Solid dosage forms chemical

In the formulation screening of solid dosage forms, chemical compatibility is sometimes evaluated using suspensions or slurries.653-656 Although this information may be difficult to relate to the stability of the dosage forms, it may provide some preliminary information on the stability of formulation components. 

Issues relating to chemical incompatibility and instability may be less significant for solid dosage forms compared with liquid and semi-solid preparations. 

It is evident even to the casual observer that the vast majority of pharmaceutical products are administered as solid dosage forms, which are in turn produced by the formulation and processing of powdered solids. All too often characterization of raw materials and products has centered on aspects of chemical purity, with only passing attention being given to the physical properties of the solids. However, every pharmaceutical scientist knows of at least one instance in which a crisis arose due to some variation in the physical properties of input materials, and in which better characterization would have prevented the problem. 

Dissolution characteristics of solid dosage forms, which depend on formulation in addition to the properties of the chemical itself (e.g., vehicle may decrease permeability of suspension or capsule to water and retard dissolution and diffusion). 

Particle size of chemical in solid dosage form smaller particle sizes will increase the rate and/or degree of absorption if dissolution of the chemical is the rate-limiting factor in absorption. Chemicals that have a low dissolution rate may be made in a micronized form to increase their rate of dissolution. 

Badawy, S.I., Williams, R.C., and Gilbert, D.L., Chemical stability of an ester prodrug of a glycoprotein Ilb/IIIa receptor antagonist in solid dosage forms,. Pharm. Sci., 88, 428,1999. 

This need is addressed in part by NIR-CI, in that it offers the ability to obtain high fidelity, spatially resolved pictures of the chemistry of the sample. The ability to visualize and assess the compositional heterogeneity and structure of the end product is invaluable for both the development and manufacture of solid dosage forms. NIR chemical images can be used to determine content uniformity, particle sizes and distributions of all the sample components, polymorph distributions, moisture content and location, contaminations, coating and layer thickness, and a host of other structural details. "... 

When delivered parentally or orally, a drug in solution is more rapidly bioavailable compared to a solid dosage form. The cosolvent approach also has some limitations as pointed out for other solubilization techniques. When solubilization of a drug is achieved by use of cosolvent, it must meet certain requirements, such as nontoxicity, compatibility with blood, nonsensitizing, nonirritating, and above all physically and chemically stable and inert. 

For formulated products an essential analysis is the assay for API content. This is usually performed by HPLC, but Raman spectroscopy can offer a quantitative analytical alternative. These applications have been extensively researched and reviewed by Strachan et al. [48] and provide over 30 literature references of where Raman spectroscopy has been used to determine the chemical content and physical form of API in solid dosage formulations. As no sample preparation is required the determination of multiple API forms (e.g. polymorphs, hydrates/solvates and amorphous content) provides a solid state analysis that is not possible by HPLC. However, as previously discussed sampling strategies must be employed to ensure the Raman measurement is representative of the whole sample. A potential solution is to sample the whole of a solid dosage form and not multiple regions of it. As presented in Chap. 3 the emerging technique of transmission Raman provides a method to do just this. With acquisition times in the order of seconds, this approach offers an alternative to HPLC and NIR analyses and is also applicable to tablet and capsule analysis in a PAT environment. 

On the other hand, many excipients can act to chemically stabilize an API in the solid state and in solid dosage forms. The most common class of stabilizing excipients is cyclodextrins (36). Cyclodextrins can envelop the API in their hydrophobic cavities and shield it from common degradation reactions such as hydrolysis, oxidation, or photodegradation. Some excipients or additives may also act as complexing agents that provide hydrolytic (37) and oxidative (38) stabilization. Many excipients, such as cyclodextrins, dyes, and colored additives, are capable of providing extensive photostabilization in the solid state (39-41). 

Until recently, nonparenteral routes have failed to deliver sufficient quantities of ASO to be systemically therapeutic. The recent advent of novel oral delivery technologies, coupled with the increased tissue residence time for second-generation ASOs, allows oral delivery to achieve therapeutic levels for select systemic indications. This chapter will initially outline certain more conventional aspects of parenteral dosage forms, and then focus on formulation technologies that more specifically address local treatment. For the oral route, we will pass to the biopharmaceutic considerations for both local delivery to the gut and systemic delivery via absorption from solid dosage forms. Incumbent with the discussion on formulations is the need initially to overview the physico-chemical properties of ASOs, which in large part determine their biopharmaceutic characteristics. 

Lack of the amine group "NH2 makes chitin almost chemically inactive. In addition, the availability of chitin as the second most abundant material after cellulose allows its use as an excipient in processing solid drug dosage forms. This facilitates its use with other common excipients, namely microcrystalline cellulose (MCC), lactose, starch, and calcium hydrogen phosphate. Consequently, this monograph will focus on chitin applications as a solid dosage form excipient. 

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