Floating Matrix Tablets Research Articles

Optimization of Natrosol HHX and HPC-H Controlled Floating Delivery for Prochlorperazine Maleate

Background: Prochlorperazine maleate, a well known antiemetic is used in the treatment and prevention of nausea and vomiting. The dosage of the drug is usually 5 or 10 mg thrice or four times a day. The drug has short biological half life (6-8 hours). The bioavailability of drug is 12.5%. Due to the solubility of drug in acidic pH, the drug is absorbed rapidly from stomach. Objective: The objective was to optimize effervescent floating matrix tablets for the drug which enhance the oral bioavailability and prevent first pass metabolism of the drug by retaining the drug in stomach. Method: The formulations were prepared by direct compression method. 32 full factorial design was used to optimize the concentration of release retarding agents. Hydroxyethyl cellulose HHX and hydroxypropyl cellulose-H were used as release retarding agents. Sodium bicarbonate and citric acid were used as gas forming agents. The tablets were evaluated for pre-compression and post-compression parameters. Results: From the factorial batches, formulation H7 containing 70% of hydroxyethyl cellulose HHX and 12% hydroxypropyl cellulose-H was found to be the optimized batch. Formulation H7 followed Korsmeyer Peppas release kinetics, with sustained drug release of 93.64±6.4 % and floating for 10 hours. In-vivo X-ray placebo study of optimized batch (H7) showed retention of tablet in stomach for 6±0.5 hours. Conclusion: The study proved successful floating delivery of Prochlorperazine maleate in stomach. Keywords: Prochlorperazine maleate, floating, hydroxyethyl cellulose, hydroxypropyl cellulose, gastric retention.

Quality by design approach for development and optimization of Quetiapine Fumarate effervescent floating matrix tablets for improved oral bioavailability

The aim of the investigation was to develop and optimize the effervescent floating matrix tablets of Quetiapine Fumarate (QF) by using 23 factorial design. Amount of hydroxyl propyl methyl cellulose K4M (HPMC K4M (A1)), amount of hydroxyl propyl methyl cellulose K15M (HPMC K15M (A2)) and amount of sodium bicarbonate (A3) (as gas-generating agent) were considered as independent variables and floating lag time (FLT, B1) (sec), percent drug release in 2 h (B2, Q2) and 6 h (B3, Q6) as dependent variables, respectively. Floating tablets of QF were prepared by effervescent technique using direct compression method. Drug-excipient compatibility studies were conducted by using DSC and FTIR techniques. The floating tablets were evaluated for physical characteristics, drug content, swelling index, in vitro buoyancy and in vitro release studies. Optimized formulation contains 25 mg of A1, 12.5 mg of A2 and 25 mg of A3 which resulted in 32 s of B1, 32.89 ± 3.1 % of B2, and 73.61 ± 1.8 % of B3, respectively. DSC and FTIR studies revealed that no interaction between the drug and excipients in the developed formulation. The drug release followed Higuchi model and the Fickian transport. Physico-chemical stability studies revealed that the optimized formulation was stable for 90 days. Based on the physical evaluation and in vitro drug release characteristics, it was concluded that QF was suitable for incorporation into a floating drug delivery system.

Design and development of controlled release floating matrix tablet of Nicorandil using hydrophilic cellulose and pH-independent acrylic polymer: in-vitro and in-vivo evaluations

Objectives: The purpose of the study was to develop a floating matrix tablet of Nicorandil using blends of hydrophilic cellulose and pH-independent acrylic polymer to improve the therapeutic effectiveness of the drug in cardiovascular disease.Methods: Nicorandil tablets were prepared by direct compression and evaluated for drug-excipients compatibility, in-vitro buoyancy and in-vivo γ-scintigraphy study. The selected formulation (FT5) was also evaluated for stability study and the in-vivo absorption in rabbits to compare the pharmacokinetic parameters with the commercially available immediate release tablet of Nicorandil.Results: DSC and FT-IR studies confirmed the absence of incompatibility and were found stable at refrigerator temperature (2-8°C) and at 25ºC/60% RH. The in-vivo γ-scintigraphy studies revealed that the system was floated for a period of 6 -7 h in the stomach and in-vivo absorption study showed a significant difference (p < 0.05) in the pharmacokinetic parameters (AUC increased by 3 fold and MRT by 2.5 fold) as compared to the marketed formulation.Conclusion: In conclusion, the developed Nicorandil floating matrix tablet improved the pharmacokinetics parameters (AUC and MRT) in rabbit plasma with expected lowering in side effects potential.

