Hierarchical design approach

Douglas, J. M., and Stephanopolous, G. (1995). Hierarchical approaches in conceptual process design framework and computer-aided implementation, In Foundations of Computer-Aided Process Design (L. T. Biegler and M. F. Doherty, eds.), pp. 183—197, AIChF Symposium Series, 91(304), New York. 

Oral dmg product formulation and manufacturing process development can use a hierarchical approach to meeting three conditions based on, in order of importance, bioavailability, stability, and manufacturability. The bioavailability of a drug product is the most critical condition and must meet established criteria or the product is not viable. Dmg substance properties such as salt form, solubility, and particle size can significantly affect pharmacokinetic and pharmacodynamic performance of a product. The dosage form platform, formulation design, and manufacturing process can also affect the PK/PD profile of a product. Therefore, all selections must maintain the required pharmacokinetic/pharmacodynamic outcome and work within these confines to achieve a stable and robust product/process. 

The flowsheet synthesis of continuous chemical-like process can be performed following a systematic strategy known as the hierarchical approach. The procedure, initially proposed by Jim Douglas and coworkers in the decade 1980-90 [1, 2], describes the conceptual design process as a logical sequence of analysis and synthesis steps grouped in levels. Each level involves a flowsheet development mechanism based on design decisions. The result is not a unique solution but a collection of alternative flowsheets from which an evaluation procedure eliminates the less attractive ones. 

The classical hierarchical approach of conceptual design proposed by Douglas is organized in eight levels [2], as presented in Figure 2.1 ... 

Figu re 2.1 Classical hierarchical approach of conceptual process design [2]. 

The hierarchical approach is a simple but powerful methodology for the development of process flowsheets. It consists of a top-down analysis organized as clearly defined sequence of tasks aggregated in levels. Each level handles a fundamental conceptual problem input/output structure, reactor design, structure of separa-... 

By including the reactor/separation/recycle level in the hierarchical approach, plantwide control can be considered at an early stage of design. In most cases, the separation is considered as a black-box. By black-box we mean that some targets are set, for example as species recovery or product purities. The separation is then modeled based on simple input-output component balances. The decisions to be taken and the detail of the results obtained depend on the information about the chemical reactor that is available. 

Jim Douglas (1988) of the University of Massachusetts has devised a hierarchical approach to the conceptual design of process flowsheets. Although he primarily considers the steady-state aspects of process design, he has developed several useful concepts that have control structure implications. 

Douglas, J. M. Conceptual Design of Chemical Processes, New York McGraw-Hill11988,. Ponton. J. W., and Laing, D, M. A Hierarchical Approach to the Design of Process Control Systems, Cham.. Eng. Res. Des., 71, 181-188 (.1993). 

One of the most important factors that determines the column configuration is the formulation (or goals) of the separation task with respect to the total flow sheet. Although a mixture may consist of C components, it does not mean that all C products are necessary. The components contained in streams recycled into the process (e.g., unreacted reactants recycled to the reactor) usually do not have to be separated from each other. Also separation of streams that are later mixed (blended) should be avoided, if possible. The separation system needs to be optimized together with the entire plant, either simultaneously or in a hierarchical approach, as described by Douglas (The Conceptual Design of Chemical Processes, McGraw-ffill, New York, 1988). 

Most of the studies based on virtual screeiung use a hierarchical approach combiiung several conceptually different techniques. The most common combination used is a 3D pharmacophore modeling followed by a docking study, hi Figure 15.58 is reported an illustrative example of this combined use a set of 10 known inhibitors of Human Rhinovirus Coat protein was used to design a 3D pharmacophore... 

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