Gastric Retention Time Research Articles

EFFECT OF ZEIN ON CIPROFLOXACIN FLOATING TABLETS

Objective: This work was aimed to formulate and evaluate the effect of zein on Ciprofloxacin HCl floating tablets. According to previous studies, it was set up to be useful against bacteria i.e. Helicobacter pylori which leads to peptic ulcers. Thus, it is quite necessary to enhance the Gastric Retention Time for similar medicines. Methods: 12 different floating tablets of Ciprofloxacin HCl were formulated with wet granulation method with a rise in the concentration of zein. Further, all different formulations prepared were evaluated for different parameters i.e. pre-compression considerations, along with post-compression factors like weight variation, content uniformity, thickness, visual assessment, hardness, friability, buoyancy studies i.e. total floating time as well as floating lag time, swelling index, dissolution and drug release kinetics. Results: The F6 formulation was considered to be among finest formulation with appropriate hardness. It was found that with the increasing concentration of zein, the hardness of tablets was also increased. It showed TFT of more than 7 h, FLT of 310 sec, a swelling index time of 99.5 % in 4 hr, while drug release kinetics was found to follow Higuchi Model. Conclusion: Overall it was also found that HPMCK-100M is more effective as compared to HPMC-K15M and Zein has a major role in increasing the hardness of tablets. In the future, the investigation will be continued with the following studies: An in vivo study and a long-term stability study.

RETRACTED: Corrigendum to "mPEG-b-P(Glu-co-Phe) nanoparticles increase gastric retention time and gastric ulcer treatment efficacy of 20(S)-ginsenoside Rg3" [Biomed. Pharmacother. 146 (2022) 112608

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This correction has been retracted at the request of the Editors as it has been superseded by the retraction of the article it was intended to correct.

Design and synthesis of multifunctional polymeric micelles for targeted delivery in Helicobacter pylori infection

This study aimed to design a hyaluronic acid-based targeted, mucoadhesive and mucopenetrating drug delivery system encapsulating clarithromycin that would improve the drug residence time at H. pylori infection site. Clarithromycin-loaded thiolated hyaluronic acid-co-oleic acid (CLR-thHA-co-OA), clarithromycin-loaded ureido-conjugated thiolated hyaluronic acid-co-oleic acid (CLR-Ur-thHA-co-OA), and clarithromycin-loaded papain-modified ureido-conjugated thiolated hyaluronic acid-co- oleic acid (CLR-PAP-Ur-thHA-co-OA) nanomicelles were prepared by an ultra-sonication method. FTIR data confirmed the successful grafting of the different ligands to polymer backbone. XRD analysis revealed the amorphous nature of the polymer conjugate and drug inside nanomicelles. The critical micelle concentration of PAP-Ur-thHA-co-OA nanomicelles was found to be 15.85 µg/ml. Also, the sizes of nanomicelles were in the range of 210–258 nm. TEM analysis of CLR-PAP-Ur-thHA-co-OA nanomicelles confirmed their small size and spherical shape. Zeta potential and entrapment efficiency of CLR-PAP-Ur-thHA-co-OA nanomicelles were –24 mV and 80 ± 7.2% respectively. A sustained drug release pattern was observed for all types of prepared nanomicelles, whereas CLR-PAP-Ur-thHA-co-OA ones also displayed improved stability at acidic pH. Due to the presence of thiol groups in the polymer backbone, thiolated nanomicelles displayed important mucoadhesive properties. In this regard, FDA loaded PAP-Ur-thHA-co-OA nanomicelles showed the deepest penetration distance into the mucus by cleavage of mucoglycoproteins when compared to papain-unmodified nanomicelles. Fluorescent images of gastric tissues revealed the greater gastric retention time of nanomicelles compared to the free drug. As consequence, an enhanced in vitro efficacy against H. pylori was observed by nanomicelles. The in vivo clearance study showed an improved eradication of H. pylori by CLR-PAP-Ur-thHA-co-OA nanomicelles in comparison to other nanoformulations. Thus, the newly synthesized CLR-PAP-Ur-thHA-co-OA nanomicelles have the potential to be used as an efficient nanocarrier for H. pylori infection treatment due to their enhanced mucopenetration and mucoadhesion properties, as well as their improved stability and extended drug release.

