Gastroretentive Dosage Form Research Articles

Influence of different types of low substituted hydroxypropyl cellulose on tableting, disintegration, and floating behaviour of floating drug delivery systems

The object of the present study is to evaluate the effect of application of low-substituted hydroxypropyl cellulose (L-HPC) 11 and B1 as excipients promoting floating in gastroretentive tablets. Directly compressed tablets were formed based on experimental design. Face-centred central composite design was applied with two factors and 3 levels, where amount of sodium alginate (X1) and L-HPC (X2) were the numerical factors. Applied types of L-HPCs and their 1:1 mixture were included in a categorical factor (X3). Studied parameters were floating lag time, floating time, floating force, swelling behaviour of tablets and dissolution of paracetamol, which was used as a model active substance. Due to their physical character, L-HPCs had different water uptake and flowability. Lower flowability and lower water uptake was observed after 60min at L-HPC 11 compared to L-HPC B1. Shorter floating times were detected at L-HPC 11 and L-HPC mixtures with 0.5% content of sodium alginate, whereas alginate was the only significant factor. Evaluating results of drug release and swelling studies on floating tablets revealed correlation, which can serve to help to understand the mechanism of action of L-HPCs in the field development of gastroretentive dosage forms.

Hydrogel polysaccharides of tamarind and xanthan to formulate hydrodynamically balanced matrix tablets of famotidine.

The gastroretentive dosage form of famotidine was modified using tamarind seed powders to prolong the gastric retention time. Tamarind seeds were used in two different forms having different swelling and gelling properties: with husk (TSP) or without husk (TKP). TKP (TKP1 to TKP 6) and TSP (TSP1 to TSP 6) series were prepared using tamarind powder:xanthan in the ratios of 5:0, 4:1, 3:2, 2:3, 1:4, 0:5, respectively. The matrix tablets were prepared by the wet granulation method and evaluated for pharmacopoeial requirements. TKP2 was the optimum formulation as it had a short floating lag time (FLT < 30 s) and more than 98.5% drug release in 12 h. The dissolution data were fitted to popular mathematical models to assess the mechanism of drug release, and the optimum formulation showed a predominant first order release and diffusion mechanism. It was concluded that the TKP2 prepared using tamarind kernel powder:xanthan (4:1) was the optimum formulation with shortest floating lag time and more than 90% release in the determined period of time.

Formulation and Evaluation of Floating Tablets of Cefpodoxime Proxetil

In the present investigation, an attempt was made to develop gastro retentive tablets of cefpodoxime proxetil (CP) using locust bean gum as release retarded material. CP is an orally administered, extended spectrum, semi-synthetic antibiotic of cephalosporin class. CP has a short elimination half-life and also possesses high solubility, chemical, enzymatic stability and absorption profiles in acidic pH which makes CP suitable candidate for formulating it as gastro retentive dosage form for improved bioavailability. Sodium bicarbonate and citric acid were used as effervescent agents to get desired floating properties. The tablets prepared were evaluated and found to have acceptable physicochemical properties. The in vitro release data of optimized formulation was treated with mathematical equations and was concluded that drug release followed zero order kinetics with anomalous transport mechanism. Based on the results it can be concluded that floating tablets of cefpodoxime proxetil containing locust bean gum provides a better option for controlled release action and improved bioavailability. © 2014 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved. doi: http://dx.doi.org/10.3329/jsr.v6i3.18339 J. Sci. Res. 6 (3), 563-579 (2014)

A review on floating drug delivery system

Dosage form with a prolonged GRT, that is gastro retentive dosage forms (GRDFs), will provide us with new and important therapeutic options. GRDFs extend significantly the period of time over which the drugs may be released. Thus, they not only prolonged dosing intervals, but also increase patient’s compliance beyond the level of existing controlled release dosage forms. This application is especially affective in delivery of sparingly soluble and insoluble drugs.