Formulation and Evaluation of Gastro-bilayer Floating Tablets of Simvastatin as Immediate Release Layer and Atenolol as Sustained Release Layer

Combination therapy is highly desired to deliver atenolol and simvastatin for dyslipidemia and hypertension for concomitant drug treatment. On other hand, atenolol has poor absorption in lower gastrointestinal tract, short half-life and simvastatin has poor solubility. Therefore, the present study was to develop gastro-bilayer floating matrix tablet in which simvastatin was incorporated as immediate layer and atenolol as sustained release layer. Gastro-bilayer floating tablets were prepared by direct compression method and optimized using hydroxypropyl methylcellulose K100 (37.5%) as release retardant and sodium bicarbonate as a gasforming agent. The immediate release layer comprised sodium starch glycolate as superdisintegrant. The tablets of optimized formulations floated on the test medium for more than 12 h with 9 min of floating lag time. Atenolol release was sustained for 12 h via diffusion mechanism and more than 96% release of simvastatin within 15 min was achieved. It can be concluded that, the biphasic drug release pattern was successfully achieved through the formulation of gastro-floating bilayer tablets in this study, allowing strengthened combination therapy for hypertension and dyslipidemia.

Formulation and evaluation of floating matrix tablet of Losartan for gastroretentive drug delivery

The prime aim of this research was to develop gastro-retentive delivery system of Losartan which, after oral administration should have the ability to prolong gastric residence time with desired in vitro release profile. Losartan was chosen as a model drug because it is poorly absorbed from the lower gastrointestinal tract. The tablets were prepared by direct compression technique, using various polymers, alone or in combination. The tablets were evaluated for physical characteristics viz. hardness, friability, weight variation, content uniformity, and floating capacity. Further, tablets were evaluated for in vitro release characteristics for 12 hr. Among all the formulations, tablets containing combination of xanthan gum and guar gum showed better floating capacity as well as sustained release of atenolol at the end of 8 hr. The optimized formulation F4 contains the average thickness of 2.12, average hardness of 6.7 and friability of 0.44. The F4 formulation which releases the Losartan in sustained manner in up to 12 hours. The mechanism of release of Losartan from the floating tablets was found to be diffusion couple with erosion. It was concluded that the tablets prepared by polymer HPMC K4M(15%) had efficient floating and sustained release capacity as compared to tablets prepared by using other polymers.

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

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

Development of a new single unit dosage form of propranolol HCl extended release non-effervescent floating matrix tablets: In vitro and in vivo evaluation

ABSTRACT The objective of the present investigation was to develop extended release non-effervescent floating matrix tablets of Propranolol Hydrochloride (PPH) to extend the gastric residence time (GRT) and prolong the drug release after oral administration. Different viscosity grades of Hydroxypropyl methylcellulose (HPMC) polymers such as HPMC K4M, HPMC K15M and HPMC K100M were used as drug release retardants. Glyceryl behinate (Compritol 888 ATO) and Glyceryl monosterate (Precirol ATO 5) were used as low density lipids in order to get the desired buoyancy over a prolonged period of time. The drug excipients compatibility study was carried out by using Differential Scanning Calorimetry (DSC). All the formulations were prepared by direct compression technique. The prepared tablets were evaluated for their physical characters, in vitro drug release and in vitro buoyancy. The release and floating property depends on the polymer type, polymer proportion, lipid type and lipid proportions. The drug release profiles of all the formulations were subjected to Zero order, First order, Higuchi and Peppas kinetic models, and the optimized formulation (F7) followed the Peppas model (R2= 0.987) with non-Fickian diffusion mechanism(n>0.5). The optimized formulation was subjected for in vivo radiographic studies in healthy human volunteers (n=3). These studies revealed a mean gastric residence time of 5 h (n=3). Key words: Propranolol HCl, Compritol 888 ATO, Precirol ATO 5, Non-effervescent, Floating drug delivery system and Gastric residence time.

Formulation and Evaluation of Gastroretentive Matrix Tablet of Nifedipine

The present investigation concerns the formulation and evaluation of floating matrix tablets of Nifedipine which after oral administration, are designed to prolong the gastric residence time, increase drug bioavailability and sustain the drug release. Nifedipine is a calcium channel blocker, used in treatment of moderate to severe angina and hypertension. It offers several advantages such as rapid absorption, reducing peak plasma fluctuation and ease of administration.

Borneol as Sublimable Agent in Floating Matrix Tablet

To avoid unpredictable time to float due to variable pH of the gastric fluid in each subject, sublimation technique is the new interesting approach to prepare non-effervescent floating drug delivery system (FDDS). In this study, a floating matrix tablet using borneol as sublimable agent was developed. The system consists of drug, matrix-forming polymer and sublimable agent. The highly porous and low-density floating matrix tablet was obtained when borneol was sublimated. The floating matrix tablets immediately floated and maintained buoyancy over 8 h. The sublimation of borneol increased with increasing sublimation temperature and incubation time. Increasing amount of sublimable agent exhibited lower density of the floating tablet because of higher porous structure. The results demonstrated that boneol was one of good candidates to be used as sublimable agent for non-effervescent floating tablets. However, physical properties of the matrix floating tablets were needed to be concerned.

