Granulation Technique Research Articles

FORMULATION AND EVALUATION OF DRUG RELEASE PROFILE OF HYDROPHILIC POLYMER BASED INDOMETHACIN PROLONG RELEASE MATRIX TABLETS

An oral modied release dosage forms have always been more effective therapeutic alternative to conventional dosage forms. The present invention is directed to a modied release pharmaceutical composition of indomethacin by using hydrophilic release retardant polymers like HPMC K15M, Na CMC alone or in combination. Matrix embedded prolong release tablet formulations of Indomethacin were prepared by wet granulation technique and evaluated for tablet properties such as the thickness, hardness, friability, weight variation, drug content, drug release kinetics and in vitro release studies. The inuence of drug polymer ratio on drug release was studied by dissolution test. The FTIR studies showed no interactions among drug and polymers. The tablets formulation (F7 and F8) containing combined polymers of HPMC K15M and Na CMC resulted in slower drug release rate form the matrix. So, it can be concluded that Indomethacin prolong release tablets using HPMC K15M and Na CMC as the retardant has successfully extended the release of indomethacin from its formulations. The mixing of two cellulose polymers, ionic and non-ionic, for the formulation of hydrophilic matrices, resulted in a valuable decrease in drug release rate. All the formulations showed KorsmeyerPeppa’s model as a best t.

Synchronous LC-MS/MS determination of pantoprazole and amitriptyline in rabbit plasma: application to comparative in vivo pharmacokinetic study of novel formulated effervescent granules with its marketed tablet dosage form

In the present study the bioavailability and pharmacokinetics properties of pantoprazole (proton pump inhibitor)/amitriptyline (tricyclic antidepressant) in novel formulated effervescent granules was estimated in rabbit plasma using a validated, selective and rapid LC-MS/MS method. Separation and detection of pantoprazole, amitriptyline and internal standards namely omeprazole and dothiepin, respectively, were achieved at ambient column temperature on C18. Acetonitrile: 4mM ammonium acetate solution (comprising 0.05 % formic acid) (40:60, v/v) was used as mobile phase and the flow rate of 0.6 mLmin-1 was applied. Liquid-liquid extraction technique with diethyl ether: dichloromethane (70:30, v/v) was used to extract the cited drugs from rabbit plasma. Multiple reactions monitoring (MRM) in the positive ionization mode was carried out for quantification. The method was validated over linear concentration range of 0.01-4μgmL−1 and 0.001–0.1 μgmL−1 for Pan and Ami respectively, with regression coefficient (r2) ≥ 0.9961. The intra- and inter-run precisions (%CV) were ≤4.03. The extraction recoveries were in the range of 95.92%–100.24 %. Pan and Ami were stable during three freeze-thaw cycle and post-preparative stability. The work also aimed to formulate immediate release novel effervescent granules by melt granulation technique. Nine formulae were assessed by validated dissolution test for their micrometric properties and dissolution profile. Experimental design was applied to select formula that fulfilled the desired criteria of optimum release of pantoprazole and amitriptyline with optimum micrometric properties for the study. A single period randomized open-label parallel design was applied on Chancellor's rabbit. The selected formula showed superior pharmacokinetic parameters for pantoprazole and amitriptyline than that of marketed products.

Granulation performance by hybrid centrifugal-air blast technique for treatment of liquid slag

Dry centrifugal granulation technique for treatment of liquid blast furnace (BF) slag stands out by its compact structure, easy adjustability, and smaller energy consumption. It is crucial to obtain fine particle characteristics for achieving high granulation performance and then high heat recovery rate. A three-dimensional model was established in this paper to describe theparticle characteristics of liquid BF slag by new hybrid centrifugal-air blast granulation technique. The intuitive granulation evolutions, particle mass distribution, and size uniformity, were acquired as well as accumulative mass fraction. As a result, the vertical breakage effect of blast air (20 m/s) accelerated the granulation process and led to a reduction of 14–18% in particle size, with more obvious optimization effect at low disk speed. Moreover, the general prediction correlation of particles size suitable for both the hybrid centrifugal-air blast technique and the classical centrifugal granulation technique, was established to optimize the granulation performance.

