Effect of basket mesh size on the hydrodynamics of a partially filled (500 mL) USP rotating basket dissolution testing Apparatus 1.

The USP Rotating Basket Dissolution Testing Apparatus 1 is listed in the USP as one of the tools to assess dissolution of oral solid dosage forms. Baskets of different mesh sizes can be used to differentiate between dissolution profiles of different formulations. Here, we used Particle Image Velocimetry (PIV) to study the hydrodynamics of the USP Apparatus 1 using baskets with different mesh openings (10-, 20- and 40-mesh) revolving at 100 rpm, when the vessel was filled with 500 mL. The velocity profiles throughout the liquid were found to vary significantly using baskets of different mesh sizes, typically increasing with increased size of the opening of the basket mesh, especially for axial and radial velocities. This, in turn, resulted in a significantly different flow rate through the basket, which can be expected to significantly impact the dissolution rate of the drug product. A comparison between the results of this work with those of a previous study with a 900-mL fill volume (Sirasitthichoke et al., Intern. J. Pharmaceutics, 2021, 607: 120976), shows that although the hydrodynamics in the USP Apparatus 1 changed with fill level in the vessel, the flow rate through the basket was not significantly affected. This implies that tablets dissolving in the two systems would experience similar tablet-liquid medium mass transfer coefficients, and therefore similar initial dissolution rates, but different dissolution profiles because of the difference in volume.

Polymer Characteristics for Drug Layering on Particles Using a Novel Melt Granulation Technology, MALCORE®.

MALCORE®, a novel manufacturing technology for drug-containing particles (DCPs), relies on the melt granulation method to produce spherical particles with high drug content. The crucial aspect of particle preparation through MALCORE® involves utilizing polymers that dissolve in the melt component, thereby enhancing viscosity upon heating. However, only aminoalkyl methacrylate copolymer E (AMCE) has been previously utilized. Therefore, this study aims to discover other polymers and comprehend the essential properties these polymers need to possess. The results showed that polyvinylpyrrolidone (PVP) was soluble in the stearic acid (SA) melt component. FTIR examination revealed no interaction between SA and polymer. The phase diagram was used to analyze the state of the SA and polymer mixture during heating. It revealed the mixing ratio and temperature range where the mixture remained in a liquid state. The viscosity of the mixture depended on the quantity and molecular weight of the polymer dissolved in SA. Furthermore, the DCPs prepared using PVP via MALCORE® exhibited similar pharmaceutical properties to those prepared with AMCE. In conclusion, understanding the properties required for polymers in the melt granulation process of MALCORE® allows for the optimization of manufacturing conditions, such as temperature and mixing ratios, for efficient and consistent drug layering.

A floating 3D printed polypill formulation for the coadministration and sustained release of antihypertensive drugs.

Polypharmacy is a common issue, especially among elderly patients resulting in administration errors and patient inconvenience. Hypertension is a prevalent health condition that frequently leads to polypharmacy, as its treatment typically requires the co-administration of more than one different Active Pharmaceutical Ingredients (API's). To address these issues, floating hollow torus-shaped dosage forms were developed, aiming at providing prolonged gastric retention and sustained drug release. The dosage forms (polypills) containing three anti-hypertensive API's (diltiazem (DIL), propranolol (PRP) and hydrochlorothiazide (HCTZ)) were created via Fused Deposition Modelling 3D printing. A multitude of the dosage forms were loaded into a capsule and the resulting formulation achieved prolonged retention times over a 12-hour period in vitro, by leveraging both the buoyancy of the dosage forms, and the "cheerios effect" that facilitates the aggregation and retention of the dosage forms via a combination of surface tension and shape of the objects. Physicochemical characterization methods and imaging techniques were employed to investigate the properties and the internal and external structure of the dosage forms. Furthermore, an ex vivo porcine stomach model revealed substantial aggregation, adhesion and retention of the 3D printed dosage forms in porcine stomach. In vitro dissolution testing demonstrated almost complete first-order release of PRP and DIL (93.52 % and 99.9 %, respectively) and partial release of HCTZ (65.22 %) in the 12 h timeframe. Finally, a convolution-based single-stage approach was employed in order to predict the pharmacokinetic (PK) parameters of the API's of the formulation and the resemblance of their PK behavior with previously reported data.

