Search Results (25)

Background: Rheumatoid arthritis is a chronic autoimmune disease that leads to severe disability and requires improved therapeutic strategies to optimize anti-inflammatory treatment. This study aimed to address this challenge by developing and characterizing an extended-release polymer matrix tablet containing ketoprofen and a ketoprofen–β-cyclodextrin complex with enhanced therapeutic properties. The objective was to improve inflammation management and therapeutic outcomes using a novel delivery system based on the inclusion of the active substance in cyclodextrin complexes. Methods: Tablets were formulated using ketoprofen and ketoprofen–β-cyclodextrin complexes combined with hydrophilic polymers such as Carbopol^® 971P NF, Kollidon^® VA 64, and Methocel^TM K4M. The complexes were obtained via the coprecipitation method to improve bioavailability. The kinetics of the release of ketoprofen, ketoprofen–β-cyclodextrin complex (2:1), and ketoprofen–β-cyclodextrin complex (1:1) from the tablets were investigated in vitro in artificial gastric and intestinal fluids, and drug release profiles were established. Advanced mathematical models were used to describe the nonlinear behavior of the drug–polymer systems. Results: The inclusion of ketoprofen in the β-cyclodextrin complexes was confirmed, revealing distinct release profiles. Tablets (K-3 F-3) containing the 1:1 complex showed rapid release (96.2% in 4–7 h), while tablets (K-1 F-4) containing free ketoprofen released 76% over 9–11 h. Higher polymer concentrations slowed the release due to gel barrier formation. Pharmacotechnical and stability tests supported their suitability as extended-release forms. A multifractal modeling approach described the release dynamics, treating the polymer–drug matrix as a complex system, with release curves characterized by variations in the fractal dimension and resolution. Conclusions: Specific hydrophilic polymer combinations effectively prolonged ketoprofen release. The developed matrix tablets, which were evaluated via in vitro studies and mathematical modeling, show promise for improving therapeutic outcomes and patient compliance during rheumatoid arthritis treatment. Full article

Slow-releasing tablets combined with persulfate acting as an oxidant and ferrous iron acting as an activator were manufactured for in situ chemical oxidation. The trichloroethylene (TCE) removal efficiency according to the molar ratio of the oxidizer and activator in the 0, 0.5, 1, 1.5, 2, and 2.5 molar ratio (persulfate: ferrous iron) reactors were 15%, 89%, 90%, 82%, 71%, and 55%, respectively. In a batch reactor injected with an oxidation-activation combined tablet (OACT) and a liquid oxidizing/activator, the TCE removal efficiencies were 100% and 70%, respectively, showing that the tablet form had a high efficiency in contaminant removal. The evaluation of the dissolution characteristics and TCE removal efficiency of OACT 0.5 (tablet with a 1:0.5 molar ratio of persulfate to activator) and OACT 1.0 (tablet with a 1:1 molar ratio of persulfate to activator) under continuous flow conditions showed that the TCE removal efficiency of the OACT 1.0 column was approximately 1.4 times higher than that of OACT 0.5. The longevities of persulfate and ferrous iron of the OACT 1.0 tablet were 43.2 days and 41.7 days, respectively. Thus, OACT 1.0, which was manufactured effectively, was suitable for in situ slow-release chemical oxidation systems. Full article

Three-dimensional printing by fused deposition modeling (FDM) coupled with hot-melt extrusion (HME) is a point of convergence of research efforts directed toward the development of personalized dosage forms. In addition to the customization in terms of shapes, sizes, or delivered drug doses, the modulation of drug release profiles is crucial to ensure the superior efficacy and safety of modern 3D-printed medications compared to those of conventional ones. Our work aims to solidify the groundwork for the preparation of 3D-printed tablets that ensure the sustained release of diclofenac sodium. Specifically, we achieved the fast release of a diclofenac sodium dose to allow for the prompt onset of its pharmacological effect, further sustaining by the slow release of another dose to maintain the effect over a prolonged timeframe. In this regard, proper formulation and design strategies (a honeycomb structure for the immediate-release layer and a completely filled structure for the sustained-release layer) were applied. Secondarily, the potential of polyvinyl alcohol to function as a multifaceted polymeric matrix for both the immediate and slow-release layers was explored, with the objective of promoting the real-life applicability of the technique by downsizing the number of materials required to obtain versatile pharmaceutical products. The present study is a step forward in the translation of HME-FDM-3DP into a pharmaceutical manufacturing methodology. Full article

