Drug and Excipient

In the formulation of any pharmaceutical product, it is imperative to ensure that the ingredients used are compatible with one another. Incompatibilities can occur between drug and excipient as well as between the excipients themselves. Incompatibilities may be manifested through many modes, such as acid-base interaction and complex formation, resulting in lower potency and/or stability and eventually poor therapeutic efficacy of the product. It is therefore essential to avoid incompatibilities and this is achieved by carrying out studies to detect potential interactions between the components used in the formulation. 

A big advantage of differential scanning calorimetry over the traditional stability test is the speed of determination. However, like all methods, differential scanning calorimetry has its own limitations. It is not applicable if the test materials exhibit properties that make data interpretation difficult, such as eutectic formation, coincident melting, and dissolution of one component in the melt of the other. It is not advisable to rely on differential scanning calorimetry alone to determine incompatibility. Chrzanowski et al. (30) reported that differential scanning calorimetry 

Chromatography was first used for the separation of colored leaf pigments. The operation of chromatography is based on the distribution of a material between a stationary phase and a mobile phase. The stationary phase can be a solid or a liquid supported on a solid while the mobile phase can be a gas or a liquid which flows continuously around the stationary phase. The different components in a mixture can be separated and identified as a result of differences in their affinity for the stationary phase. 

The greatest difficulty for any process technologist is to decide on the type and extent of material characterization to be undertaken such that it is cost-effective in the long run. Often, it is the problem from the production run that necessitates further material characterization to be carried out either for the purpose of resolving the problem or to prevent future occurrences. This chapter serves to identify the more common material characterization methods that can be carried out and the potentially useful information that can be inferred from the tests. It is hoped that the discussion of the many methods of material characterization could help in the choice of characterization methods for material testing. 

Heywood H. The evaluation of powders. J Pharm Phannac 1963 (suppl 15) 56T. 

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For thousands of years, nature has provided humankind with a large variety of materials for the most diversified applications for its survival, such as food, energy, medicinal products, protection and defense tools, and others. The pharmaceutical industry has benefitted from such diversity of biomaterials and has exploited the use of natural products as sources of both drugs and excipients. One example of a promising biomaterial for pharmaceutical use is xylan, a hemicellulose largely found in nature, being considered the second most abundant polysaccharide after cellulose. 

The portal of drug entry The physical form of the drug product The design and formulation of the product The method of manufacture of the drug product Various physicochemical properties of the drug and excipients... 

Table 2 Hiestand Compaction Indices for Some Drugs and Excipients... 

Before the start of any formal laboratory work, the characteristics of the drug and excipients to be used must be considered. When performing this evaluation, it is necessary to keep in mind all of the pharmacokinetic and physical changes experienced by the elderly and pediatric population. 

The extent of homogeneous mixing of pharmaceutical components such as active drug and excipients has been studied by near-IR spectroscopy. In an application note from NIRSystems, Inc. [47], principal component analysis and spectral matching techniques were used to develop a near-IR technique/algorithm for determination of an optimal mixture based upon spectral comparison with a standard mixture. One advantage of this technique is the use of second-derivative spectroscopy techniques to remove any slight baseline differences due to particle size variations. 

Table 8 Typical Properties of Some Common Drugs and Excipients Determined at a Compact Solid fraction of 0.8 to 0.9...

Lot to lot variations of several drugs and excipients are shown in Table 9. Specially crystallized lots of ibuprofen, for example, show substantial changes in Brittle Fracture and Bonding Indices. Phenacetin shows a significant increase in brittleness at higher relative humidity. It was observed by Hiestand and Smith [31] that compacts of dried phenacetin did not fracture, while the lot equilibrated at 40% relative humidity did, consistent with the Brittle Fracture Index change. 

Only the first three are discussed in any detail here. Most of these routes of administration place a drug directly or indirectly into systemic circulation. There are a number of these routes, however, by which the drug exerts a local effect, in which case most of the drug does not enter systemic circulation (e.g., intrathecal, intraventricular, intraocular, intraracistemal). Certain routes of administration may exert both local and systemic effects depending on the characteristics of the drug and excipients (e.g., subcutaneous). 

Accuracy samples are prepared by spiking bulk drug and excipients in the specified volume of dissolution fluid. The concentration ranges of the bulk drug spikes are the same... 

Table 18.2 Caco-2 permeability and human absorption of 28 marketed drugs and excipients.

Altria, K. D., Bryant, S. M., and Hadgett, T. A. (1997). Validated capillary electrophoresis method for the analysis of a range of acidic drugs and excipients. ]. Pharm. Biomed. Anal. 15, 1091—1101. 

Pharmaceutical solids can generally be described as crystalline or amorphous (or glassy). In fact, the actual solid phase composition of a pharmaceutical formulation is usually characterized by an intermediate composition, both crystalline and amorphous in character. In a multicomponent system, such as a solid formulation comprising drug and excipient(s), certain components or even a single component may be... 

More examples of forensic applications of Raman spectroscopy have been published recently. It has been used to identify individual crystals of drugs and excipients on paper currency [110], multilayer paint chips, inks, plastics [111], and fibers [112], A study demonstrated the feasibility of quantifying acetaminophen in the presence of many excipient types [113], Other studies seek to identify particulates, such as illicit or abused drugs, in fingerprints lifted at a crime scene [114,115]. 

In addition to facilitating the transfer of water, intimate contact between drugs and excipients can lead to the formation of eutectic mixtures and subsequent degradation. Mroso et al. [45] reported on mixtures of acetylsahcylic acid and alkali stearates. They demonstrated that there was a linear relationship between... 

Provide standard pharmacopoeial methods for the assay of unformulated drugs and excipients and some formulated drugs, e.g. those that lack a strong chromophore. 

Determination of physico-ehemical properties of drugs and excipients such as particle size, water content and polymorphism... 

When tablet formulations are made, usually different quality criteria have to be met, e.g., a high crushing strength, a low disintegration time, a pre-set dissolution profile. A tablet consists normally of the pharmacon (the pharmacologically active compound the drug) and excipients. Hence, a tablet can be made with different relative amounts of excipients (a mixture composition) and this creates room for optimizing a tablet... 

Drug and excipients were sieved to obtain a particle size between 45 and 90 pm. The model dmg Gly-Tyr and excipient were thoroughly dispersed in Silastic 382 plus curing agent. Dispersions were quickly transferred to a mould. After curing (24 h, 40°C), a sheet of 1.5 mm thickness was... 

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