Search Results (34)

Background/Objectives: Increasing the bioavailability of poorly absorbed drugs is a continuous challenge in modern pharmaceutical technology. This is due to the problematic nature of BCS class IV active pharmaceutical ingredients: these drugs possess poor solubility and membrane permeability. Moreover, many undergo immediate efflux and/or rapid systemic metabolism after absorption. This project aimed to improve the bioavailability of BCS class IV drugs by formulating gastroretentive self-emulsifying systems using curcumin as a model drug. Methods: The base of the systems was created by melting emulsifying agents, dissolution retardants, and PEGs together. Curcumin was added after the mixture was cooled slightly. Aqueous dispersions of several compositions were characterized by dynamic light scattering. After screening these results, the viscosities of the selected formulations were evaluated. Dissolution retardants were selected and added to the most superior samples, and their dissolution profiles were compared. Gastroretention of the final formulation was achieved by dispersing air in the molten system through melt foaming; internal structure was assessed by microCT, and physicochemical properties by PXRD and DSC. Cytotoxicity was measured in Caco-2 cells using MTT and Neutral Red assays, and transcellular transport was also studied. Results: Based on these results, a homogeneous gastric floating system was developed. We observed an advantageous cytotoxic profile and increased bioavailability. Conclusions: Overall, we were able to create a self-emulsifying gastroretentive formulation displaying extended release and gastric retention with a low amount of cost-efficient excipients. Full article

This work presents an innovative application of the sugar templating method to fabricate highly porous floating tablets based on cellulose derivatives for gastroretentive drug delivery systems (GRDDS). Ethyl cellulose (EC) and hydroxypropyl methylcellulose (HPMC) were utilized to develop formulations that optimize porosity, buoyancy, and drug release. Among the tested formulations, E₁₀H₅/CPM, consisting of 10% w/w EC and 5% w/w HPMC loaded with chlorpheniramine maleate (CPM), exhibited the most favorable properties, including high porosity (94.4%), uniform pore distribution, immediate buoyancy, and over 24 h of floating time. E₁₀H₅/CPM tablets demonstrated superior drug release performance compared to an EC-only formulation (E₁₀/CPM), attributed to the presence of HPMC, which facilitated improved hydration and diffusion. The in vitro release study showed that E₁₀H₅/CPM achieved a cumulative release of 79.01% over 72 h, following a Fickian diffusion mechanism. However, a limitation was noted in drug loading, with E₁₀H₅/CPM incorporating 6.40 mg of CPM, compared to 8.72 mg in E₁₀/CPM. Future work should focus on enhancing drug load and further optimizing polymer composition to improve the release profile. Overall, this study underscores the potential of sugar templating in developing cost-effective, scalable floating tablet formulations for improved gastric retention and localized drug delivery. Full article

Background/Objectives: This study aimed to develop gastroretentive tablets based on mucoadhesive–floating systems with encapsulated gentian (Gentiana lutea, Gentianaceae) root extract to overcome the low bioavailability and short elimination half-life of gentiopicroside, a dominant bioactive compound with systemic effect. The formulation also aimed to promote the local action of the extract in the stomach. Methods: Tablets were obtained by direct compression of sodium bicarbonate (7.5%) and solid lipid microparticles (92.5%), which were obtained with lyophilizing double emulsions. A quality by design (QbD) was employed to evaluate the impact of formulation factors and processing parameters on emulsion viscosity, powder characteristics (moisture content, encapsulation efficiency, flowability), and tablet characteristics (floating lag time, gentiopicroside release, and assessment of dispersibility during in vitro dissolution). Results: The trehalose content and high-shear-homogenization (HSH) time of primary emulsion were critical factors. Trehalose content positively influenced emulsion viscosity, moisture content, floating lag time, encapsulation efficiency, and the release rate of gentiopicroside. HSH time positively affected powder stability and negatively gentiopicroside release. The selected powder had a high gentiopicroside encapsulation efficiency (95.13%), optimal stability, and good flowability. The developed tablets exhibited adequate floating lag time (275 s), mucoadhesive properties, and gentiopicroside biphasic release (29.04% in 45 min; 67.95% in 6 h). Furthermore, the optimal tablet formulation remained stable for 18 months and was primarily digested by duodenal enzymes. Conclusions: Dual-mechanism gastroretentive tablets with encapsulated gentian root extract were successfully developed. The in vitro digestion study demonstrated that the optimal formulation effectively resisted gastric enzymes, ensuring the release of its contents in the small intestine, even in the case of premature gastric evacuation. Full article