Tailoring drug release in bilayer tablets through droplet deposition modeling and injection molding.

This study explores the innovative production of personalized bilayer tablets, integrating two advanced manufacturing techniques: Droplet Deposition Modeling (DDM) and Injection Molding (IM). Unlike traditional methods limited to customizing dense bilayer medicines, our approach uses Additive Manufacturing (AM) to effectively adjust drug release profiles. Focusing on Caffeine and Paracetamol, we found successful processing for both DDM and IM using Caffeine formulation. The high viscosity of Paracetamol formulation posed challenges during DDM processing. Integrating Paracetamol formulation for the over-molding process proved effective, demonstrating IM's versatility in handling complex formulations. Varying infill percentages in DDM tablets led to distinct porosities affecting diverse drug release profiles in DDM-fabricated tablets. In contrast, tablets with high-density structures formed through the over-molding process displayed slower and more uniform release patterns. Combining DDM and IM techniques allows for overcoming the inherent limitations of each technique independently, enabling the production of bilayer tablets with customizable drug release profiles. The study's results offer promising insights into the future of personalized medicine, suggesting new pathways for the development of customized oral dosage forms.

In-lab synthesized turn-off fluorescence sensor for estimation of Gemigliptin and Rosuvastatin polypill appraised by Spider diagram, AGREE and whiteness metrics.

Gemigliptin-Rosuvastatin single-pill combination is a promising therapeutic tool in the effective control of hyperglycemia and hypercholesterolemia. Organic sensors with high quantum yields have profoundly significant applications in the pharmaceutical industry, such as routine quality control of marketed formulations. Herein, the fluorescence sensor, 2-Morpholino-4,6-dimethyl nicotinonitrile 3, (λex; 226 nm, λem; 406 nm), was synthesized with a fluorescence quantum yield of 56.86% and fully characterized in our laboratory. This sensor showed high efficiency for the determination of Gemigliptin (GEM) and Rosuvastatin (RSV) traces through their stoichiometric interactions and simultaneously fractionated by selective solvation. The interaction between the stated analytes and sensor 3 was a quenching effect. Various experimental parameters and the turn-off mechanism were addressed. The adopted approach fulfilled the ICH validation criteria and showed linear satisfactory ranges, 0.2-2 and 0.1-1 µg/mL for GEM and RSV, respectively with nano-limits of detection less than 30 ng/mL for both analytes. The synthesized sensor has been successfully applied for GEM and RSV co-assessment in their synthetic polypill with excellent % recoveries of 98.83 ± 0.86 and 100.19 ± 0.64, respectively. No statistically significant difference between the results of the proposed and reported spectrophotometric methods in terms of the F- and t-tests. Ecological and whiteness appraisals of the proposed study were conducted via three novel approaches: the Greenness Index via Spider Diagram, the Analytical Greenness Metric, and the Red-Green-Blue 12 model. The aforementioned metrics proved the superiority of the adopted approach over the previously published one regarding eco-friendliness and sustainability. Our devised fluorimetric turn-off sensing method showed high sensitivity, selectivity, feasibility, and rapidity with minimal cost and environmental burden over other sophisticated techniques, making it reliable in quality control labs.

Unraveling the influence of solvent composition on Drop-on-Demand binder jet 3D printed tablets containing calcium sulfate hemihydrate.

