Product design suspensions

Intravenous aqueous injections provide an excellent means of achieving a rapid therapeutic response. Parenteral product design, eg, vehicle and other excipient selection, as well as choice of route of adrninistration, can prolong therapeutic activity and increase onset times. Thus, oily solutions, suspensions, or emulsions can be adrninistered by subcutaneous or intramuscular routes to create prolonged effect, ie, depot injection (28). 

Behind the relatively straightforward compositional nature of ophthalmic solutions, suspensions, and ointments, however, lie many of the same physicochemical parameters that affect drug stability, safety, and efficacy, as they do for most other drug products. But additionally, specialized dosage forms present the ophthalmic product designer with some extraordinary compositional and manufacturing challenges. These... 

Designfeed rate exceeded. At design suspension density, this results in a reduced average retention time. Within limits, this can be corrected by increasing the suspension density. An increase in production rate usually requires an increase in circulation rate to handle the additional supersaturation and the heavier fluidized bed of crystal... 

PVDE is manufactured using radical initiated batch polymerization processes in aqueous emulsion or suspension operating pressures may range from 1 to 20 MPa (10—200 atm) and temperatures from 10 to 130°C. Polymerization method, temperature, pressure, recipe ingredients, the manner in which they are added to the reactor, the reactor design, and post-reactor processing are variables that influence product characteristics and quaUty. 

Suspension polymerization of VDE in water are batch processes in autoclaves designed to limit scale formation (91). Most systems operate from 30 to 100°C and are initiated with monomer-soluble organic free-radical initiators such as diisopropyl peroxydicarbonate (92—96), tert-huty peroxypivalate (97), or / fZ-amyl peroxypivalate (98). Usually water-soluble polymers, eg, cellulose derivatives or poly(vinyl alcohol), are used as suspending agents to reduce coalescence of polymer particles. Organic solvents that may act as a reaction accelerator or chain-transfer agent are often employed. The reactor product is a slurry of suspended polymer particles, usually spheres of 30—100 pm in diameter they are separated from the water phase thoroughly washed and dried. Size and internal stmcture of beads, ie, porosity, and dispersant residues affect how the resin performs in appHcations. 

Copper-wheel engraving is used for decoration and in artware production. Abrasive compounds are appHed in water suspension to the spinning copper wheel held in a chuck. The glass is brought into contact with the wheel to produce the design (see Abrasives). 

An example of such a product is Sterile Medroxyprogestrone Acetate Suspension used for its contraceptive property. Such an injection is designed to provide up to three months of contraceptive activity. Another such product is a depot injection of leuprolode acetate, an analogue of gonadatropin-releasing hormone (see Drug delivery systems). In this case, the product is a sterilized powder of microspheres to be suspended upon the addition of an appropriate diluent and intended for monthly injection. 

Alternatively, some subunit viral vaccines can be generated by rDNA techniques and expressed in a continuous ceU line or insect ceUs. Recent advances in bioreactor design and operation have improved the successful production of IPV in large-scale bioreactors. However, roUer bottles or flasks are stiU used for most current vaccine production. Development of insect ceU culture will allow for very large-scale Hquid suspension culture (143). Several vaccine candidates such as gpl60 for HIV and gD protein for herpes have been demonstrated in the insect ceU culture system. However, no vaccine has been approved for human use. 

A suspension of crystals formed from the melt may be contacted by weU-mixed mother Hquor or the crystals may be moved countercurrently to hquor flow ia a vertical or horizontal column. In column crystallizers, crystals are moved ia a specific direction by gravity or rotating blades. The crystals are melted by the addition of heat when they reach a designated end of the crystallizer a portion of the melt is removed as product and the remainder is returned to the system to flow countercurrently to and to wash the product crystals. 

A fines removal system is installed on the crystallizer designed in the first example. Assuming that the cut size for the fines removal system is 50 im and the ratio of mean residence times for product and fines, rp/rp( = 7), is 10, calculate the mean product residence time now required to produce the same dominant size of 600 pm at the same production rate and suspension density. 

Scale-up techniques for using the results of pilot plant or bench scale test w ork to establish the equivalent process results for a commercial or large scale plant mixing system design require careful specialized considerations and usually are best handled by the mixer manufacturer s specialist. The methods to accomplish scale-up will vary considerably, depending on whether the actual operation is one of blending, chemical reaction tvith product concentrations, gas dispersions, heat transfer, solids suspensions, or others. 

Seawater systems should be designed to avoid excessive water velocities, turbulence, aeration, particulates in suspension, rapid changes in piping section and direction. Likewise, extended periods of shutdown should also be avoided since stagnation of contained seawater, will result in bacterial activity and HjS production with consequential and perhaps serious corrosion and health and safety problems. 

---