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. Full article

Gastroretentive drug delivery systems (GRDDSs) have gained substantial attention in the last 20 years due to their ability to retain the drug in the stomach for an extended time, thus promoting an extended release and high bioavailability for a broad range of active pharmaceutical ingredients (APIs) that are pH-sensitive and/or have a narrow absorption window. The currently existing GRDDSs include floating, expanding, mucoadhesive, magnetic, raft-forming, ion-exchanging, and high-density systems. Although there are seven types of systems, the main focus is on floating, expanding, and mucoadhesive systems produced by various techniques, 3D printing being one of the most revolutionary and currently studied ones. This review assesses the newest production technologies and briefly describes the in vitro and in vivo evaluation methods, with the aim of providing a better overall understanding of GRDDSs as a novel emerging strategy for targeted drug delivery. Full article

Curcumin and resveratrol are polyphenolic compounds that have been shown to exhibit synergistic therapeutic properties including anti-inflammatory, anticancer, and antiulcer activities, which may be exploited for the treatment of gastric diseases. However, both compounds have poor aqueous solubility and rapid metabolism, resulting in a low oral bioavailability. In situ gelling, liquid formulations were developed to produce a gastroretentive, raft-forming delivery vehicle to improve bioavailability. Solid dispersions containing a mixture of curcumin and resveratrol with Eudragit^® EPO (Cur/Res-SD) were first prepared using solvent evaporation, to improve the solubility and dissolution of the compounds. Solid dispersions of a weight ratio of 1:10 curcumin/resveratrol to Eudragit^® EPO were subsequently incorporated into in situ gelling, liquid formulations based on the gelling polymers, sodium alginate (low viscosity and medium viscosity), pectin, and gellan gum, respectively. Calcium carbonate and sodium bicarbonate were included to produce carbon dioxide bubbles in the gel matrix, on exposure to gastric fluid, and to achieve flotation. Moreover, the calcium ions acted as a crosslinking agent for the hydrogels. Optimized formulations floated rapidly (<60 s) in simulated gastric fluid (pH = 1.2) and remained buoyant, resulting in the gradual release of more than 80% of the curcumin and resveratrol content within 8 h. The optimized formulation based on medium-viscosity sodium alginate exhibited enhanced cytotoxic activity toward human gastric adenocarcinoma cell lines (AGS), compared with unformulated curcumin and resveratrol compounds, and increased anti-inflammatory activity against RAW 264.7 macrophage cells compared with the NSAID, indomethacin. These findings demonstrate that in situ gelling, liquid formulations, loaded with a combination of curcumin and resveratrol in the form of solid dispersions, show potential as gastroretentive delivery systems for local and systemic effects. Full article

