Pharmaceutical Manufacturing Handbook: Production and

is characterized by a transient overdose, a relatively short period of appropriate
dosing, followed by a prolonged period of underdosing. Ocular inserts were developed
in order to overcome these disadvantages by providing a more controlled,
sustained, and continuous drug delivery by maintaining an effective drug concentration
in the target tissues and yet minimizing the number of applications [238] .
Ocular inserts probably represent one of the oldest ophthalmic formulation
approaches. In 1948 the British Pharmacopoeia described an atropine - in - gelatin
wafer and ever since then numerous systems have been developed applying various
polymers and different release principals. However, the diffi culty of insertion by the
patient, foreign - body sensation, and inadvertent loss of inserts from the eye make
these systems less popular, especially among the elderly. Furthermore, the high cost
involved in manufacture prevented the insert market from taking off [197] .
Two products, Alza Ocusert and Merck Lacrisert, have been marketed, although
Ocusert is no longer available. Ocusert is a membrane - controlled reservoir system
for the treatment of glaucoma. It contains pilocarpine and alginic acid in the core
reservoir, sandwiched between two transparent, lipophilic ethylenevinyl acetate
(EVA) rate - controlling membranes, which allow the drug to diffuse from the reservoir
at a precisely determined rate for a period of seven days. This system is nonbiodegradable
and must therefore be removed after use. Lacrisert, on the other
hand, is a soluble minirod of hydroxypropylmethyl cellulose without any active
ingredient. The system is placed in the conjunctival sac, where it softens within an
hour and completely dissolves within 14 – 18 h. Lacrisert stabilizes and thickens the
precorneal tear fi lm and prolongs the tear fi lm break - up time, which is usually
accelerated in patients with dry - eye syndrome (keratoconjunctivitis sicca) [239] .
A number of ocular inserts using different techniques, namely soluble, erodible,
nonerodible, and hydrogel inserts with polymers such as cellulose derivates, acrylates,
and poly(ethylene oxide), have been investigated over the last few decades.
An example of a degradable matrix system is the pilocarpine - containing inserts
formulated by Saettone et al. [148] . Pilocarpine nitrate and polyacrylic acid were
incorporated into a matrix containing polyvinyl alcohol and two types of hydroxypropyl
methylcellulose. It was shown that all inserts signifi cantly increased the pharmacological
effect (miotic response) compared to a solution of pilocarpine nitrate.
Sasaki et al. [151] prepared nondegradable disc - type ophthalmic inserts of
β - blockers using different polymers. They found that inserts made from
poly(hydroxypropyl methacrylate) were able to control the release of tilisolol
hydrochloride.
Numerous studies have also been performed on soluble collagen shields. Collagen
shields are fabricated from porcine scleral tissue, which has a similar collagen
composition to that of the human cornea. Drug loading is typically achieved by
soaking the collagen shield in the drug solution prior to application. Designed to
slowly dissolve within 12, 24, or 72 h, collagen shields have attracted much interest
as potential sustained ocular drug delivery systems over the last years [240] .
5.9.4
CONCLUSION
CONCLUSION 753
Although conventional eye drops still represent about 90% of all marketed ophthalmic
dosage forms, there have been signifi cant efforts towards the development
of new drug delivery systems.