of drug release profiles, as well as the potential for FT-NIR spectroscopy to predict the physical characteristics of SLS 3D printed drug products (drug release and density) as a non-destructive quality control method at the point-of-care.

The Use of Novel, Rapid Analytical Tools in the Assessment of the Stability of Tablets—A Pilot Analysis of Expired and Unexpired Tablets Containing Nifuroxazide

In the analysis of finished pharmaceutical products, numerous innovative analytical techniques are often used, i.e., Raman spectroscopy, scanning electron microscopy, computer microtomography, directional hemispherical reflectance, and hyperspectral analyses. These techniques allow for the identification of changes in solid phases. Many advantages over other techniques can be attributed to these techniques, e.g., they are rapid, non-destructive, and comprehensive. They allow for the identification of changes occurring in solid phases. However, the above-mentioned methods are still not standard procedures in pharmaceutical research. The present study aimed to assess the possible usefulness of total directional hemispherical reflectance (THR), hyperspectral imaging, and computer microtomography to evaluate the stability of tablets containing nifuroxazide during storage. In the study, expired and unexpired coating tablets containing nifuroxazide (n = 10 each) were analyzed. In addition, four unexpired tablets were stored at 40°C over 3 months (stressed tablets). Reflectance was determined with seven wavelength bands from 335 nm to 2500 nm using an SOC-410 Directional Hemispherical Reflectometer (Surface Optics Corporation, San Diego, CA, USA). A Specim IQ hyperspectral camera (Spectral Imaging Ltd., Oulu, Finland) was used with a wavelength range of 400–1030 nm. Tablets were also scanned using X-ray microtomography (Phoenix vǀtomeǀx, GE Sensing &amp; Inspection Technologies GmbH, Wunstorf, Germany). The results indicated that total reflectance was lower in expired tablets than in unexpired tablets in all spectral bands, except for 700–1100 nm and 1700–2500 nm. In turn, the stressed tablets showed higher THR values than expired tablets in all spectral bands, except for 1000–1700 nm. In addition, hyperspectral analysis of the homogeneity of the tablets, as well as X-ray microtomographic analysis of tablet density and coating thickness, indicated that these parameters differed significantly between the analyzed tablets.

Negative porosity issue in the Heckel analysis: A possible solution

A parameterization of compaction simulator generated dynamic compression profile with a few grams of powder provides important information about the material deformation and compact elasticity. The Heckel equation is by far the most popular choice among pharmaceutical scientists for such parametrization. A general approach of Heckel analysis uses pycnometric powder density (ρP0) for relative density calculation. However, as ‘in-die’ tablet bulk density at applied compression pressure (ρBP) becomes greater than or equal to the measured ρP0, the general approach typically poses a negative porosity challenge at high compression pressure regions. It is only theoretically possible to have a tablet with zero or negative porosity. Negative porosity may be detected during ‘in-die’ compression analysis, but it will not exist after ejection of the tablet in practical aspect. Thus, the present work proposes a new approach to using pycnometric tablet density (ρPP) in the relative density calculations of Heckel analysis. This ρPP may be a better representation of actual tablet particle volume, as it is composed of non-accessible intra-particulate pores, which are broken under applied compression pressure. A new approach showed its immunity for Heckel high-pressure negative porosity. It enables the utilization of the compression and decompression phases of dynamic compression profiles to evaluate macroscopic compaction performance. The proposed approach was validated with a reported modified Heckel approach. The Heckel parameters computed with both methodologies for microcrystalline cellulose and lactose were not statistically different. However, a modified Heckel approach was unable to compute Heckel parameters of poorly compacting starch unlike the new approach. A modified Heckel approach became invalid during starch compaction at low compression pressures (below 400 MPa), where starch was forming weaker but still intact tablets. Certainly, a complete Heckel profiling with a new approach could save time and costs in an early development stage for designing and screening scientifically based lead prototype formulations.

Are There Differences in the Homogeneity of the Parts of Tablets Obtained after Subdivision?-A Preliminary Assessment Using an X-ray Microtomography.

