Gastric Residence Times Research Articles

Floating drug delivery system- a review

In the recent years, scientific and technological advancements have been made in the research and development of novel drug delivery systems by overcoming various physiological problems such as short gastric residence times and unpredictable gastric emptying times. Several approaches are utilized in the prolongation of the gastric residence times, such as floating drug delivery systems, swelling and expanding systems, polymeric bioadhesive systems, modified-shape systems, high-density systems and other delayed gastric emptying devices. Floating Drug Delivery Systems (FDDS) is one amongst the GRDFs used to achieve prolonged gastric residence time. The purpose of writing this review on floating drug delivery systems (FDDS) was to compile the recent literature with special focus on the principal mechanism of floatation to achieve gastric retention. The recent developments of FDDS including the physiological and formulation variables affecting gastric retention, approaches to design single-unit and multiple-unit floating systems, and their classification and formulation aspects are covered in detail. This review also summarizes the in-vitro techniques, in- vivo studies to evaluate the performance and application of floating systems, and applications of these systems.

Does age affect gastric emptying time? A model-based meta-analysis of data from premature neonates through to adults.

Purpose. Gastric emptying (GE) is often reported to be slower and more irregular in premature neonates than in older children and adults. The aim of this study was to investigate the impact of age and other covariates on the rate of GE. Methods. The effect of age on the mean gastric residence times (MGRT) of liquid and solid food was assessed by analysing 49 published studies of 1457 individuals, aged from 28 weeks gestation to adults. The data were modelled using the nonlinear mixed‐effects approach within NONMEM version 7.2 (ICON, Dublin, Ireland), with evaluation of postnatal age, gestational age and meal type as covariates. A double Weibull function was selected as a suitable model since it could account for the typical biphasic nature of GE. Results. Age was not a significant covariate for GE but meal type was. Aqueous solutions were associated with the fastest emptying time (mean simulated gastric residence time of 45 min) and solid food was associated with the slowest (98 min). Conclusions. These findings challenge the assertion that GE is different in neonates, as compared with older children and adults due to age, and they reinforce the significance of food type in modulating GE. © 2015 The Authors. Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd.

Gastro retentive Ethyl Cellulose Floating Microspheres containing ATENOLOL

Controlled release (CR) dosage forms have been extensively used to improve therapy with several important drugs. Incorporation of the drug in a controlled release gastro -retentive dosage forms (CR-GRDF) which can remain in the gastric region for several hours would significantly prolong the gastric residence time of drugs and improve bioavailability, reduce drug waste, and enhance the solubility of drugs that are less soluble in high pH environment. Several approaches are currently utilized in the prolongation of the GRT, including floating drug delivery systems (FDDS), swelling and expanding systems, polymeric bioadhesive systems, high-density systems, modified-shape systems and other delayed gastric emptying devices. In this review, current recently developments of Stomach Specific FDDS are discussed that helps to overcome physiological adversities like short gastric residence times and unpredictable gastric emptying times

A Comprehensive Review on Gastro-Retentive Floating Drug Delivery Systems

In recent years scientific and technological advancements have been made in the research and development of novel drug delivery systems by overcoming physiological troubles such as short gastric residence times and unpredictable gastric emptying times. Floating drug delivery systems are designed to prolong the gastric residence time after oral administration, at particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability. Floating drug delivery systems are the systems which are retained in the stomach for a longer period of time and there by improve the bioavailability of drug. The single unit dosage forms have the disadvantage of a release all or nothing during emptying process while the multiple unit particulate system pass through the GIT to avoid the vagaries of gastric emptying and thus release the drug more uniformly. The uniform distribution of these multiple unit dosage forms along the GIT could result in more reproducible drug absorption and reduced risk of local irritation. The purpose of designing multiple-unit dosage form is to develop a reliable formulation that has all the advantages of a single-unit form and also is devoid of any of the above mentioned disadvantages of single unit formulations. This review explains briefly about advantages, disadvantages, mechanism, types, factors, evaluation and application of these systems.

