Form and Routes of Administration

Some of the dosage formulations available for protein pharmaceuticals are listed in Table 5.7. An examination of Table 5.7 reveals that no protein drug up until this time has been formulated for oral administration. Most protein drugs are administered by means of injection (parenteral administration). Parenteral administration includes intravenous, intra-arterial, intracardiac, intraspinal or intrathecal, intramuscular, intrasynovial, intracuta-neous or intradermal, subcutaneous injections, and injection directly into a dermal lesion (e.g., a wart). The parenteral route of administration requires a much higher standard of purity and sterility than oral administration. It also may require trained 

ITABLE 5.7. Some dosage formulations and sites used in administration of biopharmaceuticals 

Parenteral Solutions, Blood clotting factors, colony- 

Intracardiac, Intraspinai or Intrathecal, Intramuscular, Intrasynoviai, Intracutaneous or Intradermal, Subcutaneous powders to be reconstituted into solution enzymes, hormones, vaccines 

Local injection Solutions Interferon for direct injection into wart 

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The physical characteristics should be considered (in combination as appropriate) in relation to the proposed dosage form and route of administration. Factors to be considered extend to solubility characteristics, crystal form and properties, moisture or solvent content, particle size and size distribution (which may affect bioavailability, content uniformity, suspension properties, stability, and preclinical or clinical acceptability), polymorphism, etc. 

Patients currently receiving theophylline products - Determine, where possible, the time, amount, dosage form, and route of administration of the last dose the patient received. 

CDER-approved products are considered those subject to an approved NDA or ANDA. Some information on which components/materials aie used in CDER-approved products is available from the Agency (e.g., FDA, CDER, Inactive Ingredient Guide, 1996, Division of Drug Information Resources). When infonnation is not available, an applicant should use reliable sources of infonnation to determine that the component or material has been used in and has been in contact with a CDER-approved product of the same dosage form and route of administration, as appropriate. The applicant should identify in the supplement or annual report the basis for the conclusion that the component or material is used in a CDER-approved product. 

Pharmacokinetic principles, in addition to clinical factors such as the state of the patient, are utilized in determining dosage regimens. Factors that relate to the safety and efficacy of the drug, such as activity-toxicity relationships (therapeutic window and side effects), and pharmaceutical factors, such as dosage form and route of administration, must be considered.16... 

Method development includes feasibility and optimization to meet the predefined study requirements. The appropriate standard calibrator range and concentrations of VS and QC (see discussion below) should be established for the dosage form and route of administration. The lessons learned during method development are critical for the development of specific parameters for the performance of the assay. For example, the number of validation batches and acceptance criteria should be described in a validation plan, and the standard operating procedure (SOP) should be written before conducting the pre-study validation. The correct approach should be to develop a valid (acceptable) method, rather than simply... 

Drug products can be considered to be pharmaceutical equivalents if such products (1) contain the same active ingredients, (2) are of the same dosage form and route of administration, and (3) are identical in strength and concentration. The term therapeutic equivalence is also used to describe pharmaceutical equivalence. Pharmaceutically equivalent drag products may differ in attributes such as shape, color, excipients, and release mechanisms. Pharmaceutical equivalence is of importance in the development of generic drags. See http //www.fda.gov. 

Table 19 Dosage forms and routes of administration of avermectins to various animal species...

Products categorised as GSL medicines have strict controls concerning their strength, use, pharmaceutical form and route of administration. The maximum dose or maximum daily dose will also be controlled for medicines for internal use. Another control that may be enforced is pack size, with a limit to the size of pack allowed as a GSL medicine. Examples of GSL medicines that have controlled pack sizes include ... 

Generic Substitution The substitution of drug products that contain the same active ingredients and are chemically identical in strength, concentration, dosage form, and route of administration to the drug product prescribed. 

It is this parameter that ultimately determines the activity, toxicity, stability and dosage form, and route of administration. The United States Pharmacopoeia (USP) classifies drugs based on their solubility (Table 4). 

Match np the strength and dosage form and route of administration so that the same products are being compared (pharmaceutical equivalent). 

The absorption rate constant is a constant for a given drug formulation, dosage form and route of administration. That is, the same drug... 

Note Peak plasma concentration is always directly proportional to the dose administered, regardless of the route of administration or the health of the subject (healthy or renally impaired) as long as a first-order process is occurring. Therefore, administration of a 500 mg dose of the same drug via identical formulation, dosage form and route of administration will give a y-intercept of 7 mg % and a peak plasma concentration of 2.898 mg % (2.898 mg 100 mL ). The peak plasma concentration in a renally impaired subject will be higher than in a normal subject nonetheless, it will be directly proportional to the administered dose. 

No malformations were found in fetuses of rats treated with doses up to 10.3 g/kg prepared Sichuan aconite, although the body weight and food consumption were reduced in the pregnant rats. Fetuses of rats administered 8.3 g/kg of Aconitum kusnezoffii had a reduction in body length and breastbone calcification (Xiao et al. 2005). The dosage form and route of administration used in this study was not specified in the English language abstract but is likely to have been a decoction administered orally (Xiao et al. 2005). 

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