Gastro Retentive Research Articles

Development and In vitro Evaluation of Pantoprazole-Sustained Release Effervescent Floating Tablets for Effective Management of Ulcer

Introduction: Pantoprazole is a very suitable drug for the treatment of numerous acid-related conditions in humans and mammals. Owing to its short half-life (0.9 – 1.9 h), it is ideal for sustained release formulation. Methods: This study was aimed at developing pantoprazole gastroretentive (GR) controlledrelease tablets and to determine the effects of this formulation and processing parameters on drug release and other critical quality attributes of directly compressed tablets produced using different matrix-forming polymers, namely, Hydroxypropyl methylcellulose (HPMC), chitosan, sodium alginate, maize starch, kappa- carrageenan, and propyl vinyl pyrrolidine PVP K30 when formulated into effervescent Floating Drug Delivery Systems (FDDS). Results: The buoyancy lag time of less than 5 seconds and a total floating time of more than 12 hours for all batches is a good indication of achieved floatation for FDDS. Conclusion: Validation processes initiated with the five batches indicated that the polymer blends had the potential for the formulation of pantoprazole FDDS and, hence, could enhance patient compliance and better treatment outcomes due to their sustained release potentials.

Design and Evaluation of Gastro-Retentive Floating Tablets of Ibandronic acid

The objective of this study is Preparation and evaluation of gastro-retentive floating tablets of Ibandronic acid by direct compression method polymers or combination. In this study, Ibandronic acid, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastro retentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDDs are an approach to prolong gastric residence time, there by targeting site-specific drug release in the upper GIT for local or systemic effect. GRDF tablets of Ibandronic acid (200 mg) were characterized with the effects of Carbopol 934P, HPMC 4KM and Na-CMC at various ratios on swelling, floating, physical integrity. A prolonged dissolution profile of Ibandronic acid GRDF tablets developed in this study was observed for its thickness, friability, hardness, drug content and in-vitro drug release. Formulated Floating tablets of Ibandronic acid gave satisfactory results for various physicochemical parameters like hardness, friability, thickness, weight variation and content uniformity. Sodium bicarbonate has predominant effect on the buoyancy lag time, while HPMC K4M has predominant effect on total floating time and drug release. From the study it is evident that a promising controlled release floating tablets of Ibandronic acid can be developed to increase gastric residence time and thereby increasing its bioavailability. Both doses significantly reduced the occurrence risk of new vertebral fractures by 50–52 percent when compared to the effects of the placebo drug. Keywords: Gastro retention, Ibandronic acid, floating tablet, Carbopol, GRDF, GRFT.

Optimization of ticagrelor tablet for gastro-retentive drug delivery using full factorial design

Purpose: To identify the optimized region of formulation using quality by design for developing ticagrelor gastro-retentive (GR) tablets. 
 Methods: A 23 + 3 full factorial design of experiments study was used to identify three factors (polyethylene oxide (PEO), compression, and volume of granulating fluid) involved in the wet granulation and compression process of ticagrelor GR tablets. Hardness, friability, content, dosage unit uniformity, and pH 1.2 dissolution rate (at 4, 8, and 12 h) were evaluated as critical quality attributes via analysis of variance using Design Expert software. 
 Results: All seven models were significantly influenced based on analysis of variance results (p < 0.05). Hardness and friability were significantly affected by compression (p < 0.0001). Content uniformity was significantly affected by the interaction between compression and granulating water volume for wet granulation (p < 0.05), and dosage unit uniformity was significantly affected by the volume of granulating fluid for wet granulation (p < 0.05). However, all results were within acceptable ranges. Polyethylene oxide (PEO) (4 h, p < 0.05; 8 h, p < 0.05; 12 h, p < 0.05) and compression (4 h, p < 0.05; 8 h, p < 0.05; 12 h, p < 0.05) had negative effect on pH 1.2 dissolution rate. 
 Conclusion: Design of experiment (DoE) approach has been used to optimize region of PEO, compression, and volume of granulating fluid for formulation development. This outcome is expected to be a basis for further research to develop TCG GR tablets on a large production scale.