Three-dimensional printing has revolutionized drug manufacturing and has provided a solution to the limitations associated with the conventional manufacturing method by designing complex drug delivery systems with customized drug release profiles for personalized therapies. The present investigation aims to design a gastric floating tablet with prolonged gastric floating time and sustained drug release profile. In the present study, a gastro retentive floating device (GRFD) was designed and fabricated using a fused deposition modelling (FDM)-based 3D printing technique. This device acts as a multifunctional dosage form exhibiting prolonged gastric retention time and sustained drug release profile with improved oral bioavailability in the upper gastrointestinal tract. Commercial polyvinyl alcohol (PVA) and polylactic acid (PLA) filaments were used to design GRFD, which was comprised of dual compartments. The outer sealed compartment acts as an air-filled chamber that imparts buoyancy to the device and the inner compartment is filled with a commercial propranolol hydrochloride immediate-release tablet. The device is designed as a round-shaped shell with a central opening of varying size (1 mm, 2 mm, 3 mm, and 4 mm), which acts as a drug release window. Scanning electron microscope (SEM) images were used to determine morphological characterization. The in vitro buoyancy and drug release were evaluated using the USP type II dissolution apparatus. All the designed GRFDs exhibit good floating ability and sustained drug release profiles. GRFDs fabricated using PLA filament show maximum buoyancy (>24 h) and sustained drug release for up to 10 h. The floating ability and drug release from the developed devices were governed by the drug release window opening size and the filament material affinity towards the gastric fluid. The designed GRFDs show great prospects in modifying the drug release characteristics and could be applied to any conventional immediate-release product. Full article

Sangelose^® (SGL) is a novel hydroxypropyl methylcellulose (HPMC) derivative that has been hydrophobically modified. Due to its high viscosity, SGL has the potential as a gel-forming and release-rate-controlled material for application in swellable and floating gastroretentive drug delivery systems (sfGRDDS). The aim of this study was to develop ciprofloxacin (CIP)-loaded sfGRDDS tablets comprised of SGL and HPMC in order to extend CIP exposure in the body and achieve optimal antibiotic treatment regimes. Results illustrated that SGL-HPMC-based sfGRDDS could swell to a diameter above 11 mm and showed a short floating lag time (<4 s) and long total floating time (>24 h) to prevent gastric emptying. In dissolution studies, CIP-loaded SGL-HPMC sfGRDDS demonstrated a specific biphasic release effect. Among the formulations, the SGL/type-K HPMC 15,000 cps (HPMC 15K) (50:50) group exhibited typical biphasic release profiles, with F4-CIP and F10-CIP individually releasing 72.36% and 64.14% CIP within 2 h dissolution, and sustaining release to 12 h. In pharmacokinetic studies, the SGL-HPMC-based sfGRDDS demonstrated higher C_max (1.56–1.73 fold) and shorter T_max (0.67 fold) than HPMC-based sfGRDDS. Furthermore, SGL 90L in GRDDS indicated an excellent biphasic release effect and a maximum elevation of relative bioavailability (3.87 fold). This study successfully combined SGL and HPMC to manufacture sfGRDDS that retain CIP in the stomach for an optimal duration while improving its pharmacokinetic characteristics. It was concluded that the SGL-HPMC-based sfGRDDS is a promising biphasic antibiotic delivery system that can both rapidly achieve the therapeutic antibiotic concentration and maintain the plasma antibiotic concentration for an extended period to maximize antibiotic exposure in the body. 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

The convenient and highly compliant route for the delivery of active pharmaceutical ingredients is the tablet. A versatile platform of tablets is available for the delivery of therapeutic agents to the gastrointestinal tract. This study aimed to prepare gastro retentive drug delivery floating tablets of silymarin to improve its oral bioavailability and solubility. Hydroxypropyl methylcellulose (HPMCK4M and HPMCK15), Carbopol 934p and sodium bicarbonate were used as a matrix, floating enhancer and gas generating agent, respectively. The prepared tablets were evaluated for physicochemical parameters such as hardness, weight variation, friability, floating properties (floating lag time, total floating time), drug content, stability study, in vitro drug release, in vivo floating behavior and in vivo pharmacokinetics. The drug–polymer interaction was studied by Differential Scanning Calorimetry (DSC) thermal analysis and Fourier transform infrared (FTIR). The floating lag time of the formulation was within the prescribed limit (<2 min). The formulation showed good matrix integrity and retarded the release of drug for >12 h. The dissolution can be described by zero-order kinetics (r² = 0.979), with anomalous diffusion as the release mechanism (n = 0.65). An in vivo pharmacokinetic study showed that Cmax and AUC were increased by up to two times in comparison with the conventional dosage form. An in vivo imaging study showed that the tablet was present in the stomach for 12 h. It can be concluded from this study that the combined matrix system containing hydrophobic and hydrophilic polymers min imized the burst release of the drug from the tablet and achieved a drug release by zero-order kinetics, which is practically difficult with only a hydrophilic matrix. An in vivo pharmacokinetic study elaborated that the bioavailability and solubility of silymarin were improved with an increased mean residence time. Full article