RECENT ADVANCEMENTS AND DEVELOPMENTS IN FLOATING DRUG DELIVERY SYSTEM - AN APPROACH FOR GASTRO RETENTION

Technological attempts have been made in the research and development of rate controlled oral drugdelivery systems to overcome physiological adversities, such as short gastric residence times (GRT) andunpredictable gastric emptying times (GET). Several approaches are currently utilized in the prolongationof the GRT, including floating drug delivery systems (FDDS), swelling and expanding systems, polymericbioadhesive systems, high density systems, modified shape systems and other delayed gastric emptyingdevices. In this review, current & recent developments of stomach specific FDDS are discussed. Therecent developments of FDDS including the physiological and formulation variables affecting gastricretention, approaches to design floating systems, and their classification and formulation aspects arecovered in detail. Although tremendous advances have been seen in oral controlled drug delivery systemin the last two decades, this system has had limited success in the case of drugs with a poor absorptionwindow throughout the GIT (Gastro Intestinal Tract).

Bilayer Floating Tablets for Gastroretentive Drug Delivery System


 Oral delivery of the drug is by far the most preferable route of drug delivery due to the ease of administration, patient compliance and flexibility in the formulations but has a drawback of non-site specificity and short gastric resident time. In recent years, scientific and technological advancements have been made in the development of novel drug delivery systems by overcoming physiological troubles such as short gastric residence times and unpredictable gastric emptying times. Among Several approaches of floating systems, Bilayer floating technology is considered as promising approach. It combines the principle of bilayer technology and floating mechanism. The combined principle of bilayer floating tablet helps to release initial dose from the immediate release layer to reach the plasma concentration and then the floating layer absorbs gastric fluid forming an impermeable colloidal gel barrier on its surface, maintains a bulk density less than unity and thereby remains buoyant in stomach providing steady state concentration of drug in system. This review focuses on bilayer floating tablet technology a new era of gastro retentive drug delivery system, its advantages over conventional tablets and it also summarizes the bilayer tablet presses used in the industry, formulation design and evaluation parameters of bilayer floating tablets.

A Review of Floating Drug Delivery Systems

Floating drug delivery systems improves the drug bioavailability and patient compliance by increasing the gastric residence time and controlling the drug release. In recent decades, there have been numerous attempts to overcome the barriers like short gastric residence times and unpredictable gastric emptying times. In this review, the technological and research advancements made in floating systems are discussed.

Preparation and characterisation of gastroretentive alginate beads for targeting H. pylori

There are various obstacles in the eradication of Helicobacter pylori (H. pylori) infections including low drug levels due to short gastric residence times and poor accessibility of the drug at the site of the infection. In this study, calcium alginate beads containing metronidazole were prepared by ionotropic gelation with diameters ranging from 2 to 3 mm and bulk densities ranging from 0.11 to 0.23 g/cm3. These beads failed buoyancy tests and released the drug rapidly. The formulation was modified in order to improve floating and modify their drug release profile through addition of oil and coating with chitosan. Upon modification, buoyancy improved and drug release was sustained. This novel formulation will ensure retention for a longer period in the stomach and control the release of drug, ensuring high local drug concentrations, leading to improved eradication of the bacteria.

The role of individual gastric emptying of pellets in the prediction of diclofenac in vivo dissolution

The objective of the present study was to check for the possibility to successfully predict individual in vivo dissolution/absorption profiles resulting from fasted administration of a diclofenac extended release pellet formulation. For this purpose dissolution profiles were generated with different dissolution setups using a set of media reflecting pH-conditions in the different segments of the gastrointestinal tract. Since gastric emptying of pellets seemed to be a critical factor for in vivo drug release, a set of different gastric residence times was screened in in vitro studies. Subsequently, in vitro release profiles were first directly compared with the individual in vivo absorption profiles and in a second step a mathematical model, which had been developed in a previous study, was applied to calculate predicted individual in vivo release profiles based on in vitro release profiles and individual gastric emptying. The comparison of predicted individual in vivo release profiles and individual in vivo absorption profiles showed a high degree of similarity, thus confirming the suitability of a set of different gastric residence times used in in vitro drug release testing. Additionally, obtained results indicated that a substantial part of variability of diclofenac absorption profiles can be explained by the variability of pellet gastric emptying kinetics.

