Gastroretentive Floating Drug Delivery System Research Articles

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

Formulation, development and optimization of gastroretentive floating drug delivery system of Olmesartan Medxomil

Formulation, development and optimization of gastroretentive floating drug delivery system of Olmesartan Medxomil

Techniques of Gastroretentive Floating Drug Delivery Advancement: A Review

The objective of preparing this article on gastroretentive floating drug delivery systems was to compile the recent literature with special focus on various gastroretentive approaches that have recently become leading methodologies in the field of site-specific orally administered controlled release drug delivery. Gastric emptying is a complex process and makes in vivo performance of the drug delivery systems uncertain. In order to understand various physiological difficulties to achieve gastric retention. In this article we have summarized important factors controlling gastric retention. Gastroretention would also facilitate local drug delivery to the stomach and proximal small intestine. So, gastroretention could help to provide greater availability of new as well as older generation products (5-FU) and consequently improved therapeutic activity with versatile clinical use and thus can provide required benefits to patients. In order to avoid various variability, efforts have been made to increase the retention time of the drug-delivery systems for more than 12 hours. The floating or hydrodynamically controlled drug delivery systems are useful in such application. From the formulation and technological point of view, the floating drug delivery system is comparatively easy and logical approach. The present review addresses briefly about the gastroretentive floating drug delivery systems . It also summarizes methods of evaluation of various floating dosage forms and applications of these systems.

GASTRORETENTIVE FLOATING MICROSPHERE OF NATEGLINIDE: FORMULATION, EVALUATION AND EFFECT OF DRUG-POLYMER RATIO

The study aims to develop gastroretentive floating drug delivery system of nateglinide which is used in the treatment of type – II diabetes. Due to the short biological half life of drug (about 1.5 hours), frequent dosing is required to maintain its therapeutic effect. Therefore, to prolong the gastric retention of nateglinide, its oil entrapped floating microspheres (different formulations with different drug to polymer ratio) were prepared using sodium alginate by emulsion gelation method. The prepared floating microspheres were subjected to evaluation for surface characteristic, entrapment efficiency, swelling index, in vitro buoyancy and in vitro drug release. The scanning electron microscope photograph indicated that the prepared microspheres were discrete and almost spherical in shape with a hollow inner core. The entrapment efficiency was found to be in the range of 80.47 % to 91.33% for all the formulations. Drug entrapment efficiency decreased with increasing polymer concentration in floating microspheres. Average buoyancy was found to be 93 % to 98% for all the formulations. The in vitro floating test clearly showed that most of the microspheres floated for around 12 hrs. The increase in polymer concentration slightly decreased the percent yield and the drug entrapment. On the other hand the increased polymer concentration resulted into increased degree of swelling and percent buoyancy. All the formulations showed good in vitro drug release with first order release by matrix diffusion process. Overall, among the different polymer-drug ratios investigated, 1:6 drug to polymer ratio showed the best buoyancy, highest swelling index, good drug release with good entrapment efficiency. It was concluded that drug-loaded floating alginate microspheres appeared to be a suitable delivery system for nateglinide for potential therapeutic use as a hypoglycemic agent.

Design and Evaluation of a Novel Gas Formation-Based Multiple-Unit Gastro-Retentive Floating Drug Delivery System for Quetiapine Fumarate

Purpose: To develop a gastro-retentive formulation of quetiapine fumarate in the form of floating minitablets.Methods: The system consisted of core units prepared by direct compression process, which were coated with three successive layers, namely, an inner seal coat, effervescent layer and an outer polymeric layer of polymethacrylates.Results: Mini-tablets coated with Eudragit RS 30D (5, 7.5 and 10%) released . 85% of the drug after 12 h, while those coated with Eudragit RL 30D (5, 7.5 and 10%) released . 85% drug within the same period. Drug release kinetic studies showed that drug diffusion fitted best to zero order and Higuchi models, indicating that drug release was anomalous non-Fickian transport. In vivo gastric residence time results indicate that the units remained in the stomach for about 6 h (n = 3). There was nosignificant change in dissolution profiles before and after storage at 40‹C and 75% RH for 6 months.Conclusion: The developed floating mini-tablets of quetiapine fumarate exhibit prolonged release for .12 h, and thus may improve bioavailability and minimize fluctuations in plasma drug concentrations. Keywords: Mini-tablets; Floating delivery system; Effervescence, Polymeric membrane, Controlled release, Quetiapine fumarate

Formulation of Gastroretentive Floating Drug Delivery System of Indomethacin

Formulation of Gastroretentive Floating Drug Delivery System of Indomethacin

Formulation of gastroretentive floating drug delivery system using hydrophilic polymers and its in vitro characterization

