Gastroretentive Dosage Form Research Articles

A novel mechanical antrum model for the prediction of the gastroretentive potential of dosage forms

The development of gastroretentive dosage forms can be significantly enhanced by the reliable estimation of gastroretentive properties in vitro. In this context, it is mandatory to consider the propulsive contraction waves that occur in the antral region of the stomach, since they are regarded as the major physiological hurdle to overcome. Therefore, the aim of this study was to develop an in vitro model that allowed the evaluation of the gastroretentive potential of objects with different properties (e.g. size, shape and elasticity). The model enabled a realistic simulation of the human antrum and occurring contraction waves. We could demonstrate that larger objects made of elastic polyurethane foam were more rapidly emptied by the model than smaller objects having the same shape. Compared to this, rigid as well as slippery objects showed decreased gastroretentive properties. In contrast, a self-formed trichobezoar ‐ an indigestible object known to remain in the stomach − showed the highest gastroretentive potential. We suggest that the gastroretentive potential of objects of a certain size increases if they exhibit compressible and elastic properties along with certain dimensions. The data showed that the development of novel gastroretentive dosage forms may be facilitated with the aid of the mechanical antrum model.

GASTRORETENTIVE MICROBALLOONS OF RIBOFLAVIN: FORMULATION AND EVALUATION

Gastroretentive dosage forms are useful to extend release of drugs having a narrow window of absorption in the upper intestine and for drugs degraded by higher pH or for drugs with local action in the proximal part of the GI tract. In the present study, an attempt was made to prepare microballoons of riboflavin by emulsion solvent diffusion method by using HPMC and ethylcellulose in order to extend the drug release in the upper GIT, which may result in enhanced absorption and thereby improved bioavailability. The size and surface morphology of riboflavin microballoons were characterized by optical and scanning electron microscopy. FTIR and DSC studies revealed no drug excipient interaction. Average particle size of microballoons was found to be between 126.8±2.26 to 163.4±2.52 μm. Microballoons were found to be spherical in shape with smooth surface texture. Percentage yield of the microballoons was satisfactory. In vitro buoyancy of the optimized riboflavin microballoons was found to be 96.24±0.08%, indicating good floating in stomach. Cumulative amount of drug release from microballoons at the end of 12 hr was 99.78±2.78 % and followed Highuchi diffusion kinetics and super case II transport.

Novel expandable gastro retentive system by unfolding mechanism of levetiracetam using simple lattice design – Formulation optimization and in vitro evaluation

The aim of the present study was to develop and characterize a novel expandable gastro-retentive dosage form (GRDF), based on unfolding mechanism. The dosage form consists of a drug loaded the polymeric patch, folded into a hard gelatin capsule. Gastro retention obtained from unfolding and swelling of the patch and its adhesion to the gastric mucosa. Therefore in this work, a gastro retentive patch of levetiracetam was developed using simple lattice design considering concentration of Hydroxy Propyl Methyl Cellulose, Carbopol 934P and Xanthan gum as independent variables. A response surface plot and multiple regression equations were used to evaluate the effect of independent variables on dependent variables such as mucoadhesive strength (g/cm2) and t90 (h). The prepared patches were evaluated for weight and thickness variation, mechanical properties, in vitro drug release and unfolding behavior. The absence of drug-polymer interaction and uniform drug dispersion in the polymeric patches was revealed by FT-IR, DSC, XRD and SEM. The results indicates, the novel GRDF based on unfolding mechanism can be alternative for other mucoadhesive dosage forms which will provide sustained release for 12h.

Design and evaluation of a Sustained Release Gastroretentive Dosage form of Captopril

Design and evaluation of a Sustained Release Gastroretentive Dosage form of Captopril

An Review on Floating Mucoadhesive Drug Delivery System

A gastro retentive dosage form will release the drug over an extended period in the stomach and upper gastrointestinal tract (GIT) thus enhancing the opportunity for absorption. Various approaches have been proposed to control the gastric residence of drug delivery system in the upper part of the GIT including floating drug delivery system. Formulation of Gastro-Retentive dosage forms (GRDFs) containing suitable drug candidate which would remain in stomach and/or upper part of GIT for prolonged period of time there by is maximizing the drug release at desired site within the time before GRDFs leave the stomach and or upper part of GIT. Oral route has been the adopted and most convenient route for the drug delivery. Floating dosage forms have been developed to float over GI fluids and to release the drug over a desired period of time. Floating drug delivery system also name as hydrodynamically balanced system (HBS). Bioadhesion can be defined as the process by which a natural or a synthetic polymer can adhere to a biological substrate. When the biological substrate is a mucosal layer then, the phenomenon is known as mucoadhesion.