Aim: The study aimed to analyze the weight and homogeneity of the parts of tablets containing carbamazepine and tablets with trazodone hydrochloride, obtained after subdivision with a kitchen knife. X-ray microtomography was used for homogeneity analysis. Methods: 30 tablets with carbamazepine and 30 tablets with trazodone hydrochloride were analyzed in terms of weight uniformity after subdivision. Then, seven tablets of each type were analyzed using an X-ray microtomography (Phoenix vǀtomeǀx, General Electric). The absorption of X-rays by an object is proportional to its density. In turn, measurement of the density of the analyzed object in a microtomographic image is the grayscale level. Based on the correlation between the grayscale value and the reference density, from the calibration phantom, we were able to determine the density of any area of the tablet’s scan. Results: During the subdivision, the weight loss exceeded 3% for two carbamazepine tablets, while for trazodone tablets, none lost more than 3%, which is the limit recommended by Food and Drug Administration (FDA). As to the density of the tablets resulting from the microtomographic analysis, two of the whole tablets containing trazodone hydrochloride had a significantly higher density than the remainder (p < 0.001). Similarly, some differences in density were observed in the analysis of the density of tablets of carbamazepine (p = 0.008). Parts of one of the analyzed tablets with trazodone obtained after subdivision differed in terms of pixel brightness, thus density. On the other hand, the uniform density was observed for parts of the split tablets containing carbamazepine. Conclusions: Parts of the trazodone hydrochloride tablets obtained after subdivision differed in terms of homogeneity and weight. Microtomographic methods may be an interesting and useful method for evaluating the uniformity of compounds in solid dosage forms.

ИЗУЧЕНИЕ ТЕХНОЛОГИЧЕСКИХ ХАРАКТЕРИСТИК СУБСТАНЦИИ VMA-10-13 И ТЕХНОЛОГИЯ ИЗГОТОВЛЕНИЯ ТАБЛЕТОК

Abstract. Currently, intensive research is being conducted in the study of new biologically active substances for medical use that will be effective and safe for human use. Before the production of a medicinal product, the technological parameters and characteristics of a pharmaceutical substance must be carefully studied and scientifically substantiated. When creating and modernizing the technology of dosage forms, one of the most important stages is the assessment of bioavailability. It, in turn, depends on the physico-chemical properties of the active substance. The present work is devoted to the study of the technological properties of the original pharmaceutical substance of the quinazoline derivative, used as an active substance for the development of the composition and technology for obtaining a dosage form for oral use in the form of tablets using solid dispersion. The technological characteristics of a new biologically active compound –a derivative of quinazoline: 3-[2-(2-Methylphenylamino)-2-oxoethyl]-quinazoline-4(3H)–oh (laboratory code: VMA–10–13), capable of influencing pharmacological activity in the production of the dosage form, have been studied. The study examined key indicators: residual moisture, bulk density, flowability, ejection pressure, compressibility and disintegration of model tablets. The composition and technology of obtaining a solid dosage form (tablets) using a solid dispersion with improved biopharmaceutical characteristics have been developed. The main pharmaceutical and technological indicators of tablet quality are determined: average weight and disintegration. The data obtained allowed us to assume the content and course of further stages of pharmaceutical development.

Impact of unloading kinematics on the occurrence of capping during the production of pharmaceutical tablets

Capping is a common defect that can occur during the manufacturing of pharmaceutical tablets. Several studies showed that decreasing the unloading speed of the manufacturing cycle plays a role in the occurrence of such defects. Following this idea, we study in this work the influence of the unloading step on capping using a compaction simulator.Measuring the die wall pressure made it possible to detect precisely that tablets capped just after the unloading (some milliseconds only). To evaluate the impact of the unloading speed on capping, we developed a two-step unloading phase controlled by three manufacturing parameters. It was possible to mitigate capping by decreasing the speed at which the contact between the punches and the tablet was lost. Capping seemed due to dynamical effects related to the release of the axial pressure. The modification of the unloading step to mitigate capping led to significant changes in tablet density but no clear trends were found for the residual die-wall pressure and tablet strength.This work made it possible to improve the understanding of capping. Moreover, the two-step unloading cycle gave a new idea for possible modifications that could be done on rotary presses in order to mitigate capping.

Direct Granule Feeding of Thermal Droplet Deposition 3D Printing of Porous Pharmaceutical Solid Dosage Forms Free of Plasticisers

PurposeTo develop a new direct granule fed 3D printing method for manufacturing pharmaceutical solid dosage forms with porous structures using a thermal droplet deposition technology.MethodsEudragit® E PO was used as the model polymer, which is well-known to be not FDM printable without additives. Wet granulation was used to produce drug loaded granules as the feedstock. The flow and feedability of the granules were evaluated. The physicochemical properties and in vitro drug release performance of the granules and the printed tablets were fully characterised.ResultsUsing the method developed by this study, Eudragit E PO was printed with a model drug into tablets with infills ranging from 30–100%, without additives. The drug was confirmed to be molecularly dispersed in the printed tablets. The printing quality and performances of the porous tablets were confirmed to be highly compliant with the pharmacopeia requirement. The level of infill density of the porous tablets had a significant effect on their in vitro drug release performance.ConclusionThis is the first report of thermal droplet deposition printing via direct granule feeding. The results of this study demonstrated that this new printing method can be used as a potentially valuable alternative for decentralised pharmaceutical solid dosage form manufacturing.