Gastro Retentive Drug Delivery System: A Review

Gastro Retentive Drug Delivery Systems (GRDDs) are an approach to prolonging gastric residence time by targeting the release of specific drugs at the top of the GIT for local or systemic effect. The Gastro Retentive Dosage Forms (GRDFs) is a very long-term time used to improve treatment with several important drugs. GRDDs are one example of a novel strategy to extending gastric residence duration, concentrating on the local or systemic effects of particular medications released in the stomach. GRDFs can provide prolonged and continuous drug release to the upper part of the Gastro Intestinal System (GIT), which greatly extends the duration of the drug release, improves the bioavailability of drugs with narrow therapeutic windows, and thus extends the dose interval and improves the patient's compliance. GRDFs enable the drug to be released longer and continuously to the upper part of GIT, thereby significantly extending the time when the drug is released and improving the bioavailability of a drug with narrow therapeutic windows, thus prolonging the dose interval and increasing patient compliance.

In Vivo Pharmacokinetic Studies of Acyclovir Gastro Retentive Mucoadhesive Microspheres Aided by Azadirachta indica Fruit Mucilage

In Vivo Pharmacokinetic Studies of Acyclovir Gastro Retentive Mucoadhesive Microspheres Aided by Azadirachta indica Fruit Mucilage

FORMULATION AND EVALUATION OF GASTRO-RETENTIVE MICROSPHERE OF SAXAGLIPTIN ANTIDIABETIC AGENT

The objective of this study was to develop a gastro-retentive microsphere of Saxagliptin. Saxagliptin is an orally active hypoglycemic drug of the newdipeptidylpeptidase-4(DPP4) inhibitor class of drug. Nine formulations of Saxagliptin microsphere are prepared by Emulsion solvent diffusion method using polymers like Eudragit RS 100 and Ethyl cellulose at different drug to polymer ratios and Polyvinyl Alcohol as Stabilizing agent by Emulsion Solvent Diffusion Method. The formulations were optimized on the basis of percent buoyancy and in vitro drug release. The prepared microspheres were evaluated for physicochemical parameters and found to be within range. KEYWORDS: Gastro retentive, Saxagliptin, Ethyl cellulose, Floating microsphere, Eudragit RS 100, Polyvinyl alcohol

An Insight on Novel Approaches & Perspectives for Gastro-Retentive Drug Delivery Systems.

The conventional oral drug delivery systems face a lot of difficulties in the gastrointestinal tract, such as inappropriate drug release and reduction in the efficacy of the doses, which makes this system less susceptible to the delivery of drug formulation. For the enhancement of therapeutic efficacy and bioavailability of the drug, many efforts have been made. The drug candidates which are not stable at alkaline pH and soluble in acidic medium were selected to increase their therapeutic effectiveness through gastro retentive drug delivery systems (GRDDS). This article discusses various factors which alter the gastro retention time (GRT) of the gastro retentive drug delivery system in the stomach and intestine (duodenum). It emphasizes on the novel approaches made for the delivery and release of drugs with the use of magnetic systems, floating (low-density) systems, super porous hydrogels, raft systems, mucoadhesive systems, high-density systems and expandable systems. Along with the applications, the key aspects of in vivo, in vitro & clinical studies in different approaches to GRDDS have been addressed. In addition, future perspectives have been summarized to reduce gastric transit time in fasting and fed conditions.

Review on Gastroretentive Drug Delivery System

GRDDSs are an innovative tactic in this area (Gastro Retentive Drug Delivery System). GRDDSs can improve the regulated administration of drugs with an absorption window by continuously releasing the drug for a long period before it reaches its absorption site. The aim of this study was to investigate, compile, and succinctly summarise both recent and older literatures, with a focus on methods being applied right now to prolong gastric residency duration. They include of high density systems, floating systems, swelling and expanding systems, bio/mucoadhesive systems, and various delayed gastric emptying devices. The current study briefly discusses the categorization, formulation concerns for gastroretentive drug delivery systems, variables affecting stomach retention, advantages, limitations, and applications. To understand the many physiological hurdles involved in establishing stomach retention, we have highlighted important factors impacting it. Then, we assessed the various gastroretentive techniques that have been devised and developed up to this point, including high density (sinking), floating, bio- or mucoadhesive, expandable, unfoldable, ultra porous hydrogel, and magnetic systems. Additionally, the advantages of gastroretentive medicine administration systems were thoroughly covered.

