Gastroretentive Drug Delivery System Research Articles

Gastroretentive Swellable and Floating Systems: An Innovative and Promising Strategy for Drug Delivery-A Comprehensive Review

Gastroretentive drug delivery systems (GRDDs) have emerged as an innovative and promising approach for enhancing the bioavailability and therapeutic efficacy of drugs with narrow absorption windows in the upper gastrointestinal tract (GIT). Among various GRDDs, swellable and floating systems have garnered significant attention due to their ability to prolong gastric residence time, improve drug dissolution, and facilitate sustained drug release (SDR). This comprehensive review provides a detailed exploration of the principles, mechanisms, and advancements in swellable and floating Gastroretentive systems. The key strategies, such as the use of hydrophilic polymers, gas-generating agents, and superporous hydrogels, are discussed. These systems offer benefits in treating conditions like peptic ulcers, gastroesophageal reflux disease, and infections, where prolonged localized drug action is desirable. A critical assessment of recent preclinical and clinical studies highlights the therapeutic potential of GRDDs in optimizing drug delivery for poorly soluble drugs and drugs with short half-lives. Challenges such as variability in gastric retention, potential toxicity of excipients, and patient-specific factors are also examined. It includes the outlining future trends in GRDDs, focusing on the incorporation of nanotechnology, 3D printing, and biocompatible materials to overcome existing limitations and further enhance therapeutic outcomes. This highlight of review article is initially introduction of GRDDs and their significance, mechanism and their classification of GRDDs, intermediately describe brief on swelling and floating GRDDs system with their application, lastly it describes the recent advances in patent, clinical trials and marketed products for GRDDs swellable and floating system. Keywords: Drug delivery; GRDDs; floating; swellable; gastroretentive; system; advance approach

A Comprehensive Review on Role of Natural Polymers in Gastro Retentive Drug Delivery System (GRDDS)

Abstract: This review is to present a general outline of potent & promising natural polymers (on which only slight research is done) along with their attributes & their pharmaceutical functions in the development of GRDDS (gastro retentive drug delivery system). Therefore, there is a need of more attention & focus on some of these natural polymers which are playing a crucial & indispensable role in the fabrication of GRDDS. Recent & current research trends shows that progressively natural polymers are replacing synthetic polymers in the fabrication of GRDDS as they are more safe, non-toxic, biodegradable, biocompatible, economical, regulatory acceptance, etc. Also, it has been noticed by the researchers that natural polymer due to their properties have successfully amplified gastric residence time, dissolution & bioavailability of the gastroretentive dosage forms.

Formulation and Evaluation of Gastroretentive Bilayer Tablets

Gastroretentive bilayer tablets were designed to prolong the gastric residence time after oral administration and to achieve immediate release of lansoprazole and controlled release floating layer of clarithromycin to treat gastric ulcers. Instant release layer has a combination of super disintegrating agents. A combination of effervescent mechanism is used. HPMC K5 was used as swelling polymer and citric acid, sodium bicarbonate as gas generating agent to reduce the floating lag time. Bilayer floating tablets were prepared with varying proportions of instant layer and sustained release floating approaches. The prepared formulations were evaluated for various tablet and floating parameters. Tablet properties were found to be within the limits according to procedures prescribed in USP. They had a floating lag time around 3-7 seconds and floating time more than 24 hours. The cumulative % drug release in simulated gastric fluids after 10 hours was 70% - 95%. The mechanism of drug release was analyzed by fitting the release data into various kinetic models. It was found that all the formulations best fit the Higuchi’s model. Keywords: Gastroretentive drug delivery system; Bilayer tables, Instant release layer, Floating layer, Lansoprazole, Clarithromycin.

Design and Evaluation of New Gel-Based Floating Matrix Tablets Utilizing the Sublimation Technique for Gastroretentive Drug Delivery.