The aim of the present research is to formulate and evaluate the gastroretentive floating drug delivery system of antihypertensive drug, propranolol HCl. Gastroretentive floating tablets (GRFT) were prepared by using a synthetic hydrophilic polymer polyethylene oxide of different grades such as PEO WSR N-12 K and PEO 18 NF as release retarding polymers and calcium carbonate as gas generating agent. The GRFT were compressed by direct compression strategy and the tablets were evaluated for physico-chemical properties, in vitro buoyancy, swelling studies, in vitro dissolution studies and release mechanism studies. From the dissolution and buoyancy studies, F 9 was selected as an optimized formulation. The optimized formulation followed zero order rate kinetics with non-Fickian diffusion mechanism. The optimized formulation was characterised with FTIR studies and observed no interaction between the drug and the polymers.

Formulation and evaluation of gastroretentive floating drug delivery system of dipyridamole

A multiple-unit floating alginate bead drug delivery system with prolonged stomach retention time was developed in this study. The floating alginate beads were prepared by ionic cross-linking method, using CaCO3 as the gas-forming agent. Over 92% of the beads remained floating after 9 h. In order to prepare sustained-release dosage forms of dipyridamole, the solid dispersion technique was applied using a blend of Eudragit L100 and Eudragit RLPO. Afterwards, the solid dispersions of dipyridamole were incorporated into the floating alginate beads. The drug release was modified by changing the ratio of Eudragit RLPO and Eudragit L100 in the solid dispersions. The in vivo results showed that the relative bioavailability of alginate beads was enhanced by approximately 2.52-fold compared with that of the commercial tablet. Therefore, our study illustrated the potential use of floating alginate beads combined with the solid dispersion technique for the delivery of acid-soluble compounds, such as dipyridamole.

In vitro and in vivo evaluation of gastroretentive floating drug delivery system of ofloxacin

This study aimed to develop hydrophilic matrix based controlled release gastroretentive drug delivery system of ofloxacin and conducting its in vitro and in vivo evaluations. Effervescent floating gastroretentive drug delivery system of ofloxacin was prepared utilizing Box–Behnken statistical design with 3 factors, 3 levels and 15 experimental trials. Formulation optimization was done by setting targets on selected responses. In vivo studies were carried out for the optimized formulation with 12 healthy human volunteers and obtained pharmacokinetic parameters were compared with the marketed once daily formulation, “Zanocin OD”. Optimized formulation showed satisfactory controlled in vitro drug release for more than 12 h with excellent buoyancy properties (floating lag time <1 min, floating duration >16 h). Optimized and marketed formulations were found to have similar in vitro release profile (f2 = 79.22) and also were found to be bioequivalent. Serum ofloxacin concentration was well maintained above its reported minimum inhibitory concentrations for most of the pathogens for sufficiently longer duration. Cmax and AUC values of optimized formulation were found to be significantly higher than of marketed product despite their bioequivalence. Bettertherapeutic effect can be expected since ofloxacin exhibits concentration dependent killing. Hence, gastroretention can be a promising approach to enhance bioavailability of ofloxacin with narrow absorption window in upper GIT.

Formulation development and in vitro and in vivo evaluation of gastroretentive floating drug delivery system of Lafutidine

Formulation development and in vitro and in vivo evaluation of gastroretentive floating drug delivery system of Lafutidine

Formulation development and in vitro and in vivo evaluation of gastroretentive floating drug delivery system of Lafutidine

Lafutidine a newly developed histamine H2‐receptor antagonist was retained in the stomach and assist in improving the oral sustained delivery of drugs in the gastrointestinal tract. A floating drug delivery system (FDDS) was developed using the gas forming agents, such as sodium bicarbonate, citric acid with hydrochlorides, such as hydroxyl propyl methyl cellulose (HPMCK 4M, HPMCK15M) and novel Carbopol 71G. Polymer with lower viscosity was found to be beneficial than higher viscosity polymer in improving the release properties of gastroretentive FDDS. The prepared tablets of various formulations were evaluated for a total floating time, buoyancy lag time, and percentage drug released.The formulation code HF3 having HPMCK4M showed better results it may be useful for prolonged drug release in the stomach to improve the bioavailability and reduced the dose frequency. Non‐Fickians release transport was confirmed as the drug release mechanism from the optimized formulation by Korsmeyer‐Peppas. In vivo study was per formed using the rabbits by X‐ray imaging technique; radiological evidences suggest that, a formulated tablet was well floated more than 10 h in rabbit’s stomach.Optimized floating tablets showed no significant changes in the physical appearance, drug content, total buoyancy time, and also in vitro dissolution pattern after storage at 40°C/75% relative humidity for 3 months.

Characterization and in vitro drug release studies of a natural polysaccharide Terminalia catappa gum (Badam gum).