Emphasizing the pharmaceutical consideration behind the development of gastro-retentive dosage form

Recent technological and scientific research has been devoted to the development of rate controlled drug delivery systems to overcome physiological adversities such as short gastric residence times and unpredictable gastric emptying times. The floating or hydro-dynamically controlled drug delivery systems are useful in such application. The objective of our review is to compile the recent advancements and developments regarding the novel dosage form i.e. the floating drug delivery systems (FDDS) that can be retained in the stomach for a prolonged period of time and gives therapeutic action in a predetermined manner. In these review article,the various aspects of pharmaceutical floating drug delivery system(FDDS) were compiled together and the target ordinance are specifically the M. Pharm and B Pharm students so that their knowledge towards the subject concern can be enhanced and also at the same time can be motivated towards the publication.

ETHYLCELLULOSE FLOATING MICROSPHERES OF ANTIDIABETIC AGENT: IN VITRO AND IN VIVO EVALUATION

Objective: To develop and evaluate floating type gastro-retentive dosage form, appropriate for controlled release of repaglinide (RG) having a narrow therapeutic window.Methods: Repaglinide loaded microspheres (MS) using biological macromolecule ethylcellulose (EC) was prepared by a solvent diffusion-evaporation technique using polyvinyl alcohol (PVA) emulsifier. Compatibility of drug and polymer was studied by Fourier-transform infrared spectroscopy (FTIR). During formulation, various process optimisation parameters studied were stirring speed, the concentration of drug, polymer and emulsifier. Characterization and in vitro evaluation was performed. In vivo antidiabetic activity was performed on alloxan induced diabetic rats followed by histopathological screening.Results: The average particle size was in the range of 174-243 µm. Yield, entrapment and buoyancy of microspheres were 68.4­­-79.8, 58.6-73.1 and 71.8-84.1% respectively. 65.1% release of drug from optimised formulation was obtained which follows first-order kinetics (r2 = 0.989). Optimised formulation treated group shows significant (p<0.01) decrease in glucose level of blood as compared to pure drug treated group during the later hours of study with satisfactory results of histology.Conclusion: The investigation revealed the promising potential of gastro retentive microspheres for delivering RG for the treatment of non-insulin dependent diabetes mellitus (NIDDM).

Physico-chemical evaluation of Gastroretentive Ranitidine Hydrochloride: An Anti-Ulcer Drug

Background and Objectives: The prevention and treatment of peptic ulcers has become an important challenge in the current medicine world. Modern progress in novel drug delivery system aims to improve the efficacy of the drug molecule by formulating a dosage form of RHCL. One of the most feasible approaches for achieving a prolonged and predictable drug delivery profile in GI tract is to control the gastric residence time. Therefore, a multi-unit gastro retentive dosage form of RHCL capable of floating on simulated gastric fluid for more than 12 hours was formulated and evaluated.Materials and Methods: Nine batches of the light liquid paraffin entrapped emulsion gel beads were prepared by a new emulsion gelation technique using sodium alginate and xanthan gum as polymers. The polymeric solution was extruded into Calcium chloride solution by the use of 21G needles. Morphology of beads, drug content, drug entrapment efficiency, floating lag time and buoyancy were studied. Compatibility study of Ranitidine HCl with polymers used in the formulation was performed using DSC and FT-IR.Results: Mean surface diameter were between 1.220 ± 2.259% (F1) to 1.230 ± 2.316% (F9) and floating lag time were between 6 minute (F9) to 11 minute (F1). All formulations were buoyant for more than 12 hours in simulated gastric fluid at 37ºC. The drug content and drug entrapment efficiency among the formulations were between 17.48%~19.68% and 71.06% ~84.32% respectively. Formulation F1 showed lowest drug content and drug entrapment efficiency while F9 showed highest drug content and drug entrapment efficiency. F4 showed most acceptable sustained drug release profile.Conclusion: The gastro retentive drug delivery system designed as floating beads was found to be satisfactory drug delivery system for Ranitidine HCl to improve the bioavailability of the drug. Janaki Medical College Journal of Medical Sciences (2015) Vol. 3 (2): 4-12

