Ultrahigh-performance liquid chromatography Q-Exactive-Orbitrap mass spectrometry and molecular network analysis alongside network pharmacology to elucidate the active constituents and mechanism of action of Huahong tablet in treating pelvic inflammatory disease.

RATIONALE: Huahong tablet, a commonly used clinical Chinese patent medicine, shows good efficacy in treating pelvic inflammation and other gynaecological infectious diseases. However, the specific composition of Huahong tablets, which are complex herbal formulations, remains unclear. Therefore, this study aims to identify the active compounds and targets of Huahong tablets and investigate their mechanism of action in pelvic inflammatory diseases. METHODS: We utilised ultrahigh-performance liquid chromatography Q-Exactive-Orbitrap mass spectrometry and the relevant literature to identify the chemical components of Huahong tablets. The GNPS database was employed to further analyse and speculate on the components. Potential molecular targets of the active ingredients were predicted using the SwissTargetPrediction website. Protein-protein interaction analysis was conducted using the STRING database, with visualisation in Cytoscape 3.9.1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID database. Additionally, a traditional Chinese medicine-ingredient-target-pathway network was constructed using Cytoscape 3.10.1. Molecular docking validation was carried out to investigate the interaction between core target and specific active ingredient. RESULTS: A total of 66 chemical components were identified, and 41 compounds were selected as potential active components based on the literature and the TCMSP database. Moreover, 38 core targets were identified as key targets in the treatment of pelvic inflammatory diseases with Huahong tablets. GO and KEGG enrichment analysis revealed 986 different biological functions and 167 signalling pathways. CONCLUSION: The active ingredients in Huahong tablets exert therapeutic effects on pelvic inflammatory diseases by acting on multiple targets and utilising different pathways. Molecular docking confirmed the high affinity between the specific active ingredients and disease targets.

Tabletized Nanomedicine: From the Current Scenario to Developing Future Medicine.

The limitations of conventional therapeutic treatments prevailed in the development of nanotechnology-based medical formulations, termed nanomedicine. Nanomedicine is an advanced medicine that often consists of therapeutic agent(s) embedded in biodegradable or biocompatible nanomaterial-based formulations. Among nanomedicine approaches, tablet (oral) nanomedicine is still under development. In tabletized nanomedicine, the dynamic interplay between nanoformulations and the intricate milieu of the gastrointestinal tract simulates a pivotal role, particularly accentuating the influence exerted upon the luminal, mucosal, and epithelial cells. In this work, we document the perspectives and opportunities of nanoformulations toward the development of tabletized nanomedicine. This review also unveils the notion of integrating nanomedicine within a tablet formulation, which facilitates the controlled release of drugs, biomolecules, and agent(s) from the formulation to achieve a better therapeutic response. Finally, an attempt was made to explore current trends in nanomedicine technology such as bacteriophage, probiotic, and oligonucleotide tabletized nanomedicine and the combination of nanomedicine with imaging agents, i.e., nanotheranostics.

Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis.

This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). Fourier Transform (FT) IR analysis affirmed polymer compatibility, while differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP's carboxymethyl groups (-CH2-COO-) heightened divalent cation reactivity, and crosslinking with CaCl2 produced Ca-CAP through -CH2-COO- and Ca2+ interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP's potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.

Isoquinoline-based intrinsic fluorescence assessment of erythropoiesis-stimulating agent, Roxadustat (FG-4592), in tablets: applications to content uniformity and human plasma evaluation.

In the present study, a first validated and green spectrofluorimetric approach for its assessment and evaluation in different matrices was investigated. After using an excitation wavelength of 345 nm, Roxadustat (ROX) demonstrates a highly native fluorescence at an emission of 410 nm. The influences of experimental factors such as pH, diluting solvents, and different organized media were tested, and the most appropriate solvent choice was ethanol. It was confirmed that there was a linear relationship between the concentration of ROX and the relative fluorescence intensity in the range 60.0-1000.0 ng ml-1, with the limit of detection and limit of quantitation, respectively, being 17.0 and 53.0 ng ml-1. The mean recoveries % [±standard deviation (SD), n = 5] for pharmaceutical preparations were 100.11% ± 2.24%, whereas for plasma samples, they were 100.08 ± 1.08% (±SD, n = 5). The results obtained after the application of four greenness criteria, Analytical Eco-Scale metric, NEMI, GAPI, and AGREE metric, confirmed its eco-friendliness. In addition, the whiteness meter (RGB12) confirmed its level of sustainability. The International Council for Harmonisation (ICH) criteria were used to verify the developed method through the study in both spiked plasma samples and content uniformity evaluation. An appropriate standard for various applications in industry and quality control laboratories was developed.

