Pharmaceutical Manufacturing Handbook: Production and

PACKAGING MATERIALS 169
Topical delivery systems are self - contained, discrete dosage forms that are
designed to deliver drug for an extended period via intact skin or body surface, for
example, transdermal, ocular, and intrauterine.
These systems may be constructed of a plastic or polymeric material loaded with
active ingredients or a coated metal. Each of these systems is generally marketed
in a single - unit soft blister pack or a preformed tray with a preformed cover or
overwrap. The compatibility and safety for topical delivery systems are addressed
in the same manner as for topical drug products. Performance and quality control
should be addressed for the rate - controlling membrane.
Sterile Products
Nonsolids An SVP may be packaged in a disposable cartridge, a disposable syringe,
or a fl exible bag made of polymeric plastic. Flexible bags are typically constructed
with multilayered plastic (Table 2 ).
An LVP may be packaged in a vial, a fl exible bag, or, in some cases, a disposable
syringe. Packaging material for cartridges, syringes, vials, and ampules are usually
composed of polypropylene (Table 2 ).
Stoppers and septa in cartridges and syringes are typically composed of elastomeric
materials. An overwrap may be used with fl exible bags to retard solvent loss
and to protect the fl exible packaging system from rough handling.
Diazepam in intravenous fl uid containers and administration sets exhibited
a loss during storage due to adsorption onto and absorption into plastics
[11, 12] .
Absorption of clomethiazole edisylate and thiopental sodium into PVC infusion
bags was observed [28] .
The pH dependence of adsorption/absorption of acidic drug substances such as
warfarin and thiopental and basic drug substances such as chlorpromazine and diltiazem
indicates that only the un - ionized form of the drug substance is adsorbed
onto or absorbed into PVC infusion bags [29] .
The absorption was correlated to the octanol – water partition coeffi cients of the
drugs, suggesting that prediction of absorption from partition data is possible [30,
31] . Polymers such as Nylon - 6 (polycaprolactam) are known to adsorb drug substances
such as benzocaine [32] .
The ophthalmic drug products are usually solutions marketed in a LDPE bottle
with a dropper built into the neck. A few solution products use a glass container
due to stability concerns regarding plastic packaging components.
3.2.2.4
Metal as Packaging Material
Metal tubes constructed of a single material are the packaging material of choice
for topical dosage forms and may be tested readily for stability with a product. Tubes
with a coating, however, present additional problems. The inertness of coating material
must be established through adequate tests and guarantee that it completely
covers underlying material. The coating material must be resistant to creaking,
leaking, leaching, and solvent erosion. For example, frequently used aluminum tubes
have demonstrated reactivity with fatty alcohol emulsions, mercurial compounds,
and preparations with pH below 6.5 and above 8.0. Nonreactive, epoxy linings have
been found to make aluminum tubes resistant to attack [6] .