A gel-based floating matrix tablet was formulated and evaluated using the sublimation technique to enhance gastroretentive drug delivery. Anhydrous theophylline was employed as the active pharmaceutical ingredient, combined with sublimation agents and hydroxypropyl methylcellulose as the gel-forming polymer. The resulting tablets exhibited high porosity, immediate floatation, and sustained buoyancy for over 8 h. Optimization of the floating behavior and drug release profiles was achieved by adjusting the viscosity of and hydroxypropyl methylcellulose and the concentration of sublimation agents, specifically ammonium carbonate and menthol. These agents were selected for their effectiveness in creating a porous structure, thus reducing tablet density and enhancing floatation. Higher HPMC viscosity resulted in increased floating force, slower drug release, and improved swelling properties due to a slower erosion rate. A critical assessment of the balance between tablet porosity, mechanical strength, and drug release kinetics indicates that ammonium carbonate provided superior tablet hardness and lower friability compared to menthol, favoring a controlled release mechanism. The release dynamics of theophylline were best described by the anomalous (non-Fickian) diffusion model, suggesting a combined effect of diffusion and erosion. This research advances the development of gastroretentive drug delivery systems, highlighting the potential of sublimation-based floating matrix tablets for sustained drug release.

Gastro-retentive drug delivery system of hypertension drug: Formulation and evaluation study

Introduction: Hypertension, a major global health concern, necessitates effective management through sustained drug delivery systems. Gastro-retentive drug delivery systems (GRDDS) offer a strategic advantage by prolonging the residence time of drugs in the stomach, thus enhancing therapeutic efficacy and patient adherence. This study aims to develop and evaluate a GRDDS for antihypertensive drugs to achieve extended gastric retention and controlled release. Methods: A GRDDS was formulated using a combination of hydrophilic and hydrophobic polymers to ensure buoyancy and extended gastric retention. The formulation process involved selecting optimal polymer concentrations and incorporating release-modulating agents. In vitro evaluations included buoyancy studies, swelling behavior analysis, and drug release kinetics under simulated gastric conditions. Additionally, in vivo studies were conducted to assess the system’s gastric retention and pharmacokinetic profile in an animal model. Conclusion: The developed GRDDS demonstrated effective gastric retention and a controlled release profile for the antihypertensive drug. In vitro results confirmed the system’s ability to maintain buoyancy and provide sustained drug release. In vivo studies supported these findings, showing improved drug bioavailability and stable plasma levels. This GRDDS represents a promising advancement in hypertension management, potentially enhancing therapeutic outcomes and patient compliance. Further research and clinical trials are recommended to validate these preclinical results and optimize the system for broader application.

Preparation and in vitro characterization of graphene oxide impregnated superporous hydrogel beads: an effective approach of gastro-retentive drug delivery system

ABSTRACT The remarkable properties of graphene oxide, a shining dynamo, opened new possibilities for delivering the drug. The present work aims to fabricate a graphene-based porous hydrogel system that fades its side effects and encourages its utilization as a drug carrier. Graphene oxide was impregnated in the polymeric matrix for gastro-retentive drug delivery. Porogen was added to create a superporous structure. The extrusion-dripping technique is used to fabricate low density, super porous, and floating hydrogel beads, which were considered a practical approach to target the drug in a controlled and sustained manner in the stomach. The fabricated graphene oxide impregnates superporous beads were characterized by physicochemical analysis, morphological parameters, PXRD, swelling study, drug-release pattern, and in-vitro floating ability. The homogenous nature of fabricated samples was analyzed by weight and size variation. Micrometric properties were estimated to calculate the density and flow ability of superporous beads. The stability and shelf life of prepared hydrogels were performed by accelerated stability analysis according to ICH guidelines. Doxorubicin was chosen as a model anticancer drug. The pi–pi stacking technique is responsible for a considerable loading of the drug onto graphene oxide (GO). However, the successful preparation of low-density graphene oxide impregnates superporous hydrogel beads shows excellent floating ability, thus making it a promising candidate for stomach targeting.

