Gastroretentive Delivery System Research Articles

Simultaneous Delivery of Curcumin and Resveratrol via In Situ Gelling, Raft-Forming, Gastroretentive Formulations.

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.

DEVELOPMENT AND EVALUATION OF FLOATING BEADS OF BACLOFEN AS A GASTRORETENTIVE DOSAGE FORM

Gastro retentive delivery systems are designed to be retained in the stomach for a prolonged time and release their active ingredients and thereby enable sustained and prolonged input of the drug to the upper part of the gastrointestinal (GI) tract. The goal of any drug delivery system is to provide a therapeutic amount of drug to proper site in the body to achieve promptly and then maintain a desired drug concentration. Baclofen is a gamma-aminobutyric acid (GABA) agonist used as a skeletal muscle relaxant used for the relief of painful and uncomfortable muscle spasms caused by a variety of conditions. Twelve different formulation of Baclofen floating beads were successfully developed using emulsion solvent diffusion method. The beads had good yield and showed high, drug entrapment efficiency. The flow properties of beads were within the acceptable range and therefore would be easily filled into capsules. Study concludes successfully delivery of Baclofen by the means of floating beads.

Design and Development of Esomeprazole Loaded Polymeric Microballons as A Gastroretentive Delivery System

Design and Development of Esomeprazole Loaded Polymeric Microballons as A Gastroretentive Delivery System

Polymeric Excipients in the Technology of Floating Drug Delivery Systems.

The combination of targeted transport and improvement of the release profile of the active pharmaceutical ingredient (API) is a current trend in the development of oral medicinal products (MP). A well-known way to implement this concept is to obtain floating gastroretentive delivery systems that provide a long stay of the dosage form (DF) on the surface of the stomach contents. The nomenclature of excipients (Es) of a polymeric nature used in the technology of obtaining floating drug delivery systems (FDDS) is discussed. Based on the data presented in research papers, the most widely used groups of polymers, their properties, and their purpose in various technological approaches to achieving buoyancy have been determined. In addition, ways to modify the release of APIs in these systems and the Es used for this are described. The current trends in the use of polymers in the technology of floating dosage forms (FDF) and generalized conclusions about the prospects of this direction are outlined.

Development of Lipid-Based Gastroretentive Delivery System for Gentian Extract by Double Emulsion-Melt Dispersion Technique.

Gentian (Gentiana lutea L., Gentianaceae) root extract (GRE) is used for the treatment of gastrointestinal disorders. However, its bioactive potential is limited in conventional forms due to the low bioavailability and short elimination half-life of the dominant bioactive compound, gentiopicroside. The aim of study was to encapsulate GRE in the lipid-based gastroretentive delivery system that could provide high yield and encapsulation efficiency, as well as the biphasic release of gentiopicroside from the tablets obtained by direct compression. Solid lipid microparticles (SLM) loaded with GRE were prepared by freeze-drying double (W/O/W) emulsions, which were obtained by a multiple emulsion–melt dispersion technique, with GRE as the inner water phase, Gelucire® 39/01 or 43/01, as lipid components, with or without the addition of porous silica (Sylysia® 350) in the outer water phase. Formulated SLM powders were examined by SEM and mercury intrusion porosimetry, as well as by determination of yield, encapsulation efficiency, and flow properties. Furthermore, in vitro dissolution of gentiopicroside, the size of the dispersed systems, mechanical properties, and mucoadhesion of tablets obtained by direct compression were investigated. The results have revealed that SLM with the macroporous structure were formulated, and, consequently, the powders floated immediately in the acidic medium. Formulation with porous silica (Sylysia® 350) and Gelucire® 43/01 as a solid lipid was characterized with the high yield end encapsulation efficiency. Furthermore, the mucoadhesive properties of tablets obtained by direct compression of that formulation, as well as the biphasic release of gentiopicroside, presence of nanoassociates in dissolution medium, and optimal mechanical properties indicated that a promising lipid-based gastroretentive system for GRE was developed.

