Drug substances properties

Depending on the drug substance properties and the medical indication, the appropriate formulation is chosen. Drug substances which have a good solubility may be formulated in a simple tablet formulation, while drug substance candidates with low solubilities require special delivery systems like microemulsion formulations. 

TABLE 5.2 Drug Substance Properties that are Important in the Selection of Manufacturing Platforms... 

The current bottleneck is that many of the drug substance properties important for developability are only obtained in early development, at a time where it is late to introduce chemical changes in the structure of the molecule. 

Solid form selection involves the preparation and property evaluation of many derivatives of an active molecule. Drug substance properties of importance in the drug development process may be categorized as shown in Table 1. These properties depend on the nature of the drug substance and the final formulation. Many bioactive organic molecules contain ionizable groups such as carboxylic... 

What are the desired drug substance properties for drug product formulation, and how are they taken care of in the process ... 

Drug substance properties should be carefully evaluated. These property will dictate the excipients, method, and process selection for ASD product. The properties to be considered are solubility in organic and aqueous solvents, miscibility with polymers, melting point, particle size, and thermal stability. These properties determine manufacturability, product performance, and long-term stability. For example, hot melt extrusion cannot be used for thermally labile drug molecules (Forster et al. 2001 Vasconcelos et al. 2007 Leuner and Dressman 2000). Qn the other hand, for spray drying process, drug solubility determines the selection of the solvent as well as inlet process temperature (Vasconcelos et al. 2007 Leuner and Dressman 2000). 

McPhiUips in M. E. Goldberg, ed.. Pharmacological and Biochemical Properties of Drug Substances, Vol. 1, American Pharmaceutical Association,... 

Chemical development Proof of structure and configuration are required as part of the information on chemical development. The methods used at batch release should be validated to guarantee the identity and purity of the substance. It should be established whether a drug produced as a racemate is a true racemate or a conglomerate by investigating physical parameters such as melting point, solubility and crystal properties. The physicochemical properties of the drug substance should be characterized, e.g. crystallinity, polymorphism and rate of dissolution. 

The development of the most appropriate route for administration is influenced by a number of factors, including the location of the target within the body, the desired speed and duration of the therapeutic effect and the properties and characteristics of the drug substance. 

Polymorphism is an important aspect of the physical properties of a drug substance. One of the characteristics of a metastable polymorph (to be discussed in some detail at a later point) is that it is more soluble than its stable counterpart. The solubility profile of the polymorph will be as shown in Fig. 5 A is the stable form, with solubility of 31 mg/mL. B is the profile of the metastable form, with solubility of 46 mg/mL. This solubility (circles) is usually not achieved, and precipitation of the stable form occurs at a point beyond the solubility of A, and the trace becomes B. 

The surface characteristics of a batch of a drug substance may greatly influence its properties in processing (flow, dissolution). Crystals may crystallize in... 

JI Wells. Pharmaceutical Preformulation The Physicochemical Properties of Drug Substances. Chichester, England Ellis Horwood LTD, 1988, pp 209-210. 

The new millenium professional pharmacist with rigorous training in the scientific and clinical properties of drug substances and pharmaceutical formulations should be well able to dispassionately evaluate bioe-quivaleny data and give an objective, professional opinion as to validity of data purported to demonstrate generic bioequivalence. 

Water uptake causes a host of problems in drug products and the inactive and active ingredients contained in them. Moisture uptake has been shown to be an important factor in the decomposition of drug substances [1-8]. Moisture has also been shown to change surface properties of solids [9,10], alter flow characteristics of powders [11,12], and affect the compaction properties of solids [13]. This chapter discusses various mathematical models that can be used to describe moisture uptake by deliquescent materials. 

Methoxypurine was found to crystallize as a hemihydrate from /V,/V -dimethyl formamide, and as a trihydrate from water [63]. Thermal treatment of the trihydrate could be used to obtain the hemihydrate. Zafirlukast was obtained in the form of monohydrate, methanol, and ethanol solvatomorphs, with the drug substance adopting a similar conformation in all three structures [64], In the isostructural methanol and ethanol solvates, the solvent molecules are hydrogen-bonded to two zafirlukast molecules, while in the monohydrate, the water molecules are hydrogen-bonded to three zafirlukast molecules. The structures of the acetone and isopropanol solvatomorphs of brucine have been reported, where the solvent controlled the self-assembly of brucine on the basis of common donor-acceptor properties [65],... 

J. I. Wells, Pharmaecutical Preformulation. The Physicochemical Properties of Drug Substances, Halsted Press, New York, 1988. 

The pharmaceutical community is rapidly becoming aware of the need to obtain proper physical characterization of raw materials, drug substances, and formulated products. The present volume seeks to address these concerns by outlining a comprehensive program for this work. The modem and highly regulated industry cannot tolerate the inconsistent practices of the past, when the only physical properties documented were those that a particular lab knew how... 

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