FORMULATION AND EVALUATION OF GASTRORETENTIVE MICROBALLOONS OF ACEBROPHYLLINE FOR THE TREATMENT OF BRONCHIAL ASTHMA

ABSTRACTObjective: Gastroretentive dosage forms are an approach for prolonged and predictable drug delivery in the upper gastrointestinal tract to controlthe gastric residence time. Microballoons are considered as one of the most promising buoyant drug delivery systems as they possess the advantagesof both multiple-unit systems and good floating properties. Acebrophylline is a xanthine derivative with potent bronchodilator, mucosecretolytic, andanti-inflammatory property. It is used to treat bronchial asthma and chronic obstructive pulmonary diseases.Methods: Microballoons of acebrophylline were prepared by emulsion solvent diffusion method using hydroxypropyl methylcellulose (HPMC) andethyl cellulose (EC) as polymer. The microballoons were evaluated with their micromeritic properties, particle size, tapped density, compressibilityindex, angle of repose, percentage yield, in vitro buoyancy, entrapment efficiency, drug-polymer compatibility, scanning electron microscopy (SEM),and drug release kinetics.Results: The mean particle size of the microballoons formulation MB1 to MB6 containing HPMC and EC was in the range between 226±16 and 577±10,respectively. The mean particle size of microballoons was found to increase with increasing polymer concentration. The micromeritic properties werefound be good, and SEM confirmed their hollow structure with smooth and dense which helped to prolong floating to increase residence time instomach. The in vitro drug release studies showed controlled release of acebrophylline microballoons in the simulated gastric fluid more than 12 hrs.Conclusions: The results showed that the prepared floating microballoons of acebrophylline prove to be potential multiple-unit delivery devicesadaptable for safe and effective sustained drug delivery.Keywords: Microballoons, Acebrophylline, Bronchial asthma, Hydroxypropyl methylcellulose, Ethyl cellulose.

Recent Advances in Gastro-Retentive Drug Delivery Systems

Controlled gastric retention of solid dosage form may be achieved by the mechanisms of floatation, muco-adhesion, sedimentation, expansion or by a modified shaped system. The purpose of this paper is to review the recent literature and current technology used in the development of gastroretentive drug delivery systems. Oral sustained release gastroretentive dosage forms offer many advantages for drugs having absorption from upper gastrointestinal tract and improve the bioavailability of medications that are characterized by a narrow absorption window. Gastroretention would also facilitate local drug delivery to the stomach and proximal small intestine. So, gastroretention could help to provide greater availability of new products and consequently improved therapeutic activity and required benefits to patients. The purpose of writing the article 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. In particular, bioadhesive, size-increasing and floating drug delivery systems are presented and their major advantages and shortcomings are critically discussed in this review. Thus, gastroretention could help to provide greater availability of new products and consequently improved therapeutic activity and substantial benefits to patients

Preparation and Optimization of floating microbeads of ciprofloxacin HCl

The objective of this work is to generate a gastro retentive sustained release dosage form of a water soluble drug, Ciprofloxacin, from a fully aqueous environment avoiding the utilize of any organic solvent. A new emulsion gelation system is used to arrange emulsion gel beads by sodium alginate as the polymer. The gel beads containing is set up by gently mixing or homogenizing oil and water phase containing sodium alginate which is then extruded in to calcium chloride solution. The effects of factors like concentration of oil, curing time, and drug: polymer ratio, alginate: pectin proportion and therapeutic agent on drug entrapment efficiency, floating lag time, and morphology and drug release are study. Minimizing the curing time of beads leaded to enhanced drug entrapment efficiency. The use of sodium alginate and combinations of sodium alginate and pectin are used to study the effect on the sustaining property of the formed beads. It is found that sodium alginate was not sufficient to uphold the drug release at gastric pH. Instead of it, suitable amalgamation of alginate and pectin could afford the sustain release of drug. The results confirm that these beads can entrap even a water soluble drug as Ciprofloxacin in sufficient amount and also can successfully distribute the drug in stomach for a extend duration of time.

