Gastroretentive Floating Drug Delivery System Research Articles

Green synthesis of polyacrylamide grafted Neem Gum for gastro retentive floating drug delivery of Ciprofloxacin Hydrochloride: In vitro and in vivo evaluation

Gastro retentive Floating Drug Delivery Systems (GFDDS) are typically designed to enhance the efficiency of drugs; absorbed in the stomach and possess a short elimination half-life by controlling the drug release rate. This study presents, that Acrylamide Grafted Neem gum (AAm-g-NG) was synthesized for the development of tablet-based GFDDS by using the Microwave-assisted technique for the delivery of Ciprofloxacin Hydrochloride (CFX.HCL). Formulations were evaluated for pre-and post-compression studies like bulk, tapped density, angle of repose and hardness, friability, drug content, weight variation, and drug release, which satisfied all the official requirements of the tablet dosage form. The Structural characterization of the synthesized AAm-g-NG was studied by various analytical techniques like NMR, DSC, FTIR, XRD, and SEM. AAm-g-NG showed a significant swelling index, Water Retention Capacity, Waterlogged capacity, viscosity, and in vitro buoyancy compared to NG and HPMC K100 M. AAm-g-NG was also studied for hemolysis and cytotoxicity; found to be biodegradable and exhibited no toxicity in the Caco-2 cell line. The optimized batch F5 showed controlled drug release of 89% ± 3.56 at 12 h in pH 1.2 and in vivo gastric retention was approx. 8 h in rabbits. The ability of AAm-g-NG graft copolymer to extend the drug release with enhanced gastric retention is well supported by in vivo buoyancy studies and its satisfactory physicochemical properties make it a promising vehicle for gastro retentive system.

DEVELOPMENT AND CHARACTERIZATION OF GASTRO RETENTIVE TABLETS OF CLARITHROMYCIN FOR ANTIULCER EFFECT

Gastroretentive floating drug delivery system (GFDDS) is used to prolong the gastric residence time after oral administration, at a particular site and controlled or modified the release of drug from the formulation.The purpose of the present study is to develop a gastro retentive floating drug delivery system to achieving controlled release so that is improves bioavailability of the formulation, Structure activity relationship based on Biopharmaceutical Properties of Clarithromycin indicates good biopharmaceutical Properties. Floating dosage form of Clarithromycin was designed for the treatment of gastric ulcer caused by Helicobacter pylori. The granules were prepared by wet granulation method and evaluated for flow property, Carrs' index, bulk density, tapped density and Hausner ratio. The dosage form was designed by using polymers of different viscosity as gelling agents, sodium bicarbonate as gas generating agent and other excipients. The granules were further subjected to tablet preparation and the prepared tablets were subjected for evaluated on the basis of different evaluation parameters like hardness, in vitro buoyancy, in vitro drug release. Incorporation of gas generating agent together with polymer improved drug release Optimized formulation (F7) containing Clarithromycin, HPMC, 90 SH , HPMC K4M , sodium bicarbonate, released approximately 86.6% drug in 10 hrs. and the floating lag time was found to be 25 sec. KEYWORDS: GFDDS, Helicobacter pylori, gelling agents, in vitro buoyancy, HPMC, wet granulation.

A Comprehensive Review on Microbubble Concept, Development and Its Application in Therapeutic Drug Delivery and Clinical Management of Disease.

The general purpose of this review was to briefly describe the Gastro-Retentive Drug Delivery System (GRDDS) and to primarily focus on mechanisms of flotation for gastric retention. The principle mechanism of Floating Drug Delivery Systems (FDDS) is mainly based on hydro-dynamically controlled low-density system, which gets swollen when comes in contact with the gastric environment and remains buoyant for an extended period of time with improved bioavailability and therapeutic efficacy. The main perspective of this review was to focus on microbubble drug delivery due to its wide range of applications. Microbubble is a new, economically viable, and non-invasive technique that is alternative to conventional techniques. The size of microbubbles ranges from 1-100 micrometers, which contain oxygen or air and remain suspended for prolonged drug release. Due to its great potential, microbubble is used in the therapeutic delivery of drug molecules or genetic material at their specific targeted site in various diseases. The recent research also suggests that ultrasound-mediated microbubble is more frequently used in the biomedical field for imaging of site-specific molecule targeting for the detection of disease and site-specific drug delivery. Gastro-retentive floating drug delivery system was considered as the most favorable approach for site-specific drug delivery. But nowadays, microbubble is gaining more popularity for its potential applications in the biomedical field. In recent years, there is much progress in microbubble for site-specific delivery of a drug or genetic material. Recent research also suggests that the ultrasound- mediated microbubble has shown a positive impact on the diagnosis and clinical management of various diseases such as liver cirrhosis, brain tumor, ocular, and urinary tract infection.