Recently, binder jet printed modular tablets were loaded with three anti-viral drugs via Drop on Demand (DoD) technology where drug solutions prepared in ethanol showed faster release than those prepared in water. During printing, water is used as a binding agent, whereas ethanol is added to maintain the porous structure of the tablets. Thus, the hypothesis is that the porosity would be controlled by manipulating the percentage of water and ethanol. In this study, Rhodamine 6G (R6G) was selected as a model drug due to its high solubility in water and ethanol, visualization function as a fluorescent dye, and potential therapeutic effects for cancer treatment. Approximately, 10 mg/ml R6G solutions were prepared with five different water-ethanol ratios (0-100, 75-25, 50-50, 75-25, 100-0). The ink solutions were printed onto blank binder jet 3D-printed tablets containing calcium sulphate hemihydrate using DoD technology. The tablets were dried at room temperature and then characterized using SEM-EDX, fluorescent microscope, TGA, XRD, FTIR, and DSC as well as in vitro release studies to investigate the impact of water-ethanol ratio on the release profile of R6G. Results indicated that the solution with higher ethanol ratio penetrated the tablets faster than the lower ethanol ratio, while the solution prepared with pure water was first accumulated onto the tablets' surface and then absorbed by the tablets. Moreover, tablets with more water content gained more weight and thickness. The EDX analysis and fluorescent microscope showed the uniform surface distribution of the drug. The SEM images revealed the difference in the tablet surface among the five formulations. Furthermore, the TGA data presents a notable increase in water loss, with XRD analysis suggesting the formation of gypsum in tablets containing elevated water content. The release study exhibited that the fastest release was from WE0-100, whereas the release rate decreases as the content of water increases. The WE0-100 releases more than 40 % drug within the first hour which is almost twice as high of the WE100-0 formulation. This DoD technology could distribute drugs onto the tablet's surface uniformly. The calcium sulfate would transform from hemihydrate to dihydrate form in the presence of water and therefore, those tablets treated with higher water content led to slower release. In conclusion, this study underscores the substantial impact of the water-ethanol ratio on drug release from binder jet printed tablets and highlights the potential of DoD technology for uniform drug distribution and controlled release.

Application of PAT Probes in Aluminum Phosphate Adjuvant Manufacturing.

PURPOSE: This study is focused on monitoring process parameters and quality attributes of aluminum phosphate (AlPO4) using multiple in-line probes incorporated into an industrial-scale adjuvant suspension manufacturing unit. METHODS: The manufacturing of aluminum adjuvant suspension was monitored at manufacturing scale using conductivity, turbidity, infrared, and particle sizing and count probes to follow the continuous evolution of particle formation and size distribution, and the reaction kinetics during the synthesis of AlPO4. RESULTS: The data showed that AlPO4 forms large particles at the early stages of mixing, followed by a decrease in size and then stabilization towards the later stages of mixing and pH adjustment. The results provided a complementary view of process events and assisted in optimizing several parameters, e.g., flow rate of reactants AlCl3 and Na3PO4 solutions, mixing rate, pH, and conductivity of AlPO4, as well as adjuvant quality attribute such as particle size, thus streamlining and shortening the process development stage. CONCLUSION: The results of this study showed the usefulness of the in-line probes to automate continuous assessment of AlPO4 batch-to-batch consistency during in-house adjuvant production at the industrial scale.

An investigation into the effects of ink formulations of semi-solid extrusion 3D printing on the performance of printed solid dosage forms.