Formulation and evaluation of atenolol floating bioadhesive system using optimized polymer blends.

Introduction:Oral sustained release gastro retentive dosage forms offer several advantages for drugs having absorption from the upper gastrointestinal tract to improve the bioavailability of medications which have narrow absorption window. The aim of the study was to develop a floating bioadhesive drug delivery system exhibiting a unique combination of floatation and bioadhesion to prolong the residence in the stomach using atenolol as a model drug.Methods:Prior to compression, polymeric blend(s) were evaluated for flow properties. The tablets were prepared by direct compression method using bioadhesive polymer like Carbopol 934P and hydrophilic polymers like HPMC K4M, HPMC K15M, and HPMC K100M. The prepared tablets were evaluated for physical characteristics, bioadhesive strength, buoyancy lag time, swelling index and in vitro drug release studies.Results:The mean bioadhesive strength was found to be in the range of 16.2 to 52.1 gm. The optimized blend (F11) showed 92.3% drug releases after 24 hrs. Whilst, increase in concentration of carbopol 934P, bioadhesive strength and swelling index was increased with slow release. The n values of optimized formulations were found in the range of 0.631-0.719 indicating non-fickian anomalous type transport mechanism.Conclusion:The study aided in developing an ideal once-a-day gastro retentive floating drug delivery system with improved floating, swelling and bioadhesive characteristics with better bioavailability.

Carboxymethyl starch mucoadhesive microspheres as gastroretentive dosage form

Carboxymethyl starch microspheres (CMS-MS) were produced from carboxymethyl starch powder (CMS-P) with a degree of substitution (DS) from 0.1 to 1.5 in order to investigate the influence of DS on physicochemical, drug release and mucoadhesion properties as well as interactions with gastrointestinal tract (GIT) epithelial barrier models. Placebo and furosemide loaded CMS-MS were obtained by emulsion-crosslinking with sodium trimetaphosphate (STMP). DS had an impact on increasing equilibrium water uptake and modulating drug release properties of the CMS-MS according to the surrounding pH. The transepithelial electrical resistance (TEER) of NCI-N87 gastric cell monolayers was not influenced in presence of CMS-MS, whereas that of Caco-2 intestinal cell monolayers decreased with increasing DS but recovered initial values at about 15h post-treatment. CMS-MS with increasing DS also enhanced furosemide permeability across both NCI-N87 and Caco-2 monolayers at pH gradients from 3.0 to 7.4. Mucoadhesion of CMS-MS on gastric mucosa (acidic condition) increased with the DS up to 55% for a DS of 1.0 but decreased on neutral intestinal mucosa to less than 10% with DS of 0.1. The drug release, permeability enhancement and mucoadhesive properties of the CMS-MS suggest CMS-MS with DS between 0.6 and 1.0 as suitable excipient for gastroretentive oral delivery dosage forms.

Utilization of ionotropic gelation technique for bioavailability enhancement of cinnarizine: in-vitro optimization and in-vivo performance in human

Gastro retentive drug delivery system techniques were adopted to deliver drugs having narrow absorption window from a particular site in the GIT. Therefore, gastro retentive dosage forms were retained in the stomach, thus improving absorption and bioavailability would be improved consequently. In this study, cinnarizine (CNZ) was employed as the model drug. CNZ is a poorly soluble basic drug, suffering from low and erratic bioavailability. This is attributed to its pH-dependant solubility (highly soluble at pH < 4). CNZ is characterized by short half-life (3–6 h). Accordingly, floating CNZ emulsion gel calcium pectinate beads were developed. A mixture design was employed to study the effect of the percent of LM pectin (A), the percent of GMO (B) and the percent of Labrafac Lipophile (C) simultaneously on the percent of drug released and loaded. The optimized floating CNZ emulsion gel calcium pectinate beads and Stugeron® (the marketed reference product) were compared through a pharmacokinetic study carried on healthy human volunteers. Fortunately, simple floating CNZ emulsion gel calcium pectinate beads were prepared with zero-order release profile for 12 h. A promising in-vivo CNZ controlled release dosage form with higher bioavailability, when compared to once daily administration of Stugeron® tablets was achieved.