Advances in Functionalized Hybrid Biopolymer Augmented Lipid-based Systems: A Spotlight on Their Role in Design of Gastro Retentive Delivery Systems

Biopolymers are the polymers extracted from living organisms either from renewable plant or animal sources are gaining importance due to their better biodegradability, biocompatibility, less/no immunogenicity, less/no toxicity, and availability

Gastro Retentive Dosage Forms: An excellent carrier system for treatment of Peptic Ulcer

Peptic ulcer (gastric ulcer and duodenal ulcer) is very common chronic disorder of stomach which is mainly caused by the damage or impairment of stomach lining. Various factors such as pepsin, gastric acid, H. pylori, NSAIDs, prostaglandins, mucous, bicarbonate and blood flow to mucosa play an important role in causing peptic ulcer. In this review article, our main focus is on some important approaches (floating, bioadhesive, high density, swellable and magnetic systems) which are helpful in gastro retention of different dosage forms for treatment of peptic ulcer. Various factors such as composition of meal, nature of meal, gender, age, posture, size, shape, density of the dosage form influence the efficiency of above approaches. Currently, a lot of work is running to improve different types of gastro retentive delivery systems of a wide range of drugs and compensate the effects of above factors. In the future, it is anticipated that they will become of growing significance, finally leading to improved efficiency of various types of pharmacotherapies.

A Recent Update on Formulation and Development of Gastro-Retentive Drug Delivery Systems

Oral route has been the most convenient and accepted route of drug delivery. Owing to tremendous curative benefits of the oral controlled release dosage forms are being preferred as the interesting topic in pharmaceutical field to achieved improved therapeutics advantages. Gastro retentive drug delivery system is novel drug delivery systems which has an upper hand owing to its ability of prolonged retaining ability in the stomach and thereby increase gastric residence time of drugs and also improves bioavailability of drugs. Concept of novel drug delivery system arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations. In this context, various gastro retentive drug delivery systems have been used to improve the therapeutic efficacy of drugs that have a narrow absorption window, are unstable at alkaline pH, are soluble in acidic conditions, and are active locally in the stomach. Concept of novel drug delivery system arose to overcome the certain aspect related to physicochemical properties of drug molecule and the related formulations. Various approaches are currently used including gastro retentive floating drug delivery systems, swelling and expanding system, polymeric bio adhesive systems, modified shape systems, high density system and other delayed gastric emptying devices. Moreover, future perspectives on this technology are discussed to minimize the gastric emptying rate in both the fasted and fed states. The present review briefly addresses the physiology of the gastric emptying process with respect to floating drug delivery systems. The purpose of this review is to bring together the recent literature with respect to the method of preparation, and various parameters affecting the performance and characterization of floating microspheres. Attempt has been made to summarize important factors controlling gastro retentive drug delivery systems. Overall, this review may inform and guide formulation scientists in designing the gastro retentive drug delivery system.

Glutaraldehyde-crosslinked chitosan-polyethylene oxide nanofibers as a potential gastroretentive delivery system of nizatidine for augmented gastroprotective activity

Nizatidine (NIZ), a histamine H2-receptor antagonist, is soluble and stable in the stomach, however, it exhibits a short half-life and a rapid clearance. Therefore, chitosan (CS) and polyethylene oxide (PEO) nanofibers (NFs) at different weight ratios were prepared by electrospinning and characterized. The selected uncrosslinked and glutaraldehyde-crosslinked NFs were investigated regarding floating, solid-state characteristics, in vitro release, and in vitro cytotoxicity. The cytoprotective activity against ethanol-induced gastric injury in rats was evaluated through macroscopical, histopathological, immunohistochemical, and oxidative stress examinations. NFs based on 8:2 CS:PEO exhibited the smallest diameter (119.17 ± 22.05 nm) and the greatest mucoadhesion (22.82 ± 3.21 g/cm2), so they were crosslinked with glutaraldehyde. Solid-state characterization indicated polymers interaction, a successful crosslinking, and NIZ dispersion in NFs. Crosslinking maintained swollen mats at pH 1.2 (swelling% = 29.47 ± 3.50% at 24 h), retarded their erosion at pH 6.8 (swelling%= 84.64 ± 4.91% vs. 25.40 ± 0.79% for the uncrosslinked NFs at 24 h), augmented the floating up to 24 h vs. 10 min for the uncrosslinked NFs at pH 1.2 and prolonged the drug release (%drug released ≥ 93% at 24 h vs. 4 and 5 h for the uncrosslinked NFs at pHs 1.2 and 6.8, respectively). The viability of Caco-2 cells ≥ 86.87 ± 6.86% revealed NFs biocompatibility and unreacted glutaraldehyde removal. Crosslinking of 8:2 CS:PEO NFs potentiated the antiulcer activity (38.98 vs. 8.67 for the uncrosslinked NFs) as well as it preserved the gastric wall architecture, COX-2 expression, and oxidative stress markers levels of the normal rats.