Helicobacter pylori: An Overview on Antimicrobials and Drug Delivery Systems for its Eradication

Since the discovery of Helicobacter pylori (H. pylori) in the early 1980s, its eradication has been one of the most important global challenges in gastroenterology. Various circumstances make the treatment with antimicrobials particularly difficult. One problem has been that antibiotics commonly used were designed for the treatment of infections throughout the body rather than for delivering high concentrations locally within the stomach. Many gastroretentive dosage forms were developed in order to eradicate the infection, yet additional advancements are still needed to eliminate the infection completely and decrease its prevalence worldwide. An overview on different antimicrobials and a literature survey about different drug delivery systems used in eradication of H. pylori infection are presented in this review.

Sinking-Magnetic Microparticles Prepared by the Electrospray Method for Enhanced Gastric Antimicrobial Delivery

A targeted oral drug delivery system is useful to improve the treatment of gastrointestinal diseases. A high density sinking dosage form can sink to the bottom of the stomach near the pylori sections to enhance gastric retention. However, it is difficult to achieve a high density sinking system using the traditional technology. In the current study, novel stomach-specific sinking magnetic microparticles (SMMPs) were prepared via the monoaxial electrospray method for enhanced gastric antimicrobial delivery. The size of SMMPs was approximately 5 μm, and the Fe3O4 nanoparticles were observed in the SMMPs by transmission electron microscopy (TEM). The density of SMMPs increased as the concentration of Fe3O4 nanoparticles in the electrospray inlet flow increased, with the maximum true density of approximately 3.52 g/cm(3). The SMMPs displayed strong magnetism in vitro and in vivo. They can settle down in water within 120 s in vitro, and the settling time decreased to 20 s under a magnetic field. Furthermore, an in vivo γ scintigraphy study demonstrated that (131)I labeled SMMPs were retained in the stomach for over 8 h, and an external permanent magnet can increase their gastric retention time even further. Using Helicobacter pylori as a model bacterium, amoxicillin-loaded SMMPs exhibited a significantly greater eradication of H. pylori compared to the free drug, in vivo. Our results suggested that electrospray is an effective technique to prepare the high density gastroretentive dosage forms. We have shown that stomach-specific SMMPs can supply better treatment for H. pylori infections and have the potential to be used in clinical practice.

Exploring the Potential of Gastro Retentive Dosage Form in Delivery of Ellagic Acid and Aloe vera Gel Powder for Treatment of Gastric Ulcers

Approach of novel drug delivery system (NDDS) overcomes the limitations of conventional dosage forms. However, this concept is still not practiced to a large extent in delivery of herbal drugs in Ayurveda. Thus, the potential of herbal drugs has not been explored to its fullest. Hence, there is a growing need to amalgamate the concept of NDDS in delivery of herbal constituents. The present investigation is designed to deliver and retain two herbal constituents in stomach for better action against Helicobacter pylori induced gastric ulcers. The objective was to develop a bilayer floating tablet of ellagic acid and Aloe vera gel powder through rational combination of excipients to give the lowest possible lag time with maximum drug release in the period of 4 h. Formulation F9 containing 100 mg of HPMC K15M, 27 mg of crospovidone, 80 mg of mannitol and effervescent agents in the ratio 1:2 gave 92% drug release and desired floating properties. In vivo studies showed that combination of ellagic acid and Aloe vera gave 75 % ulcer inhibition in comparison to 57% ulcer inhibition in the group which was administered with ellagic acid alone. This suggests the use of bilayer floating tablet in gastric ulcer treatment.