Diacerein-Loaded novel gastroretentive nanofiber system using PLLA: Development and in vitro characterization

The purpose of this research is to describe the utility of nanofibers as a gastroretentive dosage form and improve the solubility of diacerein (DIA) by using the above approach. Poly L-(lactic acid) (PLLA) nanofibers loaded with DIA were prepared using the electrospinning technique. The nanofibers developed were characterized for morphology, tensile strength, floating behavior, drug entrapment, drug solubility, mucoadhesive detachment force, and drug release profile. The results demonstrated that the drug-loaded nanofibers were smooth, discrete, & non-woven. Analysis by X-ray crystallography (XRD) revealed that the drug in the nanofiber was present in the amorphous state, which largely contributes to higher drug solubility in the nanofibers developed. The buoyancy study demonstrated that the nanofibers developed exhibited zero lag time. Approximately 61.3% of drug was released in 30 h, thus facilitating the slow release of the drug from the nanofiber system. Finally, we concluded that the electrospun nanofibers developed offer a promising gastroretentive drug delivery system to deliver DIA with improved solubility.

Density-dependent gastroretentive microparticles motion in human gastric emptying studied using computer simulation

Density-dependent gastroretentive drug delivery systems have been used to prolong the gastric retention time of drugs since the 1960s. The design of density-dependent gastroretentive dosage forms, however, usually focuses on specific parameters rather than combines with the fluid dynamics of dosage form in the gastric emptying. Therefore, the purpose of the present study was to develop a 2-D model of multiple-phase flows for the simulation of gastric emptying and gastroretentive microparticles motion, and the influence of microparticle density, microparticle viscosity, and gastric juice viscosity on the gastric retention were studied. The recirculating flows, formed in the gastric emptying, could mix the conventional-density microparticles and transport them to the pylorus. However, the low-density microparticles remained floating on the surface of gastric juice, while the high-density microparticles could sink and deposit in the bottom of the stomach. The remaining integral area of microparticles was higher than 90% after 18.33min of simulation when the density of microparticles was lower than 550kg/m3 or higher than 2500kg/m3, which was higher compared to conventional-density microparticles (67.05%). These results are in good agreement with experimental data previously reported. In addition, the viscosity of microparticle and gastric juice also influenced the remaining integral area of gastroretentive microparticles. This study shows that the multiple-phase computational fluid dynamics models could provide detailed insights into the fluid dynamics of density-dependent gastroretentive microparticles in gastric emptying, which offers a powerful tool to further understand the mechanism of gastric retention for gastroretentive dosage forms and study the influence of different parameters on their ability for gastric retention.

Formulation Development and Evaluation of Gastro-Retentive Drug (Torsemide) Delivery System for Diuretic Drug

Gastro-retentive Drug Delivery System is system which improves the Gastric Residence time and hence improves its bioavailability. In the current study indicates that the optimized gastro-retentive tablet of Torsemide, prepared using Sodium Alginate and HPMC K15M can successfully be employed as an oral controlled release drug delivery system. Tablet was formulated by using different Formulation indicated by F1 to F9 respectively. These formulations were evaluated for the pre compression and post compression parameters. The optimized Formulation was subjected to stability studied at 40oC under humidity conditions (75%) for a period of four week. From the result it was observed that there was no significant change in physiochemical properties as well as in drug release profile even after storage at 40oC for four week. In-vitro drug release study of formulation also done for optimized batch after stability study and found unaffected. High floating ability of the formulation is likely to increase its GI residence time, and eventually, improve the extent of bioavailability. Gastroretentive dosage form of Torsemide will reduce the frequency of administration of drug and helps to minimize dose of drug and side effects associated with the drug.