Understanding the Roles of Excipients in Moisture Management in Solid Dosage Forms.

Excipients are ubiquitous in pharmaceutical products, and often, they can also play a critical role in maintaining product quality. For a product containing a moisture-sensitive drug, moisture can be deleterious to the product stability during storage. Therefore, using excipients that interact with moisture in situ can potentially alleviate product stability issues. In this study, the interactive behavior of starch with moisture was augmented by coprocessing maize starch with sodium chloride (NaCl) or magnesium nitrate hexahydrate [Mg(NO3)2·6H2O] at different concentrations (5 and 10%, w/w). The effect of the formulation on drug stability was assessed through the degradation of acetylsalicylic acid, which was used as the model drug. The results showed that coprocessing of the starch with either NaCl or Mg(NO3)2·6H2O impacted the number of water molecule binding sites on the starch and how the sorbed moisture was distributed. The coprocessed excipients also resulted in lower drug degradation and lesser changes in tablet tensile strength during post-compaction storage. However, corresponding tablet formulations containing physical mixtures of starch and salts did not yield promising outcomes. This study demonstrated the advantageous concomitant use of common excipients by coprocessing to synergistically mitigate the adverse effects of moisture and promote product stability when formulating a moisture-sensitive drug. In addition, the findings could help to improve the understanding of moisture-excipient interactions and allow for the judicious choice of excipients when designing formulations containing moisture-sensitive drugs.

Integrative Salt Selection and Formulation Optimization: Perspectives of Disproportionation and Microenvironmental pH Modulation.

We report a novel utilization of a pH modifier as a disproportionation retardant in a tablet formulation. The drug molecule of interest has significant bioavailability challenges that require solubility enhancement. In addition to limited salt/cocrystal options, disproportionation of the potential salt(s) was identified as a substantial risk. Using a combination of Raman spectroscopy with chemometrics and quantitative X-ray diffraction in specially designed stress testing, we investigated the disproportionation phenomena. The learnings and insight drawn from crystallography drove the selection of the maleate form as the target API. Inspired by the fumarate form's unique stability and solubility characteristics, we used fumaric acid as the microenvironmental pH modulator. Proof-of-concept experiments with high-risk (HCl) and moderate-risk (maleate) scenarios confirmed the synergistic advantage of fumaric acid, which interacts with the freebase released by disproportionation to form a more soluble species. The resultant hemifumarate helps maintain the solubility at an elevated level. This work demonstrates an innovative technique to mediate the solubility drop during the "parachute" phase of drug absorption using compendial excipients, and this approach can potentially serve as an effective risk-mitigating strategy for salt disproportionation.

Fabrication of 3D-Printed Hydrocortisone Triple Pulsatile Tablet Using Fused Deposition Modelling Technology.

Hydrocortisone (HC) is the optimal drug for adolescents diagnosed with congenital adrenal hyperplasia (CAH). Because traditional dosage regimens HC are inconvenient, our study used fused deposition modeling (FDM) three-dimensional (3D) printing technology to solve the problems caused by traditional preparations. First, we designed a core-shell structure tablet with an inner instant release component and an outer delayed release shell. The instant release component was Kollicoat IR: glycerol (GLY): HC = 76.5:13.5:10. Then, we used Affinisol® HPMC 15LV to realize delayed release. Furthermore, we investigated the relationship between the thickness of the delayed release shell and the delayed release time, and an equation was derived through binomial regression analysis. Based on that equation, a novel triple pulsatile tablet with an innovative structure was devised. The tablet was divided into three components, and the drug was released multiple times at different times. The dose and release rate of the tablets can be adjusted by modifying the infill rate of the printing model. The results indicated that the triple pulsatile tablet exhibited desirable release behavior in vitro. Moreover, the physicochemical properties of the drug, excipients, filaments, and tablets were characterized. All these results indicate that the FDM 3D printing method is a convenient technique for producing preparations with intricate structures.

Computer-aided optimization of carbidopa/levodopa orally disintegrating tablets.