More Good News About Polymeric Plant- and Algae-Derived Biomaterials in Drug Delivery Systems

Natural polymers are continuously investigated for use in pharmaceutical and tissue engineering applications due to the renewability of their supply. Besides the conventional use of natural materials in dosage form design such as fillers, they are progressively investigated as functional excipients in specialised dosage forms. The hydrophilic nature of natural polymers together with their non-toxic and biodegradable properties make them useful in the design of modified release dosage forms. Matrix type tablets and beads made from natural gums and mucilages often exhibit sustained drug release through erosion in combination with swelling. Natural polymers are used to reach different pharmaceutical objectives, for instance, inulin and pectin are plant derived polymers that have suitable properties to produce colon-specific drug delivery. Alginate is an example of a natural polymer that has been used in the formulation of gastro-retentive dosage forms. Different cellulose derived polymers have been investigated as coating materials for dosage forms. Natural polymers can be chemically modified to produce molecules with specific properties and formation of co-polymers or polymer mixtures provide new opportunities to develop innovative drug delivery systems.

Preparation and Evaluation of Novel Expandable Drug Delivery System with Captopril

Aims: The purpose of this research is to develop a novel expandable gastroretentive dosage form (GRDF), based on an unfolding mechanism. It consists of a drug loaded bilayer polymeric film, folded into a hard gelatin capsule. Gastric retention is achieved due to unfolding of the dosage form within 15-20 min. Captopril is selected as the drug candidate for this work. Due to its narrow absorption window, Captopril has to be administered to the upper parts of the intestine in order to maintain sustained therapeutic levels. This may be achieved by a GRDF. Methodolgy: Films were prepared by solvent-casting technique using Ethyl cellulose, HPMC E15 and Eudragit RLPO as polymers and dibutyl-phthalate as the plasticizer in both layers. The film with zigzag folding in the capsule was shown to unfold in the gastric juice and provide drug release up to 12 h in the acidic medium. The films were evaluated for weight & thickness variation, mechanical properties, in vitro drug release and unfolding behaviour based on the mechanical shape memory of polymers. Absence of drug polymer interaction and uniform drug dispersion in the polymeric layers was revealed by DSC, XRD and SEM studies. The GRDF location in the gastrointestinal tract was determined by X-ray studies. Results: X-ray studies revealed that the GRDF is retained in the stomach up to 6± 0.5 h in fasting condition and 8 h in fed state. Conclusion: The polymers used in the development of GRDFs were safe and proper combination of these polymers will yield a novel expandable GRDF with good in vitro drug release in acidic media, mechanical properties, unfolding behaviour. These outcomes demonstrate that the GRDF may be used to improve Captopril therapy and can be applied to extend the absorption of other narrow absorption window drugs that require continuous input. Keywords: Captopril, ethyl cellulose, expandable drug delivery systems, gastric retention, hydroxy propyl methyl cellulose, mechanical properties.

Novel sustained release and swellable gastroretentive dosage form for ciprofloxacin hydrochloride.

Introduction:The present study aims at developing a gastroretentive swellable and floating matrix tablet formulation of ciprofloxacin hydrochloride (HCl) for the effective treatment of infections caused by susceptible organisms. Ciprofloxacin HCl is a fluoroquinoline antibiotic drug. Ciprofloxacin HCl is more stable in acidic medium and it has a narrow absorption window which is sited at the stomach and proximal portions of the small intestine, so it covers the required criteria for selection of drug for gastroretentive dosage form.Materials and Methods:Ciprofloxacin HCl gastroretentive tablets were formulated by using direct compression method and different grades of hydroxypropyl methylcellulose as suspending and stabilizing agent (polymer), sodium starch glycolate (SSG), crospovidone as disintegrates, sodium bicarbonate as alkalizing agent and magnesium stearate as lubricant.Results:The tablets were evaluated for post compression parameters. All the parameters were within the pharmacopoeial limits.Conclusion:The in vitro dissolution studies showed that the drug release was fast in formulations F2, F4 and F6 containing SSG as super disintegrant when compared with all other formulations. In SEM study of F2 formulation shows maximum swelling and porosity observed after 12 h. Hence, formulation F2 shows the best formulation among the six formulations containing different binders and super disintegrants.