Plant Gum Aided Mucoadhesive Microspheres to Eradicate Helicobacter pylori and Its Optimization with Design-Expert's Central Composite Design

Aim: The aim of the work was to explore the mucoadhesive properties of Mastic gum by involving it in mucoadhesive microspheres with Amoxicillin Trihydrate as a model drug. Using Carbopol-934P and varying amounts of Mastic gum. Methods: 9 interpretations of mucoadhesive microspheres were made by using Design expert software. A central composite design was applied to test the impact of independent variables (Carbopol-934P and mastic gum levels) on drug released at 10h and mucoadhesive strength as the response. Results: A congeniality and physical exam was conducted on the microspheres to see if Amoxicillin Trihydrate (ATH) was present, including its liberation. In formulations that contain lower levels of MG, mucoadhesion strength increased and drug released at the end of 10h was greater. Conclusion: Since MG acts as a release retardant, the amount of drug released is slightly reduced when higher levels are present in formulations. ATH gastro retention for eradicating with Mastic gum aided mucoadhesion (as this gum is proven H. pylori activity) is capable of completely capturing the gastrointestinal tract and effectively delivering the medication to the stomach.

Formulation and Characterization of Expandable Tablet of Diacerein using Swellable Polymers

Some of the drugs have poor absorption because of a narrow absorption window in the gastrointestinal tract (GIT). To improve the absorption of such drugs in the GIT, gastro-retentive drug delivery techniques play an important role. Diacerein is an antirheumatic drug used for joint pain and arthritis. The expandable gastro-retentive tablets were prepared to attain an extended therapeutic action of Diacerein. Expandable tablets were formulated to prolong gastric retention, enhance the bioavailability of the drug candidate and attain a desirable size greater than the diametric size of the pyloric sphincter (i.e., 13 mm in diameter) of the tablet after administration by expandable technique. The expandable tablet was formulated using swellable polymers and polyelectrolytes, i.e., HPMCK 100, PEO, chitosan, and carbopol. The proposed expandable tablets were evaluated by preliminary evaluation parameters, micromeritic investigations, all physicochemical evaluations including swelling index, weight variation, drug content, in-vitro release studies and their release kinetics. Method: The wet granulation method is used for the preparation of expandable tablets of Diacerein. Result: The release of Diacerein from all formulations was studied in phosphate buffer pH 1.2 at 37±5°C. The net results conclude that the formulation having HPMC K 100, PEO with the addition of carbopol (formulation C1) showed the maximum swelling index as compared to others. And it was found that formulation C1 is the most superior and reliable formulation in terms of all physicochemical parameters and in-vitro drug release studies. The best formulation obtained from in-vitro drug release studies was shown.
 Keywords: Gastro retentive, expandable system, noval drug delivery system, controlled drug delivery system, gastric transit time, swellable polymers, GIT.

Design and Development of Gastro-retentive Drug Delivery System for Trazodone Hydrochloride: a Promising Alternative to Innovator's Controlled-Release Tablet.

Trazodone hydrochloride (TZN) is a serotonin reuptake inhibitor that treats a major depressive disorder. It exhibits a short plasma half-life of 4.1 h and shows pH-dependent solubility. Above its pKa (6.74), solubility of TZN is very low, affecting its dissolution in the lower part of GIT. Hence, the present work aimed to develop gastro-retentive floating tablet of TZN. Central composite design was employed to optimize the formulation. Formulation variables like the concentration of HPMC-K100M, Polyox WSR 303 Leo, and sodium bicarbonate were evaluated for the responses like floating lag time and drug release. X-ray imaging study was performed on rabbits to determine the in vivo gastric retention of the optimized formulation. The accelerated stability study was conducted on optimized tablets as per ICH guidelines. Floating lag time and f2 value of the optimized formulation were found to be 2.51±0.02 min and 62.79, respectively. X-ray imaging studies in rabbits determined the in vivo gastro retention time. After 12 h of administration, tablet remained in the gastric region, indicating better retentive power. Accelerated stability studies showed sufficient formulation stability even after 3 months of storage. All these studies depict that the floating gastro-retentive system could be used as an alternative to the innovator formulation.

Administration strategies and smart devices for drug release in specific sites of the upper GI tract

Targeting the release of drugs in specific sites of the upper GI tract would meet local therapeutic goals, improve the bioavailability of specific drugs and help overcoming compliance-related limitations, especially in chronic illnesses of great social/economic impact and involving polytherapies (e.g. Parkinson's and Alzeimer's disease, tubercolosis, malaria, HIV, HCV). It has been traditionally pursued using gastroretentive (GR) systems, i.e. low-density, high-density, magnetic, adhesive and expandable devices. More recently, the interest towards oral administration of biologics has prompted the development of novel drug delivery systems (DDSs) provided with needles and able to inject different formulations in the mucosa of the upper GI tract and particularly of esophagus, stomach or small intestine. Besides comprehensive literature analysis, DDSs identified as smart devices in view of their high degree of complexity in terms of design, working mechanism, materials employed and manufacturing steps were discussed making use of graphic tools.