Semi-solid extrusion (SSE) 3D printing has recently attracted increased attention for its pharmaceutical application as a potential method for small-batch manufacturing of personalised solid dosage forms. It has the advantage of allowing ambient temperature printing, which is especially beneficial for the 3D printing of thermosensitive drugs. In this study, the effects of polymeric compositions (single hydroxypropyl methylcellulose (HPMC) system and binary HPMC + polyvinylpyrrolidone (PVP) system), disintegrant (silicon oxide (SiO2)), and active pharmaceutical ingredients (tranexamic acid (TXA) and paracetamol (PAC)) on the printability of semisolid inks and the qualities of SSE printed drug-loaded tablets were investigated. Printability is defined by the suitability of the material for the process in terms of its physical properties during extrusions and post-extrusion, including rheology, solidification time, avoiding slumping, etc. The rheological properties of the inks were investigated as a function of polymeric compositions and drug concentrations and further correlated with the printability of the inks. The SSE 3D printed tablets were subjected to a series of physicochemical properties characterisations and in vitro drug release performance evaluations. The results indicated that an addition of SiO2 would improve 3D printing shape fidelity (e.g., pore area and porosity) by altering the ink rheology. The pores of HPMC + PVP + 5PAC prints completely disappeared after 12 hours of drying (pore area = 0 mm2). An addition of SiO2 significantly improved the pore area of the prints which are 3.5 ± 0.1 mm2. It was noted that the drug release profile of PAC significantly increased (p < 0.05) when additive SiO2 was incorporated in the formulation. This could be due to a significantly higher porosity of HPMC + PVP + SiO2 + PAC (70.3 ± 0.2%) compared to HPMC + PVP + PAC (47.6 ± 2.1%). It was also likely that SiO2 acted as a disintegrant speeding up the drug release process. Besides, the incorporation of APIs with different aqueous solubilities, as well as levels of interaction with the polymeric system showed significant impacts on the structural fidelity and subsequently the drug release performance of 3D printed tablets.

Engineering of 3D printed personalized polypills for the treatment of the metabolic syndrome.

Metabolic syndrome is a collection of abnormalities, including at least three of the following insulin resistance, hypertension, dyslipidemia, type 2 diabetes, obesity, inflammation, and non-alcoholic fatty liver disease. 3D printed solid dosage forms have emerged as a promising tool enabling the fabrication of personalized medicines and offering solutions that cannot be achieved by industrial mass production. Most attempts found in the literature to manufacture polypills for this syndrome contain just two drugs. However, most fixed-dose combination (FDC) products in clinical practice required the use of three or more drugs. In this work, Fused deposition modelling (FDM) 3D printing technology coupled with hot-melt extrusion (HME) has been successfully applied in the manufacture of polypills containing nifedipine (NFD), as an antihypertensive drug, simvastatin (SMV), as an antihyperlipidemic drug, and gliclazide (GLZ) as an antiglycemic drug. Hanssen solubility parameters (HSPs) were utilized as predictors to guide the formation of amorphous solid dispersion between drug and polymer to ensure miscibility and enhanced oral bioavailability. The HSP varied from 18.3 for NFD, 24.6 for SMV, and 7.0 for GLZ while the total solubility parameter for the excipient mixture was 27.30.5. This allowed the formation of an amorphous solid dispersion in SMV and GLZ 3D printed tablets compared to NFD which was partially crystalline. Popypill showed a dual release profile combining a faster SMV release (< 6h) with a 24 h sustained release for NDF and GLZ. This work demonstrated the transformation of FDC into dynamic dose-personalized polypills.

[Technology and principle of improving solubility of Dioscoreae Rhizoma formula granules based on powder modification].

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) µm to(37.91±0.42) µm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.

Manipulating drug release from 3D printed dual-drug loaded polypills using challenging polymer compositions.

Combining multiple medications in a single dosage form has emerged as an important strategy for treating complex diseases and could help tackle the growing issue of polypharmacy. In this study we investigated the suitability of different dual-drug designs for achieving simultaneous, delayed and pulsatile drug release regimes using two model formulations: an immediate release erodible system of Eudragit E PO loaded with paracetamol; and an erodible swellable system of Soluplus loaded with felodipine. Both binary formulations, despite not fused deposition modelling (FDM) printable, were successfully printed using a thermal droplet-based 3D printing method, Arburg Plastic Freeforming (APF), and exhibited good reproducibility. X-ray powder diffraction (XRPD), Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Differential Scanning Calorimetry (DSC) were used to assess drug-excipient interaction. The printed tablets were evaluated for drug release using in vitro dissolution testing. We found the simultaneous and delayed release designs were effective at generating the intended drug release profiles, giving insight into the types of dual-drug designs which can be used to create complex release profiles. In contrast the pulsatile tablet release was non-defined, highlighting the design limitations when using erodible materials.

Disulfiram 3D printed film produced via hot-melt extrusion techniques as a potential anticervical cancer candidate.