Formulation and evaluation of gastroretentive microballoons containing baclofen for a floating oral controlled drug delivery system.

The objective of the present study was to fabricate and evaluate a multiparticulate oral gastroretentive dosage form of baclofen characterized by a central large cavity (hollow core) promoting unmitigated floatation with practical applications to alleviate the signs and symptoms of spasticity and muscular rigidity. Solvent diffusion and evaporation procedure were applied to prepare floating microspheres with a central large cavity using various combinations of ethylcellulose (release retardant) and HPMC K4M (release modifier) dissolved in a mixture of dichloromethane and methanol (2:1). The obtained microspheres (700-1000 µm) exhibit excellent floating ability (86 ± 2.00%) and release characteristics with entrapment efficiency of 95.2 ± 0.32%. Microspheres fabricated with ethylcellulose to HPMC K4M in the ratio 8.5:1.5 released 98.67% of the entrapped drug in 12 h. Muscle relaxation caused by baclofen microspheres impairs the rotarod performance for more than 12 h. Abdominal X-ray images showed that the gastroretention period of the floating barium sulfate- labeled microspheres was no less than 10 h. The buoyant baclofen microspheres provide a promising gastroretentive drug delivery system to deliver baclofen in spastic patients with a sustained release rate.

Development and Evaluation of Gastroretentive Atenolol Tablets

The low oral bioavailability of atenolol is primarily because of its poor absorption from the lower gastrointestinal tract. Gastroretentive dosage forms provide an opportunity to deliver the drug with absorption window in the proximal part of the GIT thereby increasing their bioavailability. The objective of this study was to develop a dosage form for atenolol with the objective of increasing the gastric residence and there by its oral bioavailability. Different formulations of floating tablets of atenolol (AT1-AT10) were prepared by varying the composition of hydroxypropyl methyl cellulose (HPMC) K100, lactose and citric acid. The tablets were evaluated for various parameters like friability, weight variation, content variation, floating lag time, total buoyancy and in vitro dissolution. The physicochemical properties of the prepared formulations were found to possess adequate physical integrity. Formulation AT8 showed the lowest floating lag time with 14 h buoyancy. Drug release was found to be dependent on the concentration of HPMC K100 and lactose in the formulation. Further, the increase in amount of citric acid leads to increase in atenolol release rate while reduces the floating time. The findings revealed that the formulation AT8 retarded the atenolol release (~73% in 12 h) and followed zero order kinetics. The in vitro data observed here substantiate the potential of the prepared formulation to provide adequate drug release and buoyancy to improve the bioavailability of atenolol, which necessitate further in vivo studies.

Formulation optimization of gastroretentive drug delivery system for allopurinol using experimental design

Objectives: The objective of the study was to develop gastroretentive dosage form (GRDF) for allopurinol (ALP) using combined approaches of mucoadhesion and floating systems. GRDF was systematically optimized using 32-full factorial design.Methods: Concentrations of sodium carboxymethyl cellulose (X1) and concentration of polyoxyethylene oxide WSR 303 (X2) were selected as independent variables, whereas gastroretentive parameters like total floating time (TFT) (Y1), mucoadhesive force (MF) (Y2), time required for 10% drug release (Y3) and time required for 80% drug release (Y4) were selected as dependent variables in development of robust GRDF of ALP. GRDF was evaluated for gastroretentive parameters such as floating lag time (FLT) and TFT, MF using texture analyzer and ex vivo residence time using modified disintegration test apparatus. Roentgenography study of optimized formulation was conducted to evaluate in vivo gastro retentive behavior using albino rabbits.Results: Developed tablets showed immediate in situ gas generation and exhibited FLT of 1.68 s after placing into simulated gastric fluid, which lead to buoyancy as well as controlled drug release for 24 h with zero-order drug release kinetics. The optimized formulation was selected based on in vitro drug release characteristics. In vivo retention of optimized formulation was corroborated using roentgenography studies.Conclusion: The study concluded that the combination of mucoadhesive and floating approaches for GRDF aids to achieve desired gastroretentive performance and drug release properties for ALP. The formulation scientists may adopt these formulation strategies for drugs suitable for the development of GRDF.