Liquids, semisolids scale

Fig. 3 shows a pilot plant layout with restricted personnel access. This design would support the development and clinical manufacture of solid dosage forms, liquids, semisolids, aerosols, and sterile products. Multipurpose rooms are incorporated in each area to maximize the use of portable equipment, and scale factors similar to those shown in Table 1 are employed. Isolation suites are indicated in the manufacturing area their purpose and design are discussed in more detail later. The sterile area is isolated from the main corridor by the interior corridor design. At the far left, the main corridor provides access for future facility expansion, if necessary. 

A clue to the resolution of the scale-up problem for liquids and semisolids resides in the recognition that their processing invariably involves the... 

TRANSPORT PHENOMENA IN LIQUIDS AND SEMISOLIDS AND THEIR RELATIONSHIP TO UNIT OPERATIONS AND SCALE-UP... 

Insofar as the scale-up of pharmaceutical liquids (especially disperse systems) and semisolids is concerned, virtually no guidelines or models for scale-up have generally been available that have stood the test of time. Uhl and Von Essen (55), referring to the variety of rules of thumb, calculation methods, and extrapolation procedures in the literature, state, Unfortunately, the prodigious literature and attributions to the subject [of scale-up] seemed to have served more to confound. Some allusions are specious, most rules are extremely limited in application, examples give too little data and... 

Unfortunately, the publication by Williams and coworkers is one of the only reports of a scale-up problem involving liquids or semisolids in the pharmaceutical literature. A number of papers that purport to deal with scale-up issues and even go so far as to compare the properties of small versus large batches failed to apply techniques, such as dimensional analysis, that could have provided the basis for a far more substantial assessment or analysis of the scale-up problem for their system. Worse yet, there is no indication of how scale-up was achieved or what scale-up algorithm(s), if any, were used. Consequently, their usefulness, from a pedagogical point of view, is minimal. In the end, effective scale-up requires the complete characterization of the materials and processes involved and a critical evaluation of all laboratory and production data that may have some bearing on the scalability of the process. 

The first step in the scale-up process is the selection of a suitable preliminary formula for more critical study and testing based on certain agreed-upon initial design criteria, requirements, and/or specifications. The work is performed in the development laboratory. The formula selected is designated as the (lx) laboratory batch. The size of the (lx) laboratory batch is usually 3-10 kg of a solid or semisolid, 3-10 liters of a liquid, or 3000 to 10,000 units of a tablet or capsule. 

Berkeley Scarifier as described by Haley et al. (1974). Materials are tested undiluted, and 0.5 ml liquid, or 0.5 g solid or semisolid material is applied. Each test site is covered with two layers of 1-in square surgical gauze secured in place with tape. The entire trunk of the animal is then wrapped with rubberized cloth or other occlusive impervious material to retard evaporation of the substances and hold the patches in one position. The wrappings are removed 24 h after application and the test sites are evaluated for erythema and edema using a prescribed scale. Evaluations of abraded and intact sites are recorded separately. Test sites are evaluated again 48 h later (72 h after application) using the same scale. 

Block, L. H. (2002), Nonparenteral liquids and semisolids, in Levin, M., Ed., Pharmaceutical Process Scale-Up, Marcel Dekker, New York, pp. 57-94. 

There are many advantages for choosing to develop and scale-up a capsule formulation over a tablet. As there is no need to form a compact that must withstand rigorous handling, development timelines can be reduced. Encapsulated products allow for easier blinding of clinical supplies and the ability to manufacture unique fills such as tablets in capsules, sustained release pellets, liquids, or semisolids. However, the costs of the capsule shells add an additional expense above the costs of tablet manufacture. 

Theeuwes F, Yum SI (1976) Principles of the design and operation of generic osmotic pumps for the delivery of semisolid or liquid drug formulations. Annals Biomed Eng 4 343-353 Thorsen T, Maerkl SJ, Quake SR (2002) Microfluidic large-scale integration. Science 298 580-584... 

Acrylonitrile is not conveniently polymerized in bulk except on a scale of only a few grams. The reaction is rapid, highly exothermic (18 kcal per mole), and difficult to control. Polymer is insoluble in the monomer, and heat is not easily removed from the resulting sluny or semisolid mass. Polymerization in homogeneous solution is limited by the fact that only a few liquids dissolve the polymer. Reactions in some of these liquids lead to polymers of low molecular weights because of chain transfer, or are objectionable because of toxicity, cost, or difficulty in solvent recovery. 

Burskirk, G.A., V.P. Shah, D. Adair. 1994. Workshop III report Scale-up of liquid and semisolid disperse systems. EurJ Pharm Biopharm 40 251-254. 

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