Cervical cancer is known globally as one of the most common health problems in women. Indeed, one of the most convenient approaches for its treatment is an appropriate bioadhesive vaginal film. This approach provides a local treatment modality, which inevitably decreases dosing frequency and improves patient compliance. Recently, disulfiram (DSF) has been investigated and demonstrated to possess anticervical cancer activity; therefore, it is employed in this work. The current study aimed to produce a novel, personalized three-dimensional (3D) printed DSF extended-release film using the hot-melt extrusion (HME) and 3D printing technologies. The optimization of the formulation composition and the HME and 3D printing processing temperatures was an important factor for overcoming the DSF heat-sensitivity issue. In addition, the 3D printing speed was specifically the most crucial parameter for alleviating heat-sensitivity concerns, which led to the production of films (F1 and F2) with an acceptable DSF content and good mechanical properties. The bioadhesion film study using sheep cervical tissue indicated a reasonable adhesive peak force (N) of 0.24 ± 0.08 for F1 and 0.40 ± 0.09 for F2, while the work of adhesion (N.mm) for F1 and F2 was 0.28 ± 0.14 and 0.54 ± 0.14, respectively. Moreover, the cumulative in vitro release data indicated that the printed films released DSF for up to 24 h. HME-coupled 3D printing successfully produced a patient-centric and personalized DSF extended-release vaginal film with a reduced dose and longer dosing interval.

A Snapshot of Current Updates and Future Prospects of 3D Printing in Medical and Pharmaceutical Science.

3D printing in other fields, such as aviation, is quite old, but in the pharmaceutical area, it is an emerging technique. 3D printing is used to formulate various drug delivery systems and dosage forms with complex geometry. It allows large and fast production of products according to the need of the patient. Today, it is the widely used manufacturing technique in the healthcare field for the engineering of tissues and tissue models, production of medicines and medical devices, organ and tissue bioprinting, implant manufacturing, and production of polypills, vaginal rings, orodispersible films, etc. It allows the production of various dosage forms with complex release profiles containing multiple active ingredients. It is used for manufacturing medicines according to the need of individual patients focusing on the concept of personalized medicines. The idea of customized medicines allows change of dosage and design of the product as per individual and with decreased side effects. This review details various techniques of 3D printing used, such as stereolithography, fused deposition modeling, inkjet printing, etc., and applications and dosage forms developed with the latest patents. The significant challenges in the emergence of the 3D printing technique are the involvement of complex combinations to achieve desired properties, and also, the bioprinter involved provides slow and less resolution. The materials prepared by this technique are both biocompatible and printable, due to which additive manufacturing is increasing in the field of medicine.

Enhanced in-situ liquid transport investigation setup for pharmaceutical tablet disintegration analysis using terahertz radiation.

The disintegration process of pharmaceutical solid dosage forms commences on contact with the dissolution medium and continues with subsequent spontaneous imbibition of the medium in the tablet matrix. Identifying the location of the liquid front in situ during imbibition, therefore, plays a significant role in understanding and modelling the disintegration process. Terahertz pulsed imaging (TPI) technology can be used to investigate this process by its ability to penetrate and identify the liquid front in pharmaceutical tablets. However, previous studies were limited to samples suitable for a flow cell environment, i.e. flat cylindrical disk shapes; thus, most commercial tablets could only be measured with prior destructive sample preparation. This study presents a new experimental setup named open immersion to measure a wide range of pharmaceutical tablets in their intact form. Besides, a series of data processing techniques to extract subtle features of the advancing liquid front are designed and utilised, effectively increasing the maximum thickness of tablets that can be analysed. We used the new method and successfully measured the liquid ingress profiles for a set of oval convex tablets prepared from a complex eroding immediate-release formulation.

Comparison of vial heat transfer coefficients during the primary and secondary drying stages of freeze-drying.