Freeze-Dried Highly Porous Matrix as a New Gastroretentive Dosage Form for Ecabet Sodium: In Vitro and In Vivo Characterizations

AbstractThe aims of the present study were to prepare hydroxypropylmethyl cellulose-based matrix tablets prepared using the freeze-drying method for gastroretentive delivery of ecabet sodium (ECS), a locally acting antigastric ulcer drug, and to perform in vitro/in vivo characterizations.The freeze-dried gastroretentive tablets (FD-GRTs) had porous structures, while they had good friability as a pharmaceutical dosage form. The porous structures lowered the tablet density, allowing the tablet to float without any lag time. Buoyancy of FD-GRT was maintained until they were entirely disintegrated during an in vitro release study. Release rate of ECS could be controlled by the amount of ethylcellulose (EC) in FD-GRT. As amount of EC in the composition was increased, there was a decrease in both release rate and erosion rate of FD-GRT. When administered to a miniature pig, FD-GRT remained in the stomach for more than 12h, which was significantly longer than a conventional sustained release tablet. The new FD-GRT do not contain any excipients for buoyancy and do not require any lag time for buoyancy, consequently it could be considered to be safer and more effective than conventional floating-type GRT.

Unfolding type gastroretentive film of Cinnarizine based on ethyl cellulose and hydroxypropylmethyl cellulose

The present work was based on the development and characterization of unfolding type gastro retentive dosage form appropriate for controlled release of Cinnarizine (CNZ), a drug with narrow therapeutic window. The drug loaded polymer film of biological macromolecules, i.e., ethyl cellulose (EC) and hydroxypropylmethyl cellulose (HPMC K15) was folded into hard gelatin capsules. The film was folded in different patterns for characterizing their unfolding behavior. The polymeric film revealed a fast release during the first hour followed by a more gradual drug release during a 12-h period following a non-Fickian diffusion process. Tensile strength of polymeric film was optimized using different amount (0.2–0.7ml) of polyethylene glycol (PEG 400). Various physical parameters were studied for evaluating their performance as a gastroretentive dosage form. Drug and polymers were found to be compatible as revealed by differential scanning calorimetry (DSC) study and scanning electron micrograph (SEM) study revealed uniform dispersion of CNZ in polymeric matrices. The results indicate that unfolding type gastro retentive drug delivery system holds lots of potential for drug having stability problems in alkaline pH or are which mainly absorbed in acidic pH.

Formulation and Evaluation of Sustained Release Mucoadhesive Atenolol Tablets for Gastric Retention

An oral sustained release gastroretentive dosage form comes out as better alternative for drugs having narrow absorption window. Atenolol conventional tablets have been reported by many scientists to exhibit poor oral bioavailability and fluctuations in plasma drug concentration. This results, either in precipitation of side effects or reduction in drug concentration at the target site. Thus objective of present study was to develop, optimize and evaluate a gastroretentive, mucoadhesive tablet for sustained release. A 22 factorial design was employed to systematically study the drug release profile and bioadhesive strength. Sodium carboxymethyl cellulose (CMC) and carbopol 934P were selected as independent variables. Tablets were prepared by direct compression and were evaluated for tablets characteristics, swelling study, adhesion strength and percent drug released. Optimized formulation was compared with marketed formulation (ATEN-50). In vitro wash off test was applied to study the gastroretentive behavior.Tablets prepared show good tablet characteristics, optimum swelling behavior and high adhesion strength. The optimized batch follows zero order drug release profile with non fickian transport mechanism. The mucoadhesion time for optimised batch (M4) was found to be more than four hours and compared with plain tablet which was found to be very less (less than half hour).Thus, the gastroretension by mucoadhesion proven to be a potential tool for drug atenolol which improves its bioavailability with reduction in dosing frequency and dose related side effects.

Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate.

In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs) of chitosan (CS) and hydroxyethyl cellulose (HEC) at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed.

