Oral solid dosage forms

The most common solid dosage forms of granulated or powdered materials are prepared by compression. Many tablets are coated to minimize the unpleasant taste of certain substances or to protect the ingredients against decomposition and enhance the appearance. 

a binding or adhesive granulating agent is required which may be added in solution or mixed with the tablet ingredients as a dry powder for subsequent activation by moisturing with an appropriate solvent. Many binders are hydrophilic colloids as, for example, polysaccharides (Table 5). 

In order to reach a rapid disintegration after addition of a polysaccharide binder, addition of small quantities of appropriate enzymes may be useful (Table 6). 

Special solid oral dosage forms are the controlled-release tablets. In some cases, it is desirable that the release of the drug from the tablet should be more gradual than in the normal case. This controlled slow release can be achieved in different ways. 

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KS Murthy, I Ghebre-Sellassie. Current perspectives on the dissolution stability of solid oral dosage forms. J Pharm Sci 82 113-126, 1993. 

Waiver of in vivo bioavailability and bioequivalence studies for immediate release solid oral dosage forms based on a biopharmaceutics classification system. Center for Drug Evaluation and Research, Food and Drug Administration, issued 8/2000, posted 8/31/2000. http //www.fda.gov/cder/guidance/ index, htm... 

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. 

The dosage forms most commonly employed for pediatric formulations are liquids and chewable tablets. A perceived unpleasant taste is much more evident with these dosage forms than when a drug is administered as a conventional solid oral dosage form. Second, it is widely believed that children younger than the age of 6 years have more acute taste perception than older children and adults. Taste buds and olfactory receptors are fully developed in early infancy. Loss of taste perception accompanies the aging process. 

Solid oral dosage forms, particularly tablets, are the preferred type of formulation in the United States. Not only are these products widely accepted by consumers, but they are also relatively cheaper to develop and manufacture than oral liquids or suspensions, par-enterals, or suppositories. Figure 4 shows, quite clearly, that even the elderly primarily make use of solid oral dosage forms [162]. 

FDA Guidance for Industry Waiver of in vivo Bioavailability and Bioequivalence Studies for Immediate Release Solid Oral Dosage Forms Containing Certain Active Moieties/ Active Ingredients Based on a Biopharmaceutics Classification System, CDER-GUID 2062dft.wpd Draft, Jan. 1999. 

CDER Waiver of in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms based on a biopharmaceutics classification system Food and Drug Administration, 2000. 

CDER Guidance for Industry. SUPAC-IR Immediate-Release Solid Oral Dosage Forms Scale-Up and Post-Approval Changes Chemistry, Manufacturing and Controls, In Vitro Dissolution Testing, and In Vivo Bioequivalence Documentation US Food and Drug Administration, 1995. 

Extended Release Solid Oral Dosage Forms Development, Evaluation and Application of In vitro/In vivo Correlations. Center for Drug Evaluation and Research (CDER) FDA 1997. 

Dissolution testing has become an important component of the assessment of the quality of solid oral dosage forms and oral suspensions. The basic procedures for these oral dosage forms have been extended to transdermal delivery systems as well. The release rate for modified-release oral dosage forms adds a level of sophistication to the concept of dissolution testing, setting acceptance criteria at multiple time points. 

The desire of USP experts for contributed dissolution procedures for most official immediate-release solid oral dosage forms was not fulfilled. In 1980, a policy giving a framework for the comprehensive application of a dissolution test procedure was formulated. The policy recognized three classes of products for which the dissolution test could be applied with increasing brand-linked specificity. First Case conditions were intended for the most general class where either the basket at 100 rpm or the paddle at 50 rpm was... 

A general chapter giving the dissolution test for solid oral dosage forms was first described in the EP in 1991 (20). As mentioned above, the EP has no product monographs in which to elaborate specific dissolution procedures. 

EP. Dissolution test for solid oral dosage forms. In European Pharmacopoeia. 2nd ed. Fifteenth Fascicule. Sainte-Ruffine Maisonneuve S. A., 1991 v.5.4-l- v.5.4-8. 

Over the last quarter century the dissolution test has emerged as a most powerful and valuable tool to guide formulation development, monitor the manufacturing process, assess product quality, and in some cases to predict in vivo performance of solid oral dosage forms. Under certain conditions, the dissolution test can be used as a surrogate measure for bioequivalence (BE) and to provide biowaivers, assuring BE of the product. Dissolution test has turned out to be a... 

Guidance for Industry Dissolution Testing of Immediate Release Solid Oral Dosage Form, August 1997. 

There are a number of FDA regulatory guidances that are associated with IVIVC development and validation, as well as the application of IVIVC to SUPAC. The specific IVIVC guidance for oral modified-release formulations was first published in September 1997 (1). There are several guidances on SUPAC, including those for both modified release (2) and immediate-release solid oral dosage forms (3). The recent... 

Variation of temperature is usually not an issue for solid oral dosage forms, since experiments are always conducted at body temperature (37°C). For dosage forms applied on the skin, this can be a further consideration e.g., drug-release testing of transdermal products is typically performed at the average temperature of body surface 32°C (5). 

Additional criteria for waiver of evidence of in vivo BA/BE are given in 21 CFR 320.22 (d)(3). For certain solid oral dosage forms (other than a delayed or extended-release dosage forms), a waiver for the submission of in vivo evidence of BA/BE is possible if the drug product has been shown to meet the requirements of an in vitro dissolution test, which in turn has been shown to correlate with in vivo data. A biowaiver may also be addressed to a reformulated solid oral dosage form identical to another drug product except for color, flavor, or preservatives for which the same manufacturer has obtained approval, if BA data are available for the approved... 

Figure 2 Prerequisites of preapproval waivers of in vivo studies for solid oral dosage forms with different strength supported by in vitro dissolution data.

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