Parenteral administration, ophthalmic

Pregnancy Pharmacokinetic Rapidly category C ophthalmic metabolized in the GI tract and liver and excreted in the urine Minimal absorption after inhalation well absorbed after parenteral administration Ophthalmic May have systemic absorption from drainage into nasal pharyngeal passages. Mydriasis occurs within several minutes. Persists several hours vasoconstriction occurs within 5 min last less than 1 hr... 

Current guidelines for toxicity evaluation of ophthalmic formulations involve both single and multiple applications, dependent on the proposed clinical use [39]. The multiple applications may extend over a 9-month period and incorporate evaluations of ocular irritation and toxicity, systemic toxicity, and determinations of systemic exposure (toxicokinetics). In many cases the systemic exposure from an ocular route is less than by parenteral administration, information that will assist in determining whether additional studies may be needed to establish systemic safety of the ophthalmic preparation. U.S. and international guidance documents are available [71,72], and regulations and tests have been summarized for ophthalmic preparations [39,73,74],... 

For drug preparations that will be used for internal or mucous membrane administration (i.e., parenteral preparations, ophthalmics, creams and salves, etc.), additional testing must be performed to assure that any leachants will not cause biological reactions that may be detrimental to the patient. To do this, a test protocol has been established that screens materials used in containers to test for biological interactions. This protocol should be applied to any plastic container closure systems regardless of the type of container that will directly contact pharmacopeial preparations in storage before they are invasively used. This includes all closure systems for parenteral vials. ... 

Pharmaceutically, osmotic effects are important in the parenterals and ophthalmic fields, and work is usually directed at formulating to avoid the side-effects or finding methods of administration to minimize them. The ophthalmic respose to various concentations of sodium chloride is shown in Table 6.10 (Flynn 1979). 

Formulations in nanosuspensions are used in different routes of administrations, such as oral, parenteral, topical, ophthalmic, mucoadhesive, pulmonary, and targeted drug delivery. 

In-depth discussions of the anatomy of the eye and adnexa have been adequately covered elsewhere in the pharmaceutical literature [13-17] and in recent texts on ocular anatomy. Here a brief overview is presented of the critical anatomical features that influence the nature and administration of ophthalmic preparations. In this discussion, consideration will be given primarily to drugs applied topically, that is, onto the cornea or conjunctiva or into the palpebral fornices. Increasingly, drugs are being developed for administration by parenteral-type dosage forms subconjunctivally, into the anterior and posterior chambers, the vitreous chamber, Tenon s capsule, or by retrobulbar injection. 

Table 3 indicates the preclinical safety studies for CAPTISOL (25) conducted as of 2005. The strategic safety plan for CAPTISOL was designed based on the guidelines discussed in the 1990s by the International Pharmaceutical Excipients Council which resulted in the May 2005 issuance of the FDA Guidance (26) Nonclinical Studies for the Safety Evaluation of Pharmaceutical Excipients. These studies and others in the CAPTISOL Drug Master File have delineated the safety of CAPTISOL (SBE7-P-CD) for parenteral, ophthalmic, oral, nasal, and inhalation administration. 

To date, the clinical administration of ASOs has focused on local or parenteral routes using simple saline solutions. Intravenous dosing in animals has been shown to lead to an accumulation of oligonucleotide in specific cells, such as endothelial and phagocytic cells, and organs such as the kidneys and liver. These observations suggest optimal targets for clinical applications, for example liver diseases such as hepatitis C or ophthalmic indications such as the intraocular treatment of CMV retinitis. 

All routes of drug administration can affect ocular structures and functions. OADRs have been associated with topical ophthalmic administrations as well as local injections. Systemically, oral drug administration has been implicated most frequently in the development of OADRs. However, parenteral as well as inhaled or nasally applied drugs have also produced OADRs. Topical application to the skin, particularly if it is abraded or burned, may result in sufficient systemic absorption to lead to ocular side effects. Dermatologic use of antibiotics has resulted in ocular hypersensitivity reactions. 

Sterility is defined as the total absence of all viable life forms. Parenteral products and ophthalmic products are expected to be sterile. Parenteral products must be sterile because their route of administration overrides the body s external physical barriers to infection. Ophthalmic products must be sterile because eye damage is often irreparable. No distinction can be made between microorganisms that are known to be specific causative agents of disease and those that are not. 

As excipients, CDs have been widely used to cover the bitter taste of drugs, to increase their dissolution rates, to reduce irritation reactions and in low concentrations to suppress the haemolysis induced by some drugs [180]. Great effort has been made to develop CD-based drug formulations with different administrative routes, including parenteral, oral, pulmonary, nasal [181], transdermal, rectal [182] and ophthalmic [183] drug delivery [184]. 

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