Efficacy of gastro-retentive forms of ecabet sodium in the treatment of gastric ulcer in rats

The purpose of the present study is to investigate the influence of gastric retention of ecabet sodium (ECS) on its mucoprotective effect in rat ulcer models. Mini-tablets containing 9 mg ECS were prepared using the direct compression method. The release rates of ECS mini-tablets were controlled by the amount and viscosity grade of hydroxypropylmethyl cellulose incorporated. Gastric retention of ECS mini-tablets after oral administration to rats was visually confirmed using a fluorescence imaging system. Because ECS mini-tablets exhibited size-dependent gastric retention, their gastric retention time was prolonged as the release rate decreased. In the in vivo efficacy study, gastro-retentive dosage forms of ECS did not influence the mucoprotective effect in the immediate irritation model but enhanced the effect in the delayed irritation model compared with ECS suspension. This finding indicates that the duration of the mucoprotective effect of ECS can be extended by the employment of gastro-retentive dosage formulations and provides a rationale for development of ECS gastro-retentive dosage forms.

Polyethylene Oxide Based pH-independent Drug Delivery System: Formulation and Optimization by Central Composite Design

Present study deals with formulation and optimization of mucoadhesive alginate beads. Due to pH dependent solubility behavior observed for majority weakly basic drugs, stomach was selected as preffered site for delivery. Gastroretentive dosage form of model drug quetiapine fumarate was developed owing to its high solubility at low pH and polyethylene oxide as mucoadhesive polymer. Ionotropic gelation technique was utilized to prepare beads by applying a central composite design. Two independent factors sodium alginate (X1) and Polyox®303WSR (X2) were studied to derive beads possessing desirable and optimized characteristics. Physicochemical and performance based characterization was performed for developed formulation. Percentage yield of all the batches was above 85%. Despite of a constant fall in adhering percent with time, accetable adherance of beads was found upto 10 h. Derived optimized mucoadhesive beads were having spherical shape and average diameter of 773.7 μm. Percentage yield, % drug entrapment and adhering percentage at 10 h of optimized batch were found to be 91.7%, 85%, and 41%, respectively. Drug release kinetics of optimized batch met the set criteria and followed Hixon-Crowell model. The Fourier transform infrared spectroscopy illustrated stable nature of drug in the beads and proved the absence of any drug-excipient interactions. Beads were found stable throughout the accelerated stability testing period of three months. Gastroretentive beads can be a platform for drug delivery of weakly basic drugs having pH dependent solubility. Keywords: Alginate beads, central composite design, gastro retention, ionic gelation, mucoadhesion, quetiapine fumarate.

Studies on development and characterization of gastroretentive drug delivery system for antibiotics: Cefdinir

Aims/objectiveOral SR gastroretentive dosage forms offer many advantages for drugs having absorption from upper GIT and improve the bioavailability of medications that are characterized by narrow absorption window. Cefdinir is a third generation cephalosporin with broad spectrum of activity with low bioavailability (20–30%) and short biological half life (1–2 h). It has better absorption from upper part of gastrointestinal tract. The purpose of present study was to formulate and develop a new GRDDS using bilayered tablet technology for cefdinir as a model drug. MethodsCefdinir bilayer tablets (CBT) were prepared by using double compression cup and core method. First layer, floating matrix layer contained different rate retarding polymers and effervescent mixture. Second layer is loading layer contained cefdinir and fast releasing components (soluble starch, sodium bicarbonate and citric acid). All CBT were evaluated for their pre and post compression parameters. ResultsPrecompression and post compression parameter of all CBT were within the pharmacopeial limits. In vitro buoyancy behavior and matrix integrity study revealed that FLT of optimized formulation was 1.57 ± 0.52 min and the tablet remained floatable throughout the study. In vitro drug release of optimized CBT follows initially first order release upto 30 min (till their release of loading layer), then zero order release upto 12 h and kinetic profile followed the Peppas (R2 = 0.9838) and zero order (R2 = 0.9986). FTIR studies revealed no drug–excipients interactions. Stability studies conducted for optimized formulation did not show any change in physical appearance, drug content, floatability, matrix integrity. ConclusionKinetics of CBT showed biphasic release in the first phase, immediate dose was released in less than 60 min and second phase was released from matrix layer as a controlled zero order fashion. Cefdinir is a suitable drug for development of gastroretentive bilayer tablet.

