Particle size parenteral preparations

For parenteral uses, the sizes of MLVs prepared by the above methods need to be small enough t pass through the aseptic Liter. Three methods that are used in reducing the particles sizes will bi discussed as follows sonication, high-pressure homogenization, and extrusion. 

Suspensions are coarse dispersions of finely divided solids in a liquid. The solid particles have a mean particle size greater than 0.1 pm in diameter. Pharmaceutical suspensions are administered orally, topically, and parenterally and should avoid the following problems sedimentation, caking, flocculation, and particle growth. Physicochemical principles in the solid/liquid interface will be discussed in this section as they pertain to the preparation of good pharmaceutical suspensions. 

There are additional constraints when manufacturing parenteral emulsions that must be sterile and of fine particle size. Perfluorochemical and fat emulsions are usually prepared by homogenization at high temperature and pressure, as a large output of energy is required to produce droplet sizes considerably less than 1 pm. Although heat sterilization is widely used, this places a severe test on the stability, and emulsions are sometimes prepared from sterile components under strict aseptic conditions and further sterilized by filtration. ... 

Variations in assay results can be avoided by the preparation of homogeneous, well-mixed, or non-settling fine particle suspensions (size 1-10 pm). Particle size reduction results in slow, more uniform settling rates. The bioavailability of drugs is improved by reducing the size of suspension particles. Furthermore, drug particles smaller than 20 pm produce less pain and tissue irritation when injected parenterally. However, fine particles may have a deleterious effect on chemical stability because of their high dissolution rate. 

FAT EMULSION For parenteral nutrition a fat emulsion for intravenous administration is used. Preparations contain a fractionated soya-oil emulsified with some fractionated egg phospholipids. About 60% of the fatty acids are essential fatty acids the particle size and biological properties are similar to those in natural chylomicrones. 

More surprisingly, CyDs can in addition directly influence nanosphere characteristics by stabilizing interfaces during the preparation process, as described for emulsions [39]. Thus, it appears that the type of CyD used influences the particle size, their surface potential, and the total amount of CyD associated into the nanospheres [39]. Among CyDs, HP- 8-CyD leads to spheres with the smallest size (interesting in parenteral administration) and a neutral surface. 

It is possible to prepare various kinds of nanoparticles with different surface charges and particle sizes depending on the polymer composition and preparation technique. As a result, the particle size of nanoparticles varies from 10 nm to 200 nm and the surface charge - -5 mV to -1-50 mV. In this manner, drug carrier systems can be formed through different routes such as oral, parenteral and other mucosal routes for local or systemic therapy, with high cellular interaction, loading capacity, transfection efficiency and low toxicity. 

Chitosan was also formulated in a controlled-release protein delivery system using bovine serum albumin (BSA) as a model drug. Chitosan was reacted with sodium alginate in the presence of tripolyphosphate for bead formation [94]. Parenteral administration of proteins/peptides requires repeated injections because of their extremely short biological half-life. Daily multiple injections are highly risky and require close medical supervision. On this basis, bovine serum albumin (BSA)-loaded chitosan microspheres were prepared to test the drug release behavior in buffers with different pH values. BSA-chitosan microspheres with particle sizes in the range from 5 to 10 pm... 

Fat-emulgated preparations for parenteral administration have been elaborated for clinical applications. Since these are administered to the patients intravenously, the size of fat emulsion particles should not exceed the size of the largest naturally occurring lipoproteins-chylomicrons, i.e. about I fiin. Fat emulsions on the basis of com oil (preparation lipomaize), cottonseed oil (lipofundin, lipomol). 

Because of its efficient droplet size reduction, high-pressure homogenization can be used for preparing parenteral fat emulsions.Here the requirement is that number of droplets or particles above 1 pm should be limited and no particle should be larger than 5 pm. 

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