Finished dosage form, solids

A drug product is a finished dosage form (e.g., tablet, capsule, or solution) that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients [21 CFR 314.3(b)]. A solid oral dosage form includes tablets, chewable tablets, capsules, and soft gelatin capsules. 

Because of the interactions existing between different materials as well as between like materials, the performance of excipients in a formulation could be different from the performance of the excipients themselves. The most frequently used procedures in pharmaceutical processing for solid dosage formulations are mixing, granulation, and compaction, as well as storage of finished dosage forms. The effects of adsorption on these procedures have been studied, observed, and utilized widely in the pharmaceutical industry. 

Once this has been done, one can proceed to actual product testing utilizing these parameters and their specifications to validate that the process will produce acceptable product. The testing can be conducted on samples during the manufacture (in-process tests) or on the finished product (finished product tests). Each product may have its own idiosyncrasies requiring special tests, but generally the in-process and finished product tests that would be required for all solid dosage forms in process validation are as follows. 

According to 21CFR 211.110(a), pharmaceutical manufacturers are legally required to demonstrate the adequacy of mixing to ensure uniformity of in-process powder blends and finished dosage units. The uniformity of dose unit is usually a product specification for oral solid dosage forms and is tested to ensure it meets the compendial acceptance criteria. 

Pharmaceutical Excipients are components of finished drug products and site active components are recognized in the USP/NF. A list of key excipients for solid dosage forms is given ... 

The physical properties of the solid state seen in crystals and powders of both drugs and pharmaceutical excipients are of interest because they can affect both the production of dosage forms and the performance of the finished product. Powders, as Pilpel reminded us, can float like a gas or flow like a liquid but when compressed can support a weight. Fine powders dispersed as suspensions in liquids are used in injections and aerosol formulations. Both liquid and dry powder aerosols are available and are discussed in Chapter 9 some properties of compacted solids are dealt with in Chapter 6. In this chapter we deal with the form and particle size of crystalline and amorphous drugs and the effect these characteristics have on drug behaviour, especially on drug dissolution and bioavailability. 

The pharmaceutical analysis of finished solid oral dosage forms is discussed in Chapter 6 from the standpoint of what makes this type of delivery form unique and successful (i.e., the physical properties and the state of the drug substance... 

In the preformulation study, the comprehension of physicochemical properties regarding water-solid surface interaction is beneficial to the handling, formulation, and manufacture of the finished products. Data on sorption/de-sorption isotherm, hydration of salts of drug product, water sorption of pharmaceutical excipients, and kinetics of water adsorption or desorption of a substance can be obtained effectively by the dynamic vapor sorption method. The knowledge may be utilized for dosage form design and supports the understanding of the mechanism of action. 

Microbial limits. A decision tree is provided to aid in selecting if, and when, microbial testing should be performed on finished oral solid dosage forms. Skip testing might be an appropriate approach in this case. 

After tablets, hard gelatin capsules are the most common solid dosage form. Hard gelatin capsules are rigid two-piece capsules made from gelatin, water and colourants. The capsules are produced as empty shells consisting of a cap and body, which during the manufacture of the finished product are separated, filled with the formulation and then rejoined. 

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