This study uses a heat flux sensor and temperature probes to directly measure vial heat transfer coefficients (Kv) during primary and secondary drying stages of lyophilization. It is observed that Kv is 40-80% smaller during secondary drying than primary drying, and this value exhibits a weaker dependence on chamber pressure than in primary drying. These observations arise because water vapor in the chamber significantly decreases between primary and secondary drying, which alters the gas conductivity between the shelf and vial. This study tabulates Kv values for secondary drying for different vials and different chamber pressures, and demarcates the contributions from gas conduction. Lastly, the study performs an energy budget analysis on two different vials (10R glass vial and 10 mL plastic vial) to determine the major factors that contribute to vial energy consumption. During primary drying, the majority of energy supplied goes towards sublimation, while for secondary drying, the majority of energy goes towards heating the vial wall rather than desorbing bound water. We discuss the consequences of this behavior for heat transfer modeling. During secondary drying, the heat of desorption can be neglected in thermal modeling for some materials (e.g., glass) but not others (e.g., plastic vials).

Extrusion 3D printing of minicaplets for evaluating in vitro & in vivo praziquantel delivery capability.

This study aimed to explore extrusion three dimensional (3D) printing technology to develop praziquantel (PZQ)-loaded minicaplets and evaluate their in vitro and in vivo delivery capabilities. PZQ-loaded minicaplets were 3D printed using a fused deposition modelling (FDM) principle-based extrusion 3D printer and were further characterized by different in vitro physicochemical and sophisticated analytical techniques. In addition, the % PZQ entrapment and in vitro PZQ release performance were evaluated using chromatographic techniques. It was in vitro observed that PZQ was fully released in the gastric pH medium within the period of gastric emptying, that is, 120 min, from the PZQ-loaded 3D printed minicaplets. Furthermore, in vivo pharmacokinetic (PK) profiles of PZQ-loaded 3D printed minicaplets were systematically evaluated using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The PK profile of the PZQ-loaded 3D printed minicaplets was established using different parameters such as Cmax, Tmax, AUC0-t, AUC0-∞, and oral relative bioavailability (RBA). The Cmax value of pristine PZQ was found at 64.79 ± 13.99 ng/ml, while PZQ-loaded 3D printed minicaplets showed a Cmax of 263.16 ± 47.85 ng/ml. Finally, the PZQ-loaded 3D printed minicaplets showed 9.0-fold improved oral RBA compared with that of pristine PZQ (1.0-fold). Together, these observations potentiate the desired in vitro and improved in vivo delivery capabilities of PZQ from the PZQ-loaded 3D printed minicaplets.

Improving drug release rate, drug-polymer miscibility, printability and processability of FDM 3D-printed tablets by weak acid-base interaction.

Slow drug release, low drug-polymer miscibility, poor printability of polymers used, and high processing temperature are major challenges in developing FDM 3D-printed tablets. These challenges were addressed in this investigation by having a model basic drug, haloperidol (mp: 151.5 °C), interact with a weak acid, malic acid (mp: 130 °C), during the melt extrusion of formulations into filaments used for 3D-printing. Malic acid was selected as it was previously reported that it did not form any crystalline salt with haloperidol but its addition to aqueous media could greatly increase the solubility of haloperidol from âˆ¼ 1 µg/mL to > 1 g per mL of water by acid-base supersolubilization. Concentrated solutions of haloperidol-malic acid mixtures produced amorphous materials upon drying. It has been observed in the present investigation that similar interaction between haloperidol and malic acid may also occur in the absence of water. Upon heating, haloperidol-malic acid mixtures at 1:1 and 1:2 molar ratios turned amorphous starting at âˆ¼ 50 °C, which is much below the melting point of either component. When Kollidon® VA64, a brittle and non-printable polymer, was used as the polymeric carrier, the acid-base interaction greatly reduced the melt viscosity of haloperidol-malic acid-Kollidon® VA64 ternary mixtures. Consequently, melt extrusion of filaments and printing of tablets using such mixtures could be performed at much lower temperatures than those with haloperidol-Kollidon® VA64 binary mixtures. The filaments containing 15 % and 30 % haloperidol along with malic acid and Kollidon® VA64 could be printed into tablets at relatively low temperatures of 125 and 100 °C, respectively, thus making Kollidon® VA64 not only printable but also doing so at low temperatures. Up to 50 % w/w drug load in filaments was achieved without any crystallization of haloperidol or malic acid. Drug release at pH 2 and 6.8 from printed tablets with 100 % infill was 80 % in < 30 min. Thus, the acid-base interaction can successfully resolve multiple development challenges encountered with FDM 3D-printed tablets.

