A review on key aspects of wet granulation process for continuous pharmaceutical manufacturing of solid dosage oral formulations

Background: Orodispersible Tablets (ODTs) are an option to facilitate the intake of pharmaceutical solid dosage forms, which dissolve in the mouth within 30 seconds releasing the drug immediately with no need for water intake or chewing. Objective: The main goal of our study is the technological development of lactose-free orodispersible tablets that contain ketoprofen. Methods: We assessed different variables during the pharmaceutical development of ODTs: compression techniques conducted after a wet granulation process, aiming to optimize the flow properties of the formulation, and a suspension freeze-drying molded in blisters. We developed three formulations for each method, each containing one of the superdisintegrants: croscarmellose, crospovidone, or starch glycolate. Result: During the production of ODTs, we performed quality control of the granulation process, since the production of pellets contributed to the enhancement of the disintegration time and content homogeneity. Quality control tests for ODTs produced by freeze-drying were also satisfactory, despite significant changes in the final physical aspect of these products when compared to that of ODTs produced by compression. In addition, the disintegration times of ODTs produced by freeze-drying were substantially higher. Furthermore, these tablets displayed greater friability and pose a challenge to the control of a standard individual weight. Conclusion: Among the superdisintegrants, croscarmellose contributed most significantly to reduce the disintegration time and to dissolve KTP effectively in 20 minutes.

Download Full-text

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

Download Full-text

Grey-Box Approach for the Prediction of Variable Residence Time Distribution in Continuous Pharmaceutical Manufacturing

IFAC-PapersOnLine ◽

10.1016/j.ifacol.2020.12.2774 ◽

2020 ◽

Vol 53 (2) ◽

pp. 10360-10365

Author(s):

A. Elkhashap ◽

R. Meier ◽

D. Stenger ◽

D. Abel

Keyword(s):

Residence Time ◽

Time Distribution ◽

Residence Time Distribution ◽

Pharmaceutical Manufacturing ◽

Continuous Pharmaceutical Manufacturing

Download Full-text

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

Download Full-text

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.

Download Full-text

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.

Download Full-text