OBJECTIVE: This study aimed to optimize the formulation of carbidopa/levodopa orally disintegrating tablets (ODTs) in order to improve their disintegration performance, and facilitate easier medication intake for Parkinson's patients. METHOD: The response surface methodology (RSM) was used to optimize the formulation, with the content of cross-linked polyvinylpyrrolidone (PVPP), microcrystalline cellulose (MCC), and mannitol (MNT) as independent variables, and disintegration time as the response parameter. Python was utilized to model Carr Indices and mixing time to determine the suitable mixing time. Direct compression (DC) was used for the preparation of ODTs. RESULT: The optimization process resulted in the following values for the independent variables: 7.04% PVPP, 22.02% MCC, and 16.21% MNT. By optimizing the mixing time using Python, it was reduced to 14.19 min. The ODTs prepared using the optimized formulation and a mixing time of 14.19 min exhibited disintegration times of 16.74 s in vitro and 17.63 s in vivo. The content uniformity of levodopa and carbidopa was found to be 100.83% and 99.48%, respectively. CONCLUSION: The ODTs optimized using RSM and Python demonstrated excellent disintegration performance, leading to a decrease in the time the drug exists in solid form in the oral cavity. This improvement in disintegration time reduced the difficulty of swallowing for patients and enhanced medication compliance, while still ensuring that ODTs prepared by DC had sufficient mechanical strength to meet storage and transportation requirements.

Non-destructive visualization of internal structural changes in humidified magnesium oxide tablets using X-ray computed tomography.

Detailed examinations of the internal structure of tablets are imperative for comprehending their formulation, physical attributes, and ensuring their safe utilization. While X-ray computed tomography (CT) is valuable for noninvasively analyzing internal structural changes, the influence of humidity on these structural changes remains unexplored. Accordingly, we aimed to assess the viability of X-ray CT in non-destructively evaluating the internal structure of humidified magnesium oxide (MgO) tablets. MgO tablets were subjected to conditions of 40 °C and 75% humidity for 7 days, weighed pre- and post-humidification, and subsequently stored at room temperature (22-27 °C) until day 90. Their internal structure was evaluated using X-ray CT. We observed a substantial increase in the weight of MgO tablets concomitant with moisture absorption, with minimal changes observed upon storage at room temperature. The skewness reduced immediately post-moisture absorption, remained almost the same post-storage at room temperature, and failed to revert to pre-humidification levels during the storage period. These findings highlight the utility of X-ray CT as an effective tool for non-destructive, three-dimensional, and detailed evaluation of internal structural transformations in MgO tablets.

UV-VIS imaging-based investigation of API concentration fluctuation caused by the sticking behaviour of pharmaceutical powder blends.

Surface powder sticking in pharmaceutical mixing vessels poses a risk to the uniformity and quality of drug formulations. This study explores methods for evaluating the amount of pharmaceutical powder mixtures adhering to the metallic surfaces. Binary powder blends consisting of amlodipine and microcrystalline cellulose (MCC) were used to investigate the effect of the mixing order on the adherence to the vessel wall. Elevated API concentrations were measured on the wall and within the dislodged material from the surface, regardless of the mixing order of the components. UV imaging was used to determine the particle size and the distribution of the API on the metallic surface. The results were compared to chemical maps obtained by Raman chemical imaging. The combination of UV and VIS imaging enabled the rapid acquisition of chemical maps, covering a substantially large area representative of the analysed sample. UV imaging was also applied in tablet inspection to detect tablets that fail to meet the content uniformity criteria. The results present powder adherence as a possible source of poor content uniformity, highlighting the need for 100% inspection of pharmaceutical products to ensure product quality and safety.

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.

Intrinsic dissolution rate modeling for the pharmacopoeia apparatus rotating disk compared to flow channel method.

For a solid understanding of drug characteristics, in vitro measurement of the intrinsic dissolution rate is important. Hydrodynamics are often emphasized as the decisive parameter influencing the dissolution. In this study, experiments and computational fluid dynamic (CFD) simulations showed that the mixing behavior in the rotating disc apparatus causes an inhomogeneous flow field and a systematic error in the calculation of the intrinsic dissolution rate. This error is affected by both the experimental time and the velocity. Due to the rotational movement around the tablet center, commonly utilized in pharmacopeia methods, a broad variance is present with regard to the impact of fluid velocity on individual particles of the specimen surface. As this is significantly reduced in the case of uniform overflow, the flow channel is recommended for investigating the dissolution behavior. It is shown that rotating disc measurements can be compared with flow channel measurements after adjusting the measured data for the rotating disc based on a proposed, representative Reynolds number and a suggested apparatus-dependent correction factor. Additionally, modeling the apparatus-independent intrinsic dissolution rate for different temperatures in the rotating disc apparatus is possible using the adapted Levich's equation.

A new insight into the mechanism of the tabletability flip phenomenon.