Three-dimensional printing (3DP) technology enables an important improvement in the design of new drug delivery systems, such as gastroretentive floating tablets. These systems show a better temporal and spatial control of the drug release and can be customized based on individual therapeutic needs. The aim of this work was to prepare 3DP gastroretentive floating tablets designed to provide a controlled release of the API. Metformin was used as a non-molten model drug and hydroxypropylmethyl cellulose with null or negligible toxicity was the main carrier. High drug loads were assayed. Another objective was to maintain the release kinetics as robust as possible when varying drug doses from one patient to another. Floating tablets using 10–50% w/w drug-loaded filaments were obtained by Fused Deposition Modelling (FDM) 3DP. The sealing layers of our design allowed successful buoyancy of the systems and sustained drug release for more than 8 h. Moreover, the effect of different variables on the drug release behaviour was studied. It should be highlighted that the robustness of the release kinetics was not affected by varying the internal mesh size, and therefore the drug load. This could represent a step forward in the personalization of the treatments, a key advantage of 3DP technology in the pharmaceutical field. Full article

Overactive bladder (OAB) is a symptomatic complex condition characterised by frequent urinary urgency, nocturia, and urinary incontinence with or without urgency. Gabapentin is an effective treatment for OAB, but its narrow absorption window is a concern, as it is preferentially absorbed from the upper small intestine, resulting in poor bioavailability. We aimed to develop an extended release, intragastric floating system to overcome this drawback. For this purpose, plasticiser-free filaments of PEO (polyethylene oxide) and the drug (gabapentin) were developed using hot melt extrusion. The filaments were extruded successfully with 98% drug loading, possessed good mechanical properties, and successfully produced printed tablets using fused deposition modelling (FDM). Tablets were printed with varying shell numbers and infill density to investigate their floating capacity. Among the seven matrix tablet formulations, F2 (2 shells, 0% infill) showed the highest floating time, i.e., more than 10 h. The drug release rates fell as the infill density and shell number increased. However, F2 was the best performing formulation in terms of floating and release and was chosen for in vivo (pharmacokinetic) studies. The pharmacokinetic findings exhibit improved gabapentin absorption compared to the control (oral solution). Overall, it can be concluded that 3D printing technology is an easy-to-use approach which demonstrated its benefits in developing medicines based on a mucoadhesive gastroretentive strategy, improving the absorption of gabapentin with potential for the improved management of OAB. Full article