Formulation of Non-effervescent Floating Dosage Form of Metronidazole using Sintering and Sublimation Technique

The aim of this study was to formulate a novel non-effervescent floating dosage form of metronidazole using the sublimation and sintering technique. Granules were formulated using the wet granulation technique. Ammonium bicarbonate (30% w/w) was incorporated as the sublimating agent. The granules were characterized for micromeritic properties. Thereafter, the granules were compressed using a single punch tableting machine and the physicotechnical properties were evaluated. The metronidazole tablet was then sintered at 70oC for 12 h. All granules were free flowing and compressible. The metronidazole tablets had no floating lag time showing that tablets floated instantaneously. FTIR and DSC studies showed that metronidazole and the excipients used in the formulation were compatible. Azadirachta indica gum was used in the formulation of non-effervescent floating dosage form of metronidazole using sublimation and sintering technique which is beneficial in sustained release formulations.
 Dhaka Univ. J. Pharm. Sci. 20(1): 11-17, 2021 (June)

Natural Polymer Chitosan as Super Disintegrant in Fast Orally Disintegrating Meloxicam Tablets: Formulation and Evaluation.

The aim of the present investigation was to formulate fast disintegrating tablets of meloxicam by wet granulation technique using medium molecular weight chitosan. The orally disintegrating tablets of meloxicam with chitosan showed good mechanical and disintegration properties and good dissolution rate when prepared in tablet press using 10.8 kN and 11.0 kN compression force. Chitosan is a suitable biopolymer to moderate the disintegration process in orally disintegrating tablets.

Formulation, In-Vitro Evaluation and Comparative Study Ofitopride Hydrochloride Loaded Sustained Release Matrix Tablet Using Okra Mucilage as a Natural Binder

Natural polymers are abundantly available in plants with their wider pharmaceutical applications and are preferred more than some synthetic polymers because of their biodegradable, biocompatible and non-toxic properties. The study aims to formulate Itopride Hydrochloride loaded Sustained Release (SR) matrix tablet from the mucilage extracted from okra plant (Abelmoschus esculantus) and carry out the comparative study on the release retardant effect of synthetic binders like HPMC K100M and sodium carboxymethyl cellulose and their combinations. The extraction of the mucilage was carried by the maceration process. The formulation of Itopride loaded SR matrix tablet was carried by moist granulation technique. The micrometric, physiochemical studies and purity tests confirms the suitability of mucilage as an excipient. Pre-compression study suggests good flow property of the powders. The minimum angle of repose was observed in F7 with 29.03±0.6º and F2 exhibited maximum angle of repose with 34.30±0.5º. Carr's index and Hausner's ratio was lower in F1 with 11.56±0.4 and 1.11±0.3 respectively. Drug-excipient interaction study performed using FTIR spectrophotometry suggested no interaction between the drug and excipients. The in-vitro drug release of Itopride Hydrochloride loaded SR tablet up to 12 hours in 0.1 N HCl was conducted and observed to be maximum in F3 with 87.34±5.33% and minimum in F6 with 77±5.65 %. Drug release from the formulations were significant compared to the marketed product of Itopride Hydrochloride (p<0.05). The data were analyzed by Tukey post hoc multiple comparison test.

Exploitation of Design-of-Experiment Approach for Design and Optimization of Fast-Disintegrating Tablets for Sublingual Delivery of Sildenafil Citrate with Enhanced Bioavailability Using Fluid-Bed Granulation Technique.

Sildenafil citrate undergoes first-pass metabolism, resulting in poor oral bioavailability at 25–41% of the administered dose. This study aimed to design and optimize fast-disintegrating tablets for the sublingual delivery of sildenafil citrate to improve bioavailability and facilitate rapid onset of action. The design-of-experiment (DoE) approach using 32 full factorial design was conducted to develop a new formulation of sildenafil fast-disintegrating sublingual tablets (FDSTs) using the fluid-bed granulation technique. The levels of partially pre-gelatinized starch (5–15%) and microcrystalline cellulose (10–60%) were selected as independent formulation variables. The prepared FDSTs were investigated for physical properties. Further, the optimum formulation was chosen for in vivo study in rabbits. Regression analysis showed that independent variables have a significant (p < 0.05) influence on critical attributes of FDSTs. The optimized formulation showed acceptable mechanical strength (friability < 1.0%) with very fast disintegration (14.561 ± 0.84 s) and dissolution (94.734 ± 2.76% after 15 min). Further, the optimized formulation demonstrated a significant increase (p < 0.01) in Cmax and AUC0–∞ with short tmax compared to the market product (Viagra®). Based on these results, using the DoE approach, a high level of assurance was achieved for FDSTs’ product quality and performance.