Comprehensive review on characterizations and application of gastro-retentive floating drug delivery system

Current pharmaceutical situation focuses on the preparation of gastro-retentive floating drug delivery system (GRFDDS). This systems has gained noteworthy interest in the past decades. These are the low density systems that float over the gastric contents and remain buoyant in the stomach for a prolonged period of time without affecting the gastric emptying rate. GRFDDS is used to delay the residence time of delivery in stomach. The controlled gastric retention of solid dosage forms may be achieved by the mechanism of mucoadhesion, floatation, sedimentation, expansion, modified shape systems or by the administration of pharmacological agents that delaying gastric emptying. This results in targeting of release of drug at a specific site for the systemic or local effects. GRDDS is used to overcome challenges associated with conventional oral dosage forms and to release the drug at a specific absorption site to improve bioavailability of particular drug substance. Some floating drug delivery systems have shown the capability to accommodate these variations without affecting drug release. This review mainly focuses characterizations and application of gastro-retentive floating drug delivery systems.

Comprehensive review on characterizations and application of gastro-retentive floating drug delivery system

Comprehensive review on characterizations and application of gastro-retentive floating drug delivery system

Gastro Retentive Floating Drug Delivery System: An Overveiw

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

Preparation and evaluation of cefuroxime axetil gastro-retentive floating drug delivery system via hot melt extrusion technology

Cefuroxime Axetil (CA) is a poorly soluble, broad spectrum antibiotic which undergoes enzymatic degradation in gastrointestinal tract. The objective of the present study was to develop lipid-based gastro-retentive floating drug delivery systems containing CA using hot-melt extrusion (HME) to improve absorption. Selected formulations of CA and lipids were extruded using a twin screw hot-melt extruder. Milled extrudates were characterized for dissolution, floating strength, and micromeritic properties. Solid-state characterization was performed using differential scanning calorimetry (DSC), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and hot-stage microscopy. In vitro characterization demonstrated that the formulations exhibited a sustained drug release profile for 12 h. All formulations showed desired floating and flow properties. Solid-state characterization revealed no phase separation and no chemical interactions between the drug and excipients. Based on in vitro study results, an optimized formulation (F8) was further evaluated for in vivo performance. Oral bioavailability (Cmax and AUC0–24h) of F8 was significantly higher than that of pure CA. This study describes the use of lipid-based gastro-retentive floating drug delivery systems to achieve desired sustained release profile for more complete dissolution which could potentially reduce enzymatic degradation. This study also highlights the effectiveness of HME technology to improve dissolution and bioavailability.

Modeling, design and manufacture of innovative floating gastroretentive drug delivery systems based on hot-melt extruded tubes

The problem of many gastroretentive systems is the mechanistic connection of drug release and gastric retention control. This connection could be successfully separated by formulating hollow tubes via hot-melt extrusion and sealing both tube ends, which led to immediately floating devices. The tube wall consisted of metformin crystals embedded in an inert polymer matrix of Eudragit® RS PO and E PO. Very high drug loadings of up to 80% (w/w) were used without generating a ‘burst release’. Sustained release profiles from four to more than twelve hours were achieved by varying the polymer proportions without affecting the floatability. Buoyancy was found to mainly depend on the cylinder design, i.e. the outer to inner diameter ratio. This allowed the polymer/metformin composition to be changed without affecting buoyancy, i.e. a separation of floatability and release control was achieved. A prediction model was implemented that allowed for the buoyancy force to be determined with high accuracy by selecting a suitable ratio of outer to inner diameter of the modular tube die. Wall thickness and mass normalized surface area were identified as geometric parameters that mainly influenced the release properties. Conclusively, this study offers a highly flexible and rational manufacturing approach for the development of gastroretentive floating drug delivery systems.