Clozapine (CZP) is the only effective drug in schizophrenia resistant to typical antipsychotics. However, existing dosage forms (oral or orodispersible tablets, suspensions or intramuscular injection) show challenging limitations. After oral administration, CZP has low bioavailability due to a large first-pass effect, while the i.m. route is often painful, with low patient compliance and requiring specialised personnel. Moreover, CZP has a very low aqueous solubility. This study proposes the intranasal route as an alternative route of administration for CZP, through its encapsulation in polymeric nanoparticles (NPs) based on Eudragit^® RS100 and RL100 copolymers. Slow-release polymeric NPs with dimensions around 400–500 nm were formulated to reside and release CZP in the nasal cavity, where it can be absorbed through the nasal mucosa and reach the systemic circulation. CZP-EUD-NPs showed a controlled release of CZP for up to 8 h. Furthermore, to reduce mucociliary clearance and increase the residence time of NPs in the nasal cavity to improve drug bioavailability, mucoadhesive NPs were formulated. This study shows that the NPs already exhibited strong electrostatic interactions with mucin at time zero due to the presence of the positive charge of the used copolymers. Furthermore, to improve the solubility, diffusion and adsorption of CZPs and the storage stability of the formulation, it was lyophilised using 5% (w/v) HP-β-CD as a cryoprotectant. It ensured the preservation of the NPs’ size, PDI and charge upon reconstitution. Moreover, physicochemical characterisation studies of solid-state NPs were performed. Finally, toxicity studies were performed in vitro on MDCKII cells and primary human olfactory mucosa cells and in vivo on the nasal mucosa of CD-1 mice. The latter showed non-toxicity of B-EUD-NPs and mild CZP-EUD-NP-induced tissue abnormalities. Full article

Solid dosage forms based on hypromellose (HPMC) with prolonged/extended drug release are very important from the research and industrial viewpoint. In the present research, the influence of selected excipients on carvedilol release performance from HPMC-based matrix tablets was studied. A comprehensive group of selected excipients was used within the same experimental setup, including different grades of excipients. Compression mixtures were directly compressed using constant compression speed and main compression force. LOESS modelling was used for a detailed comparison of carvedilol release profiles via estimating burst release, lag time, and times at which a certain % of carvedilol was released from the tablets. The overall similarity between obtained carvedilol release profiles was estimated using the bootstrapped similarity factor (f₂). In the group of water-soluble carvedilol release modifying excipients, which produced relatively fast carvedilol release profiles, POLYOXᵀᴹ WSR N-80 and Polyglykol^® 8000 P demonstrated the best carvedilol release control, and in the group of water-insoluble carvedilol release modifying excipients, which produced relatively slow carvedilol release profiles, AVICEL^® PH-102 and AVICEL^® PH-200 performed best. Full article

Niclosamide (NICLO) is a recognized antiparasitic drug being repositioned for Helicobacter pylori. The present work aimed to formulate NICLO nanocrystals (NICLO-NCRs) to produce a higher dissolution rate of the active ingredient and to incorporate these nanosystems into a floating solid dosage form to release them into the stomach slowly. For this purpose, NICLO-NCRs were produced by wet-milling and included in a floating Gelucire l3D printed tablet by semi-solid extrusion, applying the Melting solidification printing process (MESO-PP) methodology. The results obtained in TGA, DSC, XRD and FT-IR analysis showed no physicochemical interactions or modifications in the crystallinity of NICLO-NCR after inclusion in Gelucire 50/13 ink. This method allowed the incorporation of NICLO-NCRs in a concentration of up to 25% w/w. It achieved a controlled release of NCRs in a simulated gastric medium. Moreover, the presence of NICLO-NCRs after redispersion of the printlets was observed by STEM. Additionally, no effects on the cell viability of the NCRs were demonstrated in the GES-1 cell line. Finally, gastroretention was demonstrated for 180 min in dogs. These findings show the potential of the MESO-PP technique in obtaining slow-release gastro-retentive oral solid dosage forms loaded with nanocrystals of a poorly soluble drug, an ideal system for treating gastric pathologies such as H. pylori. Full article