A Review on Formulation and Development of Solid Self-Nano Emulsifying Drug Delivery Systems

This article describes current strategies to enhance aqueous solubility and dissolution rate of poor soluble drugs. Most drugs in the market are lipophilic with low or poor water solubility. There are various methods to enhance solubility: co-solvency, particle size reduction, salt formation and Self Nanoemulsifying drug delivery systems, SEDDS is a novel approach to enhance solubility, dissolution rate and bioavailability of drugs. The study involves formulation and evaluation of solid self-Nano emulsifying drug delivery system (S-SNEDDS) to enhance aqueous solubility and dissolution rate. Oral route is the most convenient route for non-invasive administration. S-SNEDDS has more advantages when compared to the liquid self-emulsifying drug delivery system. Excipients were selected depends upon the drug compatibility oils, surfactants and co surfactants were selected to formulate Liquid SNEDDS these formulated liquid self-nano emulsifying drug delivery system converted into solid by the help of porous carriers, Melted binder or with the help of drying process. Conversion process of liquid to solid involves various techniques; they are spray drying; freeze drying and fluid bed coating technique; extrusion, melting granulation technique. Liquid SNEDDS has a high ability to improve dissolution and solubility of drugs but it also has disadvantages like incompatibility, decreased drug loading, shorter shelf life, ease of manufacturing and ability to deliver peptides that are prone to enzymatic hydrolysis.&#x0D;

Impact of hydrophilic binders on stability of lipid-based sustained release matrices of quetiapine fumarate by the continuous twin screw melt granulation technique

Dose dumping is the major drawback of sustained release (SR) matrices. The current research aimed to develop the stable lipid-based SR matrices of quetiapine fumarate (QTF) using GeleolTM (glyceryl monostearate; GMS) as the lipid matrix carrier and KlucelTM EF (HPC EF), Kollidon® VA64, and Kollidon® 12PF as hydrophilic binders. Formulations were developed using advanced twin screw melt granulation (TSMG) approach and the direct compression (DC) technique. Compared with the blends of DC, the granules of TSMG exhibited improved flow properties and tabletability. Solid-state characterization by differential scanning calorimetry of the prepared granules exhibited the crystalline nature of the lipid. Fourier transform infrared spectroscopy demonstrated no interaction between the formulation ingredients. The compressed matrices of TSMG and DC resulted in the sustained release of a drug over 16–24 h. Upon storage under accelerated conditions for 6 months, the matrices of TSMG retained their sustained release characteristics with no dose dumping in alcohol, whereas the matrices of DC resulted in the dose dumping of the drug attributing to the loss of matrix integrity and phase separation of lipid. Thus, it is concluded that the uniform distribution of a softened binder into a molten lipid carrier results in the stable matrices of TSMG.

Mechanistic understanding of the effects of process and design parameters on the mixing dynamics in continuous twin-screw granulation

Wet granulation is a size enlargement process in which fine powders are agglomerated into larger granules via the presence of a liquid binder. Among various types and modes of granulation processes, twin-screw granulation is a popular continuous wet granulation technique. The typical residence time that powders spend in a twin-screw granulator are in the order of seconds, hence, the rigorous mixing of solid and liquid particles across particle sizes and equipment geometry becomes even more important. This study aims to improve the mechanistic understanding of the effect of process and screw parameters on the mixing dynamics inside a twin-screw granulator using dispersion coefficient as a key metric. The dispersion coefficient quantifies the dispersion and is directly proportional to the extent of mixing occurring inside the granulator. An analysis of the experimentally obtained dispersion coefficient is performed to understand the effect of key process and design parameters such as feed rate, screw speed, number of kneading elements and, stagger angle. A semi-mechanistic model that incorporates these parameters was developed to estimate and predict the dispersion coefficient. The model accurately predicts the dispersion coefficient values and the goodness-of-fit values (R2) for the test set and full data set were found to be equal to 0.920 and 0.932 respectively. This model was further tested by predicting the complete RTD curves using the predicted dispersion coefficients. The average goodness-of-fit value (R2) for the prediction of RTD curves for all the experimental runs was calculated to be equal to 0.698.

Continuous Twin Screw Granulation: A Review of Recent Progress and Opportunities in Formulation and Equipment Design.