English

English

Novel swellable polymer of orchidaceae family for gastroretentive drug delivery of famotidine.

This study aimed to develop hydrophilic, gastroretentive matrix tablets of famotidine with good floating and swelling properties. A novel gastroretentive drug delivery formulation was designed using salep, also known as salepi, a flour obtained from grinding dried palmate tubers of Orchis morio var mascula (Orchidaceae family). The main polysaccharide content of salep is glucomannan, highly soluble in cold and hot water, which forms a viscous solution. Salep was characterized for physicochemical properties, thermal stability, chemical interaction, and surface morphology using X-ray diffraction analysis, differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscopy. Ten different formulations (S1–S10) were prepared using famotidine to salep ratios from 1:0.5 to 1:5. Results demonstrated that all formulations were able to sustain the drug release for more than 24 hours. The S5 formulation, with a famotidine to salep ratio of 1:2.5, had the shortest floating lag time of 35 seconds and 100% drug release within 24 hours. The dissolution data were fitted into popular mathematical models to assess the mechanism of drug release. S5 showed Zero order release (R=0.9746) with Higuchi diffusion (R=0.9428). We conclude that salep, a novel polymer, can be used in controlled release formulations to sustain release for 24 hours, due to inherent swelling and gelling properties.

Optimization and Evaluation of Solubility-Modulated Gastroretentive Floating Matrix Tablet of Furosemide

The objective of the present study was to prepare delivery system for furosemide which has poor solubility and has specific absorption in stomach. Solid dispersion of furosemide (SD) was prepared in polyethylene glycol 6000 and characterized using differential scanning calorimetry. Floating gastroretentive tablets of the prepared solid dispersion were then prepared by wet granulation technique, using polymer Methocel K100M CR (HPMC) and sodium bicarbonate. A 32 factorial design was applied systematically to study the effect of the amount of HPMC (X1) and sodium bicarbonate (X2) on the floating lag time (YFLT) and amount of drug release at the end of 1st hr (Y60), 6th hr (Y360) and 12th hr (Y720). The solubility of SD was higher than that of drug alone and the physical mixture. The results of multiple regression analysis, when applied to responses obtained for experimental design batches, indicated that low level of HPMC and high level of sodium bicarbonate decreased the floating lag time, while the amount of drug released at all time points decreased with increase in level of HPMC. Swelling behavior of experimental design batches was studied and its relationship with mechanism of drug release was interpreted. Batch D3 came close to satisfying the drug release and floating criteria. Drug compatibility with the excipients used was ascertained using FTIR. Stability studies were carried out at recommended storage conditions and the tablets were found to be stable. Delivery system could be developed for furosemide which addressed the solubility and site specificity issues of drug.&#x0D;

Gamascintigraphic in Vivo-in Vitro Evaluation of Floating Matrix Tablet

Abstract: The aim of the present work was to develop hydrodynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus site specific oral controlled release floating drug delivery system was developed. Formulation includes the use of rate controlling polymer such as Locust Bean gum (LBG) in combination of HPMC K4M and gas generating agent Sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables namely amount of HPMC K4M, LBG and three dependent responses such as Cumulative drug release, Floating lag time, Floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastroretentive formulation, the in vivo Gamascintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of Atenolol with improved bioavailability. Key words: Floating tablet, factorial design, Gamascintigraphy, antihypertensive model drug, HPMC, Locust bean gum.

Polymers derived from Xanthomonas campesteris and Cyamopsis tetragonolobus used as retardant materials for the formulation of sustained release floating matrix tablet of atenolol

The objective of the present study was to develop, optimize, in vitro, and in vivo evaluation of floating matrix tablet of atenolol using polymer blend derived from Xanthomonas campesteris and Cyamopsis tetragonolobus that are characterized by release requirements of sustained-release product and to improve the oral bioavailability of the drug. A 32 full factorial design was employed to optimize the tablets, where content of polymer blend (X1) and ratio of xanthan gum-to-guar gum (X2) were considered as independent variables. The effects of independent variables on dependent variables, i.e. floating time, diffusion exponent, and time to release 50% of atenolol were evaluated. The in vivo pharmacokinetic parameters of the optimized formulation were compared with the marketed sustained release formulation of atenolol (Aten®). The optimized formulation containing 20% (w/w) of polymer blend and 50:50 ratio of xanthan gum-to-guar gum was able to float more than 12h and showed the desired sustained drug release from the tablets. In vivo retention studies in rabbit stomach showed the gastric residence of tablet up to 6h. The in vivo study of optimized tablets illustrated significant improvement in the oral bioavailability of atenolol in rabbits. It can be concluded that floating matrix tablet of atenolol prepared by using xanthan gum and guar gum has potential for sustained release of the drug as well as improved oral bioavailability through enhanced gastric residence time of formulation in stomach.