Formulation and Evaluation of Gastroretentive Floating Dosage Forms of Clarithromycin

The objective of the present investigation is to formulate gastro retentive floating drug delivery systems (GRFDDS) of clarithromycin for the treatment of Helicobacter pylori, to prolong the gastric residence time after oral administration, at a particular site and controlling the release of drug especially useful for achieving controlled plasma level as well as improving bioavailability and to study the effect of formulation variables on floating lag time, t50 (time required to release 50% of the drug) and t90 (time required to release 90% of the drug). The GRFDDS contains hydroxypropyl methylcellulose (HPMC) and hydroxyl propyl cellulose (HPC) as a release retarding polymer. The concentration of sodium bicarbonate (NaHCo3) was optimized. The tablets were prepared by wet granulation method. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, drug release and rate order kinetics. From the results, FHM4 was selected as an optimized formulation based on their 12 hrs drug release, minimal floating lag time and maximum total floating time. The optimized formulation followed first order rate kinetics with erosion mechanism. The optimized formulation was characterized with FTIR studies and no interaction between the drug and the polymers were observed.

Recent Trends in Development of Gastro-Retentive Floating Drug Delivery System: A Review

Recent Trends in Development of Gastro-Retentive Floating Drug Delivery System: A Review

DESIGN AND DEVELOPMENT OF GASTRORETENTIVE DRUG DELIVERY SYSTEM OF CIPROFLOXACIN HYDROCHLORIDE

Objective: The aim is to prepare the floating tablet of ciprofloxacin and to improve their bioavailability in the treatment against the Gram-positive and Gram-negative microorganisms. Ciprofloxacin HCL is an acidic drug used for respiratory tract infection, diarrhea, skin infection, thyroid fever, and urinary tract infection. The ciprofloxacin HCL is primarily absorbed in the stomach and it has low bioavailability. Due to its low availability, it was chosen as an appropriate drug for the scheme of the gastroretentive floating drug delivery system. Method: Ciprofloxacin HCl is an acidic drug which was made by wet granulation process using various polymers, which include hydroxypropyl methylcellulose K4M, Eudragit, and Guar gum with a different composition. The gas generating agents such as saleratus and citric acid were used for the preparation. The prepared granules were subjected to pre-compression parameters technique and the formulated tablets were subjected to post-compression parameters, respectively. Result: The Fourier-transform infrared analysis reveal that the drug and excipients used for the formulations were compatible with each other. All formulated granules having good flow properties and all the post-compression parameter are within the limit in which the F4 formulation shows optimum drug release of about 98.7% at 12 h and which has the buoyancy lag time of about 134 s and floating time about 12.5 h. Kinetic treatment revealed of the optimized preparation is based on Korsmeyer–Peppas model. The value n=0.861 states the process of non-Fickian diffusion. Conclusion: Based on above observation found in the work, it was concluded that ciprofloxacin HCl can formulate as a floating drug delivery system which helps in increasing the gastric residence time, as a result, it increases the bioavailability and half-life of ciprofloxacin HCl.

Formulation development and evaluation of gastroretentive floating drug delivery system using natural polymer.

Formulation development and evaluation of gastroretentive floating drug delivery system using natural polymer.

Formulation and Characterization of Gastroretentive Floating Tablets of Atorvastatin Calcium Using Central Composite Design

The aim of the study was to develop a gastroretentive floating drug delivery system of atorvastatin calcium by effervescence technique. Design/methodology/approach : The objective behind the study was to investigate the effect of concentration of HPMC K4M (X), concentration of guar gum (X), concentration of sodium bicarbonate (X) on the release of 1 2 3 atorvastatin calcium using central composite design.The floating tablets were formulated using atorvastatin calcium (20% w/w), HPMC K4M (5-15% w/w), guar gum (5-15% w/w), sodium bicarbonate (4-12% w/w), lactose (q.s.), talc (2% w/w) and magnesium stearate (1% w/w). Atorvastatin calcium floating tablets were evaluated for physical characterization viz. hardness, swelling index, floating capacity, weight variation, friability, in vitro drug release and kinetic studies. Findings : All tablets were floated for more than 12 hrs in 0.1 N HCl at 37±0.5°C and the in vitro drug release was found to be vary from 79% to 93%. The percentage cumulative drug released was maximum at low value of HPMC, low value of guar gum and high value of sodium bicarbonate. A mathematical model was developed to formulate floating tablets of atorvastatin calcium. The data fitting to Korsemeyer-Peppas equation revealed that the release mechanism from the dosage form followed the non-fickian transport. Value : The gastroretentive floating tablets of atorvastatin calcium will enhance the patient compliance and play a vital role in improving patient's quality of life.