Continuous twin screw wet granulation is one of the key continuous manufacturing technologies that have gained significant interest in the pharmaceutical industry as well as in academia over the last ten years. Given its considerable advantages compared to wet granulation techniques operated in batch mode such as high shear granulation and fluid bed granulation, several equipment manufacturers have designed their own manufacturing setup. This has led to a steep increase in the research output in this field. However, most studies still focused on a single (often placebo) formulation, hence making it difficult to assess the general validity of the obtained results. Therefore, current review provides an overview of recent progress in the field of continuous twin screw wet granulation, with special focus on the importance of the formulation aspect and raw material properties. It gives practical guidance for novel and more experienced users of this technique and highlights some of the unmet needs that require further research.

FORMULATION, OPTIMIZATION AND EVALUATION OF MOXIFLOXACIN HYDROCHLORIDE GASTRO RETENTIVE TABLETS

The objective of the current study was to develop gastro retentive formulation of moxifloxacin. HCl using various drug release modifiers and performing in vitro and in in vivo evaluations. Moxifloxacin is a novel synthetic fluoro quinolone antibacterial agent. Floating, muco adhesive tablets of moxifloxacin. HCl were prepared using variable amounts of HPMCK100M, Lannea coromandelica gum by direct compression technique and wet granulation technique, respectively. Formulations were developed, optimized and checked for pharmacopoeial tests. Results show that all the batches lie within the standard limits. Dissolution parameters of all formulations were sy=ubjected to kinetic fitting and various statistical parameters were determined. Formulation (FS5 ) containing 50 mg of HPMCK100M and 50 mg of LCG, is the best formulation showing similarity f2 =71.734, f1 = 4.271 with the marketed product (Avelox). It follows Higuchi's kinetics, non-fickian diffusion first order kinetics(n=0.717). In vivo studies were performed for the FS5 with 6 healthy rabbits and pharmacokinetic parameters were determined, compared with Avelox and it was found that FS5 produced similar results. Stability studies were performed for FS5 as per ICH guidelines. Results were found to be satisfactory. FS5 is expected to improve patient compliance by means of providing good clinical outcome

Advances in Twin-Screw Granulation Processing.

Twin-screw granulation (TSG) is a pharmaceutical process that has gained increased interest from the pharmaceutical industry for its potential for the development of oral dosage forms. The technology has evolved rapidly due to the flexibility of the equipment design, the selection of the process variables and the wide range of processed materials. Most importantly, TSG offers the benefits of both batch and continuous manufacturing for pharmaceutical products, accompanied by excellent process control, high product quality which can be achieved through the implementation of Quality by Design (QbD) approaches and the integration of Process Analytical Tools (PAT). Here, we present basic concepts of the various twin-screw granulation techniques and present in detail their advantages and disadvantages. In addition, we discuss the detail of the instrumentation used for TSG and how the critical processing paraments (CPP) affect the critical quality attributes (CQA) of the produced granules. Finally, we present recent advances in TSG continuous manufacturing including the paradigms of modelling of continuous granulation process, QbD approaches coupled with PAT monitoring for granule optimization and process understanding.

Synergistic application of twin-screw granulation and selective laser sintering 3D printing for the development of pharmaceutical dosage forms with enhanced dissolution rates and physical properties

This study demonstrated the first case of combining a novel continuous granulation technique with powder-bed fusion-based selective laser sintering (SLS) process to enhance the dissolution rate and physical properties of a poorly water-soluble drug. Selective laser sintering and binder jetting 3D printing processes have gained much attention in pharmaceutical dosage form manufacturing in recent times. These powder bed-based 3D printing platforms have been known to face printing and uniformity problems due to the inherent poor flow properties of the pharmaceutical physical mixtures. To address this issue a hot-melt extrusion-based versatile granulation process equipped with a process analytical technology (PAT) tool for the in-line monitoring of critical quality attributes (i.e., solid-state) of indomethacin was developed. The collected granules with enhanced flow properties were mixed with Kollidon® VA64 and a conductive excipient for efficient sintering. These mixtures were further characterized for their bulk properties observing an excellent flow and later subjected to an SLS-3D printing process. The physical mixtures, processed granules, and printed tablets were characterized using conventional as well as advanced solid-state characterizations. These characterizations revealed the amorphous nature of the drug in the processed granules and printed tablets. Further, the in vitro release testing of the tablets with produced granules as a reference standard depicted a notable dissolution advantage (100% drug released in 5 min at >pH 6.8) over the pure drug and the physical mixture. Our developed system known as DosePlus combines innovative continuous granulation and SLS-3D printing process which can potentially improve the physical properties of the bulk drug and formulations in comparison to when used in isolation. This process can further find application in continuous manufacturing of granules and additive manufacturing of pharmaceuticals to produce dosage forms with excellent uniformity and solubility advantage.