Exploring the Potential of Pectin for Gastro Retentive Drug Delivery Systems: From Orchard to Drug Delivery

Significant progress has been made in the field of gastroretentive drug delivery systems using natural polysaccharides. These improvements aim to improve the effectiveness and absorption of different medicinal agents. Pectin has received substantial attention in recent years due to its distinctive structural characteristics, abundant availability, biocompatibility, lack of toxicity, and wide range of applications. The global utilization of pectin in drug delivery systems has expanded significantly. Pectin is used to achieve flotation and mucoadhesive properties, which enhance gastric residence length and improve therapeutic effectiveness. The article aims to comprehensively examine the information on several pectin-based formulations for medication delivery that are designed to remain in the stomach for an extended period of time. Furthermore, this article emphasizes the diverse physicochemical and biological properties of pectin and modified pectin, as well as their prospective uses in numerous fields. This publication also presents the significant advantages, challenges, potential future developments, and patents on pectin-based gastroretentive drug delivery systems.

GASTRORETENTIVE EFFERVESCENT FLOATING TABLETS (GREFT) OF DRUGS ACTING ON CARDIOVASCULAR DISEASES

Incidences of Cardio Vascular Diseases (CVDs) are increasing in an alarming proportion in India. Conventional oral dosage forms cannot be retained in the stomach for long owing to gastric emptying. Moreover, drugs which are commonly employed in management of chronic CVDs either have reduced solubility at alkaline pH, undergo colonic degradation, exhibit site-specific absorption or varying bioavailability with combination therapy. Gastro-retentive drug delivery systems (GRDDS) are designed to overcome these challenges. Since 2006, Food and Drug Administration has approved only few GRDDS for treating CVDs. The aim of the present review is to summarize the outcomes of research carried on GRRDS with drugs for CVDs since last 15 y and comprehensive analysis of limitations of such studies due to which no product has been approved or commercialized in over last 18 y. Literature survey includes single unit, multi-particulate, monolayer and bilayer dosage forms with or without effervescence-inducing agents and made of natural and/or synthetic polymers like hydroxypropylmethyl cellulose, natural gums etc. Efforts have been made to compile in vitro buoyancy data such as floating lag time, total floating time, swelling index, release profile and release kinetics. Among various studies reported on monolayer and bilayer Gastro-Retentive Effervescent Floating Tablets, only 3 involved bioavailability studies in human volunteers. Toxicity studies in animals or stability studies are totally lacking. Observation with floating-type multi-particulate GRDDS is more disappointing. lack of safety, efficacy data, stability data, in vivo imaging studies and in vitro-in vivo correlation data might be actually responsible for lack of commercialization of any GRDDS for drugs acting on CVDs in 21st century.

Advanced interpenetrating polymer networks for innovative gastroretentive formulations targeting Helicobacter pylori gastric colonization

The escalating challenges of Helicobacter pylori-induced gastric complications, driven by rising antibiotic resistance and persistent cancer risks, underscore the demand for innovative therapeutic strategies. This study addresses this urgency through the development of tailored semi-interpenetrating polymer networks (semi-IPN) serving as gastroretentive matrices for amoxicillin (AMOX). They are biodegradable, absorb significant volume of simulated gastric fluid (swelling index > 360 %) and exhibit superporous microstructures, remarkable mucoadhesion, and buoyancy. The investigation includes assessment at pH 1.2 for comparative analysis with prior studies and, notably, at pH 5.0, reflecting the acidic environment in H. pylori-infected stomachs. The semi-IPN demonstrated gel-like structures, maintaining integrity throughout the 24-hour controlled release study, and disintegrating upon completing their intended function. Evaluated in gastroretentive drug delivery system performance, AMOX release at pH 1.2 and pH 5.0 over 24 h (10 %-100 %) employed experimental design methodology, elucidating dominant release mechanisms. Their mucoadhesive, buoyant, three-dimensional scaffold stability, and gastric biodegradability make them ideal for accommodating substantial AMOX quantities. Furthermore, exploring the inclusion of the potassium-competitive acid blocker (P-CAB) vonoprazan (VONO) in AMOX-loaded formulations shows promise for precise and effective drug delivery. This innovative approach has the potential to combat H. pylori infections, thereby preventing the gastric cancer induced by this pathogen.