A Mini Review on Mucoadhesion

The concept of mucoadhesion was started in early 1980’s with the aim of controlled delivery of drugs. Mucoadhesion is simply defined as the adhesion between two materials, in which one is the mucosal surface and the another one is the mucoadhesive dosage form. In the recent decades, mucoadhesive drug delivery system draw the attention in the gastroretentive delivery system. Mucoadhesive drug delivery systems interact with the mucus layer covering the mucosal epithelial surface, and mucin molecules and increase the residence time. Mucoadhesive dosage forms are designed to increase the retention of the drug/dosage form at the application site, to provide a controlled release of drug for increased curative consequence. The medications which have local action or those which have maximum absorption in gastrointestinal tract require increased duration of stay in GIT. Mucoadhesive drug delivery systems were prepared by using either natural or synthetic polymers, which is interacting with the mucous layer and used to prevail over the physiological barriers for extended drug delivery. The mucoadhesive ability of a dosage form is depending upon variety of factors, such as the nature of the mucosal tissue and the physicochemical properties of the polymeric formulation. This review article aims to provide an overview of the various theories of mucoadhesion, properties of mucoadhesive materials, methods to study the mucoadhesion, and finally various mucoadhesive dosage forms.

Domperidone resinate complex as new formulation for gastroretentive drug delivery

PurposeThe present work aims to develop and characterize domperidone resinate complex to be loaded into a gastroretentive delivery system. The formed resinate complex will be used to control the drug release in the stomach from inside the gastroretentive delivery system. MethodsResinate complexes were formulated by a simple aqueous binding method. Screening of different types of resins was carried out. Domperidone binding study was tested at various drug and resin concentrations. Physicochemical characterizations were carried out to evaluate the prepared resinate complex. These studies included flow properties, in vitro drug release in simulated gastric fluid (SGF), Differential scanning calorimetry (DSC), Mass spectroscopy and XPRD evaluations. Also, the stability study of the selected resinate complex was conducted at 25 °C and 40 °C for up to one month. ResultsDomperidone and Dowex 50WX2 in a ratio of 1:3 have formed a resinate complex that has shown acceptable flow properties, thermal properties and short-term chemical stability at 25 °C and 40 °C. Domperidone release profile from resinate in SGF has shown slow controlled release characteristics. ConclusionThe domperidone stable complex with Dowex ion exchange resin has the potential for further development as gastroretentive drug delivery system as a mean of controlling the drug release.

Management of Type II Diabetes using Metformin- Loaded Microparticulate Gastroretentive Delivery Systems

Metformin is an oral anti-hyperglycemic derivative extensively used for the treatment of type II diabetes. Following oral administration, metformin exhibits an incomplete absorption and therefore repeated administrations of high doses of this drug are required for successful therapy due to its short biological half-life. For this, development of novel drug delivery systems for metformin might be useful to decrease the dosing frequency, to enhance its bioavailability, to reduce gastrointestinal adverse effects, and to be helpful for effective use of metformin in diabetes treatment. In this review, we present microparticulate gastroretentive delivery systems developed to enhance the oral bioavailability of metformin.

Self-inflating floating nanofiber membranes for controlled drug delivery.

Floating gastro-retentive delivery systems can prolong the gastric residence providing sustained drug release. In this study, we report on self-inflating effervescence-based electrospun nanofiber membranes embedding polyethylene oxide/sodium bicarbonate cast films. In this system, sodium bicarbonate results in an effervescence effect by creating carbon dioxide gas upon contacting an acidic gastric fluid, with the resulting gas bubbles being entrapped within the swollen network of nanofibers. Eudragit RL and RS polymers are utilized as a host material to manipulate release kinetics of incorporated drugs. Pramipexole, a common medication for chronic Parkinson's disease (PD), is used as a model drug. Uniform and bead-free nanofibers with diameters of~300nm were obtained. Although floating nanofibers initially exhibited high water contact angles (WCA), water droplets were quickly absorbed into the surface and the WCA decreased to~0° within 60s. Floating lag time, total floating time, swelling properties and drug release profiles were investigated both in a simulated gastric fluid (pH 1.2 buffer solution) and in a simulated intestinal fluid (pH 6.8 buffer solution) at 37°C. All floating nanofiber formulations began to float instantly with nearly zero floating lag time and did not sink into the solution even after 24h. By comparison, the same formulations without sodium bicarbonate cast films could not maintain continuous floating beyond 15min. The floating nanofiber pouches presented lower initial release of between 20 and 57 %, compared to that of non-floating nanofiber pouches (40-82% within 2h). Clearly, floating nanofibers reduced the initial burst release and provided sustained drug release. This demonstrates the potential to result in 'once-a-day' oral introduction of drugs that normally must be taken frequently. Effervescence-based floating nanofibers present a novel and promising prototype delivery system for the drug delivery in the upper gastro-intestinal (GI) tract.