Novel risperidone orally disintegrating minitablets for pediatric use: patient acceptance and dose adjustment

Objective Risperidone is a potent psychotropic agent has been approved for symptomatic treatment of irritability in children and adolescents with autism spectrum disorders. However, its bitter taste and dose adjustment of liquid dosage forms are a main hurdle for patient acceptance. Significance Thus, this recent study investigate the formulation of taste masked risperidone orally disintegration minitablets (ODMT) as a way of enhancing patient acceptance. Methods Taste masked risperidone hydrogenated castor oil or Cetyl alcohol based granules were prepared using a simple melt granulation technique in different drug to lipid ratios; drug release, bitterness score of the prepared granular formulations were evaluated. DSC was also performed to detect the possible drug lipid interaction. The selected lipid-based granules were further compressed into ODMT formulations. Bitterness score was assessed by gustatory sensation test and results were compared to marketed liquid formulations of risperidone. Results All the prepared ODMT formulations showed high content uniformity, with minimum dose fluctuation compared to marketed oral liquid preparations. Conclusion In conclusion, risperidone lipid-based granules could be formulated in different ratios by simple techniques and commonly used excipients into taste masked risperidone ODMT with accurate and flexible doses suitable for pediatric use with high taste preference and acceptability.

H. SABDARIFFA CALYCES ASH: ANTIANXIETY AND ANTIDEPRESSANT ACTIVITY EVALUATION AND PREPARATION OF ITS TABLETS

Objective: Ash and its preparations have been used in Ayurveda for the treatment of various ailments since 7th century AD. Numerous studies suggest that the elements present in ash have significant role in affective disorders. Thus, the present study aimed at evaluating the antianxiety and antidepressant activity of total ash of H. sabdariffa calyces, and also of the tablets of total ash.&#x0D; Methods: Powdered calyces were taken in tared silica crucible, and were incinerated at a temperature not exceeding 450 °C. The resultant ash was cooled and weighed. This was evaluated for antianxiety and antidepressant activity using an elevated plus maze and Porsolt’s swim test, respectively. Further, the ash samples were analysed through ICP-MS to know their composition. The ash was formulated into tablets using the wet granulation technique, using only organic excipients.&#x0D; Results: Results indicated that the total ash of H. sabdariffa calyces exhibited significant (p&lt;0.001) antianxiety and antidepressant activity at 50 and 100 mg/kg, po, respectively. The activities were comparable to the standard drugs. ICP-MS analysis showed the presence of magnesium, phosphorous, potassium and calcium as major elements. Tablets of H. sabdariffa total ash were as effective (p&lt;0.001) as the total ash.&#x0D; Conclusion: Magnesium, phosphorous, potassium and calcium have been reported to play a significant role in affective disorders, explaining, thereby, as to why ash of H. sabdariffa calyces exhibited anti-anxiety and antidepressant activity.

Formulation Development and Evaluation of New Albendazole Tablets with Integrated Quality by Design (QbD) Approach

Hydatid disease occurs in most areas of the world and currently affects about one million people. Albendazole is an orally administered broad spectrum anthelmintic drug approved by US FDA in 1996. Literature review suggests Albendazole is low solubility compound and most of the studies were performed to improve the solubility with traditional approach of product development. The present study was aimed to apply Design of Experiments (DoE) in the development and optimization of drug release from new Albendazole tablets using three factor two level (23) full factorial designs with integrated Quality be Design (QbD) approach. New Albendazole tablets were formulated using micronized grade of the Albendazole active and excipients were selected inline with market reference product. Quality target product profile (QTPP) and Critical quality attributes (CQAs) were designed. Risk assessment was used to identify the Formulation variables impacting CQA dissolution. The amount of Formulation variables were optimized on the basis of drug release profiles at 15 minutes and 30 minutes of different formulation batches manufactured based on 23 full factorial design. Tablets were prepared by wet granulation technique and evaluated for various physicochemical parameters and in vitro drug release. Formulation trials dissolution results at 15 minutes and 30 minutes were evaluated to derive the concentration of Formulation variables which will achieve the release of more than 80%. Analysis of variance (ANOVA) analysis, Pareto chart and Contour plot were used to predict the values of formulation variables and their effect on dissolution. Updated risk assessment of the Formulation Variables was performed and justification was provided for reduction of risk from medium to low level. Optimized formulation from DOE had comparable dissolution profile with market reference tablet. Stability studies of new Albendazole tablets 200 mg were conducted at ICH accelerated conditions and found to be stable. Thus studies revealed that full factorial experimental design could efficiently be applied for optimization of formulation variables affecting drug release. New Albendazole tablets 200 mg successfully formulated with application of the integrated quality by design (QbD) and design of experiment (DOE) approach and thereby achieved comparable release profile with market reference product.&#x0D;