Hypolipidemic effect of [6]-Gingerol-loaded Eudragit polymeric nanoparticles in high-fat diet-induced rats and Gamma scintigraphy evaluation of gastric-retention time

Nanocarriers for Alzheimer’s disease: Research and patent updateKamla Pathak, Shashi Kiran Mishra, Amit Porwal, Shiv Bahadur

HPMC Based Gastro Retentive Drug Delivery System of Effervescent Guifenesine Tablet for Dry Cough

Recent advances in Novel Drug Delivery System is aim to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for administration and to achieve better patient compliance. The controlled release drug delivery systems owning the capacity to be engaged in the stomach remains entitled as Gastro Retentive Drug Delivery Systems. One of the novel approaches for better patient compliance is floating drug delivery. Number of Gastro Retentive dosage forms has been designed to prolong gastric residence time. We are trying to overcome less gastric retention time and trying to reduce the dosing frequency. Gastroretentive systems can remain in the gastric region for several hours and hence significantly prolong the gastric residence time of drugs. Present study involves preparation of floating tablet of Guaifenesin with HPMC K10 and K15M floating tablet were designed to achieve the extended release or retention in GIT, which may result enhance in absorption and leads to increase in bioavaibility. The aim of the present work is to develop safe, effective HPMC based gastro retentive drug delivery system of effervescent Guaifenesin tablet for dry cough with extended release profile.

α-Amylase interaction with soluble fibre: Insights from diffusion experiment using fluorescence recovery after photobleaching (FRAP) and permeation experiment using ultrafiltration membrane

The modulation of starch hydrolysis by soluble fibres has been reported in both in vitro and in vivo conditions. Several mechanisms have been put forward including increased gastric retention time, and altered gastric digesta rheology affecting overall mass transfer (enzyme, substrate and hydrolysed products). The direct inhibition of amylase activity by soluble fibres has also been reported but little is known on the mechanisms. Herein we studied the interaction of porcine α-amylase with soluble fibre at low concentrations (to reduce the effect of viscosity). Two methods were performed, free diffusion of α-amylase in fibre solution using fluorescence recovery after photobleaching (FRAP) and forced elution of α-amylase in fibre solution through ultrafiltration membrane. The results provided the evidence that α-amylase potentially binds with soluble fibre. The degree of diffusion (D/D0 from FRAP experiments) by arabinoxylan and β-glucan at the concentration level of 0.05% and 0.5% w/v is significantly lower than that of pectin. The permeation experiment using ultrafilter membrane showed that the effect of arabinoxylan on intensity retention of fluorescence-labelled α-amylase was found to be in between β-glucan and pectin; pectin has a higher level of intensity retention than arabinoxylan and β-glucan. The results suggested that the interaction (primarily due to binding) could be more pronounced in neutral fibre (β-glucan and arabinoxylan) than the charged polymer (pectin). Overall, this short communication provided a new perspective of soluble fibre-enzyme interactions and experimental approaches for further research.

Design and Evaluation of Gastroretentive Multiple Units of Dipyridamole: in-vitro and in-vivo human studies

Objective: The pH dependent solubility of Dipyridamole was made to select as a model drug for the formulation of gastroretentive drug delivery system. Dipyridamole is highly soluble in acidic pH and as the pH increases the solubility of the drug decreases. The study was planned to formulate, characterize with in-vitro and in-vivo evaluation in human volunteers.
 Method: In this study floating mini matrix tablets of Dipyridamole was formulated using HPMC grade polymers by wet granulation method and prepared multiple units equivalent to one dose were filled in one 000 size empty gelatin capsule. The prepared multiple units were subjected to physical evaluation, in-vitro drug release, and stability studies as per ICH guidelines. The in-vivo radiographic studies were conducted for determining the residence time of dosage form in human subjects.
 Results: All the prepared batches showed good physical properties and in-vitro buoyancy. The optimized FD7 formulation remained buoyant for more than 12 h with drug release of more than 90% in 12 h. The drug release kinetics for optimized formulation FD7 followed a first order kinetics with non fickian mechanism. Formulation FD7 was selected as the best formulation based on the in-vitro characteristics and subjected for stability and in-vivo radiographic studies. These studies revealed that the multiple units were stable during the stability period and remained in the stomach for upto 6 h in human subjects.
 Conclusion: Based on in-vitro characteristics and in-vivo radiographic studies, formulation FD7 was concluded as the best formulation among others. Due to increase in gastric retention time, by choosing floating mini matrix tablets we can improve patient compliance and ensure better disease management.
 Keywords: Dipyridamole, Mini matrix tablets, In-vitro buoyancy, Stability studies Radiographic Studies