The main objective of the present study is the physicochemical characterization of naturally available Terminalia catappa gum (Badam gum [BG]) as a novel pharmaceutical excipient and its suitability in the development of gastroretentive floating drug delivery systems (GRFDDS) to retard the drug for 12h when the dosage form is exposed to gastrointestinal fluids in the gastric environment. As BG was being explored for the first time for its pharmaceutical application, physicochemical, microbiological, rheological, and stability studies were carried out on this gum. In the present investigation, the physicochemical properties, such as micromeritic, rheological, melting point, moisture content, pH, swelling index, water absorption, and volatile acidity, were evaluated. The gum was characterized by scanning electron microscopy, differential scanning calorimetry (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). Gastroretentive floating tablets of BG were prepared with the model drug propranolol HCl by direct compression methods. The prepared tablets were evaluated for all their physicochemical properties, in vitro buoyancy, in vitro drug release, and rate order kinetics. PBG 04 was selected as an optimized formulation based on its 12-h drug release and good buoyancy characteristics. The optimized formulation was characterized with FTIR, DSC, and PXRD studies, and no interaction between the drug and BG was found. Thus, the study confirmed that BG might be used in the gastroretentive drug delivery system as a release-retarding polymer.

Statistical optimization of a novel excipient (CMEC) based gastro retentive floating tablets of propranolol HCl and it's in vivo buoyancy characterization in healthy human volunteers.

The objective of the present investigation is to formulate gastro retentive floating drug delivery systems (GRFDDS) of propranolol HCl by central composite design and to study the effect of formulation variables on floating lag time, D1hr (% drug release at 1 hr) and t90 (time required to release 90% of the drug). 3 factor central composite design was employed for the development of GRFDDS containing novel semi synthetic polymer carboxymethyl ethyl cellulose (CMEC) as a release retarding polymer. CMEC, sodium bicarbonate and Povidone concentrations were included as independent variables. The tablets were prepared by direct compression method and were evaluated for in vitro buoyancy and dissolution studies. From the polynomial model fitting statistical analysis, it was confirmed that the response floating lag time and D1hr is suggested to quadratic model and t90 is suggested to linear model. All the statistical formulations followed first order rate kinetics with non-Fickian diffusion mechanism. The desirability function was used to optimize the response variables, each having a different target, and the observed responses were highly agreed with experimental values. Statistically optimized formulation was characterized by FTIR and DSC studies and found no interactions between drug and polymer. The results demonstrate the feasibility of the model in the development of GRFDDS containing a propranolol HCl. Statistically optimized formulation was evaluated for in vivo buoyancy studies in healthy humans for both fed and fasted states. From the results, it was concluded that gastric residence time of the floating tablets were enhanced at fed stage but not in fasted state.

Bioavailability enhancement of baclofen by gastroretentive floating formulation: statistical optimization, in vitro and in vivo pharmacokinetic studies

Objectives: The study was aimed to improve bioavailability of baclofen by developing gastroretentive floating drug delivery system (GFDDS).Methods: Preliminary optimization was done to select various release retardants to obtain minimum floating lag time, maximum floating duration and sustained release. Optimization by 32 factorial design was done using Polyox WSR 303 (X1) and HPMC K4M (X2) as independent variables and cumulative percentage drug released at 6 h (Q6h) as dependent variable.Results: Optimized formulation showed floating lag time of 4–5 s, floated for more than 12 h and released the drug in sustained manner. In vitro release followed zero ordered kinetics and when fitted to Korsemeyer Peppas model, indicated drug release by combination of diffusion as well as chain relaxation. In vivo floatability study confirmed floatation for more than 6 h. In vivo pharmacokinetic studies in rabbits showed Cmax of 189.96 ± 13.04 ng/mL and Tmax of 4 ± 0.35 h for GFDDS. The difference for AUC(0–T) and AUC(0–∞) between the test and reference formulation was statistically significant (p > 0.05). AUC(0–T) and AUC(0–∞) for GFDDS was 2.34 and 2.43 times greater than the marketed formulation respectively.Conclusion: GFDDS provided prolonged gastric residence and showed significant increase in bi oavailability of baclofen.

