MANUFACTURING OF EFFERVESCENT FORMS IN PHARMACEUTITAL INDUSTRY Part 1: “Introduction of effervercent dosage form”

1. Introduction

Effervescence has proved its utility as an oral delivery system in the pharmaceutical and dietary industries for decades. In Europe, effervescent dosage forms are widespread, and their use is growing in the United States and other countries. Effervescent granulation is an important step of “fizzy” dosage forms production that most of the time cannot be avoided to achieve the desired characteristics of the effervescent tablets, for example, the stability of the final dosage forms.

This dosage form is easier to administer, particularly helpful to patients, like children, who are not able to swallow capsules or tablets. However, the manufaturing of them is more complex than conventional forms, especially in selecting technology and processing equipment.

 

2. The effervescent reaction

Effervescence is the evolution of gas bubbles from a liquid, as a result of a chemical reaction. The most common reaction for pharmaceutical purpose is the acid-base reaction between sodium bicarbonate and citric acid.

 

3. Formation and raw materials

The effervescent dosage form basically consists of:

 - The medicament

 - Acid materials, for example: citric acid, tartatic acid, ascorbic acid, anhydride acid, acid salts

 - Sources of CO2 (alkaline materials), mainly NaHCO3 and Na2CO3

 - Binders

 - Lubricants

 - Additives: coloring agents, sweeteners, flavors…

Acid materials and alkaline materials acount for most of this form’s volume

 

4. Manufacturing of effervescent dosage

Because most of materials in effervescent dosage form are hygroscopic, the manufacturing of this form must be strickly controlled, for example, the air in the whole factory must be controlled below 23oC - 20%RH in order to avoid the effervescent reaction to start prior to use the tablets.

Manufacturing effervescent drugs on a largescale is usually done in a semicontinuous procedure, by paying attention to synchronize all the process steps, to achieve the largest production throughput. A continuous process flow, with continuous feedingof raw materials and collection of granules, can be performed by extrusion of thewet mass and drying in a continuous fluid-bed dryer. Granulation of effervescent mixtures must be, most of the times, executed in batches and is definitely the most critical step of this particularkind of pharmaceutical manufacturing, as it hardly influences the characteristics of the final forms, granules, or tablets, and consequently the following steps of production. Machinery and technology for effervercent dosage require the high-safety funtion, explosion-proof and must be qualified strickly before operation

 

5. Granulation method

At the present, the wet granulation is the most preferred method for effervescent granulation because it assures homogeneous granules, suitable for compression, able to provide uniform tablets either in terms of weight or active ingredient content. There are two processes for wet granulation: single-step and multi-step.

 

Reference: D.M. Parikh, Ed., Handbook of Pharmaceutical Granulation (Marcel Dekker Inc., New York, New York, USA, 1997)

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