Gastric Floating Drug Delivery System Research Articles

Preparation, optimization and in vivo study of gastric floating tablets of constunolide and dehydrocostus lactone with ideal therapeutic effect on gastric diseases

Costunolide (COS) and dehydrocostus lactone (DEH), as natural phytochemical components, mainly originated from Aucklandiae radix (AR) and Vladimiriae radix (VR) used in the treatment of gastric diseases in traditional Chinese medicine. The α-methylene-γ-butyrolactone ring structure is the same active part of COS and DEH, and shows good curative effects, such as breast cancer, leukemia and gastric related diseases. Furthermore, the previous research of the lab team found that the combination of COS and DEH promoted the repair of gastric ulcer and effectively alleviated intestinal metaplasia of gastric mucosa. Nevertheless, the rapid gastric emptying process and inefficient gastrointestinal absorption resulted in low oral bioavailability of COS and DEH. Based on floating and swelling technology, this study developed a gastric floating drug delivery system for prolonging gastric residence time to delay the drug release in the stomach and enhance the bioavailability of COS and DEH. The gastric floating tablets of COS and DEH were prepared by the direct powder compression method, and the optimized formulation contained 30% HPMC K15 M and 10% NaHCO3. The results of response variable showed that the floating lag time was 13.50 ± 1.87 s, total floating time was 11.83 ± 0.41 h, 2 h and 12 h cumulative drug release was 29.87 ± 2.22%, 70.89 ± 4.27%, respectively. Additionally, the physicochemical properties of the floating tablets were characterized by friability, hardness, weight variation, Fourier transform infrared spectrum (FT-IR), differential scanning calorimeter (DSC) and X-ray diffraction (X-RD). The study on release kinetics showed that the drug release mechanism of gastric floating tablets of COS and DEH was both diffusion and matrix erosion. Moreover, scanning electron microscope (SEM), swelling and erosion indexes studies further explained the release mechanism. Furthermore, in vivo X-ray imaging of male New Zealand rabbits proved the gastric retention effect of the gastric floating tablets in the stomach (10 ± 3.46 h). The results of these experiments demonstrated that the gastric floating tablets of COS and DEH had the potential for a good gastric residence time and sustained release effect.

Preparation of clarithromycin floating core-shell systems (CSS) using multi-nozzle semi-solid extrusion-based 3D printing

Matrix erosion is unavoidable during the release of poorly soluble drugs from gastric floating delivery system (GFDDS), which shortens the floating time and diminishes drug release. We fabricated a core-shell system (CSS) consisting of a low-density drug-loaded shell and a floating core using multi-nozzle semi-solid extrusion (SSE) 3D printing technology. The clarithromycin (CAM) loading capacity of the shell was 81.7%. The floating core paste provided structural support during printing and formed a hollow structure in CAM CSS, which increased the buoyancy in the early stage of drug release. In addition, the floating core had numerous micro-airbags that swelled when the solution penetrated the core, and generated CO2. The micro-airbag structure and CO2 generation further increased the buoyancy of CSS. The CAM CSS achieved 74.5% (w/w) drug loading, 8 h sustained release, and immediate and prolonged floating (>10 h). This structure of CSS and floating core provide a novel perspective for constructing a stable gastric floating drug delivery system.

FLOATING DRUG DELIVERY SYSTEM OF NSAIDS TO INCREASE GASTRIC RETENTION TIME IN UPPER PART OF GASTROINTESTINAL TRACT

The purpose of the present work is to prolong the gastric residence time of Lornoxicam by developing gastric floating drug delivery system. Lornoxicam is non-steroidal anti-inflammatory drugs. Its short half life 2 to 3 hrs and maximal absorption of upper part of gastrointestinal tract. The residence time of the dosage form in the stomach depends upon various factors like pH, size of the dosage form, food intake, and biological factors which include age, body weight gender, posture, and diseased states Floating tablet prepared by melt granulation techniques, using bees wax as a binder and the other polymers include HPMC 50cPs,15cPs,5cPs and Sodium Alginate. The Prepared granules were then evaluated for Precompression Properties. The best batches were then tabulated, and Evaluation was carried out for the following parameters with in vitro release, buoyancy, Floating Lag timed. Batch F12 and F13 Showed best Floating time of 12hrs and Floating Lag time of 60 second.