Optimization and characterization of gastroretentive floating drug delivery system using Box-Behnken design

Context: One among many strategies to prolong gastric residence time and improve local effect of the metronidazole in stomach to eradicate Helicobacter pylori in the treatment of peptic ulcer was floating drug delivery system particularly effervescent gastroretentive tablets.Objective: The objective of this study was to prepare and evaluate, effervescent floating drug delivery system of a model drug, metronidazole.Methods: Effervescent floating drug delivery tablets were prepared by wet granulation method. A three-factor, three levels Box-Behnken design was adopted for the optimization. The selected independent variables were amount of hydroxypropyl methylcellulose K 15M (X1), sodium carboxy methylcellulose (X2) and NaHCO3 (X3). The dependent variables were floating lag time (YFLT), cumulative percentage of metronidazole released at 6th h (Y6) and cumulative percentage of metronidazole released at 12th h (Y12). Physical properties, drug content, in vitro floating lag time, total floating time and drug release behavior were assessed.Results: YFLT range was found to be from 1.02 to 12.07 min. The ranges of other responses, Y6 and Y12 were 25.72 ± 2.85 to 77.14 ± 3.42 % and 65.47 ± 1.25 to 99.65 ± 2.28 %, respectively. Stability studies revealed that no significant change in in vitro floating lag time, total floating time and drug release behavior before and after storage.Conclusion: It can be concluded that a combination of hydroxypropyl methylcellulose K 15M, sodium carboxy methylcellulose and NaHCO3 can be used to increase the gastric residence time of the dosage form to improve local effect of metronidazole.

Barium Ions Crosslinked Alginate and Sterculia Gum-Based Gastroretentive Floating Drug Delivery System for Use in Peptic Ulcers

The gastro-retentive drug delivery system is required to improve the bioavailability and therapeutic efficacy of the drugs used for the diseases associated with the stomach. Both sterculia gum and alginate enhance the repair of mucosal damage in the GI tract and pantoprazole is a therapeutic agent for GI tract ulcers. Ionotropic gelation of these polysaccharides for the release of pantoprazole will develop the double potential drug delivery systems. Therefore, in the present study, an attempt has been made to synthesize a gastro-retentive floating drug delivery system by simultaneous ionotropic gelation of alginate and sterculia gum using BaCl2 as a crosslinker. The beads have been characterized by SEMs, EDAX, and FTIR analysis. The swelling of beads has been carried out as a function of pH of the swelling media. In addition, in vitro release dynamics of an anti-ulcer model drug pantoprazole from drug-loaded beads in different release media have been carried out for the evaluation of the drug release mechanism and diffusion coefficients. Release of drug from beads occurred through a Fickian-type diffusion mechanism. The present drug delivery sytem may have a double potential, first due to the therapeutic importance of the sterculia–alginate-based polymer matrix and second, release of pantoprazole in a controlled and sustained manner.

Floating Microspheres: Recent Trends in the Development of Gastroretentive Floating Drug Delivery System

Oral controlled release systems are designed to release the drug in-vivo with prediction so as to increase efficacy, minimize adverse effects and increase bioavailability of drugs. Floating drug delivery systems (FDDSs) are expected to remain buoyant in a lasting way upon the gastric contents. The various buoyant preparations include hollow microspheres, granules, powders, tablets, capsules, pills and laminated films. Floating microspheres are especially gaining attention due to their wide applicability in the targeting of drugs to the stomach. These floating microspheres have the advantage that they remain buoyant and distributed uniformly over the gastric fluid to avoid the vagaries of gastric emptying and release the drug for prolonged periods of time. Multiparticulate low-density particles can successfully prolong the gastric retention time of drugs. This article provides an overview of two important approaches utilized to prepare and improve the performance of floating microspheres.

Formulation and evaluation of multiple tablets as a biphasic gastroretentive floating drug delivery system for fenoverine

A biphasic gastroretentive drug delivery system of fenoverine was developed to maintain constant plasma concentration. The delivery system consisted of a loading-dose tablet and a floating multiple matrix tablet prepared by the direct compression process. The drug release from biphasic GRDDS in 0.1 mol L(-1) HCl and SGF (enzyme free) was sustained over 12 h with buoyant properties. Stability studies showed no significant change in dissolution profiles (f2 value > 50). Based on the release kinetics, it can be concluded that the floating multiple matrix tablet containing HPMC was a particularly suitable gastroretentive drug delivery system with a zero-order release profile.

Gastroretentive floating sterculia–alginate beads for use in antiulcer drug delivery

To improve the bioavailability and therapeutic efficacy of the drugs used for the diseases associated with the stomach, the retention of drug delivery systems in the stomach for longer time is requred. Therefore, in the present study, an attempt has been made to synthesize gastro-retentive floating drug delivery system by simultaneously ionotropic gelation of alginate and sterculia gum by using CaCl 2 as crosslinker. The beads thus formed have been characterized by scanning electron micrographs (SEMs), electron dispersion X-ray analysis (EDAX), Fourier transform infrared spectroscopy (FTIR) analysis. The swelling of beads has been carried out as a function of various reaction parameters and pH of the swelling media. In addition, in vitro release dynamics of anti-ulcer model drug pantoprazole from drug loaded beads in different release media has been carried out for the evaluation of the drug release mechanism and diffusion coefficients. Release of drug from beads occurred through Fickian type diffusion mechanism.