FABRICATION AND EVALUATION OF LABORATORY SCALE MINIGRANULATOR USING THE CONCEPT OF DESIGN OF EXPERIMENTS

The main objective of the present work was to design, fabricate and evaluate a laboratory scale mini granulator for applications in the research and development department. The Box and Behnken design was adopted to identify the critical parameters in the wet granulation process. The granules and tablets were characterized. The spherical granules obtained by using the fabricated mini granulator were of size 600 to 750 μ. On the other hand, the manual method (mortar and pestle) resulted in the formation of larger granules (800-950 μ). Recovery of granules by both the manual method and laboratory scale mini granulator were 71 and 90%, respectively. From the Box and Behnken design, an optimized formula was achieved with granulation time of 10 min, binder concentration 2.35 % and impeller speed 3000 rpm. Use of the mini granulator is recommended for screening of various formulations at R&D centers and also at colleges where the availability of drug is a few grams.

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Prediction of quality attributes (mechanical strength, disintegration behavior and drug release) of tablets on the basis of characteristics of granules prepared by high shear wet granulation

PLoS ONE ◽

10.1371/journal.pone.0261051 ◽

2021 ◽

Vol 16 (12) ◽

pp. e0261051

Author(s):

Amjad Khan

Keyword(s):

Expert System ◽

Drug Release ◽

Mechanical Strength ◽

Wet Granulation ◽

High Shear ◽

Process Variables ◽

Crushing Strength ◽

Granulation Process ◽

Binder Concentration ◽

High Shear Wet Granulation

High shear wet granulation is commonly applied technique for commercial manufacturing of tablets. Granulation process for tablets manufacturing is generally optimized by hit and trial which involves preparation of granules under different processing parameters, compression of granules and evaluation of the resultant tablets; and adjustment is made in granulation process on the basis of characteristics of tablets. Objective of the study was to optimize the process of high shear wet granulation and prediction of characteristics of tablets on the basis of properties of granules. Atenolol granules were prepared by high shear wet granulation method, using aqueous solution of polyvinyl pyrrolidone (PVP k-30) as binder. Concentration of binder solution and granulation time were taken as process variables, both studied at three levels. Different combinations of process variables were determined by Design Expert software. Granules were evaluated for different parameters on the basis of SeDeM-ODT (Sediment Delivery Model-Oro Dispersible Tablets) expert system. Granules from all the trials were compressed using round (10.5 mm) flat faced punches at compression weight of 250 mg/tablet. Tablets were evaluated of different quality control parameters as per USP. Results showed that both the process variables had positive effect on mechanical strength of tablets and negative effect on disintegration and dissolution rate. Granule prepared with highest level of binder concentration (15%) and highest granulation time (60 sec) resulted in tablets with highest crushing strength (11.8 kg), specific crushing strength (0.328 kg/mm2), tensile strength (0.208 kg/mm2), lowest value of friability (0.19%) and highest disintegration time (10.9 min), as predicted from granules characteristics on the basis of SeDeM-ODT expert system. Drug release from Trial-13 (processed under highest level of both process parameters) was also lower than rest of the trials. It is concluded from the study that quality characteristics of tablets can be predicted from granules characteristics using SeDeM-ODT expert system. Furthermore, SeDeM-ODT expert system can also be used for optimization of the process of high shear wet granulation.

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Formulation and Evaluation of Baclofen Orally Disintegrating Tablets

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2009.2.4.7 ◽

1970 ◽

Vol 2 (4) ◽

pp. 733-738

Author(s):

Dumpeti Janardhan ◽

Joginapally Sreekanth ◽

P.Theja Pavan Kumar ◽

M.Vamshi Krishna

Keyword(s):