Design and Evaluation of Controlled Release Gastric Floating Drug Delivery System of Proton Pump Inhibitor

Design and Evaluation of Controlled Release Gastric Floating Drug Delivery System of Proton Pump Inhibitor

FORMULATION AND EVALUATION OF GASTRORETENTIVE FLOATING TABLETS OF CANDESARTAN CELEXETIL BY DIRECT COMPRESSION

The objective was to develop optimized gastric floating drug delivery system (GFDDS) of candesartan celexetil floating tablets by using various polymers like Eudragit and MCC. In the present work, attempts have been made to prepare candesartan celexetil by direct compression method by using Citric acid, NaHCO3, Magnesium stearate, Eudragit and MCC. Formulations (F1 to F4) of floating tablets of candesartan celexetil were prepared using variable concentrations of Eudragit and MCC. The prepared formulations were evaluated for thickness, hardness, weight variation, friability, drug content and uniformity. The buoyancy lag time and the total floating time was studied for all the formulations. Formulation F4 of sustained release tablet of Candesartan celexetil containing a combination of both polymers was found to be the optimized formulation for 13 hours release as it fulfilled all the requirement of floating drug delivery system of sustained release dosage form.

Formulation of Gastric Floating System Using Bio-Sourced Terminalia Catappa Gum and in vivo Evaluation.

A central composite design was applied to design a novel gastric floating drug delivery system comprising propranolol HCl in Terminalia catappa gum and to evaluate the buoyancy, in vitro drug release behavior, and pharmacokinetic parameters. All formulations exhibited good buoyancy properties in vitro reflected by floating lag time of 1-110 sec, total floating time of 9-16 h and prolonged release behaviour (upto 12 h). Statistically optimised formulation (PBGRso) was orally administered to human volunteers under both fasted and fed conditions to evaluate gastric floating behavior under different food conditions by X-ray evaluation. In vivo studies of optimised formulations revealed that the gastric residence time of floating tablets was enhanced in the fed but not in the fasted state. Pharmacokinetic studies of the optimised Terminalia catappa formulation and a commercial product (Ciplar LA 80) carried out on healthy human volunteers showed a significant improvement in the bioavailability (132%) of propranolol HCl released from from the experimental Terminalia catappa formulations compared with Ciplar LA 80.

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)

Formulation and Evaluation of Metaprolol tartarate Non-effervescent Gastric Floating tablets

Plan: The objective of this study was to develop Gastric floating drug delivery system containing Metoprolol and having a bulk density lower than that of gastric fluid remaining buoyant on the stomach contents. Preface: Metaprolol tartarate is having short to moderate half life 3-7 hrs, low bioavailability hence it is worth able to formulate Metaprolol in floating drug delivery. The GRDDS can improve the controlled delivery of the drugs which exhibit an absorption window by continuously releasing the drug for a prolonged period before it reaches its absorption site, thus ensuring its optimal bioavailability Methodology: Percentage drug content in all floating tablet formulations was found to be 95.85% to 103.33% which was within Pharmacopoeial limit. In- vitro drug release profile from all formulations (F1-F10) showed sustained release of Metoprolol Tartarate over a period of 10 hours. Outcome: Among all the formulation, F3 showed drug release up to 94.71% at the end of 10 hours. The mechanism of the drug release from F3 was anomalous transport, first order release kinetics. Stability studies on optimized batch showed no significant effect on physical properties, drug content, floating behavior and drug release.

Design Optimization and Evaluation of Gastric Floating Matrix Tablet of Glipizide

Purpose: To formulate an optimized gastric floating drug delivery system (GFDDS) containing glipizide with carbomers and cellulosic polymers.Method: Central composite design (CCD) was employed in formulating the GFDDS using hydroxypropyl methylcellulose K4M (HPMC K4M) (A) and Carbopol 934P (CP934P) (B), as independent variables. Floating lag time (FLT), total floating time (TFT) and time required to release 50 % of the drug (T50) were selected as dependent variables. The dissolution data obtained were fitted to various release models and the floating profiles of the formulations analyzed.Results: HPMC K4M loading clearly enhanced floating properties while CP934P showed negative effect on floating properties but was helpful in controlling drug release. The quadratic mathematical model developed was used to predict optimum formulations. The computer optimization process, contour plots and response surface plots predicted the concentration of independent variables A and B to be 47.32 and 8.4 mg, respectively, for maximum TFT and T50 at the same time for least FLT. Predicted concentration of independent variables showed the same results experimentally, with -0.75 - 1.47 percentage errors.Conclusion: CCD demonstrated the role of the derived equations, contour plots and response surface plots in predicting the values of independent variables for the preparation and optimization of glipizide gastric floating matrix tablet.Keywords: Effervescent, Floating tablet, Design of Experiment, Release kinetics, Central composite design, Optimization.