Herbal carrier-based floating microparticles of diltiazem hydrochloride for improved cardiac activity

Purpose: To formulate and characterize a gastroretentive floating drug delivery system for diltiazem hydrochloride using psyllium husk and sodium alginate as natural herbal carriers to improve the therapeutic effect of the drug in cardiac patients.Methods: Floating microparticles containing diltiazem hydrochloride were prepared by the orifice ionic gelation technique. Various physicochemical properties of the floating microspheres were characterized, including drug content, particle size, surface morphology, in vitro drug release, and in vivo antihypertensive effect.Results: The diltiazem hydrochloride microparticles exhibited a high drug content ranging from 63.23 ± 1.14 to 85.56 % ± 1.14 %. The particle size was 891.40 ± 2.14, 928.40 ± 1.79, 900.65 ± 2.22, and 1345.40 ± 1.36 μm (p < 0.05 compared to blank microspheres for formulations FDD1, FDD2, FDD3, and FFD4), respectively. Scanning electron microscopy showed that all the formulations had a smooth spherical surface with little pores and few cracks. The maximum floatability value was 83.11 % ± 3.18 % for FDD1. All of the formulations showed good in vitro drug release profiles, with a maximum release of 87.4 % of the drug at the end of 12 hours. The in vivo antihypertensive effects of the microparticles in human subjects were significant (p < 0.05 compared to normal controls), with a reduction in diastolic blood pressure from 120 to 78 mmHg at the end of 4 hours compared to diltiazem sustained-release tablets.Conclusion: Psyllium husk and sodium alginate-based microspheres can be suitably prepared for the controlled delivery of diltiazem hydrochloride to cardiac patients. However, further study is required to develop the delivery system.Keywords: Diltiazem, Cardiac disease, Psyllium husk, Sodium alginate, Microsphere, Microparticle, Controlled drug release, Gastroretentive, Floating drug delivery

Formulation and In vitro Evaluation of Floating Microspheres of Misoprostol

Misoprostol is a synthetic prostaglandin PGE1 analogue, which has proved to be an effective anti-secretory agent for oral use. The major indications of Misoprostol are in the prevention and treatment of NSAID-induced gastric and duodenal ulcers. Its half-life is 20-40 minutes. More than one third of patients with ulcers are resistant to H2 antagonists. So, these patients can be healed on Misoprostol. The objective of the present study was to formulate gastroretentive floating drug delivery system of an antiulcer drug Misoprostol. Floating microspheres of Misoprostol were prepared by an emulsification solvent evaporation technique using hydroxy propyl methyl-cellulose (HPMC K 100M) and ethyl cellulose. The percentage yield and drug entrapment efficiencies of these floating microspheres were within the range between: 70 ± 2.8 to 98 ± 2.9 % and 39.27 to 82.39 %, respectively. The determined mean particle size for all the microspheres were 250 ± 7.28 to 400 ± 2.32 µm. The flowability of these microspheres was found good. A high performance liquid chromatography (HPLC) method with ultra-violet (UV) detection was selected for the method of analysis. The drug release was found to delay for 12 hours with the increasing drug to polymer ratio. The drug release kinetics followed Korsemeyer-Peppas and Higuchi model with anomalous (non-Fickian) diffusion mechanism for the drug release. The FTIR and DSC studies showed that there was an absence of chemical interaction between the drug and the excipients. The in vitro drug release from Misoprostol floating microspheres showed the drug release was dependent on the drug to polymer ratio. The drug release was found delayed with the increasing drug to polymer ratio.

Glimepiride Micro balloons: A Novel Approach for Bioavailability Enhancement by Gastro-Retentive Floating Drug Delivery System

Glimepiride Micro balloons: A Novel Approach for Bioavailability Enhancement by Gastro-Retentive Floating Drug Delivery System

Formulation and In vitro Characterization of Hydrochlorothiazide Gastroretentive Floating Drug Delivery System