Enhanced Bioavailability via Extended Gastric Retention

The ability to prolong gastric residence times with the use of gastric retentive systems is particularly useful for drugs that act locally in the stomach and for those having site-specific absorptions in the upper intestine. Drugs entrapped into these dosage forms also display pharmacokinetic parameters that favor greater safety and efficacy. Many gastric retentive platforms have been studied and some have successfully been utilized in marketed drug products. There are typically three approaches that these platforms take to reside in the stomach longer. They alter the size, density, or adhesion of the delivery system in the gastric environment which leads to changes in drug liberation and absorption. This has a direct effect on the therapeutic effectiveness of the drug they are carrying. The development of these dosage forms is not however without its challenges and further research in this area is needed that shows true gastric retention has occurred. The purpose of this paper is to briefly describe gastric retention approaches and to highlight the enhanced bioavailability, safety, and other benefits of these formulations.

American Alligator Digestion Rate of Blue Crabs and Its Implications for Stomach Contents Analysis

Stomach contents analysis (SCA) provides a snap-shot observation of a consumer's diet. Interpretation of SCA data can be complicated by many factors, including variation in gastric residence times and digestion rates among prey taxa. Although some SCA methods are reported to efficiently remove all stomach contents, the effectiveness of these techniques has rarely been tested for large irregular shaped prey with hard exoskeletons. We used a controlled feeding trial to estimate gastric residency time and decomposition rate of a large crustacean prey item, the Blue Crab (Callinectes sapidus), which is consumed by American Alligators (Alligator mississippiensis), an abundant apex predator in coastal habitats of the southeastern United States. The decomposition rate of C. sapidus in the stomachs of A. mississippiensis followed a predictable pattern, and some crab pieces remained in stomachs for at least 14 days. We also found that certain portions of C. sapidus were prone to becoming caught within the stomach or esophagus, meaning not all crab parts are consistently recovered using gastric lavage techniques. However, because the state of decomposition of crabs was predictable, it is possible to estimate time since consumption for crabs recovered from wild alligators. This information, coupled with a detailed understanding of crab distributions and alligator movement tactics could help elucidate patterns of cross-ecosystem foraging by the American Alligator in coastal habitats.

Gastric pH and Gastric Residence Time in Fasted and Fed Conscious Beagle Dogs using the Bravo® pH System

To further characterize the time course of gastric pH with respect to meals and gastric residence times (GRTs) in dogs, continuous pH measurements were recorded with Bravo capsules, which were attached to the dogs' stomach mucosa or administered as free capsules, respectively. Experiments took place in home or study cages, and meals were administered at designated times. Up until 2 h prior to mealtime, the fasted gastric pH remained constantly acidic (∼2.0) regardless whether the dogs were in the study or home cages. However, as feeding time became imminent, the pH was typically elevated for dogs in home cages, whereas the pH remained acidic for dogs in study cages. For both monitoring locations, the gastric pH remained acidic during meal consumption and for at least 10 h after meals. The GRT between fasted (25 ± 32 min) and fed (686 ± 352 min) conditions was significantly different with considerable inter- and intrasubject variability. Fasted gastric pH was similar to that of literature monkey and human values but differed after meals as the dog gastric pH remained acidic unlike monkey and human. In dogs, the fasted GRT was remarkably rapid and under fed conditions, longer than that observed in humans.

Effect of particle size and food on gastric residence time of non-disintegrating solids in beagle dogs

The gastric residence times of various sizes of radio-opaque particles and tablets were measured in beagle dogs by X-ray, both in the fasted state and after a single meal. During the course of the studies, changes in intragastric pH were also monitored with a radiotelemetric pH sensor, the Heidelberg capsule. The gastric residence time increased with increasing particle size and with particles greater than or equal to 5 mm in diameter approached a plateau value both in the fasted state and after feeding. This value was about 7.5 h after feeding and about 1.5 h in the fasted state, and probably corresponded to the occurrence of the interdigestive migratory myoelectric complex (IMMC wave). The pH in the stomach was variable in the fasted state, but an abrupt pH increase (up to pH 6-7) was observed during the emptying of larger tablets. In some instances this high pH in the stomach was maintained until the next IMMC wave occurred. The gastric emptying of larger tablets administered with food was also associated with an abrupt pH increase.