Terahertz frequency domain sensing for fast porosity measurement of pharmaceutical tablets

Porosity is an important property of pharmaceutical tablets since it may affect tablet disintegration, dissolution, and bio-availability. It is, therefore, essential to establish non-destructive, fast, and compact techniques to assess porosity, in situ, during the manufacturing process. In this paper, the terahertz frequency-domain (THz-FD) technique was explored as a fast, non-destructive, and sensitive technique for porosity measurement of pharmaceutical tablets. We studied a sample set of 69 tablets with different design factors, such as particle size of the active pharmaceutical ingredient (API), Ibuprofen, particle size of the filler, Mannitol, API concentration, and compaction force. The signal transmitted through each tablet was measured across the frequency range 500–750 GHz using a vector network analyzer combined with a quasi-optical set-up consisting of four off-axis parabolic mirrors to guide and focus the beam. We first extracted the effective refractive index of each tablet from the measured complex transmission coefficients and then translated it to porosity, using an empirical linear relation between effective refractive index and tablet density. The results show that the THz-FD technique was highly sensitive to the variations of the design factors, showing that filler particle size and compaction force had a significant impact on the effective refractive index of the tablets and, consequently, porosity. Moreover, the fragmentation behaviour of particles was observed by THz porosity measurements and was verified with scanning electron microscopy of the cross-section of tablets. In conclusion, the THz-FD technique, based on electronic solutions, allows for fast, sensitive, and non-destructive porosity measurement that opens for compact instrument systems capable of in situ sensing in tablet manufacturing.

3D Printed Intragastric Floating and Sustained-Release Tablets with Air Chambers

This work aimed to use hot-melt extrusion (HME) and dual fused deposition modeling (FDM) 3D printing technology to develop a novel intragastric floating and sustained-release drug delivery system. The intragastric floating and sustained-release tablet was engineered by employing hydroxypropyl methylcellulose (AffinisolTM HPMC HME 15LV) for a drug-loaded core and polylactic acid (PLA) for an insoluble shell with an air chamber. Filaments for the drug-loaded core were compounded using a single-screw hot melt extruder. 3DMAX software was utilized to design a core with a complementary shell which consisted of a hollow chamber at the top and a drug-release window with different sizes (radius in 1.5, 2.5, 3, 3.5, 4.5 mm) at the bottom. Pharmaceutical characterization, solid dispersion evaluation, and drug release behavior were studied. The model drug in all formulations kept stable, and part of the drug in the extruded filaments and 3D printed tablets became amorphous. The introduction of an air chamber reduced the tablet density to below 0.9 g/cm3 and the 3D printed tablets floated immediately and continuously during the drug release process. The presence of the insoluble shell greatly prolonged the drug release time, and the drug release rate was positively correlated with the area of the release window. In addition, compared with shellless tablets, the 3D printed tablets with air chambers (radius in 4.5 mm) showed closer zero-order drug release for 24 h and released drug by diffusion-erosion combined mechanism. The developed intragastric floating and sustained-release tablets with air chambers could be applied to various drugs and provided a new way for the development of personalized drug delivery systems.

A semi-empirical model for estimation of flaw size in internally defective tablets.

Capping is a mechanical defect in tablets, which is attributed to multiple factors including intrinsic material properties and tableting conditions. A suitable non-destructive approach using acoustically derived elastic modulus has showed distinctive features between a defective tablet and a defect-free tablet. In this work, a semi-empirical model was developed to estimate flaw size in an internally defective tablet from the relationship among elastic modulus, tablet density, and time of flight (acoustic wave to traverse through the tablet). The model was found fundamentally consistent where the derived flaw size showed clear dependence on powder mechanical properties of seven diverse formulations studied. Furthermore, the flaw size was reasonably correlated with the internal tablet microstructure illustrated by X-ray micro-tomography findings, both qualitatively and quantitatively. This model could thus be efficiently implemented for risk-based evaluation of internal defects in visibly intact tablets to ensure robustness of drug products.

