Dosage Form And Routes Of Administration

Without exception, biotechnology-based pharmaceuticals must be formulated into dosage forms suitable for human administration in a safe and effective manner. These formulations must be stable under defined storage conditions for a defined period of time and be uniformly reconstitutable during that time. Hence biopharmaceuticals must be in compliance with stringent manufacturing guidelines and pass quality control and quality assurance standards for all bulk materials used to formulate the product. These bulk materials are formulated into appropriate dosage forms designed for specific 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 adminis tration). 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

Route of Administration

Dosage Formulation

Examples

Parenteral Intravenous, Intraarterial, Intracardiac,

Intraspinal or Intrathecal,

Intramuscular,

Intrasynovial,

Intracutaneous or Intradermal, Subcutaneous Local injection Intrarespiratory

Topical

Intranasal

Intravitreal

Solutions, Suspensions, Lyophilized powders to be reconstituted into solution

Solutions Aerosols

Gels

Solutions Solutions

Blood clotting factors, colony-stimulating factors, antibodies and derivatives, interferons, interleukins, enzymes, hormones, vaccines

Interferon for direct injection into wart DNAse delivered to lungs to reduce mucus accumulation

Platelet-derived growth factor for wound healing

Calcitonin for Paget's disease; gonadotropin-releasing hormone (GnRH) agonist for management of endometriosis

Antisense nucleotide polymer against CMV retinitis in patients with AIDS

personnel to ensure proper administration, which adds to the cost of treatment. Products intended for subcutaneous injection, however, can be self-administered or administered by a home care provider.

A small number of biopharmaceuticals are delivered by nonparenteral means. Recombinant DNase is given by inhalation aerosol to reduce the viscosity of mucus in the lungs of patients with cystic fibrosis. A platelet-derived growth factor in the form of a gel is administered topically for wound healing. Several hormones and peptides are administered in solution by the intranasal route. A solution of an antisense drug used for the treatment of cytomegalovirus retinitis is injected directly into the eye.

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