Gastro Retentive Floating Drug Delivery System: An Overveiw

The purpose of writing this review on gastro retentive floating drug delivery systems (GRFDDS) was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. The GRFDDS are those type of systems which floats immediately upon contact with gastric fluids and currently promising the approach for increasing the bioavailability of drugs with absorption windows in stomach or upper small intestine and it also exhibit the low solubility at high pH values. In order to understand various physiological difficulties, we have summarized important factors for controlling gastric retention. Various attempts have been made to develop gastro retentive delivery systems i.e. high density, floating, bio-or mucoadhesive, expandable, unfold able, super porous hydrogel. This review also summarizes the in vitro techniques, in vivo studies to evaluate the performance floating drug delivery system (FDDS) which had been discussed by scientists to assess the efficiency and application of such systems. These types of above systems are useful for several problems encountered during the development of a pharmaceutical dosage form and the future potential of FDDS.

Fabrication of floating capsule-in- 3D-printed devices as gastro-retentive delivery systems of amoxicillin

Gastro-retentive drug delivery systems (GRDDS) provide prolonged drug release in the stomach for the treatment of some diseases located in the gastric area, and can improve patient compliance by reducing the required dosing frequency. In this study, floating 3D-printed devices combined with a commercial capsule of amoxicillin (Sia-Mox®) were developed for the treatment of H. Pylori infection. The floating 3D-printed devices (FPD) were fabricated using fused deposition modeling (FDM) 3D-printer with PVA filament followed by thermal crosslinking process. The morphology of the FPD was investigated by microscope. The water insolubilization, TGA and FT-IR were analyzed to confirm the successful crosslinking of the FPD. In vitro floating time and drug release in a simulated gastric fluid were determined using the USP dissolution apparatus II. The results showed that the floating time of the Sia-Mox® incorporated FPD was significantly longer than that of the conventional Sia-Mox® capsule, and that the floating time increased after the FPD was crosslinked. The optimal condition for the crosslinking of FPD was 140 °C for 6 h (FPD4). In vivo floating study in rabbit showed that the floating time of FPD4 was more than 10 h. The release of the drug from the Sia-Mox® in FPD4 fitted with the Higuchi model. Our results demonstrated that the development of FPD for GRDDS was successful, which the FPDs were able to float and prolong drug release.

Development of Gabapentin Expandable Gastroretentive Controlled Drug Delivery System

Expandable drug delivery systems are one of many gastroretentive delivery systems which have emerged during the last few years. Expandable systems are usually folded in a capsule and expand to dimensions greater than the pyloric sphincter upon contact with gastric fluid. This prevents them from being evacuated by gastric emptying. The main objective of developing such systems is to increase the residence time of a specific drug in stomach; controlling its release, increasing its bioavailability and decreasing its side effects and dosing frequency. An expandable gastroretentive drug delivery system containing Gabapentin was developed using experimental design (D-optimal reduced quadratic design). This system was able to unfold at stomach pH in less than 15 minutes and obtain a controlled release of 78.1 ± 4.7% in 6 hours following zero-order release kinetic model. It is rigid in stomach and its rigidity decreases at intestinal pH. FTIR analysis indicated the occurrence of hydrogen bonding in Gabapentin when present in the developed system, which might be responsible for the drug’s controlled release. XRD analysis indicated that Gabapentin physical properties changed from crystalline in the typical state to amorphous in the developed system.

Development of a gastroretentive delivery system for acyclovir by 3D printing technology and its in vivo pharmacokinetic evaluation in Beagle dogs.

Gastroretentive (GR) systems are designed to prolong gastric residence time to allow sustained absorption and improve the oral bioavailability of drugs with a narrow absorption window in the upper part of the gastrointestinal tract. The present study aimed to develop a GR system for acyclovir using 3D printing technology and evaluate its in vivo pharmacokinetics after oral administration in Beagle dogs. The system consisted of a gastro-floating device, which can float in the gastric fluid, prepared by a fused deposition modeling 3D printer and conventional acyclovir sustained-release (SR) tablet. The acyclovir SR tablet was inserted to the floating device to allow sustained release of the drug in the stomach. The buoyancy and sustained-release property of the developed GR system were determined using an in vitro dissolution test, in vivo pharmacokinetic study, and abdominal X-ray imaging in Beagle dogs. The in vivo dissolution profiles of the GR system were also predicted based on the in vivo pharmacokinetic data using a population pharmacokinetic (POP-PK) model. In the dissolution test, the sustained-release characteristic of the GR system was identified with a time corresponding to 80% dissolution (T80) of 2.52 h. Following oral administration of the GR system, the time to reach the maximum concentration (Tmax) of acyclovir was significantly prolonged, whereas the maximum concentration (Cmax) decreased and the area under the curve increased compared with those obtained after the administration of immediate-release and SR tablets, indicating prolonged absorption. By X-ray imaging, we showed that the developed GR system stayed in the stomach for more than 12 h. The POP-PK model successfully described the observed plasma concentration-time data and predicted the in vivo biphasic dissolution profiles of the GR system, which was significantly different from the in vitro dissolution. The developed GR system could be applied to various drugs and had great prospects in the design and development of novel controlled-release formulations.