Expanding the Manufacturing Approaches for Gastroretentive Drug Delivery Systems with 3D Printing Technology.

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.

FORMULATION AND EVALUATION OF LOSARTAN POTASSIUM MATRIX TABLETS BY USING DIFFERENT POLYMERS

The study aims to create a sustained release matrix tablet for Losartan potassium, an angiotensin II receptor antagonist, to improve patient compliance and maintain therapeutic blood or tissue levels for extended periods. The research investigates the role of novel semi-synthetic polymers and natural polymers in comparison to well-known release retarding agents. Gastroretentive drug delivery systems (GRDDS) are unique technologies designed to improve drug bioavailability and absorption by avoiding the first-pass effect. Losartan potassium, an angiotensin II receptor antagonist, has a bioavailability of 32% and a low elimination half-life, making it suitable for oral controlled release. The study utilized natural and synthetic polymers in matrix tablet preparation, concentration, drug particles size, additives, and excipients to modify drug release. The powder mixtures were tested for pre-compression parameters and post-compression parameters, and in-vitro dissolution studies showed good dissolution profiles for drug release. Formulations with higher concentrations and polymers sustained drug release for 24 hours. FT-IR Spectroscopy confirmed drug compatibility with polymers and other excipients KEYWORDS: matrix tablets, Losartan Potassium, flow properties, pre compression parameters post compression parameters, In-vitro dissolution.

A Complete Sojourn of Current Trends in Gastro-retentive Drug Delivery System: Recent Advances and Patent Survey.

The current work aims to provide a complete sojourn on gastro-retentive drug delivery system (GRDDS) along with formulation methods, polymer selection, and in vitro/ in vivo challenges with finished dosage forms. Ideally, a biopharmaceutical-hindered drug has a rapid clearance and erratic bioavailability due to its low aqueous solubility and permeability. Additionally, it also suffers from high first-pass metabolism and pre-systemic gut wall clearance. Gastro-retentive drug delivery systems have become an emerging technology where newer methodologies and scientific approaches have been used to provide the controlled release of drugs and provide a protective mechanism in the stomach. By the virtue of utilizing GRDDS as a dosage form, these formulations increase Gastroretention time (GRT) which prolongs the controlled release of the drug in the dosage form. GRDDS contribute to increased drug bioavailability and targeting at a site of action, which enhances therapeutic action and offers significant patient compliance. Furthermore, the present work also highlighted the critical role of polymers in favoring drug retention across GIT with the mechanism of gastro-retention and recommended concentration ranges. The emerging technology is also highlighted by the approved drug products and patented formulations in the recent decade which is depicted in a justified manner. GRDDS formulations have demonstrated clinical efficacy, which is supported by a compilation of patents for cutting-edge innovations in dosage forms that can be held in the stomach for an extended period of time.

Floating Microsphere as Gastro-Retentive Drug Delivery System

The goal of writing about floating microspheres is to gather the most recent research, paying particular attention to the basic idea of floatation as a means of achieving stomach retention. When a floating medication delivery system comes into touch with the stomach contents, it is expected to float for an extended period of time, improving the drug's bioavailability. Researchers and developers are currently working on the many floating formulations, which include films, tablets, powders, pills, capsules, granules, and capsules. Floating microspheres (FM) are becoming more and more important due to their wide range of applications in drug delivery to the stomach. These less dense floating microsphere, known as gastro retentive floating microspheres, have the capacity to float and disperse uniformly across the entire gastric fluid, reducing the likelihood of gastric emptying and guarantee a longer duration of drug release. Additionally, the floating microsphere improve patient compliance by reducing the frequency of dosing. FMs could be used to significantly improve the therapeutic efficacy of medications with short half-lives. We will go over the foundations of floating microspheres in this overview, as well as some contemporary uses for them.