Formulation and evaluation of Lamivudinefloating tablets usingCarbopol & Eudragit S 100

Lamivudinecomes underclass II drugs according to BCS classification. It is poorly water-soluble drug. It has maximum solubility in pH 1.2 and therefore it will be beneficial to retain the drug in stomach for longer period of time for better absorption. Hence, it was found necessary to develop a gastric retentive dosage form containing Lamivudinein order to increase the gastric residence time to enhance its absorption and they’re by its oral bioavailability. Also, the slow release of the drug in stomach may avoid the stomach pain associated with immediate release of the drug. The ultimate aim was to design, develop and optimize the floating tablets containing Lamivudinein order to increase its gastric retention time for enhancing absorption in stomach as well as to produce a controlled release of the drug for a longer time using polymers such as Carbopol, and EudragitS100.

RETRACTED: mPEG-b-P(Glu-co-Phe) nanoparticles increase gastric retention time and gastric ulcer treatment efficacy of 20(S)-ginsenoside Rg3

Gastric ulcer (GU) belongs to gastric mucosal irritation and damage. 20(S)-ginsenoside Rg3 (Rg3) has shown anti-oxidant, antiinflammation, and tissue repair effects which are essential for GU treatment. However, the solubility of Rg3 is poor and low gastrointestinal absorption may limit its anti-ulcer effects. As a result, we aim to increase the gastric retention time and gastric absorption of Rg3 to achieve better GU treatment efficacy. The mPEG-b-P(Glu-co-Phe) nanoparticles loaded with Rg3 (Rg3-NPs) were developed. The characteristics of Rg3-NPs, including the morphology, diameter, and stability were analyzed. The Rg3 release profiles, gastric retention of Rg3, in vitro cytotoxicity, and pharmacokinetics of Rg3 were assessed. An alcohol-induced rats GU model was performed, and the rats were randomly separated into five treatment groups. Biochemical analysis, gross evaluation, histopathology, and immunohistochemical analysis were applied to further analyze the anti-ulcer effects of Rg3-NPs. Rg3-NPs were successfully prepared and the Rg3 release was pH sensitive. The gastric retention time of Rg3 is longer in Rg3-NPs group than that in Rg3 group. By slightly increasing nitric oxide (NO), obviously increasing epidermal growth factor (EGF), EGF receptor (EGFR), and superoxide dismutase (SOD), and decreasing endothelin-1 (ET-1) and nitric oxide synthase (NOS2), Rg3-NPs possess better GU treatment efficacy than Rg3. Rg3-NPs can increase gastric retention time and gastric absorption of Rg3 and promote its GU treatment efficacy.

Development and In-vitro, In-vivo Evaluation of Gastro Retentive Floating Tablets of Felodipine

Direct compression was utilized to develop the floating tablets, because of moisture sensitivity of Felodipine(FD), formulation included polymers such as CARBOPOL 934 & HPMC K 15 M. FD Floating tablets were designed to enhance drug availability by prolonging gastric retention time (GRT). Physical properties of tablets, such as hardness, thickness, friability, and weight variation as well as drug content and floating behaviors, were evaluated. Further, tablets were studied for In vitro drug release tests for 12 hours, while floating in the dissolution medium, In- vivo imaging studies were conducted. According to FTIR studies, there is no interaction between the drug and polymer, In-vitro buoyancy of tablets was 12 hours, the in-vitro dissolution release studies exhibited sustained and prolonged drug release profiles. The release mechanism from these tablets has been confirmed to be non-Fickian diffusion, which also fits the zero order and higuchi models, GRT of floating tablets was observed to be 4 hours. Based on in –vitro characteristics, F14 is the most efficient formulation. It was exploited in- vivo imaging studies by incorporating BaSo4, and the floating concept was used to boost gastric retention time, which was initially assumed.