FORMULATION AND EVALUATION OF BUOYANT TABLETS OF KETOCONAZOLE

Objective: The primary objective of the present work was to formulate the gastro-retentive delivery system of ketoconazole (ktz) for its extensive absorption in the stomach.&#x0D; Methods: The solubility and dissolution of antifungal ktz were reported to be higher in the stomach than in the intestinal pH conditions because of its dibasic pKa values 6.51 and 2.94. Thus the development of target buoyant tablets using Hydroxy Propyl Cellulose (HPC) and Xanthan gum (Xg) as polymers along with the effect of citric acid and sodium bicarbonate as an effervescent causing agent of floatation properties and drug release profile was investigated. The formulation optimization was carried out by using a central composite design using Design Expert software by taking HPC, Xanthan gum and sodium bicarbonate as independent variables and floating lag time, in vitro drug release profile as dependent variables respectively.&#x0D; Results: The optimized formulation of ktz buoyant tablets could be developed. The amount of HPC and Xg was found to significantly influence all in vitro response parameters. The results of pre-compression and post-compression parameters of all the formulations were found to be within the standard limits. The optimized formulation exhibited floating lag time of 160 secs with sustained drug release over a period of 12 h in simulated stomach pH condition.&#x0D; Conclusion: Buoyant tablets of ktz with sustained drug release over a period of 12 h in simulated stomach conditions for enhanced drug absorption could be successfully developed.

Oil-entrapped ranitidine HCl beads heal peptic ulcers via local and systemic mechanisms

Objective: Oral gastroretentive system is one of the site-specific drug delivery system, which is designed to be retained in upper GIT for a prolonged time. Ranitidine hydrochloride (RHCl), which is used frequently in treatment of peptic ulcer, is a suitable candidate for gastroretentive delivery systems. Dependently, floating oil-entrapped alginate beads of RHCl were developed and evaluated as an approach to site-specific delivery avoiding colonic degradation and enhancing both bioavailability and the proposed local effect.Methods: Different formulations of floating beads were suggested and randomized using 24 full factorial design. Optimized formulation was subjected for in vivo studies to measure the oral bioavailability and the healing effect of induced peptic ulcers.Results: Beads size ranged from 1.32 to 2.3 mm. All beads revealed excellent floating capabilities. Optimum formulation (F12) has entrapment efficiency of 70%, drug loading of 7% and 71% RHCl released after 6 h. SEM of F12 shows a grossly spherical structure with presence of oil droplets distributed throughout structure. AUC obtained from F12 was nonsignificantly higher than that of a commercial tablet. Signs of ulcer healing appeared clearly with F12 through appearance of granulation tissue, collagen fibers and newly formed blood vessels. Healing rate and extent obtained with a commercial tablet were less than F12. Quantitative analysis confirmed histopathological findings.Conclusion: Floating oil-entrapped beads are a promising approach for RHCl delivery to remain in stomach for a longer time ensuring site-specific delivery and consequently, enhancing local healing effect of peptic ulcers.

Polysaccharides based gastroretentive system to sustain piroxicam release: Development and in vivo prolonged anti-inflammatory effect

A gastro-retentive delivery system loaded with piroxicam with a bimodal release profile in gastrointestinal-tract was developed.Piroxicam is characterized by high oral absorption, long half-life, but its elimination is impaired in elderly patients. To overcome fluctuations in plasma levels, floating gastro-retentive gel-beads with sustained release properties were manufactured using prilling. Beads matrix was designed as a hollow/multipolymeric system based on alginate, ALM-pectin and hydroxypropilmethylcellulose.This research studied variables able to affect particles micromeritics, hollow inner structure, floating properties and drug-release profiles in gastro-intestinal tract. The gastro-retentive formulation (F4) acted as a floating-system able to provide the desired bimodal drug-release pattern controlling and delaying in vitro piroxicam release. The in vivo anti-inflammatory activity of the floating beads resulted prolonged up to 48 h, compared to standard piroxicam.This formulation may be proposed to treat chronic inflammatory-diseases in elderly patients, needing a rapid onset of drug action followed by a maintenance dose.