Screening for Antinociceptive Action of Gastroretentive Drug delivery System of Tramadol hydrochloride in Mice

The floating drug delivery system is to avoid the problem of drug waste and to limit the frequency of administration. Here the drug Tramadol is being centrally acting opioid analgesic can be formulated as sustained release formulation by adopting the method gastroretentive drug delivery system through effervescent floating drug delivery system with different grades of polymer Hyperomellose. The Pharmacological activity on Mice by both Hot Plate and Tail Flick Methods also suggest that when the Tramadol Hcl increased with its dosage form shows significant Analgesic Activity in animals which shows a spontaneous dose dependent increase in Analgesic activity was found it shows that the dosage form deserve for designed method of gastroretentive drug delivery system.

ZINC PECTINATE-SESBANIA GUM-MEDIATED INTERPENETRATING POLYMER NETWORK-BASED MICROBEADS AS A CANDIDATE FOR FLOATING DRUG DELIVERY OF ESOMEPRAZOLE

This study aimed to develop esomeprazole-loaded zinc-pectinate-Sesbania gum floating microbeads, optionally supplemented with calcium silicate, as a gastro-retentive drug delivery system. The microbeads were produced using the ionic gelation method, with zinc acetate as the crosslinking agent, and were characterized through in vitro studies. The findings revealed that all formulations exhibited high drug encapsulation efficiency and sustained drug release profiles. Polymer ratios, calcium silicate incorporation, and the choice of low-density oils significantly influenced drug encapsulation efficiency and release kinetics. Notably, the B:6 batch, formulated with Sesbania gum and low methoxy pectin, demonstrated outstanding performance, releasing 95.89 ± 1.66% of the drug within 7 h, with a floating lag time of 1.18 ± 0.07 min, indicating promising in vitro gastro-retention capabilities. Analysis of P-XRD, FT-IR, SEM, and DSC data highlighted changes in crystallinity, drug–excipient compatibility, surface morphology, and thermal behavior of esomeprazole and esomeprazole-loaded microbeads. In conclusion, these floating microbeads represent a potential gastro-retentive drug delivery system, offering enhanced buoyancy and prolonged drug release, with potential therapeutic advantages for peptic ulcer management.

A recent update on gastro retentive drug delivery systems

Gastro retentive drug delivery systems (GRDDS) have garnered significant attention in recent years due to their potential to enhance therapeutic efficacy and patient compliance by prolonging gastric residence time and optimizing drug release kinetics. This review provides a comprehensive overview of the latest advancements in GRDDS, focusing on formulation strategies, design principles, and evaluation methodologies. Various approaches such as floating systems, mucoadhesive systems, expandable systems, and magnetic systems are discussed in detail, highlighting their mechanisms of action and applications in targeted drug delivery. Furthermore, recent innovations in materials science and formulation technologies have enabled the development of novel GRDDS with improved biocompatibility, stability, and controlled release profiles. The review also addresses challenges associated with GRDDS, including physiological variability, drug stability, and regulatory considerations, and proposes potential strategies to overcome these obstacles. Additionally, the clinical relevance of GRDDS in the treatment of various gastrointestinal disorders and their future prospects in personalized medicine and targeted therapy are explored. Overall, this review aims to provide valuable insights into the current state-of-the-art in GRDDS research and its implications for the advancement of drug delivery science.

Formulation and Evaluation of Microspheres Containing Mefenamic Acid by Inotropic Gelation Method

Drugs with a narrow absorption window in the gastrointestinal tract (GIT) will have poor absorption. For these drugs, gastro retentive drug delivery system offers the advantage in prolonging the gastric emptying time. Losartan potassium is prescribed to treat hypertension. The current study was projected to prepare a Losartan potassium gastro retentive drug delivery system (GRDDS) of floating tablets was planned to enhance the gastric residence time, thus prolong the drug release. Losartan potassium effervescent floating tablets were prepared by utilizing the direct impression method, using polymers such as HPMCk15, xanthan gum, microcrystalline cellulose, and Sodium carbonate, with lubricants such as magnesium stearate and talc. In the present study, sodium bicarbonate was incorporated as a gas generating agent. And combination of sodium bicarbonate and citric acid was found to achieve optimum in vitro buoyancy. Total eight formulations were designed and evaluated for pre-compression parameters known as angle of repose, bulk density, tapped density, Hausner's ratio, compressibility index, and post -compression parameters are uniformity of weight variation, hardness, thickness, friability, floating lag time, and in vitro dissolution investigation and FTIR along with DSC is carried out