Development of mucoadhesive floating hollow beads of acyclovir with gastroretentive properties

This study aimed at improving the oral bioavailability of acyclovir (ACV) through incorporating it into gastroretentive dosage form based on floating hollow chitosan beads. Hollow chitosan beads were prepared using a solvent free, ionotropic gelation method. The effect of formulation parameters, including chitosan molecular weight and drug concentration, on bead characteristics was studied. The drug containing formulations had yields >70.5 ± 0.31%. The entrapment efficiencies for the medium molecular weight chitosan formulations (56.29 ± 0.94%–62.75 ± 0.86%) was greater than the high molecular weight chitosan formulation (29.21 ± 0.89%). The density of all formulations was below that of gastric fluid, the greatest density observed was 0.60 ± 0.01 g cm−3. Unsurprisingly, the formulations were immediate bouyant to different degrees in both pH 1.2 and pH 6.8 media. In addition, the chitosan beads were all seen to swell in pH 1.2 media and demonstrated mucoadhesive properties. A sustained release profile was observed from the chitosan beads, the developed formulations released drug at slower rates than a marketed ACV oral tablet. The developed system has the dual advantages of being gastroretentive, to increase oral bioavailability and releasing drug in a controlled manner, to reduce the required frequency of administration thereby promoting patient adherence.

Development of a Novel Biodegradable Superporous Hydrogel for Gastroretentive Application

The objective of the study was to design and evaluate a novel superporous hydrogels (SPHs) for application as gastroretentive dosage form of losartan potassium. The semi-interpenetrating polymer network (IPN) SPHs of polyvinyl pyrrolidone and chitosan was synthesized by crosslinking chitosan with glyoxal. SEM photographs show the presence of interconnected pores. The prepared SPHs were highly sensitive to pH of swelling media, and showed reversible swelling and deswelling behaviors maintaining their mechanical stability. Drug release fitted best to the Korsmeyer-Peppas model. The studies showed that semi-IPN SPHs could be used as a gastroretentive drug delivery system.

Pharmacokinetics, Efficacy, and Tolerability of a Once-Daily Gastroretentive Dosage Form of Gabapentin for the Treatment of Postherpetic Neuralgia

Neurontin®, an immediate-release (IR) formulation of gabapentin, was the first drug approved by the United States Food and Drug Administration for the treatment of postherpetic neuralgia (PHN). The effective dosing regimen of gabapentin IR (G-IR) for PHN is 1800 mg/day in three divided doses. In 2011, a gastroretentive (GR) formulation of gabapentin (G-GR, Gralise®) was approved for the treatment of PHN. The effective dosing regimen of G-GR is 1800 mg, once daily taken with the evening meal. Compared with G-IR, G-GR has an apparently better tolerability profile with a 1-2 weeks shorter titration period to reach the same therapeutically effective dose. The differences in the dosing frequency and tolerability between G-IR and GR are mainly because of the difference in formulations and thus pharmacokinetic properties. The GR formulation takes advantage of normal human gastrointestinal (GI) physiology and the unique pharmacokinetic properties of gabapentin. In this review, we compare the IR and GR formulations of gabapentin, overview the GI physiology and GR mechanism of G-GR, and describe the unique pharmacokinetic properties of gabapentin. The effect of GR formulation on efficacy and the incidence of adverse events that are commonly associated with G-IR treatment in PHN patients are also discussed.