A Novel Drug Delivery System: Floating Microspheres in the Development of Gastroretentive Drug Delivery System

Gastric emptying is a complicated process in the human body because it is very inconstant, resulting in ambiguous in vivo drug delivery system efficacy. To combat this variability, scientists have been working on developing a regulated medication delivery system with a long gastric residence period. This review article on gastroretentive drug delivery systems (GRDDS) focuses on numerous gastroretentive approaches that have recently emerged as a leading methodology in the field of site-specific orally administered controlled release drug administration. Gastroretentive medicines come in a variety of forms on the market, including tablets, granules, capsules, floating microspheres, laminated films, and powders. Floating microspheres are currently garnering more attention than previous techniques because of their benefits, which include more consistent drug absorption and a lower risk of local discomfort. The primary goal of this method is to increase gastric retention time in the GIT, which is defined as more than 12 hours in the stomach with an absorption window in the upper small intestine. Longer stomach retention improves bioavailability, reduces drug waste, and boosts solubility for medications that are less soluble in a high pH environment. The medicines are released into the stomach for a long time and consistently thanks to the floating microsphere systems. The current study compiles the most recent research on the techniques of production, characterization, and numerous aspects that impact the performance of floating microspheres for oral administration.

Floating Drug Delivery System: An Overview

In recent years scientific and technological advancements have been made in the research and development of rate-controlled oral drug delivery systems by overcoming physiological adversities, such as short gastric residence times (GRT) and unpredictable gastric emptying times (GET). Several approaches are currently utilized in the prolongation of the GRT, including floating drug delivery systems (FDDS), also known as hydrodynamically balanced systems (HBS), swelling and expanding systems, polymeric bioadhesive systems, modified-shape systems, high-density systems, and other delayed gastric emptying devices. The different strategies used in the development of FDDS by constructing the effervescent and noneffervescent type of floating tablets basis of which is buoyancy mechanism. FDDS is a method to deliver the drugs that are active locally with a narrow absorption window in the upper gastrointestinal tract, unstable in the lower intestinal environment, and possess low solubility with higher pH values. The recent developments in floating drug delivery systems are containing the physiological and formulation variables impacting on gastric retention time, approaches to formulating of single-unit and multiple-unit floating systems, and their classification and formulation aspects are discussed in detail. This review also summarizes evaluation parameters and application of floating drug delivery systems.

Floating micro particles of Stavudine: An Exceptional approach for Gastric retention and Sustainable drug action

Stavudine is synthetic analog of reverse transcriptase inhibitor possessing a short half-life of 0.8 to 1.5 hours. Therefore frequent administration of the medication is required which results in poor patient acceptability The following research work aims to prepare the floating microparticles of stavudine with an intention to increase the gastric retention time. Microparticles were prepared via emulsion solvent diffusion method utilizing Eudragit S 100 and Eudragit L 100 as the rate controlling polymers. The influence of these polymers and its compositions on various formulation parameters in addition to the in vitro release characteristics of the microspheres was investigated. The particle size of the prepared microparticles were found to be in the range of 108.25µm to 152.41µm. Free flowing particles which are spherical free flowing with a buoyancy ≥12 hour in the simulated gastric fluid were obtained. The drug content of the selected micro particles (F12) showed an encapsulation efficiency of up to 85.28±0.18%. In vitro release profiles of floating microspheres indicated a sustained drug release up to 14 hours. Thus, the present formulations could be a superior alternative to conventional oral therapy due to the sustained drug action.

