Mixing/granulation

Manufacturing validation data, which should aim to identify the critical process steps, especially for nonstandard manufacturing processes such as for new dosage forms, should be discussed in the development pharmaceutics section of the application. Validation data may be accepted based on closely related products. In-process control tests and acceptance limits should be included for any aspect where conformity with the finished product tests cannot otherwise be guaranteed (e.g., mixing, granulation, emulsification and nonpharmacopeial sterilization processes). 

Full Scale Giatt Mixing. The fluidized bed granulator is one of the most important granulation methods available today, because it combines the unit operations of mixing, granulating, and drying into... 

Eddie and McIntyre, F.L. Improved Mixing. Granulation and Drying of Highly Energetic Pvromixtures Pine 8luff Arsenal, Pine Bluff. Arkansas 71602-9500 (1986). 

Garcia, David J. Aikman, Loy M. McIntyre, F.L. and Shook, Thomas E. Ramd Plant Scaie Mixing Granulation and Loading of Drv Materials Purina the Manufacture of Colored Smoke Munitions Pine Bluff Arsenal, Pine Bluff,... 

Due to this principle, a batch B defined for quality control purposes consists of a fixed number of n mini batches (subunits), i.e., B=nb.Thus, a tight in-process control of the mixing/granulation (6-9) and drying step (14) provides an excellent batch record of the quasi-continuous production of granules and an excellent opportunity for a continuous validation of the process and the equipment (14-18,32-34). 

Note If a single piece of equipment is capable of performing multiple discrete unit operations (mixing, granulating, drying), the unit was evaluated solely for its ability to dry. The drying equipment was sorted into similar classes of equipment, based upon the method of heat transfer and the dynamics of the solids bed. 

Amatol, developed by the British during the first World War, is made by mixing granulated ammonium nitrate with melted trinitrotoluene, and pouring or extruding the mixture into the shells where it solidifies. The booster cavity is afterwards drilled out from the casting. The explosive can be cut with a hand saw. It is insensitive to friction and is less sensitive to initiation and more sensitive to impact than trinitrotoluene. It is hygroscopic, and in the presence of moisture attacks copper, brass, and bronze. 

Enzymes should be added to the feed together with the pre-mix. Granulated enzyme products may readily be mixed with feed components, as they are based on normal feed components such as wheat or soy grits. A wide range of enzyme products are available. Enzyme products should contain specific enzyme activities necessary to degrade specific substances such as glucans, starch, protein, pectin-like polysaccharides, phytic acid, raffinose, stachyose, hemicellulose, and cellulose. 

To improve compaction properties of the powder mix Granulation is known to improve the compaction properties of powders that otherwise do not readily lead to compactable mixes. This is linked to the use of some excipients (i.e., binders) whose distribution within the granules lead to easier compaction. Most binders facilitate compression by softening and deforming plastically under load. 

A more intensive mixing-granulating action than that provided by conventional paddle mixers is obtained in shaft mixers operating at high rotational velocities. These machines are generally single-shaft devices in which the paddles are replaced by a series of pins, pegs or blades. They may be operated... 

A mixed granulate produced from PETP and PVC postconsumer bottles has been separated using the technology of column flotation. The aqueous separation medium pH and surfactant concentration were optimised with respect to separation efficiency, using Response Surface Methods. The study has shown that column flotation could be used to give close to 100% separation of PVC from PETP in a single operation. 15 refs. 

Amatol, developed by the British during the first World War, is made by mixing granulated anunonium nitrate with melted trinitrotoluene, and pouring or extruding the mixture into the shells where it solidifies. The booster cavity is afterwards drilled... 

Because of the interactions existing between different materials as well as between like materials, the performance of excipients in a formulation could be different from the performance of the excipients themselves. The most frequently used procedures in pharmaceutical processing for solid dosage formulations are mixing, granulation, and compaction, as well as storage of finished dosage forms. The effects of adsorption on these procedures have been studied, observed, and utilized widely in the pharmaceutical industry. 

Poska R. Integrated mixing granulating and microwave drying a development experience. Pharm Eng 1991 11(1) 8-13. 

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