Formulation and characterization of gastroretentive drug delivery system of losartan potassium

Floating matrix tablets of losartan potassium were developed with an aim to prolong its gastric residence time and increase the bioavailability of drug. Rapid gastrointestinal transit could result in incomplete drug release from the drug delivery system above the absorption zone leading to diminished efficacy of the administered dose. The tablets were prepared by wet granulation technique, using polymers Methocel K15 and Methocel K100 in combination with other standard excipients. Sodium bicarbonate was incorporated as gas generating agent. The effects of sodium bicarbonate and polymers on drug release profile and floating properties were investigated. It was found that viscosity of Methocel K15 and Methocel K100 along with sodium bicarbonate had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with high viscosity Methocel K100 was shown to be beneficial than low viscosity polymer Methocel K15 in improving the floating properties of gastric floating drug delivery system (GFDDS). The observed difference in the drug release and floating properties of GFDDS could be attributed to the difference in the basic properties of two polymers, Methocel K15 and Methocel K100 due to their water uptake potential and functional group substitution. The release mechanism were explored and described with zero-order, first-order and Korsmeyer-Peppas equations. The drug release profiles and buoyancy of the floating tablets were stable when stored at 40°C/75% RH for 6 months.DOI: http://dx.doi.org/10.3329/icpj.v2i1.12872 International Current Pharmaceutical Journal 2012, 2(1): 11-17

Formulation and evaluation of novel coated floating tablets of bergenin and cetirizine dihydrochloride for gastric delivery

A novel coated gastric floating drug-delivery system (GFDDS) of bergenin (BN) and cetirizine dihydrochloride (CET) was developed. First, the pharmacodynamic studies were performed and the results revealed that the new compounds of bergenin/cetirizine dihydrochloride had comparative efficacy as commercial products (bergenin/chlorphenamine maleate) but with fewer side effects on central nervous system (CNS). Subsequently, bergenin was formulated as an extended-release core tablet while cetirizine dihydrochloride was incorporated into the gastric coating film for immediate release. The formulation of GFDDS was optimized by CET content uniformity test, in vitro buoyancy and drug release. Herein, the effects of sodium bicarbonate (effervescent), hydroxypropyl methylcellulose (HPMC, matrix polymer) and coating weight gain were investigated respectively. The optimized GFDDS exhibited good floating properties (buoyancy lag time < 2 min; floating duration > 10 h) and satisfactory drug-release profiles (immediate release of CET in 10 min and sustained release of BN for 12 h). In vivo gamma scintigraphy proved that the optimized GFDDS could retain in the stomach with a prolonged gastric retention time (GRT) of 5 h, and the coating layer showed no side effect for gastric retention. The novel coated gastric floating drug-delivery system offers a new approach to enhance BN’s absorption at its absorption site and the efficacy of both CET and BN.

Gastric floating matrix tablets: Design and optimization using combination of polymers

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing domperidone as a model drug. Box-Behnken design was employed in formulating the GFDDS with three polymers: hydroxypropyl methylcellulose K4M (HPMC K4M) (X1), Carbopol 934P (X2) and sodium alginate (X3), as independent variables. Floating lag time (FLT), total floating time (TFT), time required to release 50% of the drug (t50) and diffusion exponent (n) were selected as dependent variables. Seventeen formulations were prepared, dissolution data obtained was fitted to the power law and floating profiles were analyzed. HPMC loading was found to be significant for floating properties. Carbopol loading had a negative effect on floating properties but was found helpful in controlling the release rate of the drug. No significant effect of sodium alginate on floating properties was observed but it was important for gel formation. The quadratic mathematical model developed could be used to predict formulations with desired release and floating properties.

Optimization of bilayer floating tablet containing metoprolol tartrate as a model drug for gastric retention

The purpose of the present study was to develop an optimized gastric floating drug delivery system (GFDDS) containing metoprolol tartrate (MT) as a model drug by the optimization technique. A 2(3) factorial design was employed in formulating the GFDDS with total polymer content-to-drug ratio (X1), polymer-to-polymer ratio (X2), and different viscosity grades of hydroxypropyl methyl cellulose (HPMC) (X3) as independent variables. Four dependent variables were considered: percentage of MT release at 8 hours, T50%, diffusion coefficient, and floating time. The main effect and interaction terms were quantitatively evaluated using a mathematical model. The results indicate that X1 and X2 significantly affected the floating time and release properties, but the effect of different viscosity grades of HPMC (K4M and K10M) was nonsignificant. Regression analysis and numerical optimization were performed to identify the best formulation. Fickian release transport was confirmed as the release mechanism from the optimized formulation. The predicted values agreed well with the experimental values, and the results demonstrate the feasibility of the model in the development of GFDDS.