Investigation on the Potential Application of Na-Attapulgite as an Excipient in Domperidone Sustained-Release Tablets.

In this study, Na-attapulgite was explored as an excipient to prepare domperidone sustained-release tablets and test them in accordance with United States Pharmacopoeia requirements. Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) were employed to explore the compatibility between Na-attapulgite and domperidone. The XRD and DSC show no interaction between the drug and Na-attapulgite. The FTIR spectrum indicates a shift in the absorption of N-H in the drug molecule, which can be explained by the hydrogen bonding interaction between the N-H in the DOM molecule and the -OH on the surface of Na-ATP. The diameter, hardness, friability and drug content of the tablets were measured, and they all met the relevant requirements of the United States Pharmacopoeia. In addition, the tablets with Na-attapulgite as excipient exhibit a better release performance within the release time of 12 h. These results demonstrate that the domperidone sustained-release tablets have been successfully prepared by using Na-attapulgite as an excipient. The doping of Na-ATP in domperidone sustained-release tablets improves the cytocompatibility. Moreover, with the increase of Na-ATP content, cells proliferate remarkably and cell activity is significantly enhanced.

Three-dimensional printed dosage forms based on disease-focussed perspectives.

OBJECTIVES: Three-dimensional printing (3DP) has gained importance worldwide recently as a novel drug manufacturing technology. 3DP technologies are suitable in the pharmaceutical field because of having the potential in personalized medicine. The aim of this review is to present an overview of the use of 3DP technologies in pharmaceutical area, their working principles and critical process parameters. In addition, this review presents an innovative approach that evaluates the use of 3DP technologies on disease to disease. KEY FINDINGS: This review covers the potential use of 3DP technologies in different diseases by evaluating them on a research basis. These diseases can be summarized as cardiovascular, neurological, respiratory, oncological, inflammatory, vaginal, dermatological and other diseases. It has been focussed on manuscripts that published after 2015. Studies on the use of 3DP in each disease group have been systematically reviewed by considering the methods, types of printers used and the prepared dosage forms. Oral formulations (tablets and films), implants, topical systems and vaccines are some of the examples of the mentioned dosage forms. SUMMARY: This review presented a systematic and novel overview of the use of 3DP in the treatment of different clinical disorders.

3D printing hybrid materials using fused deposition modelling for solid oral dosage forms.

3D printing in the pharmaceutical and healthcare settings is expanding rapidly, such as the rapid prototyping of orthotics, dental retainers, drug-loaded implants, and pharmaceutical solid oral dosage forms. Through 3D printing, we have the capability to precisely control dose, release kinetics, and several aesthetic features of dosage forms such as colour, shape, and texture. Additionally, polypills can be created with combinations of medications in one solid dosage form at completely customisable strengths that would be extremely difficult to obtain commercially. As the technology and formulations developed through 3D printing are expanding, the development of new hybrid materials to obtain superior formulations are also gaining momentum. In this review we collate data on the importance of developing hybrid formulations of polymers, drugs and excipients necessary to produce reliable and high-quality 3D printed dosage forms with a special emphasis on fused deposition modelling (FDM). FDM technology is one of the most widely used forms of 3D printing and has demonstrated compatibility with unique polymer-based hybrids to allow for enhanced drug delivery, protection of thermolabile drugs, modifiable release kinetics, and more. The data collated covers different categories of hybrids as well as the methods used to fabricate them, and their respective effects on the properties of 3D printed solid oral dosage forms. Therefore, this review will provide an overview of upcoming and emerging trends in pharmaceutical 3D printing formulation compositions.