Tabletability is an outcome of interparticulate bonding area (BA) - bonding strength (BS) interplay, influenced by the mechanical properties, size and shape, surface energetics of the constituent particles, and compaction parameters. Typically, a more plastic active pharmaceutical ingredient (API) exhibits a better tabletability than less plastic APIs due to the formation of a larger BA during tablet compression. Thus, solid forms of an API with greater plasticity are traditionally preferred if other critical pharmaceutical properties are comparable. However, the tabletability flip phenomenon (TFP) suggests that a solid form of an API with poorer tabletability may exhibit better tabletability when formulated with plastic excipients. In this study, we propose another possible mechanism of TFP, wherein softer excipient particles conform to the shape of harder API particles during compaction, leading to a larger BA under certain pressures and, hence, better tabletability. In this scenario, the BA-BS interplay is dominated by BA. Accordingly, TFP should tend to occur when API solid forms are formulated with a soft excipient. We tested this hypothesis by visualizing the deformation of particles in a model compressed tablet by nondestructive micro-computed tomography and by optical microscopy when the particles were separated from the tablet. The results confirmed that soft particles wrapped around hard particles at their interfaces, while an approximately flat contact was formed between two adjacent soft particles. In addition to the direct visual evidence, the BA-dominating mechanism was also supported by the observation that TFP occurred in the p-aminobenzoic acid polymorph system only when mixed with a soft excipient.

Combined eutexia and amorphization for simultaneous enhancement of dissolution rate of triamterene and hydrochlorothiazide: preparation of orodispersible tablets.

BACKGROUND: Triamterene is an oral antihypertensive drug with dissolution-limited poor bioavailability. It can be used as monotherapy or in fixed dose combination with hydrochlorothiazide which also suffers from poor dissolution. Moreover, co-processing of drugs in fixed dose combination can alter their properties. Accordingly, pre-formulation studies should investigate the effect of co-processing and optimize the dissolution of drugs before and after fixed dose combination. This is expected to avoid deleterious interaction (if any) and to hasten the biopharmaceutical properties. OBJECTIVE: Accordingly, the aim of this work was to optimize the dissolution rate of triamterene alone and after fixed dose combination with hydrochlorothiazide. METHODOLOGY: Triamterene was subjected to dry co-grinding with xylitol, HPMC-E5 or their combination. The effect of co-grinding with hydrochlorothiazide was also tested in absence and presence of xylitol and HPMC-E5. The products were assessed using Fourier-transform infrared (FTIR), differential scanning calorimetry, X-ray powder diffraction (XRPD), in addition to dissolution studies. Optimum formulations were fabricated as oral disintegrating tablets (ODT).Results: Co-processing of triamterene with xylitol formed eutectic system which hastened dissolution rate. HPMC-E5 resulted in partial amorphization and improved triamterene dissolution. Co-grinding with both materials combined their effects. Co-processing of triamterene with hydrochlorothiazide resulted in eutexia but the product was slowly dissolving due to aggregation. This problem was vanished in presence of HPMC-E5 and xylitol. Compression of the optimum formulation into ODT underwent fast disintegration and liberated acceptable amounts of both drugs. CONCLUSION: The study introduced simple co-processing with traditional excipients for development of ODT of triamterene and hydrochlorothiazide.

Comparison of Properties of Acetaminophen Tablets Prepared by Wet Granulation Using Freeze-Dried Versus Phase-Inversion Bacterial Cellulose as Diluent.

Bacterial cellulose (BC) is an interesting material for drug delivery applications due to its high purity. This study aimed to compare the properties of tablets prepared by the wet granulation method using bacterial cellulose prepared by different methods as a diluent, using acetaminophen as a model drug. BC used as diluents were prepared using two different methods: freeze-drying (BC-FD) and phase-inversion (BC-PI), and their characteristics were analyzed and compared with that of commercial microcrystalline cellulose PH 101 (Comprecel® M101). Acetaminophen tablets were prepared by wet granulation using BC-FD, BC-PI, or Comprecel® M101 as diluents, and their tablet properties were examined. The result showed that the morphology, polymorph, and crystallinity of BC-PI and Comprecel® M101 were similar but they were different compared with that of BC-FD. Tablets could be successfully formed using BC-PI and Comprecel® M101 as diluents without any physical defects but the tablet prepared using BC-FD as diluent appeared chipped edge. The characteristics (thickness, weight variation, hardness, friability, disintegration, drug content, and dissolution) of the tablets prepared using BC-PI diluent were also similar to those prepared using Comprecel® M101 diluent, but those of BC-FD diluent were inferior. This indicates that BC prepared in BC-PI can potentially be used as a diluent for tablets prepared by wet granulation.

Determination of omeprazole via fluorescence-quenching methodology; application to content uniformity testing.

