Properties of Excipients

For analytical sample preparation, measurement of the final pH of the sample solution (excipients, API(s), and sample solvent mixed together) will be helpful in the development of any analytical procedure. If an API is known to be stable in acidic pH (pH 1-2), then an analytical chemist will try to utilize a certain sample solvent that has a pH in the required range. However, when a dosage form is dissolved in a sample solvent, the excipients present in the formulation (and even the API) will change the pH of the solution. The final pH of the solution must be measured in order to determine the optimal pH of sample solution to achieve longest solution stability. This is particularly important for a long sequence of injections on autosamplers for analysis, so solutions do not need to be made daily. 

The objective is to determine the degradation products in the solution, not in the dosage form. It is very important to determine how the active will behave in solution. Is an API going to degrade in the solution, and to what extent These questions can be answered with solution stability studies. 

The goal of solution stability for different tests can vary. For assay and degradation product test, no new degradation products (over time and above LOQ) should be formed in solution. Certain acceptance criteria (max % increase) may be set for impurities at particular levels during the solution stability study. For assay determination (assay, CU, and dissolution), the content of assay over time should not change more than 2.0%. Also, refer to Chapter 9, which discusses method validation. 

A special consideration must be given to the effect of water on a given drug product (or a formulation). Water presents a real problem for a formulation when the drug substance or the excipients are sensitive or susceptible to hydrolysis. Whether the excipients will dissolve in certain solvents or not, their interactions with the active (in solution and solid state) are very important. 

TABLE 15-1. Common Excipients and Their Ennctional Gronps [8] 

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Many surface area studies have investigated various properties of excipients. The relationship between excipient grades, flow properties, particle sizes, and surface areas have been studied. Fast-flo lactose is manufactured to contain larger particles (approximately 50 jim) than hydrous lactose (approximately 20 /zm) [23], This has been done to improve the flow properties of the fast-flo... 

Surface area and moisture uptake have been related to the disintegration properties of excipients such as crosspovidone, starch, and alginic acid [17]. The surface areas of the three materials were measured, and a linear correlation was found between the maximum moisture sorption and specific surface area for the three disintegrants. The greater the surface area of the material, the more numerous were the sites for capillary attraction of water to its surface. It was postulated that the capillary action appears to be responsible for the disintegration properties of the materials. 

For the pharmaceutical product development scientist, there is clearly a need for objective information about the practical performance of different excipients and their various grades. In this chapter we set out to bring together the results of some of our ongoing evaluations of the physical and mechanical properties of excipients commonly used for the manufacture of solid oral dosage forms. In this particular article, we have chosen to focus on the fillers that are most commonly used in the manufacture of immediate release tablets microcrystalline cellulose (MCC), lactose, calcium phosphate, and mannitol (1). 

Physicochemical Properties of Excipients in Pressurized Metered Dose Inhalers... 

The physicochemical properties of excipients used in pMDIs are different from most dosage forms and are a derivative of the propellant system that constitutes the bulk of the formulation. The transition from CFC-based formulations to HFA-based systems has been lengthened by the historically empirical formulation approach and the dissimilarity of the physicochemical properties of the replacement HFA propellants. Both HFA 134a and HFA 227 show an increased polarity, revealed in increased dipole moments and dielectric constant. The most significant practical change has therefore been a general change in the solvency properties. 

Characterization of the physical properties of excipients is also important. This is demonstrated in Table 2 in the light of the example of hydrochlorothiazide. Tablets of greater hardness are obtained if fine instead of coarse Povidone K 90 is taken. To a certain extent, the disintegration and the release are also affected. 

Unless the drug loading is very high (>50 percent), the dissolution rate of the matrix often is determined by the properties of excipients, mainly the solubility and viscosity. The more soluble the excipients and the less viscosity generated in the diffusion layer, the faster is the matrix dissolution. 

The physical and mechanical properties of excipients were important variables in achieving performance of the final products as well. The preferred formulation strategy for a low-dose product using dry granulation is to design a cohesive blend to... 

TABLE 9.5 Analytical Techniques Used to Characterize Physical and Material Properties of Excipients... 

As discussed above, testing to conform to pharmacopeia requirements may not be sufficient to assure excipient quality in the manufacture of low-dose formulations. Often, excipients make the bulk of the dosage form and if a dry blending and direct compression is utilized, the functional properties of excipients become even more critical compared to a granulation process. Typical functional properties to be tested for excipients include the following ... 

PHARMACEUTICAL PREFORMULATION PHYSICOCHEMICAL PROPERTIES OF EXCIPIENTS AND POWDERS AND TABLET CHARACTERIZATION... 

Physicochemical properties of drug Physicochemical properties of excipients... 

Beom-Jin Lee, Kangwon National University, Chuncheon, Korea, Pharmaceutical Preformulation Physiochemical Properties of Excipients and Powders and Tablet... 

Milling can affect the adsorption of actives on the carrier surface by altering the surface properties of excipients. It was noticed that milled actives frequently failed blend uniformity criteria, but unmilled active batches consistently met the blend uniformity criteria. By adding lubricant magnesium stearate, the blending content uniformity of the milled batches can be significantly improved. A small amount of amorphous materials could affect the blending characteristics of a direct compression formulation. ... 

In the manufacturing of tablets, compaction is a very important step, and many factors are involved in affecting the properties of excipients and final products, such as surface structure and wettability of excipients. For formulations, the larger is the surface area of compressible excipients, the greater is the compressibility. ... 

Rizzuto AB, Chen AC, Veiga ME Modification of the sucrose crystal structure to enhance pharmaceutical properties of excipient... 

The following four examples are presented to illustrate the importance of understanding the properties of excipients and their stability. This information can be important to the quality of the pharmaceutical products in which they are used. This information aids in the selection of the right excipient for the product and helps in evaluation of the stability data for the final product. 

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