New Trends in Emerging Novel Nanosponges Drug Delivery

Medical professionals have long had trouble delivering medications to the correct location in the body and controlling their release to prevent overdose. Nano-sponges are novel and complicated molecules, which have the ability to alleviate these challenges. Utilizing nano-sponges allows for precise drug delivery to the desired location. Nano-sponge technology gets better patient compliance by delivering drugs to strategic locations while also extending dosing intervals. Various drug delivery techniques, such as parenteral, transdermal, oral, and immunosuppressive drugs, involve Nano-sponges. In today's world, nanosponges are used in gastro-retentive drug delivery systems.

Design and Characterization of Hallow Porous Floating Microspheres of Favipiravir

The present investigation deals with the design and characterization of favipiravir floating microspheres for gastro retentive drug delivery system by employing 3² factorial design and also to investigate the main effects of different independent variables on microspheres that float. The emulsion solvent diffusion method was used to manufacture floating microspheres with Eudragit S 100 as the polymer. These microspheres will extend the release of the medicine, reducing the frequency of administration and the harmful effects caused by fluctuations in plasma concentration with conventional dosage forms. The main effect of independent variables like polymer Eudragit S 100 concentrations (50, 100, 150 mg) and stirring time (1, 2 and 3 hours) on the performance of microspheres. Formulated microspheres were characterized for responses including drug release, particle size, and entrapment efficiency and floating time. Based on the results of the responses, the optimized composition was arrived using the response surface method graphical and numerical optimization method using design of experiments (DoE) software. Then, the optimized formulation (OFES) was prepared and evaluated for the four responses compared with predicted values to find the validity of the selected model. The optimized formulation was further analyzed for drug-excipient compatibility by fourier-transform infrared (FTIR), differential scanning calorimetry (DSC), and also analyzed by X-ray diffraction (XRD), scanning electron microscope (SEM) analysis. Further zeta potential and micrometric properties were also observed. The results for the formulation FES 1 to 9 found were, that particles size ranged from 0.192 to 0.277 μm, entrapment efficiency ranged from 68.65 ± 1.9 to 76.25 ± 3.2%, percentage drug release range was from 89.25 ± 0.24 to 93.68 ± 0 .25%, and floating time range was from 12 to 23 hours. As per the design, OFES an optimized formulation fitted with the concentration of Eudragit S 100 of 139.1 mg and stirring time of 1-hour. Regarding the kinetic release, the responses were best fitted with Higuchi model of R² value of 0.9795 with kinetic mechanism of non-fickian diffusion with R² value of 0.9499, indicating good linearity. The combination of different variables and their effects on responses were investigated well using factorial design, and an optimized formulation was developed for favipiravir.

A Review on Gastro-Retentive Drug Delivery System

The aim of this review is to focus on the various gastro retentive approaches by investigate, compile, and present in most concise way, where the gastroprotective has gained immense popularity in the field of oral drug delivery. In the field of oral drug delivery gastro-retentive drug delivery play an important role. There are various types of GRDDS approaches which can be utilized to retain the dosage form in the stomach and release the drug slowly for an extended period of time. The various GRDDS approaches include high density, low density, mucoadhesive, expandable, magnetic systems and super porous hydrogel system. GRDDS has proved to be effective in both local and systemic actions to treat gastric or duodenal ulcers. Gastro-retentive drug delivery system can be utilized to prolong the residence time of delivery system in the stomach. Where the stomach and duodenum are separated by the pylorus, which has an important role in residence time of the ingested substances in the stomach. GRDDS can be used to overcome challenges related with conventional oral dosage forms. Keywords Gastro-retentive, GRDDS, Oral route, GIT, various approaches, floating system, non-floating system, bio adhesive system.