A biogenic carrier for 5-fluorouracil (5-FU) loading and subsequent tableting as a new drug formulation for slow release has been proposed using the biomineral from blue crab carapace. Due to its highly ordered 3D porous nanoarchitecture, the biogenic carbonate carrier could achieve increased effectiveness in colorectal cancer cure provided that the formulation would successfully pass through the gastric acid conditions. Following the recently proven viability of the concept by demonstrating the slow release of the drug from the carrier using the highly sensitive SERS technique, here we investigated the 5-FU release from the composite tablet drug in pH conditions replicating the gastric environment. The released drug from the tablet was studied in solutions with three relevant pH values, pH 2, pH 3, and pH 4. The 5-FU SERS spectral signature for each pH value was used to build calibration curves for quantitative SERS analysis. The results suggested a similarly slow-releasing pattern in acid pH environments to that in neutral conditions. Although biogenic calcite dissolution was expected in acid conditions, the X-ray diffraction and Raman spectroscopy showed preservation of calcite mineral along with the monohydrocalcite during acid solution exposure for two hours. The total released amount in a time course of seven hours, however, was lower in acidic pH solutions, with a maximum fraction of ~40% of the total amount of loaded drug, for pH 2, as opposed to ~80% for neutral values. Nonetheless, these results clearly prove that the novel composite drug retains its slow-releasing character in environmental conditions compatible with the gastrointestinal pH and that it is a viable and biocompatible alternative for oral delivery of anticancer drug to reach the lower gastro-intestinal tract. Full article

N–acetyl–L–cysteine (NAC), a derivative of the L–cysteine amino acid, presents antioxidant and mucolytic properties of pharmaceutical interest. This work reports the preparation of organic-inorganic nanophases aiming for the development of drug delivery systems based on NAC intercalation into layered double hydroxides (LDH) of zinc–aluminum (Zn₂Al–NAC) and magnesium–aluminum (Mg₂Al–NAC) compositions. A detailed characterization of the synthesized hybrid materials was performed, including X-ray diffraction (XRD) and pair distribution function (PDF) analysis, infrared and Raman spectroscopies, solid-state ¹³carbon and ²⁷aluminum nuclear magnetic resonance (NMR), simultaneous thermogravimetric and differential scanning calorimetry coupled to mass spectrometry (TG/DSC–MS), scanning electron microscopy (SEM), and elemental chemical analysis to assess both chemical composition and structure of the samples. The experimental conditions allowed to isolate Zn₂Al–NAC nanomaterial with good crystallinity and a loading capacity of 27.3 (m/m)%. On the other hand, NAC intercalation was not successful into Mg₂Al–LDH, being oxidized instead. In vitro drug delivery kinetic studies were performed using cylindrical tablets of Zn₂Al–NAC in a simulated physiological solution (extracellular matrix) to investigate the release profile. After 96 h, the tablet was analyzed by micro-Raman spectroscopy. NAC was replaced by anions such as hydrogen phosphate by a slow diffusion-controlled ion exchange process. Zn₂Al–NAC fulfil basic requirements to be employed as a drug delivery system with a defined microscopic structure, appreciable loading capacity, and allowing a controlled release of NAC. Full article