A new, proven, economical spectrofluorimetric approach has been used to determine the proton pump inhibitor omeprazole (OMP). This innovative technique is based on the ability of OMP to quench the native fluorescence of the mercurochrome dye in an acidic (pH 3.6) solution. Because it was discovered that quenching is proportional to the drug concentration, this dye was used as a sensor for OMP detection. The fluorescence intensity was measured at 518/540 nm, and its linear response ranged from 0.2-10.0 µg/mL with a linear coefficient of 0.9999. The computation yielded a limit of quantification (LOQ) of 0.20 µg/mL and a limit of detection (LOD) of 0.07 µg/mL. Every circumstance and element impacting the reaction product was examined in detail. Pharmacopeial standards carried out the validation. The approved method investigated several commercial preparations and formulations, and the results were favorably compared with those provided by a reference method. According to United States Pharmacopeia (USP) rules, content consistency for two distinct formulations was evaluated.

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.

Development of multiple structured extended release tablets via hot melt extrusion and dual-nozzle fused deposition modeling 3D printing.

The study aims to fabricate extended release (ER) tablets using a dual-nozzle fused deposition modeling (FDM) three-dimensional (3D) printing technology based on hot melt extrusion (HME), using caffeine as the model compound. Three different ER tablets were developed, which obtained "delayed-release", "rapid-sustained release", and "release-lag-release" properties. Each type of tablet was printed with two different formulations. A novel printing method was employed in this study, which is to push the HME filament from behind with polylactic acid (PLA) to prevent sample damage by gears during the printing process. Powder X-ray diffractometry (PXRD) and differential scanning calorimetry (DSC) results showed that caffeine was predominately amorphous in the final tablets. The dissolution of 3D printed tablets was assessed using a USP-II dissolution apparatus. ER tablets containing PVA dissolved faster than those developed with Kollicoat IR. Overall, this study revealed that ER tablets were successfully manufactured through HME paired with dual-nozzle FDM 3D printing and demonstrated the power of 3D printing in developing multi-layer tablets with complex structures.

Impact of dry coating lactose as a brittle excipient on multi-component blend processability.

Previous work demonstrated the benefits of dry coating fine-grade microcrystalline cellulose (MCC) for enabling direct compression (DC), a favored tablet manufacturing method, due to enhanced flowability while retaining good compactability of placebo and binary blends of cohesive APIs. Here, fine brittle excipients, Pharmatose 450 (P450, 19 µm) and Pharmatose 350 (P350, 29 µm), having both poor flowability and compactability are dry coated with silica A200 or R972P to assess DC capability of multi-component cohesive API (coarse acetaminophen, 22 µm, and ibuprofen50, 47 µm) blends. Dry coated P450 and P350 not only attained excellent flowability and high bulk density but also heightened tensile strength hence processability, which contrasts with reported reduction for dry coated ductile MCC. Although hydrophobic R972P imparted better flowability, hydrophilic A200 better enhanced tensile strength, hence selected for dry coating P450 in multi-component blends that included fine Avicel PH-105. For coarse acetaminophen blends, substantial bulk density and flowability increase without any detrimental effect on tensile strength were observed; a lesser amount of dry coated P450 was better. Increased flowability, bulk density, and tensile strength, hence enhanced processability by reaching DC capability, were observed for 60 wt% ibuprofen50, using only 18 wt% of the dry coated P450, i.e. 0.18 wt% silica in the blend.

Preparation of tofacitinib sustained-release tablets using hot melt extrusion technology.

This study aimed to develop a tablet that shows a drug release profile similar to the tofacitinib sustained-release tablet (Xeljanz XR®; OROS™) using hot melt extrusion technology. Tofacitinib citrate was selected as the drug. HPMCAS, HPMCP, and Kollidon VA64 were used as thermoplastic polymers to prepare a hot-melt extrudate. The extrudate was obtained from a twin screw extruder and pelletizer. The granules were compressed using a single punch press machine and then coated. TGA, DSC, XRD, FT-IR, and SEM were performed on the hot melt extrudate to understand its physicochemical properties. Dissolution tests were performed using the paddle method (USP Apparatus II). The results showed that the crystallinity state of tofacitinib changed to amorphous after the hot melt extrusion process; however, no chemical change was observed. The drug release profile was similar to that of Xeljanz XR®, which has an initial lag time owing to its OROS™ formulation; a coating process was performed to obtain a similar drug release profile. The lag time was controlled by adjusting the thickness of the coating layer. Moreover, the extrudate size and compression force during tableting did not significantly affect drug release. In conclusion, the new tofacitinib sustained-release tablet prepared using hot melt extrusion showed a drug release behavior similar to that of Xeljanz XR®.