Yung Chi Lee

Formulation and in vivo evaluation of ocular insert containing phenylephrine and tropicamide

A Gelfoam based ocular device containing 1.7 mg of phenylephrine and 0.6 mg of tropicamide was formulated and evaluated for pupillary dilation in rabbits. The manufacturing procedure is fairly simple and the required excipients are inexpensive. The in vivo results show that the mydriatic response produced by the proposed device is larger and longer lasting than that produced by eyedrops with an equivalent amount of phenylephrine and tropicamide. The results reported in this study, along with those of previous studies, imply that Gelfoam(R) is a versatile drug carrier for either local or systemic drug delivery via the ophthalmic route.

Review on the systemic delivery of insulin via the ocular route.

Systemic drug absorption from the ocular route is well known. Although there is some absorption from the conjunctival sac, the nasal meatus is the site where the majority of systemic absorption of instilled drug takes place. This article reviews the principles of systemic absorption of insulin applied topically to the eye. The physiological and pharmaceutical considerations for formulation development and the strategy of improving the systemic absorption and bioavailability of insulin are also discussed.

Aqueous functional group activity coefficients (AQUAFAC) 4 : Applications to complex organic compounds

Abstract AQUAFAC is a group contribution scheme for the prediction of aqueous activity coefficients. When combined with the well known ideal solubility equation, AQUAFAC can be used to predict the solubility of a wide variety of organic compounds. This method has successfully predicted the aqueous solubility of simple hydrocarbons, halogenated hydrocarbons, and non-hydrogen bonding oxygen containing compounds, as well as some single hydrogen bonding compounds. In this report the AQUAFAC scheme is extended to include twenty-two new group contribution values. These values were obtained from 379 individual solubility values which represent 168 different organic nitrogen containing compounds. Regression of the observed versus predicted aqueous solubility for the new data set gives a root mean square error of 0.42 with a R 2 of 0.95. Combining this with the previous data brings the AQUAFAC database to over 2700 individual measurements for over 1100 different compounds.

Ocular devices for the controlled systemic delivery of insulin : in vitro and in vivo dissolution

Both in vitro flow-through and in vivo device removal methods were utilized to determine the dissolution rate of insulin from a Gelfoam(R) based eye device. The dissolution profiles generated by these two methods are comparable. The in vivo data suggests that there is a direct relationship between blood glucose lowering and the rate of release of insulin from the device. The in vitro dissolution results indicate that the release of insulin from the device is flow-rate dependent. The prolonged activity of the insulin is due to the gradual release of insulin from the device which results from the lachrymal systems slow and constant tear production.

Controlled delivery of pilocarpine. 2. In-vivo evaluation of Gelfoam® device

Abstract In this report, an ocular device for the controlled delivery of pilocarpine was evaluated in albino rabbits using miosis as a bioassay for efficacy. The device was fabricated using Gelfoam® (absorbable gelatin sponge, USP) in the form of a matrix system. The efficacy of the device was compared in a cross-over study to the two conventional ophthalmic pilocarpine dosage forms, the eyedrop and the gel. The in-vivo results show that the gelfoam device is more effective than the two conventional pilocarpine dosage forms in prolonging the duration of the pilocarpine activity.

AQUAFAC 5 : AQUeous Functional group Activity Coefficients; application to alcohols and acids

AQUAFAC, a group contribution method developed by Myrdal et al.(1992) for estimating the aqueous coefficients, has been studied on a large set of organic compounds including hydrocarbons, halogenated hydrocarbons, non-hydrogen bonding oxygen containing compounds, and nitrogen containing compounds. This study presented new group contribution values for alcohols and acids. This brings the number of the individual solubility values in the AQUAFAC database to over 3,150 for over 1,290 different compounds.

Effect of formulation on the systemic absorption of insulin from enhancer-free ocular devices

Several Gelfoam (absorbable gelatin sponge, USP) based surfactant free devices containing either sodium or zinc insulin were prepared with diluted acetic or hydrochloric acid. They were evaluated by the lowering of the blood glucose concentration in rabbits. The systemic absorption of insulin from the device can be enhanced by using a 5% or higher concentration of acetic acid solution as well as 1% HCl solution. The results indicate that the proposed device prepared with up to 30% of acetic acid solution produced no eye irritation. A single device containing 0.2 mg of insulin is sufficient to control the blood glucose levels in a uniform manner (60% of initial) for over 8 h.

Systemic absorption of insulin from a Gelfoam ocular device.

In previous reports (Lee et al., 1997b; Lee and Yalkowsky, 1999), it has been shown that insulin, delivered by an acidified Gelfoam (absorbable gelatin sponge, USP) based ocular device, can be efficiently absorbed into the systemic circulation without the aid of an absorption enhancer. The role of acid in the enhancer-free absorption of insulin is investigated in this report. Gelfoam ocular devices containing 0.2 mg of sodium insulin prepared with either water or 10% acetic acid were evaluated in rabbits. The results suggest that a change in the Gelfoam upon treatment with acid is responsible for the efficient systemic absorption of insulin from these enhancer-free devices.

Derivatization and high-performance liquid chromatographic analysis of pentaazapentacosane pentahydrochloride

A rapid high-performance liquid chromatographic method for determination of the dansyl derivative of pentaazapen-tacosane (PAPC) pentahydrochloride has been developed. The chromatographic system uses a reversed-phase C8 column, a mobile phase of acetic acid buffer and acetonitrile and UV detection. The dansylation conditions were optimized with a pH of 11.0 and a 20-fold dansyl chloride excess. The yield of dansyl PAPC increased 10-fold as the reaction pH was changed from 9.5 to 10.5. Under derivatization conditions of pH 8.5-11.0 and 1-30-fold excess dansyl chloride only perdansyl PAPC was found.

A comparison of AQUAFAC group q-values to their corresponding CLOGP f-values

Abstract Previous studies1,2 have shown that AQUAFAC is more accurate than the general solubility equation for the estimation of aqueous solubility. The relationship between AQUAFAC group q-values and their corresponding CLOGP f-values is investigated in this study. The q- and f-values are comparable in magnitude for hydrocarbon and halocarbou groups but not for hydrogen bonding groups.