Microballoons: An Advanced Avenue for Gastro Retentive Drug Delivery System

The motivation of writing this review on micro balloons is a Gastro retentive drug delivery system are micro balloons (hollow microsphere) are a drug delivery system that promises to be a potential approach for gastric retention. Microballoons drug delivery system is novel drug delivery on the foundation of non- effervescent system that containing empty particles of spherical shape without core ideally having a size less than 200 micrometers which is designed to be retained in the stomach for a prolonged period of time and release their active ingredients and thereby enable sustained and prolonged input of the drug in the upper part of the gastrointestinal (GI) tract. They are gastro retentive drug-delivery systems, which provide controlled release properties for a drug. Recently gastro retentive drug delivery system (GRDDS) are gaining wide acceptance for drugs with narrow absorption windows, decreased stability at high alkaline pH, and increased solubility at low pH. The design of this article is to compose the various gastro retentive arrive. In order to understand various physiological difficulties to achieve gastric retention, we have summarized important factors controlling retention i.e. high density, floating, bio-or that adheres to a mucous membrane (adjective), extensile, attractor etc. In addition of central element controlling gastro retention, superiority and finally future potential are discussed.

Formulation and Evaluation of Floating In-Situ Gel of Nicardipine Hydrochloride

The present research work aimed to formulate and evaluate a gastro retentive in situ gelling system of Nicardipine Hydrochloride using Sodium Alginate as gelling polymer, HPMC K100M as release retard polymer, calcium carbonate as a cross-linking agent, and tri-sodium citrate as fluidity enhancer agent to treat hypertension. The mechanism for the floatation was based on ionic cross-linking. Several evaluation tests were carried out for pre and final formulation evaluation. Based on the outcomes white-colored, viscous solution of uniform consistency was obtained. Batch B1 was very well prepared for the ability to control long-term drug release. The drug content was found to be > 97 %, the viscosities were in the acceptable range suitable for swallowing, and pH was found to be in the range of 7.33 – 7.68 which was compatible with oral digestion. Design expert 13 Software was used to derive results of interaction and responses based on the concentration of polymer and statistical analysis. The optimized formulation i.e., Batch B1 (0.6 % w/v and 0.5 % w/v HPMC K100M) showed a slow drug release of 96.44 % up to 12 hours. The best fit model for the drug release followed the Higuchi model which explained that the drug release occurred by the Fiskian mechanism i.e., a combination of both diffusion and erosion. The in-situ gel prepared can ultimately provide prolonged release, enhance the bioavailability of the drug and increase patient compliance.
 Keywords: - In situ gel, Ionic cross linking, Sodium alginate, HPMC K100M, Nicardipine Hydrochloride.

Development and Evaluation of Gastro Retentive Floating Drug Delivery System of Ondansetron Hydrochloride

The Aim of the present study was to develop & evaluate Gastro-retentive floating Tablet of Ondansetron hydrochloride. The Objective was to calibrate and validate the UV- spectroscopy analytical method and to prepare and optimize the GR Floating tablets of Ondansetron hydrochloride in terms of dissolution release profile. The FDDS of the drug can minimize the fluctuation of drug plasma levels and result to associated adverse reactions, dosing frequency, and improved patient compliance. Conventionally, Ondansetron hydrochloride is taken up 2-3 times daily in the treatment of nausea and vomiting. Gastro retentive floating tablet of Ondansetron hydrochloride is better suited for treatment of postoperative nausea vomiting. In the present study, nine Gastro retentive Floating tablet formulations (F1, F2.....F9) of Ondansetron hydrochloride were prepared by the method of direct compression and polymers HPMC K15 were used and Guargum and Chitosan, in different quantity to normalise their effect on the’ release profile of drug . Target release profile was >80% release of drug in 12 hours. Tablets were evaluated for various parameters namely: thickness, weight variation’, friability, hardness, assay, in-vitro buoyancy study & drug release. Formulation F8 containing Chitosan (26.66% w/w), Guargum (26.66% w/w) and Sod. Carbonate (25.83% w/w) had the desirable release profile.
 Keywords: Ondansetron hydrochloride; Gastro retentive floating tablet, Chitosan, Guar gum, Drug release