Contactless mapping of ceramic green density using optical coherence tomography

We propose a contactless method for mapping the density distribution of green ceramics using optical coherence tomography (OCT). A correlation was found between the OCT signal and density of green alumina tablets. Using this relationship, proof-of-concept mapping of model samples produced reasonable results, suggesting that high-speed, contactless mapping of the ceramic green density with micrometer-scale resolution is possible, owing to the unique features of OCT. This technique may contribute to more efficient and eco-friendly ceramics production.

FORMULATION AND EVALUATON OF FLOATING TABLET OF CEFPODOXIME PROXETIL

Ideal once daily floating drug delivery system should release the drug for 24 hours and float up to 24 hrs. Once daily floating matrix tablet of Cefpodoxime proxetil should be release the drug for 24 hours to maintain the effective plasma level. All the formulations were prepared by using two different grades of HPMC (K100 and K4), cross povidone and MCC pH 101. HPMC is a matrix forming agent. All the formulations showed buoyancy lag time of less than 5 seconds regardless of concentration of HPMC K100 M, K4 and cross povidone. It may be due to the low density of tablet. The swelling index of HPMC K100 M was found to be higher than that of HPMC K4 M. This may be due to high molecular weight and high viscosity of HPMC K100 M. The formulation F1 containing low level of HPMC K100 M (75 mg) and low level of cross povidone (75 mg) showed higher burst release and maintained drug release up to 24 hours. The tablet was remained floated for 24 hours. High level of HPMC K100 M (F2, F3, F5,F6,) results in greater amount of gel being formed. This gel increases diffusion path length of the drug and hence release rate decreases. On the same line it formulation F5 and F8 should show relatively less drug release as high level of HPMC K100 M(100 mg &amp; 125 mg respectively) is used in these formulations. But both the formulations released more than 97% drug within 24 hours. the formulations F10,F13,F14,F16,F17 released the drug within 20 hours. The formulation F11 which contains high amount of HPMC K4 M than F10 (100mg) and low level of cross povidone (75 mg) shows drug release up to 24 hours with sufficient floating duration. The formulation F15 and F18 contains high level of HPMC K4 M (125mg) and high level of cross povidone (100mg and 125mg) respectively. Both the formulations showed sustained drug release up to 24 hrs. EYWORDS: formulation, floating tablet, cefpodoxime proxetil

Development of immediate release (IR) 3D-printed oral dosage forms with focus on industrial relevance

Pharmaceutical 3D-printing represents a potentially new dosing and manufacturing approach for the pharmaceutical industry, with unique opportunities for personalization of dosage strengths. Fused deposition modelling (FDM) is a 3D-printing technique, which presents advantages for decentralized on-site manufacturing in hospitals and pharmacies. This study introduces industrially relevant development of formulations for filaments with the required mechanical properties to be 3D-printable and providing immediate release (IR) dosage forms using safe materials approved also for pediatric use. Hydroxypropyl-cellulose (HPC) SSL was chosen as hydrophilic polymer and caffeine with a load of 5-20% as thermally stable model drug. Poly-(vinyl pyrrolidone-vinyl acetate) copolymer (Kollidon VA64) and poly-(vinyl alcohol-polyethylene glycol) graft copolymer (Kollicoat IR) were additional water-soluble polymers tested in combination with HPC and xylitol and polyethylene glycol (PEG) 4000 were evaluated as hydrophilic plasticizers and PEG4000 and maltodextrin as pore formers. Formulations were hot-melt extruded using a scalable twin-screw extruder and 3D-printed into honeycomb geometry solid dosage forms with high (100%) and low (80%) infill density. Rapid or very rapid release was achieved via formulation selection and tablet design parameters. PEG4000 in combination with Kollidon VA64 demonstrated superior processability and significantly accelerated release properties of the matrix independently of infill density. Lowering caffeine content improved hot-melt extrusion processability for each formulation but prolonged dissolution. The use of Kollicoat IR resulted in superior mechanical properties of the manufactured filaments, with easy handling and successful 3D-printing for drug load of 5 to 20%. For most formulations, lowering infill density of 3D-printed tablets yielded faster drug dissolution in agreement with the literature. However, the extent of the infill density effect varied depending on formulation. Caffeine was present in stable crystalline state in 3D-printed tablets. Printing temperature appeared to be critical for drug dissolution in vitro. This wide-ranging excipient investigation epitomizes the beginning of a toolbox approach targeting FDM processability in combination with immediate release characteristics of personalized dosage forms.