Role of Floating Tablet In Oral Drug Delivery System

Oral delivery of drugs is the most commonly used mode of administration among all the routes explored for the systemic delivery of drugs by numerous different dosage forms. Many components play a significant role in the development of the drug delivery system. Differences in gastric physiology such as pH and motility, have been shown to have important effects on gastric retention time and drug delivery activity in both intra- and inter-subject variability. FDDS focuses on locally active drugs with a narrow stomach absorption window or a narrow upper small intestine absorption window, are unstable in the intestinal or colonic system, and have poor solubility at high pH values.For drugs that are locally active and have a narrow absorption window in the stomach or upper small intestine and which are unstable in the intestinal or colonic setting. FDDS is particularly interesting because it has a low solubility at high pH. The methods for constructing single and multiple unit floating structures. These systems can help with a variety of issues that arise during the production of a pharmaceutical dose.

Risk factors of postoperative pulmonary infection of gastric cancer and perioperative intervention measures

Gastric cancer is a common digestive system malignancy. Surgical operation is the main treatment of radical treatment for gastric cancer. Pulmonary infection is a common postoperative complication of gastric cancer. Because there is no clear and unified definition of pulmonary complications, the current researches show that the incidence of postoperative pulmonary infection of gastric cancer is about 1.8%-18.1%. The incidence of postoperative pulmonary infection will prolong the hospital stay, increase the cost of hospitalization, and even develop into respiratory failure leading to early postoperative death. There are many factors affecting postoperative pulmonary infection of gastric cancer, including age, smoking history, pulmonary function, pulmonary disease history, operation method, operation time, intraoperative bleeding volume, gastric tube retention time, postoperative lying time and so on. There are also many perioperative interventions. This article reviews the risk factors and perioperative interventions of postoperative pulmonary infection of gastric cancer.

A Review on Gastro-Retentive Floating Microspheres

The floating microsphere's purpose is to improve gastric retention time. Floating drug delivery systems are lower in bulk thickness than gastric juice and remain floating on gastric juice for a long period of time without impacting the gastric-emptying rate and increasing bioavailability. Gastro-retentive microspheres are particularly suitable for the continuous or late release of oral formulations with blending versatility to achieve various release patterns, low dose risk as a reproducible and short gastric retention time. The aim of this review is to address literature on the floating device, techniques, selection of suitable or inappropriate drug candidates for GRDDS, low density polymers used to swim over gastric fluid, processes, and floating microsphere assessment and application.
 Keywords: GRDDS, Floating system, Approaches, Polymer, Mechanism, Methods

Novel Swellable/Expandable Gastroretentive Floating Films of Gliclazide Folded in Capsule Shell for the Effective Management of Diabetes Mellitus: Formulation Development, Optimization and In Vitro Evaluation

Background: Gliclazide (GLZ) belongs to the second-generation of sulphonylureas; it is a drug of choice for the management of type II DM. It belongs to BCS Class II. The major site of drug absorption for GLZ is the stomach; it displays variation in the drug absorption rate and bioavailability due to the shorter gastric retention time. The floating mechanism gets affected when the gastric fluid level is not sufficiently higher, which ultimately obstructs the floating behavior, which is the major limitation of reported formulations. This limitation can be overcome by folding the film into the capsule shell dissolved in the gastric fluid and the film swells/expands to dimensions higher than pylorus sphincter (12mm), thus preventing its evacuation. Objective: The study aims to explore the floating mechanism in the design of films along with a tendency to expand by swelling and unfolding by utilizing a mixture of hydrophilic and hydrophobic polymer to achieve the controlled drug delivery and prolonged gastric retention of drug. Methods: The gastroretentive floating films were formulated by the solvent casting technique using 32 full factorial designs and subjected to in vitro evaluation parameters, drug-excipient compatibility, Xray diffraction and accelerated stability study. Results: The pre-formulation study established the purity and identification of a drug. FTIR study confirmed no drug excipient interaction. F3, F6, and F9 were optimized based on in vitro floating characteristics, swelling/expanding ability, and unfolding time. All developed formulations were unfolded within 14-22 min after capsule disintegration. The F3 was selected as the final formulation as its ability to control the release of the drug for 24 hrs followed by zero-order kinetics having super case 2 transport. XRD confirmed the amorphousness of the drug within the formulation. The stability study results revealed that the formulation was quite stable at extreme storage conditions. Conclusion: The developed novel formulation has good potential for the effective management and treatment of diabetes mellitus.

