Oral Dosage Forms

Pharmacology and Uses. Lincomycin hydrochloride (Lincocin) is available in oral dosage forms and as a sterile solution for injection. After... 

The design and fabrication of numerous commercially available controUed-release oral dosage forms have been widely reviewed (17,24—27). 

Kashihara T, Yoshioka M. Assessment in Japanese Focus Group. In Hashida M, editor, Formulation design of oral dosage forms. Yakagyo-Jiho, 1998. pp. 244-53. 

Recent studies show equal efficacy of equivalent doses of intravenous and oral dosage forms.30,31 Some clinicians are now using oral prednisone for patients experiencing relapses to avoid the discomfort, inconvenience, and expense of intravenous therapy. 

Mitchell JF, Leady MA. Oral dosage forms that should not be crushed— 2004. Hosp Pharm 2004 wall chart. 

In summary, food will delay stomach emptying and, as a result, may decrease the rate of availability of a drug from its oral dosage form. The extent of availability of that drug, however, may be increased, decreased, or unaffected by meals. Thus, it is important for the pharmacist to counsel patients on the importance of timing the taking of their medications relative to their mealtimes. 

In summary, the effect of pH on the dissolution rate of a drug from an oral dosage form depends on (a) the pH of the GI fluids, a patient variable (b) the acid or base strength of the drug, a pharmaceutical variable as well as (c) the physicochemical properties of the dosage form, another pharmaceutical variable. Furthermore, by intentionally designing the dosage form such that it buffers the diffusion layer, we can control a patient variable by a pharmaceutical variable. 

M. Rowland, Effect of some physiologic factors on bioavailability of oral dosage forms, in Dosage Form Design and Bioavailability (J. Swarbrick, Ed.), Lea Febiger, Philadelphia, 1973, pp. 181-222. 

MR Harris, I Ghebre-Sellassie. Aqueous polymeric coating for modified release oral dosage forms. In JW McGinity, ed. Aqueous Polymeric Coatings for Pharmaceutical Dosage forms, 2nd ed. New York Marcel Dekker, 1997, pp 81-100. 

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... 

FS Horn, JJ Miskel. Oral dosage form design and its influence on dissolution rates for a series of drugs. J Pharm Sci 59 827-830, 1970. 

The pharmaceutical industry directs considerable effort toward maximizing the usefulness and reliability of oral dosage forms in an effort to minimize the need for parenteral administration. Factors that... 

Chapter 661 of the USP provides criteria for the interchangeability of low- and high-density polyethylene for dry, oral dosage forms. In addition, there are standards for polyethylene terephthalate bottles and polyethylene terephthalate G bottles. USP criteria for interchangeability are listed in Table 17. These criteria allow usage of alternate materials in the same plastic class to be used prior to obtaining prior stability data. 

Applicability All plastics Dry oral dosage forms Liquid oral... 

Class II recalls are those in which the use of or exposure to a product found in violation of the law may cause a temporary health problem that is reversible, or in which the situation would not cause serious adverse health consequences. Examples of this type of recall would include uncertainty of the sterility of an injectable product, Salmonella contamination of various types of oral dosage forms, inadequate directions for use, and improper buffering of solution for injection [20]. 

There are two specific guidelines on prolonged-release oral dosage forms (3AQ10a, adopted November 1992) and on modified-release products—oral dosage forms and transdermal dosage forms (CPMP/QWP/604/96, adopted July 1999). The advice in the two documents differs in a number of ways. 

The information requirements for products such as prolonged-release oral dosage forms will depend on whether or not it has been possible, during the development of the product, to establish an in vivo-in vitro correlation between clinical data and dissolution studies. In vivo-in vitro correlations should be attempted using product at different stages of development, but bioavailability and pharmacokinetics data from pivotal clinical studies using at least pilot-scale production materials and possibly routine production material are particularly important. Where it is not possible to establish an in vivo-in vitro correlation, additional data will be required to compare the bioavailability of product developed at laboratory scale, pilot scale, and production scale. In the absence of an in vivo-in vitro correlation, the dissolution test will be a quality control tool rather than a surrogate marker for in vivo performance of the product. 

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. 

When dealing with oral dosage forms, it is important to study the various changes occurring within the oral cavity, particularly if a buccal or sublingual formulation is being considered. Table 7 lists the changes within the oral cavity that have thus far been elucidated [124,127,138-144], It is very important to note that there is a decrease in the capillary blood supply to the oral mucosa. This may make it difficult to predict accurately the absorption rates that will occur when... 

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]. 

Oral Dosage Forms. The advantages of oral dosage formulations have already been discussed. It appears that this route of delivery is preferred by physician, patients, and manufacturers alike. The relatively low cost of oral dosage forms makes them a... 

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. 

---