Development and Evaluation of Goat Milk Tablet Using Dry Granulation Techniques for Nutraceutical Purposes

There are several problems for the school children to take the pure milk especially the goat milk every day because of the unpleasant taste and smell of the goat milk are not so good. Besides, the pure milk has a short life time. It is difficult to store the goat milk in a long period of time at room temperature. The solution for this problem is change the goat milk from liquid form into the chewable milk tablet that can be easily consume by the school children. Goat milk in the form of tablet formulation will increase the shelf life of the product. Therefore, the chewable goat milk tablet can be stored in a long period of time, convenience, and suitable for distribution to remote areas. In this project, the focusing was more into the optimization of the weight adjustment of the tableting machine before and after the dry granulation to form good chewable tablet. The pre-evaluation had been done for the goat milk powder and granule after dry granulation process. It can be concluded that goat milk tablet can be an alternative to the pure goat milk. The poorly flowing properties of goat milk powder can be improved by using dry granulation techniques. Based on this study, F4D shows the best setting to produce the goat milk tablet using dry granulation technique. F4D successfully improved the flow ability and compressibility of goat milk tablet. It also produce the best goat milk tablet as it possess uniformity of weight, low friability and good hardness

Mouth Dissolving Tablets of Favipiravir using Superdisintegrants: Preparation, Optimization and In-vitro Evaluation

To formulate and evaluate the mouth dissolving tablet dosage forms of favipiravir using various superdisintegrants by using wet granulation technique.&#x0D; Batches of favipiravir Mouth dissolving tablets were formulated by using the wet granulation technique. The formulated granules were evaluated for their flow properties as a pre-compression parameter and the friability, hardness, disintegration, wetting ratio, wetting time, dissolution, and drug release parameters were evaluated as post-compression parameters. The effect of the varying concentrations of superdisintegrants on the formulation for disintegration time was ascertained and the results were compared.&#x0D; The tablet had friability and hardness values ranging from 0.60 to 0.68 % and 3.9 to 4.3 (kg/cm2). Tablet weights did not vary significantly but the disintegration time varied from 44.66 to 142.66±2.51 min and the wetting time varied from 45.33 to 144 min and the optimal batch of tablets shows a drug release of 98.8% within 60 min and first-order release kinetics of the formulations are compared.

Design of Fuzzy Ensemble Architecture Realized With the Aid of FCM-Based Fuzzy Partition and NN With Weighted LSE Estimation

Neural networks (NNs) with least square error (LSE) estimation form a certain type of single hidden layer feed-forward NNs. In this class of networks, the input connections (weights) and the biases of hidden neurons are generated randomly and fixed after being generated. The output connections are estimated by the LSE method rather than the back-propagation method. The random generation of the input connection weights and the hidden biases results in the larger number of hidden neurons to assure the quality of classification performance. To reduce the number of neurons in the hidden layer while maintaining the classification performance, we apply a “divide and conquer” strategy in this article. In other words, we divide an overall input space into several subspaces by using information granulation technique (Fuzzy C-Means clustering algorithm) and determine the local decision boundaries among related subspaces. A decision boundary defined in the input space can be considered as being composed of several decision boundaries defined in subspaces that form the entire input space. For the decision boundaries defined in the subspaces, their nonlinearity becomes lower in comparison with the one being encountered when considering the entire input space. Through the weighted LSE estimation instead of using the LSE estimation method, the connections of several NNs can be estimated without interfering with each other. After estimating the weights, the decision boundaries defined in the related subspaces are merged to a single decision boundary by using fuzzy ensemble technique. Several machine learning datasets and one real world application dataset are used to evaluate and validate the proposed fuzzy ensemble classifier. Based on the experimental results, the proposed classifier shows better classification performance when compared with the performance of some selected classifiers.