Parenteral preparation scale

The basic principles employed in the preparation of parenteral products do not vary from those widely used in other sterile and non-sterile liquid preparations. However, it is imperative that all calculations are made in an accurate and most precise manner. Therefore, an issue of a parenteral solution scale-up essentially becomes a liquid scale-up task, which requires a high degree of accuracy. A practical yet scientifically sound means of performing this scale-up analysis of liquid parenteral systems is presented below. The approach is based on the scale of agitation method. For singlephase liquid systems, the primary scale-up criterion is equal liquid motion when comparing pilot-size batches to a larger production-size batches. 

One of the most important processes involved in the scale-up of liquid parenteral preparations is mixing (1). For liquids, mixing can be defined as a... 

One of the most important processes involved in the scale-up of liquid parenteral preparations is mixing [1]. For liquids, mixing can be defined as a transport process that occurs simultaneously in three different scales, during which one substance (solute) achieves a uniform concentration in another substance (solvent). On a large, visible scale, mixing occurs by bulk diffusion, in which the elements are blended by the pumping action of the mixer s impeller. On the microscopic scale, elements that are in proximity are blended by eddy currents, and they 43... 

It is important to add heat transfer scale-up considerations to the scale-up approach for liquid parenteral solutions as heat transfer applications may play a considerable role in preparation of these products. For heat transfer applications, constant horsepower per unit volume is used to achieve approximately similar heat transfer coefficients for the same type of impeller. This approach is a close approximation since the effect of horsepower on the heat transfer coefficient (ho) is relatively small ... 

Furthermore, the drafted guide suggests that the level of end-product testing for those products will depend on the associated risk connected to the scale of operation, shelf life of the product, frequency of preparation, as well as type of product (parenterals, orals) and type of facility where the product has been prepared. 

HPH has emerged as a reliable and powerful technique for the preparation of SLN. HPH has been used for years for the production of nanoemulsions for parenteral nutrition. In contrast to other techniques, scaling up represents no or minor problems in most cases. High-pressure homogenizers push a liquid with high pressure (10 to... 

It should be mentioned that several more drastic simplifications of cocaine appeared on the scene even earlier. The only survivor is ethyl p-aminobenzoate (benzocaine, Table 13-6, No. 5). The others of interest were methyl p-amino-m-hydroxybenzoate (ortho-form), which, like benzocaine, was nontoxic, highly insoluble, and therefore not suitable for parenteral administration. Orthoform has no activity on intact skin, but it was useful as a powder on painful wounds. It was superseded commercially by the position isomer p-hydroxy-m-aminobenzoate methyl ester for reasons of cost since large-scale production of orthoform (as the pure, correct isomer) presented difficulties at the time. It should be pointed out that water-soluble hydrochlorides of the aminobenzoates can be prepared however, their solutions are much too acidic to inject. 

Amphoteric surfactants possess both an anionic and a cationic function. In small-scale preparation they are little used but their role may increase in the future. Examples are long chain betains and phospholipids (e.g. lecithin). Phospholipids play an important role as emulsifiers and micelle formers for parenteral emulsions (see Sect. 13.5.7) and micellar solutions and also in liposome technology. 

The safety of Echinacea preparations has repeatedly stimulated polemic public discussions. Large-scale drug-monitoring studies which would allow a reliable estimate of the occurrence and frequency of side-effects do not exist. Cases of severe anaphylactic reactions, mainly after parenteral application, have been reported [1, 3] however, in some of the cases a causality seems highly questionable. Nevertheless, there can be little doubt that the parenteral application of Echinacea extracts or combinations containing Echinacea bears some risk in susceptible individuals. Therefore, the majority of the manufacturers in Germany have withdrawn the... 

Riboflavin 5 -phosphate (FMN) is synthetically prepared on a large scale for use in pharmaceutical preparations, especially for parenteral administration. It has been demonstrated by reversed-phase HPLC that the chemical phosphorylation of riboflavin invariably yields a complex mixture of various riboflavin phosphates besides FMN. The HPLC chromatogram of a commercial FMN sample is shown... 

---