Ocular bioavailability of ciprofloxacin in sustained release formulations.

A novel sustained release delivery system of ciprofloxacin for the eye was developed. The system consists of a viscosity enhancer (carbopol gel or hydroxypropylmethylcellulose solution) plus a penetration enhancer (dodecylmaltoside) to overcome penetration barriers and loss due to wash-out and thus achieve the desired ciprofloxacin ocular absorption. The present studies were designed to assess the ocular penetration and bioavailability of ciprofloxacin in sustained release formulations. In vitro studies in rabbits indicated an approximate 10-fold increase in drug penetration through the rabbit cornea using the penetration enhancer, dodecylmaltoside. In vivo bioavailability studies demonstrate that these formulations provided a long drug duration in the cornea. After administration of a single topical dose of ciprofloxacin (0.3%/30 microL), corneal levels greater than the Minimum Inhibitory Concentration (MIC90) (0.5 microg/g) were observed through eight hours. These sustained release formulations delivered 10-fold more drug into the aqueous humor than the standard solution formulation. Maximum ciprofloxacin concentrations in the aqueous humor (0.5-0.7 microg/mL) were attained between one and two hours after dosing. Using these sustained release formulations, ciprofloxacin can penetrate to the anterior chamber of the eye in concentrations that are inhibitory for most gram-negative and gram-positive organisms. These topical ocular formulations have prophylactic utility for prevention of post-surgical infection, offering greater efficacy and safety than currently available treatments.

Neodymium:YAG laser interaction with Alcon IOGEL hydrogel intraocular lenses: an in vitro toxicity assay.

The objective of this study was to determine the potential toxicity generated by the interaction of the Nd:YAG laser and Alcon IOGEL intraocular hydrogel lens material. The IOGEL lens is composed of poly 2-hydroxyethylmethacrylate, containing 38% water, previously shown to be highly biocompatible in a wide range of tissue culture and implantation experiments. In this study, intraocular lenses (IOLs) immersed in serum-free cell culture medium were purposely exposed to exaggerated doses of laser energy to cause extensive damage. An IOLAB polymethylmethacrylate (PMMA) lens served as a control lens material. The resultant solutions were assayed for cytotoxicity in a bioassay system using fourth passage human corneal endothelial cells. No cytotoxicity was seen in the bioassay for the IOGEL hydrogel IOLs or the PMMA control IOL at any laser range/dosage tested over a 72-hour incubation period. Hydrogel lenses exhibited decreasing yellowing with decreasing energy levels, and no lens discoloration was apparent at the lowest level of irradiation, 5 mJ/50 laser bursts; the PMMA control lens exhibited moderate yellowing at 15 mJ/50 bursts. Lens marking was moderate for all IOGEL IOLs; the PMMA lens marking was severe at the power level tested.

Multicenter trial of an intraocular hydrogel lens implant.

Several features suggest that hydrogels may have potential advantages as an intraocular lens material. The IOGEL lens is a single piece hydrogel composed of 38% poly HEMA. Clinical experience with the IOGEL lens in Australia has been published, and the safety and efficacy of the lens is currently being investigated in a multicenter trial in Europe, the U.S.A., Canada, Australia, and Japan. This is the first large-scale study of a hydrogel implant. The IOGEL lens clinical study was initiated in May 1986 in Europe, in September 1986 in the U.S.A., and in November 1986 in Canada and Australia. The enrollment progress in May 1987 showed that 501 cases had been implanted in Europe, Canada, and Australia and 100 cases in the U.S.A. The visual acuity outcome is equivalent to that reported in the literature. Patients in the multinational trial achieved 20/40 or better in 86% of cases and in 96% of cases excluding unrelated pathologies. Although hydrogels have only had limited use in the clinical situation, the results of this study suggest that the IOGEL lens is a viable alternative to polymethylmethacrylate lens implants.

BSS Plus: a potential irrigating solution for neurosurgery.

BSS Plus is a pH-stable balanced salt solution similar to glutathione bicarbonate Ringer's solution. Extensively used in ophthalmology, it is of potential value in neurosurgery. In comparative tests of its effectiveness, 28 cats underwent bilateral irrigation of the surface of the cerebral cortex with normal saline on one side and BSS Plus on the other. After 2 hours, a marked decrease was seen in the surface pH of the hemisphere irrigated with normal saline but not of the hemisphere treated with BSS Plus. Blood-brain barrier changes (measured with Evans blue dye techniques) were more evident following saline irrigation. Somatosensory evoked potentials and cerebral blood flow were not significantly altered. Conventional light microscopy using three standard stains did not reveal a significant difference. Transmission electron microscopy studies were performed in 14 animals and scanning electron microscopy in six. In five animals both transmission and scanning electron microscopy studies were conducted after irrigation with both agents without a cottonoid cover and with immediate harvest of superficial layers from the living brain and immersion-fixation in glutaraldehyde. Tissue preservation was superior on the BSS Plus side in all studies. This agent may represent an improved irrigation solution for neurosurgery, but further studies are required.

Pharmacological study of broperamole, a chemical novel antiinflammatory compound.

N-3[5'-(3"-Bromophenyl)-2'H-tetrazole]propionyl piperidine (broperamole) was shown to elicit potent antiinflammatory activity following systemic administration to rats in acute and subchronic studies. The compound demonstrated systemic antiinflammatory activity 5-6 times that of phenylbutazone. Toical antiinflammatory activity was also demonstrated which was less than that of hydrocortisone but still should have clinical utility. Antipyretic activity, without effect on normal body temperature, was observed. Analgesic activity was not evidenced. Only at very high doses was gastric irritation noted; therefore, at anticipated human dose level, gastrointestinal toxicity in man should not occur.

Topical parabens: benefits and risks.

Parabens are the most frequently used preservative in dermatological medications. Some allergies have been reported to parabens, but these risks must be considered with respect to the benefits of parabens in concentrations used as preservatives in dermatological formulations. Considering the alternatives to parabens in preservat ives and placing perspective on the reported allergies we still find parabens to be a useful preservative with minimal risk to its benefits.