A comprehensive in vitro and in vivo evaluation of thiolated matrix tablets as a gastroretentive delivery system

The aim of this study was to investigate the potential of thiolated matrix tablets for gastroretentive delivery systems. Poly(acrylic acid)-cysteine (PAA-Cys) and chitosan-4-thiobuthylamidine (chitosan-TBA) were evaluated as anionic and cationic thiolated polymers and riboflavin was used as a model drug. Tablets were prepared by direct compression and each formulation was characterized in terms of disintegration, swelling, mucoadhesion, and drug release properties. Thereafter, the gastric residence times of tablets were determined with in vivo study in rats. The resulting PAA-Cys and chitosan-TBA conjugates displayed 172.80 ± 30.33 and 371.11 ± 72.74 µmol free thiol groups, respectively. Disintegration studies demonstrated the stability of thiolated tablets up to 24 h, whereas tablets prepared with unmodified PAA and chitosan disintegrated within a time period of 1 h. Mucoadhesion studies showed that mucoadhesion work of PAA-Cys and chitosan-TBA tablets were 1.341- and 2.139-times higher than unmodified ones. The mucoadhesion times of PAA, PAA-Cys, chitosan, and chitosan-TBA tablets were 1.5 ± 0.5, 21 ± 1, 1 ± 0.5, 17 ± 1 h, respectively. These results confirm the theory that thiol groups react with mucin glycoproteins and form covalent bonds to the mucus layer. Release studies indicated that a controlled release was provided with thiolated tablets up to 24 h. These promising in vitro results of thiolated tablets were proved with in vivo studies. The thiolated tablets showed a gastroretention time up to 6 h, whereas unmodified tablets completely disintegrated within 1 h in rat stomach. Consequently, the study suggests that thiolated matrix tablets might be promising formulations for gastroretentive delivery systems.

Swelling System: A Novel Approach Towards Gastroretentive Drug Delivery System

Swelling Drug delivery system are designed to prolong the gastric residence time after oral administration, at particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability. In recent years scientific and technological advancements have been made in the research and development of controlled release oral drug delivery systems by overcoming physiological adversities like short gastric residence times and unpredictable gastric emptying times. Swelling drug delivery systems is the system which is retained in the stomach for a longer period of time and thereby improve the bioavailability of drugs. Swelling dosage systems form important technological drug delivery systems with gastric retentive behavior and offer several advantages in drug delivery. Treatment of gastrointestinal disorders such as gastro-esophageal reflux. Improved drug absorption, because of increased GRT and more time spent by the dosage form at its absorption site. Ease of administration and better patient compliance. Minimizing the mucosal irritation due to drugs, by drug releasing slowly at controlled rate. © 2011 IGJPS. All rights reserved.

Assessing gastrointestinal motility and disintegration profiles of magnetic tablets by a novel magnetic imaging device and gamma scintigraphy

Purpose To validate Magnetic Moment Imaging (MMI) for the investigation of gastrointestinal transit and disintegration of solid dosage forms and to correlate the MMI findings with the corresponding gamma scintigraphic data. Materials and methods Three magnetic tablets (MTs) were investigated using in vitro and in vivo tests. The clinical study was a four-way, crossover study with the following arms: (a) immediate-release tablets administered in fasted state; (b) immediate-release tablets administered after 400 mL of Clinutren ® ISO; (c) enteric-coated tablets administered in the fasted state; and (d) non-disintegrating tablets studied in the lightly fed state (100 mL of Clinutren ® ISO). Results In both the in vitro and in vivo studies, tablets were detected successfully by MMI and scintigraphy. There was a good correlation between gastric residence times and positional data (in the x, y and y, z-axes). In addition, MMI revealed early swelling behaviour of the tablet matrix. There was excellent agreement for the disintegration times of MT(A) in the fasted arm (scintigraphy 12.0 ± 4.4 min, MMI 11.8 ± 4.4 min). In the MT(A)-fed arm, onset times determined by scintigraphy were delayed in three subjects when compared to the corresponding MMI results. Delayed disintegration was observed with MT(A) administered after food ( p < 0.01) in both the techniques. Conclusion The MMI device is a reliable imaging tool for tracking the transit and disintegration of a magnetic tablet through the gastrointestinal tract.