Pilot Scale ◽

Taste Masking ◽

Wet Granulation ◽

Physical Parameters ◽

Disintegration Time ◽

Granulation Process ◽

Good Taste ◽

Orally Disintegrating Tablets ◽

Human Volunteers ◽

Eudragit Epo

The purpose of this study was to evaluate the potential of polymers for masking the taste of bitter drugs when incorporated into orally disintegrating tablets. The tablets were produced by simple wet granulation technique with a model compound (baclofen) which is moderately bitter. The formulating procedure had two variables to obtain good taste masking with desirable characteristics. The optimal granulation process parameters were polymer selection and its concentration (w/w), suitable for pilot scale level. Dextrates, β- cyclodextrin, eudragit EPO and PVP K-30 were used in preparation of granules by using water and iso-propyl alcohol. Crospovidone was used intra and extra granularly as superdisintegrant. Sodium bicarbonate and citric acid were used as effervescent for fast disintegration of tablets, which also optionally act as desensitizer of taste buds. Results from evaluation of tablets indicated a disintegration time (avg) of 30-35 sec and 100% drug release was achieved within 5 min. But taste masking was achieved by only with eudragit EPO. Results from an evaluation by a panel of six human volunteers demonstrated that the orally disintegrating tablets which are prepared by using polymer Eudragit EPO (5% and 7.5% w/w of tablet) and PVP (7.5% w/w of tablet) improved taste, significantly. On studying physical parameters, F9 formulation demonstrated acceptable level of hardness and friability with good taste masking and it was thus considered as an optimized formulation

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Efficient Global Sensitivity-Based Model Calibration of a High-Shear Wet Granulation Process

Chemical Engineering Science ◽

10.1016/j.ces.2021.116569 ◽

2021 ◽

pp. 116569

Author(s):

Aaron S. Yeardley ◽

Stefan Bellinghausen ◽

Robert Milton ◽

James D. Litster ◽

Solomon F. Brown

Keyword(s):

Model Calibration ◽

Wet Granulation ◽

High Shear ◽

Granulation Process ◽

Global Sensitivity ◽

High Shear Wet Granulation

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Identifying Critical Binder Attributes to Facilitate Binder Selection for Efficient Formulation Development in a Continuous Twin Screw Wet Granulation Process

Pharmaceutics ◽

10.3390/pharmaceutics13020210 ◽

2021 ◽

Vol 13 (2) ◽

pp. 210

Author(s):

Lise Vandevivere ◽

Maxine Vangampelaere ◽

Christoph Portier ◽

Cedrine de Backere ◽

Olaf Häusler ◽

...

Keyword(s):

Dissolution Kinetics ◽

Wet Granulation ◽

Continuous Manufacturing ◽

Formulation Development ◽

Granulation Process ◽

Low Viscosity ◽

Twin Screw ◽

Poorly Soluble ◽

Selection For ◽

The Impact

The suitability of pharmaceutical binders for continuous twin-screw wet granulation was investigated as the pharmaceutical industry is undergoing a switch from batch to continuous manufacturing. Binder selection for twin-screw wet granulation should rely on a scientific approach to enable efficient formulation development. Therefore, the current study identified binder attributes affecting the binder effectiveness in a wet granulation process of a highly soluble model excipient (mannitol). For this formulation, higher binder effectiveness was linked to fast activation of the binder properties (i.e., fast binder dissolution kinetics combined with low viscosity attributes and good wetting properties by the binder). As the impact of binder attributes on the granulation process of a poorly soluble formulation (dicalcium phosphate) was previously investigated, this enabled a comprehensive comparison between both formulations in current research focusing on binder selection. This comparison revealed that binder attributes that are important to guide binder selection differ in function of the solubility of the formulation. The identification of critical binder attributes in the current study enables rational and efficient binder selection for twin-screw granulation of well soluble and poorly soluble formulations. Binder addition proved especially valuable for a poorly soluble formulation.

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A Study on the Impact of R&D Intensity on Business Performance: Evidence from South Korea

Journal of Open Innovation Technology Market and Complexity ◽

10.3390/joitmc7020135 ◽

2021 ◽

Vol 7 (2) ◽

pp. 135

Author(s):

Hun Park ◽

Jun-Hwan Park ◽

Sujin Lee ◽

Hyuk Hahn

Keyword(s):

South Korea ◽

Research And Development ◽

Business Performance ◽

Decision Makers ◽

The Other ◽

Research Groups ◽

Innovative Firms ◽

The Impact ◽

Knowledge Services

The role of R&D (research and development) intensity on the effect of knowledge services on the business performance of firms has been discussed by using PLS-SEM and PLS-MGA methods. Research groups were divided into two groups, innovative and non-innovative. Respondents were classified into innovative firms if their R&D intensity was over 3% and vice versa. PLS-SEM and PLS-MGA results were compared for two groups and valuable insights were extracted. For innovative firms, knowledge services seemed to be verified and processed by the decision makers and utilized to achieve their business performance. On the other hand, a large number of non-innovative firms seemed to have a stronger tendency to utilize knowledge services directly for their business without sufficient verification by the decision makers.