Background: Antihypertensive drug telmisartan (TEL) belongs to BCS class II, which is characterized by low water solubility and, consequently, low oral bioavailability. Gastroretentive systems may overcome the problems associated with low solubility of TEL and incomplete absorption by localizing the drug release in the stomach. The purpose of this study was to prepare TEL-loaded, oil-entrapped, floating alginate beads with the intent of enhancing the oral bioavailability of TEL for the treatment of hypertension. Methods: For the formulation and optimization of seventeen formulations of TEL-loaded oil-entrapped floating alginate beads, a central composite design was utilized. The concentration of sodium alginate (X1), the concentration of cross-linker (X2), and the concentration of sesame oil (X3) served as independent variables, whereas the entrapment efficiency (Y1), in vitro buoyancy (Y2), and drug release Q6h (Y3) served as dependent variables. Using the emulsion gelation method and calcium chloride as the cross-linking agent, different formulations of TEL alginate beads were produced. All formulations were evaluated for their entrapment efficiency percentage, in vitro buoyancy, and in vitro drug release. The optimal formulation of TEL alginate beads was prepared with and without oil and evaluated for entrapment efficiency percentage, in vitro buoyancy, swelling ratio, average size, and in vitro drug release. Using scanning electron microscopes, the surface morphology was determined. Using IR spectroscopy, the compatibility between the ingredients was determined. In vivo evaluation of the optimized formulation in comparison to the free TEL was done in hypertension-induced rats, and the systolic blood pressure and all pharmacokinetic parameters were measured. Results: The prepared beads exhibited a high entrapment efficiency percentage, in vitro buoyancy, and prolonged drug release. TEL was compatible with other ingredients, as approved by IR spectroscopy. The prepared TEL beads were spherical, as shown by the SEM. The relative bioavailability of TEL-loaded oil-entrapped beads was 222.52%, which was higher than that of the pure TEL suspension. The prepared TEL beads formulation exhibited a higher antihypertensive effect for a prolonged time compared to pure TEL suspension. Conclusions: It can be concluded that this innovative delivery method of TEL-loaded oil-entrapped beads is a promising tool for enhancing drug solubility and, thus, oral bioavailability and therapeutic efficacy, resulting in enhanced patient compliance. Furthermore, the in vivo study confirmed the formulation’s extended anti-hypertensive activity in animal models. Full article

A floating tablet system containing thiamine hydrochloride, a model drug with a narrow absorption window, was evaluated. The tablet was found to have a floating lag time of less than 30 s with a sustained drug release over 12 h during in vitro dissolution studies. The gastro-retentive property of the tablet in relation to the bioavailability of thiamine was determined in healthy human volunteers using gamma scintigraphy under fasted and fed conditions. The gastro-retentive time of the floating tablet could be prolonged up to 10 h under the fed state, compared to about 1.8 h in the fasted state. The prolonged gastric retention under the fed state resulted in a 2.8-fold increase in oral bioavailability of thiamine compared to that of the fasted state. There was also a 1.4-fold increase in thiamine absorption compared to that of a conventional immediate release tablet in the fed state. In the fasted state, the extent of thiamine absorption from the floating tablet was only about 70% of that absorbed from the immediate release tablet. Thus, to achieve a better performance, such floating tablet systems should be administered under a fed condition, to prolong the gastric retention time. Full article

An increase in resistance to key antibiotics has made the need for novel treatments for the gastric colonization of Helicobacter pylori (H. pylori) a matter of the utmost urgency. Recent studies tackling this topic have focused either on the discovery of new compounds to ameliorate therapeutic regimes (such as vonoprazan) or the synthesis of gastroretentive drug delivery systems (GRDDSs) to improve the pharmacokinetics of oral formulations. The use of semi-interpenetrating polymer networks (semi-IPNs) that can act as super-porous hydrogels for this purpose is proposed in the present work, specifically those displaying low ecological footprint, easy synthesis, self-floating properties, high encapsulation efficiency for drugs such as amoxicillin (AMOX), great mucoadhesiveness, and optimal mechanical strength when exposed to stomach-like fluids. To achieve such systems, biodegradable synthetic copolymers containing acid-labile monomers were prepared and interpenetrated with guar gum (GG) in a one-pot polymerization process based on thiol-ene click reactions. The resulting matrices were characterized by SEM, GPC, TGA, NMR, and rheology studies, and the acidic hydrolysis of the acid-sensitive polymers was also studied. Results confirm that some of the obtained matrices are expected to perform optimally as GRDDSs for the sustained release of active pharmaceutical ingredients at the gastrointestinal level, being a priori facilitated by its disaggregation. Therefore, the optimal performance of these systems is assessed by varying the molar ratio of the labile monomer in the matrices. Full article