NOVEL FLOATING AGENT SACCHAROMYCES BOULARDII FORMULATION BASED FLOATING DRUG DELIVERY SYSTEM

Objective: The objective is to design and optimize a floating tablet of furosemide using a novel floating agent Saccharomyces boulardii. Methods: In this study floating tablet based on principle of combination of floating and swelling prepared by direct compression technique. Saccharomyces boulardii probiotics preparation is used as a floating agent due to its bloating property i.e. production of CO2 gas and hydrophilic polymer HPMC E LV 15 used as swellable polymer. Furosemide is a BCS class IV drug selected as model drug which shows pH dependent solubility and permeability and it is better absorbed from the gastric region, hence to improve dissolution and residence at absorption site of such drug, floating drug delivery system is needed. Calcium hydroxide used as pH modifier which increase rate of dissolution of furosemide and also maintain integrity of tablet matrix. Formulation designed and developed using central composite design response surface methodology technique, so as to explore the effect of formulation variables such as amount of Saccharomyces boulardii preparation and calcium hydroxide on floating lag time and % drug release after 12h. Results: The numerical and graphical optimization technique were used to choose the optimal formulation. Floating lag time was found to be 12.6 min and 88.18% drug release for the optimized formulation. In vivo buoyancy studies depicted that formulation stay more then 6h in stomach. Conclusion: Study indicate that Saccharomyces boulardii is a promising floating agent, and the formulation containing this novel floating agent is suitable for gastro retention and it increases bioavailability of furosemide.

A REVIEW ON AN EMERGIN TREND BILAYER FLOATING DRUG DELIVERY SYSTEM

NDDS is advanced drug delivery system which improves drug potency, control drug release to give a sustained therapeutic effect, provide greater safety, finally it is to target a drug specifically to a desired tissue. Novel drug delivery system have been developed to overcome the limitation of conventional drug delivery systems, such as of gastric retention by decreasing fluctuations in the concentration of the drug in blood,resulting in the reduction in unwanted toxicity and poor efficiency. As compared to traditional dosage forms bilayer tablets are more efficient for sequential release of two drugs that can be different or identical. Bilayer tablet is also capable of separating two incompatible substances and also for sustained release. Gastro retentive drug delivery system retains the period of dosage forms in the stomach or upper gastro intes-tinal tract ,as to improve bioavailability and the therapeutic efficacy of the drugs. Mainly the bilayer drug delivery system is suitable for drugs whose therapethic windows are narrow in the gastrointestinal tract (GIT) and also they have low elimination half life: 3-4 h. The purpose of this review is to disclose the challenges faced during the formulation of bilayer tablets. Finally, the whole article is firmly analyzed in a concluding paragraph. KEYWORDS: Conventional drug delivery systems, Bilayer tablet, Gastro retentive, Bioavailability

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.

FORMULATION AND EVALUATION OF SUMATRIPTAN SUCCINATE AND NAPROXEN SODIUM GASTRORETENTIVE (FLOATING) BILAYERED TABLETS

The main aim of the present work was to formulate and evaluate sumatriptan succinate and naproxen sodium gastro retentive(floating) bilayered tablets. Floating bilayer tablets were formulated using direct compression method, it consist of two layers i.e IR layer containing Naproxen and floating CR layer containing sumatriptan. IR2 layer containing 2% concentration of Cross Povidone was found to be optimum and released 99.23% of naproxen in 45min. The optimized floating CR8 layer containing HPMC K 100M in 46% concentration showed 81.21% of drug release at the end of 12h. Among all formulations, IR2 & CR8 provided slow release of sumatriptan over 12h and rapid release of naproxen within 45 min, hence it is considered as an optimum bilayered formulation of sumatriptan and naproxen. The optimised formulation was fitted in the Kinetic models and it follows Korsmeyer-Peppas kinetics and the release mechanism was Case II non- fickian diffusion from these tablets.

Formulation Development and Evaluation of Gastro Retentive Matrix Tablet of Levamisole Hydrochloride

The aim of current study was to develop suitable gastroretentive tablet of Levamisole HCl for prolonging the retention of Levamisole in stomach. Floating tablets were prepared by using HPMC K4M and Carbopol 934p in combination and their effect on floating, swelling and release of Levamisole HCl was studied. Optimization of drug release were carried out by taking different concentration of HPMC K4M and Carbopol 934p. It was found that HPMC and Carbopol with concentration 35% and 22% in tablet give satisfactory release and batch was selected for 32 factorial design. In this study all the formulation were subjected to physical evaluation parameter such as Hardness, Friability, content uniformity all were found to be within limits. In-vivo study F5 formulation was carried out to check the buoyancy of tablet. Tablet float in stomach of rabbit for 8 hours without adhering to gastric mucous. Stability studies of F5 formulation indicated that formulation is stable for 3 months at 40o C and 75% RH. The formulation retained its integrity and In-vitro performance.