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Solid Form and Phase Transformation Properties of Fexofenadine Hydrochloride during Wet Granulation Process

Pharmaceutics ◽

10.3390/pharmaceutics13060802 ◽

2021 ◽

Vol 13 (6) ◽

pp. 802

Author(s):

Suye Li ◽

Hengqian Wu ◽

Yanna Zhao ◽

Ruiyan Zhang ◽

Zhengping Wang ◽

...

Keyword(s):

Phase Transition ◽

Phase Transformation ◽

Water Content ◽

Scale Up ◽

Small Scale ◽

Dissolution Behavior ◽

Wet Granulation ◽

Water Addition ◽

Granulation Process ◽

And Performance

The quality control of drug products during manufacturing processes is important, particularly the presence of different polymorphic forms in active pharmaceutical ingredients (APIs) during production, which could affect the performance of the formulated products. The objective of this study was to investigate the phase transformation of fexofenadine hydrochloride (FXD) and its influence on the quality and performance of the drug. Water addition was key controlling factor for the polymorphic conversion from Form I to Form II (hydrate) during the wet granulation process of FXD. Water-induced phase transformation of FXD was studied and quantified with XRD and thermal analysis. When FXD was mixed with water, it rapidly converted to Form II, while the conversion is retarded when FXD is formulated with excipients. In addition, the conversion was totally inhibited when the water content was <15% w/w. The relationship between phase transformation and water content was studied at the small scale, and it was also applicable for the scale-up during wet granulation. The effect of phase transition on the FXD tablet performance was investigated by evaluating granule characterization and dissolution behavior. It was shown that, during the transition, the dissolved FXD acted as a binder to improve the properties of granules, such as density and flowability. However, if the water was over added, it can lead to the incomplete release of the FXD during dissolution. In order to balance the quality attributes and the dissolution of granules, the phase transition of FXD and the water amount added should be controlled during wet granulation.

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A combined experimental and modeling approach to study the effects of high-shear wet granulation process parameters on granule characteristics

Pharmaceutical Development and Technology ◽

10.3109/10837450.2012.700933 ◽

2012 ◽

Vol 18 (1) ◽

pp. 210-224 ◽

Cited By ~ 40

Author(s):

Preetanshu Pandey ◽

Jing Tao ◽

Anwesha Chaudhury ◽

Rohit Ramachandran ◽

Julia Z. Gao ◽

...

Keyword(s):

Process Parameters ◽

Wet Granulation ◽

High Shear ◽

Granulation Process ◽

Modeling Approach ◽

High Shear Wet Granulation

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The Effect of the Wet Granulation Process on Drug Dissolution

Drug Development and Industrial Pharmacy ◽

10.3109/03639048809151936 ◽

1988 ◽

Vol 14 (10) ◽

pp. 1327-1349 ◽

Cited By ~ 6

Author(s):

Hoshang M. Unvala ◽

Joseph B. Schwartz ◽

Roger L. Schnaare

Keyword(s):

Drug Dissolution ◽

Wet Granulation ◽

Granulation Process

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Hydroxypropylcellulose controlled release tablet matrix prepared by wet granulation: effect of powder properties and polymer composition

Brazilian Archives of Biology and Technology ◽

10.1590/s1516-89132009000100021 ◽

2009 ◽

Vol 52 (1) ◽

pp. 157-162 ◽

Cited By ~ 6

Author(s):

Antonio Zenon Antunes Teixeira

Keyword(s):

Drug Release ◽

Release Rate ◽

Hydrophilic Polymers ◽

Polymer Composition ◽

Wet Granulation ◽

Granulation Process ◽

Powder Properties ◽

Low Levels ◽

Tablet Matrix ◽

Best Fit

The aim of this study was to attain 100% drug release of caffeine after 24 h from hydroxypropylcellulose (HPC) tablet matrices and to investigate the effect of co-excipient. Physical properties of the powders were evaluated and suggested for a wet granulation process. The tablet containing caffeine was formulated by different weight ratios of hydrophilic polymers. The results of polymer evaluation confirmed that the increase of HPC level with the same drug content significantly decreased the rate of drug release. The presence of co-polymer excipients carboxymethylcellulose (CMC) and polyvinylpyrrolidone (PVP) in the tablet matrix was also investigated. The release rate was also controlled by low levels of CMC (<10%) while PVP did not show any considerably effect. The best fit release rate 100% at 24 h was obtained when 10% of α-lactose monohydrate was added to the formulation.

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