Formulations based on emulsions for enhancing hydrophobic and lipophilic drug delivery and its bioavailability have attracted a lot of interest. As potential therapeutic agents, they are integrated with inert oils, emulsions, surfactant solubility, liposomes, etc.; drug delivering systems that use emulsion formations have emerged as a unique and commercially achievable accession to override the issue of less oral bioavailability in connection with hydrophobic and lipophilic drugs. As an ideal isotropic oil mixture of surfactants and co-solvents, it self-emulsifies and forms fine oil in water emulsions when acquainted with aqueous material. As droplets rapidly pass through the stomach, fine oil promotes the vast spread of the drug all over the GI (gastrointestinal tract) and conquers the slow disintegration commonly seen in solid drug forms. The current status of advancement in technologies for drug carrying has promulgated the expansion of innovative drug carriers for the controlled release of self-emulsifying pellets, tablets, capsules, microspheres, etc., which got a boost for drug delivery usage with self-emulsification. The present review article includes various kinds of formulations based on the size of particles and excipients utilized in emulsion formation for drug delivery mechanisms and the increase in the bioavailability of lipophilic/hydrophobic drugs in the present time. Full article

Three-dimensional printing technology holds marked promise for the pharmaceutical industry and is now under intense investigation. Most research is aimed at a greater efficiency in printing oral dosage forms using powder bed printing or fused deposition modeling (FDM). Oral dosage forms printed by FDM tend to be hard objects, which reduce the risk of cracking and chipping. However, one challenge in printing oral dosage forms via FDM is achieving rapid drug release, because the materials for FDM are basically thermoplastic polymers with slow drug release properties. In this study, we investigated printing a fast-dissolving oral dosage form by adding sugar alcohol to a poly(vinyl alcohol)-based formulation for FDM. Filaments which contain sugar alcohol were successfully prepared, and objects were printed with them as oral dosage forms by FDM. On drug release testing, a printed oral dosage form in a ring shape which contained 55% maltitol showed a more than 85% drug release in 15 min. In vivo oral absorption of this printed oral dosage form in dogs was comparable to that of a conventional fast-dissolving tablet. Of particular interest, the drug release profile and drug amount of the oral dosage forms can be easily controlled by a change in shape using 3D Computer Aided Design. These characteristics will encourage the prevalence of FDM by the pharmaceutical industry, and contribute to the promotion of personalized medicine. Full article

Mesoporous carriers are a convenient choice for the solidification of self-microemulsifying drug delivery systems (SMEDDS) designed to improve the solubility of poorly water-soluble drugs. They are known for high liquid load capacity and the ability to maintain characteristics of dry, free-flowing powders. Therefore, five different mesoporous carriers were used for the preparation of carvedilol-loaded SMEDDS granules by wet granulation methods—in paten (manually) and using a high-shear (HS) granulator. Granules with the highest SMEDDS content (63% and 66% of total granules mass, respectively) and suitable flow properties were obtained by Syloid^® 244FP and Neusilin^® US2. SMEDDS loaded granules produced by HS granulation showed superior flow characteristics compared to those obtained manually. All SMEDDS granules exhibited fast in vitro release, with 93% of carvedilol releasing from Syloid^® 244FP-based granules in 5 min. Upon compaction into self-microemulsifying tablets, suitable tablet hardness and very fast disintegration time were achieved, thus producing orodispersible tablets. The compaction slightly slowed down the carvedilol release rate; nevertheless, upon 1 h (at pH 1.2) or 4 h (at pH 6.8) of in vitro dissolution testing, the amount of released drug was comparable with granules, confirming the suitability of orodispersible tablets for the production of the SMEDDS loaded single unit oral dosage form. Full article

Hyperlipidemia is still the leading cause of heart disease in patients with hypertension. The purpose of this study is to make rosuvastatin calcium (ROS) and atenolol (AT) bilayer tablets to treat coexisting dyslipidemia and hypertension with a single product. ROS was chosen for the immediate-release layer of the constructed tablets, whereas AT was chosen for the sustained-release layer. The solid dispersion of ROS with sorbitol (1:3 w/w) was utilized in the immediate-release layer while hydroxypropyl methylcellulose (HPMC), ethylcellulose (EC), and sodium bicarbonate were incorporated into the floating sustained-release layer. The concentrations of HPMC and EC were optimized by employing 3² full factorial designs to sustain AT release. The bilayer tablets were prepared by the direct compression method. The immediate-release layer revealed that 92.34 ± 2.27% of ROS was released within 60 min at a pH of 1.2. The second sustained-release layer of the bilayer tablets exhibited delayed release of AT (96.65 ± 3.36% within 12 h) under the same conditions. The release of ROS and AT from the prepared tablets was found to obey the non-Fickian diffusion and mixed models (zero-order, Higuchi and Korsmeyer–Peppas), respectively. Preclinical studies using rabbit models investigated the impact of ROS/AT tablets on lipid profiles and blood pressure. A high-fat diet was used to induce obesity in rabbits. Bilayer ROS/AT tablets had a remarkable effect on decreasing the lipid profiles, slowing weight gain, and lowering blood pressure to normal levels when compared to the control group. Full article