Design and evaluation of a floating ranitidine tablet as a drug delivery system for oral application

In recent years, scientific and technological advances have been made in the research and development of rate-controlled oral drug delivery systems by overcoming physiological obstacles, such as short gastric residence times (GRT), and unpredictable gastric emptying times. Several approaches are currently utilized in the prolongation of GRT, including floating drug delivery systems (FDDs). A drug delivery system for the water-soluble H 2 -receptor antagonist drug, ranitidine hydrochloride, was developed. The floating and controlled-release properties of tablets containing ranitidine HCl, hydroxypropylmethylcellulose (HPMC), and different additives were examined. The study shows that tablet composition and mechanical strength have the greatest influence on floating properties and drug release. Sodium bicarbonate was used as gas-generating agent which enhances tablet flotation. The time taken for tablets to emerge on the water surface (floating lag time), or buoyant time, and the time during which the tablets constantly float on the water surface (duration of floating) were evaluated in a dissolution vessel. The results indicated that buoyancy is strong enough for whole tablets to travel up to the surface and remain on the surface for as long as 24 h. In vitro dissolution was carried out in simulated gastric fluid (enzyme-free) at 37 ± 0.5°C as per USP 22. Drug release from the tablets was sufficiently sustained (12 h) compared to conventional tablets. Drug release best fit both the Higuchi and Peppas models. Moreover, the effect of tablet hardness and stirring rate on the release kinetics was examined. The floating tablets were compared with conventional tablets in fasted rabbits at 150 mg equivalent dose of ranitidine HCl. The pharmacokinetic parameters, maximum plasma concentration (C max ), the time to reach maximum plasma concentration (T max ), and the area under plasma concentration curve (AUC) for 0-12 h were calculated. The relative bioavailability of the floating tablets in relation to the conventional tablets was also calculated.

Gastroretentive drug delivery systems

A controlled drug delivery system with prolonged residence time in the stomach is of particular interest for drugs that i) are locally active in the stomach, ii) have an absorption window in the stomach or in the upper small intestine, iii) are unstable in the intestinal or colonic environment, or iv) exhibit low solubility at high pH values. This article gives an overview of the parameters affecting gastric emptying in humans as well as on the main concepts used to design pharmaceutical dosage forms with prolonged gastric residence times. In particular, bioadhesive, size-increasing and floating drug delivery systems are presented and their major advantages and shortcomings are discussed. Both single- and multiple-unit dosage forms are reviewed and, if available, results from in vivo trials are reported.

Preparation of microspheres with microballoons inside for floating drug‐delivery systems

AbstractThe use of floating drug‐delivery systems is one method that is used to achieve prolonged gastric residence times. We developed a novel, multiple‐unit, floating drug‐delivery system of microspheres with microballoons inside from xanthan gum (XG) and gelatin (GA) by a water‐in‐oil method. With theophylline as the model drug, four formulations (FI–FIV) with different ratios of the two polymers were prepared. The size distribution, drug‐encapsulation efficiency, floating behavior, release characteristics, and morphological properties were investigated. The ratio of the two polymers influenced the size distribution, encapsulation efficiency, and drug release appreciably. With increasing amounts of GA, the percentage yield of the floating microspheres and the drug‐encapsulation efficiency decreased from 100 and 84.5% to 31 and 56.2%, respectively. The drug‐release rate also decreased with increasing GA content, which was attributed to an increase in the crosslinking extent. An initial burst was observed, and after that, the drug was released slowly by a near‐zero‐order pattern, which was attributed to the low solubility of theophylline and the possible complexes formed by XG and GA in the simulated gastric fluid (pH 1.2). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 197–202, 2004

Gamma scintigraphic evaluation of the fate of microcrystalline chitosan granules in human stomach

In several reports of in vitro studies it has been suggested that the mucoadhesive chitosans could be of value in preparing gastro-retentive formulations. The aim of this study was to obtain direct in vivo evidence of whether microcrystalline chitosan (MCCh) formulations acted as gastro-retentive systems in humans. Neutron-activation-based gamma scintigraphy was used to study gastric residence times of MCCh granules in healthy male volunteers. Possible effects of neutron irradiation on the properties of the MCCh granules were studied in advance, in vitro. In vivo gamma scintigraphic evaluations were carried out with the subjects in a fasted state, using granules containing 95% (F1) or 40% (F2) of MCCh of molecular weight 150 kDa. Reference formulation (F3) was lactose granules. The reference granules passed rapidly from the stomach (mean t 50% 0.5±0.3 h ( n=5)). MCCh in granules prolonged gastric residence times of the formulations in only a few cases (in one volunteer in the F1 group ( n=4) and in two volunteers in the F2 group ( n=5)). Maximum individual t 50% values were 2.1 h (F1) and 2.3 h (F2). It was concluded that the in vivo mucoadhesion of MCCh formulations is erratic, and that the formulations studied are not reliable gastro-retentive drug delivery systems.