Formulation and optimization of gastroretentive bilayer tablets of calcium carbonate using D-optimal mixture design

Abstract Gastroretentive bilayer tablets of calcium carbonate (CC) were developed using D-optimal mixture design. The effect of formulation factors such as levels of HPMC K100 M (X1), sodium bicarbonate (X2), and HPMC E15 LV (X3) on responses like floating lag time (R1) and release of CC at 1 h (R2) and 6 h (R3) was elucidated. The optimized formulations developed by numerical optimization technique were found to have short floating lag time (2.85 ± 0.98 min), minimum burst release (27.02 ± 1.18%), and controlled yet near complete release (88.98 ± 2.75%) at 6 h. In vivo radiographic studies in rabbits indicated that optimized batch displayed a mean gastric retention time (GRT) of 5.5 ± 1 h which was significantly prolonged (P < 0.05) compared to the conventional tablets that displayed a GRT of less than 1 h. The studies proved that the gastroretentive tablets can be a promising platform to improve bioavailability of nutrients having absorption window in upper gastrointestinal tract.

Drug Excipient Compatibility, Development and Preliminary Clinical Studies of Tizanidine Hydrochloride Floating Drug Delivery System

The objective of this investigation was to develop formulation of floating matrix tablets of tizanidine HCl to prolong the gastric residence time by using hydroxy propyl methyl cellulose (HPMC K15M) or xanthan gum as sole release retardant and to check the clinical response. The drug-excipients compatibility studies were conducted using DSC and also by visual observation. Incorporation of NaHCO3 in the formulation resulted incompatibility with drug and therefore, the composition was modified by replacing NaHCO3 with CaCO3 in remaining formulations. Floating matrix tablets of tizanidine were developed by direct compression method and the developed ten formulations exhibited satisfactory physicochemical characteristics and in-vitro buoyancy. Formulation (F9) was selected as optimized formulation based on physicochemical characters, in-vitro buoyancy and drug release, and was used in in-vivo radiographic studies in human volunteers by incorporating BaSO4. In radiographic studies, the gastric retention time of floating tablets was found to be 4 ± 0.86 h (n=3). Optimized floating tablets (F9) were used to know the clinical effects in patients suffering from spasticity under the observation of clinician. The optimized tizanidine HCl floating matrix tablets were developed and found to have gastric retention behaviour in stomach and further were found to have good clinical effects in patients suffering from spasticity during preliminary clinical studies.

An overview on various types of gastroretentive drug delivery system

Gastro retentive drug delivery system is one of the approaches to achieve controlled drug delivery. The gastro retentive drug delivery system is a way to prolong residence time of active pharmaceutical ingredient in gastrointestinal tract. It is also applied for targeting drug in upper gastrointestinal tract for generating local and systemic effect. Controlled drug delivery creates a window of absorption that release drug for a longer duration of time before reaching absorption site. Gastro retentive drug delivery systems have gained wide variation of oral drug distribution in the area of late. It includes all the approaches that keep the dosage form in the stomach for a longer duration of time. This also enables sustained release of active pharmaceutical ingredient which in turn overcomes many limitations of conventional drug delivery systems. It has begun tremendous advances in the field of gastro-retention to meet controlled release of drugs. Aim of research. The main aim of this survey to prolong the gastric retention dosage form in the stomach and improve the medication concentration in the stomach. Material and Method. To prepare this manuscript, various keywords were searched in different search engines such as Google, Yahoo, Bing etc. The available information in public domain was collected and classified according to delivery system. This review paper aim to provide complete information about different delivery systems related to Gastro retentive drug delivery systems (GRDDS). It is also applied for targeting drug in upper gastrointestinal tract for generating local and systemic effect. Result. After going through various literatures, it can be said that the GRDDS can improve local bioavailability and therapeutic efficacy and dosing frequency possible reduction in dose size. This paper is focused on various physiological contemplation and obtainable formulation approaches for development of gastro retentive drug delivery system. Conclusions. This article discusses various types of GRDDS and their approaches. The gastric retentive drug delivery systems improve drug absorption. Prolonged gastric retention time of therapeutic mutations provide several benefits such as improving absorption, bioavailability and enhance the therapeutic action of drug