The dissolution profile is of great importance in drug delivery and is affected by the manufacturing method. Thus, it is important to study the influence of the thermal process on drug release in emerging technologies such as 3D printing-fused deposition modeling (FDM). For this purpose, the characteristics of 3D printed tablets were compared to those of tablets prepared by other thermal methods such as hot-melt extrusion (HME) and non-thermal methods such as physical mixture (PM). Theophylline was used as a drug model and blends of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) were used as a matrix former. The solid state of the drug in all formulations was investigated by differential scanning calorimetry, X-ray powder diffraction, and Fourier-transformed infrared spectroscopy. All studied tablets had the same weight and surface area/volume (SA/V). Dissolution data showed that, for some formulations, printed tablets interestingly had a faster release profile despite having the highest hardness values (>550 N) compared to HME and PM tablets. Porosity investigations showed that 100% infill printed tablets had the highest porosity (~20%) compared to HME (<10%) and PM tablets (≤11%). True density records were the lowest in printed tablets (~1.22 g/m³) compared to tablets made from both HME and PM methods (~1.26 g/m³), reflecting the possible increase in polymer specific volume while printing. This increase in the volume of polymer network may accelerate water and drug diffusion from/within the matrix. Thus, it is a misconception that the 3D printing process will always retard drug release based on increased tablet hardness. Hardness, porosity, density, solid-state of the drug, SA/V, weight, and formulation components are all factors contributing to the release profile where the total balance can either slow down or accelerate the release profile. Full article

The formulation of active pharmaceutical ingredients (APIs) in amorphous solid dispersions (ASDs) is a promising approach to improve the bioavailability of poorly soluble compounds. However, problems often arise in the production of tablets from ASDs regarding the compressibility and recrystallization of the API. In the present study, the preparation of spray-dried ASDs of paracetamol (PCM) and four different types of polyvinylpyrrolidone (PVP) and their further processing into tablets were investigated. The influence of PVP type on the glass transition temperature (T_g) and the physical stability of ASD powders were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (XRD). ASD powders with 10 to 30% PCM were stable for at least 48 weeks. PCM contents of 40 to 50% led to recrystallization of the amorphous PCM within a few days or weeks. ASD with PVP/vinyl acetate (VA) copolymer (PVP/VA) was the most unstable and tended to recrystallize in PCM polymorphic form II. This formulation was therefore used for tablet studies. The influence of compression force on recrystallization, crushing strength, and drug release was investigated. Even high compression forces did not affect the stability of the ASD. However, the ASD tablets led to slow release of the API. Full article

Blending fertilizer with biochar followed by densification to make it into a tablet can enhance the adsorption of fertilizer on the biochar surface and reduce the nutrient loss during handling. However, the nutrient release and ammonia volatilization from biochar-blended fertilizer with and without densification are not well understood. The objectives of this study were to determine the nutrient release and ammonia volatilization from an acid soil applied with biochar-blended NPK fertilizer with and without densification. The nutrient release of biochar-blended NPK was determined using water incubation for 30 days, whereas daily loss of ammonia was measured using a closed dynamic air flow system for 10 days. The densified biochar-blended NPK caused stronger physical binding of the nutrients within the tablet in addition to stronger chemical bondings between the nutrients with the biochar’s functional groups. As a result, nutrient release in the water incubation from the biochar-blended NPK fertilizer tablet was slower. However, blending the biochar with the NPK fertilizer increased soil ammonia volatilization relative to the NPK fertilizer alone. This demonstrates that the biochar-blended fertilizer tablet has the potential to serve as a slow release fertilizer for crop cultivation. Full article