Oral solid dosage forms manufacture

Part IB Specific requirements for manufacture of oral solid dosage forms (tablets and capsules)... 

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. 

The most common method of drug delivery is the oral solid dosage form, of which tablets and capsules are predominant. The tablet is more widely accepted and used compared to capsules for a number of reasons, such as cost, tamper resistance, ease of handling and packaging, ease of identification, and manufacturing efficiency. Over the past several years, the issue of tamper resistance has resulted in the conversion of most over-the-counter drugs from capsules to predominantly all tablets. 

In the critical variables analysis phase, a statistical experimental design is created (e.g., factorial, Box-Behnken) intended to assess critical formulation and process variables in relatively small-scale manufacture. In these studies, the ranges of composition variables are chosen to at least encompass those noted in the recommendations of the AAPS-FDA Workshop on Scale-up of Immediate Release Oral Solid Dosage Forms or SUP AC. This phase is usually preceded by a development phase during which variables and levels to be studied are determined and the exact method of manufacture is established. Experimental formulations are assessed at least in terms of dissolution performance, content uniformity, and weight variation. On the basis of these studies, the specific formulations to be manufactured for biostudy are selected. 

Particle size and shape are important attributes of drug substances that can affect the dissolution rate, bioavailability, and the processing of oral solid dosage forms and the physical stability of semi-solid dosage forms. During manufacture of the bulk drug substance, the recrystallization conditions required to prepare a particular salt will inevitably influence the particle size and crystal habit conditions should be established early in the development program that routinely yield material with consistent characteristics. 

As a general rule, anhydrous forms that do not convert to the hydrate below 75% RH (at equilibrium) are likely to exhibit adequate physical and chemical stability in oral solid dosage forms. Adequate manufacturing and packaging can be designed to protect most oral solid dosage forms from exposure to >75% RH. Conversely, hydrates that do not convert to the anhydrous form until the relative humidity drops below about 20% (at equilibrium) are also likely to exhibit adequate physical stability in solid dosage forms. 

Oral Administration. Oral administration is the preferred route of administration. There is a general consensus among pediatricians and parents that children younger that 5 years of age have great difficulty with, or are unable to swallow, a solid oral dosage form. Manufacturers, therefore, have developed liquid formulations for many of the commonly used pediatric products. The liquid dosage form, however, is not free of problems. Liquid products are often unstable and have short expiration dates accurate measurement and administration of the prescribed dose is also a problem, especially in infants. 

SUPAC-IR/MR Immediate release and modified release solid oral dosage forms manufacturing equipment addendum (January 1999). 

SUPAC-IR/MR Immediate Release and Modified Release Solid Oral Dosage Forms Manufacturing Equipment Addendum. Issued 1/1999. Posted 2/25/1999. http // wwwfda.gov/cder/guidance/index.htm. 

A-5 Extended Release Solid Oral Dosage Forms Manufacturing—Equipment... 

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