The purpose of the study was to develop and optimize floating bioadhesive gastroretentive drug delivery system (GRDDS) exhibiting a unique combination of floatation and bioadhesion to prolong residence in the stomach, using hydrochlorothiazide (HCTZ) as a model drug. Formulated matrix tablets were prepared by direct compression method with two different rate controlling polymer HPMC K4M and Carbopol 971. The formulated tablets were evaluated for physical characterization, floating lag time, swelling index and drug content uniformity. The drug release study was carried out in 0.1N HCl as the medium (pH 1.2) for 8 hours using USP type II dissolution apparatus and investigated the effects of polymers on the drug release profile. In vitro buoyancy study results found to be 10–33 sec and >8 h, floating lag time and total floating time respectively. Simulated drug release pattern in different kinetic models of Korsmeyer-Peppas release suggests that the mechanism controlling of the drug release from all formulations was the anomalous non-Fickian or anomalous release. Polymer with lower viscosity (HMPC K4M) was found to be beneficial than higher viscosity polymer (Carbopol 971) in improving the release properties of gastric floating drug delivery system. Incorporation of Carbopol in formulation also helped in maintaining buoyancy of system with desirable drug release. Further study is necessary in case of in vitro- in vivo relationship, but this study will ready to lend a hand to future scientists working in this field to successfully exploit the potential of this drug delivery system for the advantage of mankind.Dhaka Univ. J. Pharm. Sci. 14(2): 163-170, 2015 (December)

Natural Macromolecules in the Development of Safe and Effective Gastroretentive Floating Microparticles of Metformin Hydrochloride

Background: Metformin hydrochloride, an oral hypoglycaemic, shows better absorption from upper part of the gastric region. Natural/herbal substances have been investigated for the development of natural polymer-based drug delivery systems owing to the desirable properties like biodegradability, biocompatibility, aqueous solubility, swelling ability, easy availability and cost effectiveness. Method: Therefore, three natural macromolecules: Glycine max (soya chunks), Metroxylon sagu (sago starch) and Plantago ovata (psyllium husk) were used for developing its gastroretentive floating microparticles for expected improvement in bioavailability. The macromolecules and the prepared microparticles were evaluated for physicochemical properties, FTIR, XRPD, DSC and dug release. Result: The percent drug content was in the range of 60.353 ± 1.25 to 92.682 ± 2.47 % for all the microparticles. All the formulations showed good swelling and floating properties (the formulation prepared with P. ovata showed the best swelling and in vitro floatability). The FTIR studies showed that the herbal carriers were compatible with the drug. XRD and DSC studies showed a transition in the physical state of the drug in the formulations from crystalline state to amorphous state. In vitro drug release studies showed good percent cumulative drug release from all the formulations (72.13 to 87.06 % at the end of 6 hour) with non-fickian diffusion process. Conclusion: Therefore, it was concluded that the herbal macromolecules may be the potential, safe and effective carriers for improving the drug delivery of the metformin like drugs by developing, effective gastroretentive floating drug delivery systems.

Formulation and evaluation of metformin HCl floating microspheres

The purpose of the present investigation was the preparation and evaluation of gastro-retentive floating drug delivery system for anti-diabetic drug metformin hydrochloride that would retain the drug in stomach and continuously release the drug in controlled manner up to a predetermined time leading to improve bioavailability. The microspheres were prepared by oil-in-oil emulsion solvent evaporation technique using ethyl cellulose, methacrylic acid copolymer (Eudragit RS100, Eudragit RSPO and Eudragit RLPO). The dried floating microspheres were evaluated for percentage yield (%), actul drug content (%), drug entrapment efficiency, floating behavior, scanning electron microscopy and in vitro drug release studies. The microspheres were found spherical, porous and free flowing with a size range. Compatibility studies were performed by fourier transform infra-redand (FTIR) and differential thermal analysis (DTA) techniques. The DTA and FTIR data stated that drug and excipient were compatible. In-vitro release kinetics were studied in different mathematical release models following the zero order, Higuchi and Korsemeyer to find out the linear relationship and release rate of drug. The drug might be released by both diffusion and erosion as the correlation coefficient (R2) best fitted with Korsemeyer model and release exponent (n) was 0.45-0.89. In most cases good in vitro floating behavior was observed and a broad variety of drug release pattern was achieved by variation of the polymer which optimized to match target release profile. The developed floating microspheres of metformin hydrochloride may be used in clinic for prolonged drug release in stomach for at least 8 hrs, thereby improving the bioavailability and patient compliance.Asian J. Med. Biol. Res. December 2015, 1(3): 396-405

Formulation and Evaluation of Gastroretentive Floating Drug Delivery System of Atenolol

Formulation and Evaluation of Gastroretentive Floating Drug Delivery System of Atenolol