Effect of HPMC and Carbopol on the release and floating properties of Gastric Floating Drug Delivery System using factorial design

The purpose of this study is to investigate the effect of formulation variables on drug release and floating properties of the delivery system. Hydroxypropyl methylcellulose (HPMC) of different viscosity grades and Carbopol 934P (CP934) were used in formulating the Gastric Floating Drug Delivery System (GFDDS) employing 2×3 full factorial design. Main effects and interaction terms of the formulation variables could be evaluated quantitatively by a mathematical model. It was found that both HPMC viscosity, the presence of Carbopol and their interaction had significant impact on the release and floating properties of the delivery system. The decrease in the release rate was observed with an increase in the viscosity of the polymeric system. Polymer with lower viscosity (HPMC K100LV) was shown to be beneficial than higher viscosity polymer (K4M) in improving the floating properties of GFDDS. Incorporation of Carbopol, however, was found to compromise the floating capacity of GFDDS and release rate of calcium. The observed difference in the drug release and the floating properties of GFDDS could be attributed to the difference in the basic properties of three polymers (HPMC K4M, K100LV and CP934) due to their water uptake potential and functional group substitution.

Effect of Formulation Variables on the Floating Properties of Gastric Floating Drug Delivery System

ABSTRACTPurpose. To evaluate the contribution of formulation variables on the floating properties of a gastric floating drug delivery system (GFDDS) using a continuous floating monitoring system and statistical experimental design. Methods. A modified continuous floating monitoring system, which consisted of an electric balance interfacing with a PC, was designed to perform the continuous monitoring of floating kinetics of GFDDS. Several formulation variables, such as different types of hydroxypropyl methylcellulose (HPMC), varying HPMC/Carbopol ratio, and addition of magnesium stearate, were evaluated using Taguchi design, and the effects of these variables were subjected to statistical analysis. Results. The continuous floating monitoring system developed was validated, using capsules with different density, and a good correlation between theoretical and experimental values was obtained (R2 = 0.9998), indicating the validity of the setup. The statistical analysis indicated that magnesium stearate had a significant effect on the floating property of GFDDS (p<0.05), and addition of magnesium stearate could significantly improve the floating capacity of the GFDDS. It was found that the HPMC of higher viscosity grade generally exhibited a greater floating capacity, but the effect was not statistically significant. For polymers with the same viscosity, i.e., K4M and E4M, the degree of substitution of the function group did not show any significant contribution. A better floating behavior was achieved at higher HPMC/Carbopol ratio. Carbopol appeared to have a negative effect on the floating behavior of GFDDS. Conclusions. It was concluded that by using a validated continuous floating monitoring system, the effect of formulation variables on the floating property of the delivery system and their ranges could be identified. Incorporation of hydrophobic agents, such as magnesium stearate, could significantly improve the floating capacity of the GFDDS.

Statistical optimization of gastric floating system for oral controlled delivery of calcium.

The development of an optimized gastric floating drug delivery system is described. Statistical experimental design and data analysis using response surface methodology is also illustrated. A central, composite Box-Wilson design for the controlled release of calcium was used with 3 formulation variables: X1 (hydroxypropyl methylcellulose [HPMC] loading), X2 (citric acid loading), and X3 (magnesium stearate loading). Twenty formulations were prepared, and dissolution studies and floating kinetics were performed on these formulations. The dissolution data obtained were then fitted to the Power Law, and floating profiles were analyzed. Diffusion exponents obtained by Power Law were used as targeted response variables, and the constraints were placed on other response variables. All 3 formulation variables were found to be significant for the release properties (P <.05), while only HPMC loading was found to be significant for floating properties. Optimization of the formulations was achieved by applying the constrained optimization. The optimized formulation delivered calcium at the release rate of 40 mg/hr, with predicted n and T50% values at 0.93 and 3.29 hours, respectively. Experimentally, calcium was observed to release from the optimized formulation with n and T50% values of 0.89 (+/- 0.10) and 3.20 (+/- 0.21) hours, which showed an excellent agreement. The quadratic mathematical model developed could be used to further predict formulations with desirable release and floating properties.