Date of Award

2003

Degree Type

Thesis

Degree Name

Master of Science in Applied Pharmaceutical Sciences

Department

Applied Pharmaceutical Sciences

First Advisor

Christopher T. Rhodes

Abstract

Liquid Avonex® (Interferon beta-1 a) manufactured by Biogen, Inc. is indicated for the treatment of relapsing forms of multiple sclerosis (MS) to slow the accumulation of physical disability and decrease the frequency of clinical exacerbations. The recommended dosage of A vonex® for the treatment of relapsing forms of MS is 30 μg injected intramuscularly once a week. Several complications have been reported following intramuscular (IM) injections, of which pain at the injection site is the most common. Though factors such as site of injection, injection volume, concentration and nature of the drug may affect the reception of pain, one factor which has not apparently been given any attention in the published literature is the ease of injectability of the syringe, which is the amount of force required to expel the drug from the syringe. This factor can be expected to have a substantial effect on the discomfort experienced by patients and on the completeness of the injection (i.e. the percentage of dose delivered). An evaluation of the published literature by the author of this thesis has failed to reveal any publications dealing with the role of injectability as a measure for easing the pain on injection. There is a need for some objective, quantitative method for measuring the ease of injectability such as may be provided by use of the Instron Series 5500.

The purpose of this study was to perform compressive studies on the intramuscular injection, Liquid Avonex® staked and luer-slip pre-filled syringes using the Instron Series 5500. The Instrument generates an expulsion force profile from which the force required for the initial movement of the plunger into the syringe (breakout force) was calculated. An ideal syringe with good ease of injectability will have minimum breakout force and a smooth expulsion profile. Thus by studying the various factors affecting the expulsion force profile, the ease of injectability of syringes was quantified. The various factors studied were age and viscosity of silicone oil, storage temperature, addition of surfactant and the speed of expulsion. The viscosity of the silicone oil and the method of siliconization were found to be critical factors defining the expulsion force profile. The 1000 cSt silicone oil was found to give better ease of injectability than the 12,500 cSt silicone oil. Increase of storage temperature, addition of surfactant and increase of expulsion speed did not have any substantial effect on the expulsion force profile of the syringe.

Pain on IM injection is also related to the mechanical properties of the needle insertion, which include the maximum force required to penetrate the muscle and the penetration profile of the needle into the muscle. Needle penetration studies were conducted to examine the injection profiles of staked and non-staked needle sharps using a model intramuscular injection pad. The results showed that nonstaked needles need lesser penetration force and show linear penetration profile in comparison with staked needles and hence cause less pain on injection.

In conclusion, the results reported in this study clearly indicate that compressive studies using the Instron Series 5500 are an effective and convenient way to quantify the ease of injectability of syringes.

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