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.

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

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

Formulation and evaluation of floating matrix tablets of acyclovir

Formulation and evaluation of floating matrix tablets of acyclovir

Drug-Excipient Interaction during Formulation Development, in vitro andin vivo Evaluation of Gastroretentive Drug Delivery System for Nizatidine

The present investigation dealswith the development and evaluation of floating tablets of nizatidine to prolong the gastric residence time, increase local delivery of drug to the H2-receptor of the parietal cell wall to reduce stomach acid secretion. The drug-excipient compatibility studies were conducted by using FTIR, DSC and visual observations. Citric acid inclusion in formulations resulted in incompatibility and the composition was modified to eliminate the problem of incompatibility. Floating matrix tablets of nizatidine were developed by direct compression method using hydroxypropyl methylcellulose (HPMC K4M) and polyox WSR 1105 alone as release retardants and sodium bicarbonate as a gas-generating agent. Alleleven formulations exhibited satisfactory physicochemical characteristics andin vitro buoyancy. Formulations F6 and F10 exhibited controlled and prolonged drug release for 10 h with zero order release. Formulation (F10) was selected as optimized formulation based on physicochemical properties and in vitro drug release and was used inradiographic studies by incorporating BaSO4. The radiographic studies were conducted in comparison with plain controlled release tablets. These studies revealed that gastric retention time of floating and plain controlled release tablets in fasting state were 2 ± 0.86 h and ≤ 0.5 h respectively in human volunteers. Gastric retention time of floating and plain controlled release tablets in fed state were 5.33 ± 0.57 h and 1.66 ± 0.28 h respectively in human volunteers. In conclusion, optimal floating matrix tablet for nizatidine with desired in vitro buoyancy, in vivo gastric retention time and prolonged release could be prepare

Formulation and Characterization of Effervescent Floating Matrix Tablets of Famotidine Hydrochloride

Gastro retentive drug delivery systems are the dosage forms which are retained in the stomach for a prolonged period of time and hence improve the bioavailability of drugs. Famotidine, an anti-ulcer drug, have less oral bioavailability (50%) because of its poor solubility in alkaline pH. Therefore, the main objective of present work is to develop floating effervescent tablets of famotidine. The tablets were prepared with polymers like HPMC K4M and HPMC K100M using directly compression technique. The floating tablets were evaluated for uniformity of weight, hardness, friability, drug content, In vitro buoyancy and dissolution studies All the prepared batches showed good In vitro buoyancy. The tablet remained buoyant for 6-10 hours. The tablets with HPMC K100M were found to float for longer duration as compared with formulations containing HPMC K4M. The In vitro dissolution studies confirmed the sustained and non fickian drug release from tablets. Stability studies showed that tablets can be stored at room temperatue.

Fabrication of Shellac-Based Effervescent Floating Matrix Tablet as a Novel Carrier for Controlling of Drug Release

The aim of this research was to elucidate the factors affecting drug release and buoyancy properties of effervescent shellac based matrix tablet. Theophylline was selected as a model drug and sodium bicarbonate was used as a gas forming agent. To fabricate floating matrix tablets, the model drug, gas forming agent and other excipients were blended, compressed and then annealed at 80C for 24 h. The factors affecting floating and drug release, including amount of SHL and gas forming agent were investigated. The result demonstrated that the hardness of all formulations before annealing was within the range of 60+10 N. After annealing process, the hardness was significantly increased especially for formulation containing high level of SHL. The hardness of tablets containing 55% w/w or more of SHL was more than 200 N. As increasing amount of SHL (&gt; 35% w/w), the more sustained drug release was also observed. The results were agreed well with the increased hardness. In addition, the tablets containing 20% w/w or more of gas forming agent were floated in 0.1 N HCl for more than 10 h, suggesting the good buoyancy characteristic. The kinetics of drug release in 0.1N HCl for all formulations were both fitted with Higuchi model and power law equation model, suggesting that the main mechanism of drug release in 0.1N HCl was obeyed the diffusion process. The result from this research could provide the basic knowledge for fabricating of SHL-based floating matrix tablet through varying amount of SHL and gastric forming agent.