Oral controlled delivery systems such as tablets are exposed to a wide range of pH conditions and mechanical agitation along the gastrointestinal tract, which leads to undesirable fluctuations in drug release rates and variable drug plasma concentrations in vivo. Due to the pH-dependent solubility of ionizable drugs, oral tablets containing ionizable drugs are particularly prone to these release rate fluctuations. In order to achieve pH-independent release, large amounts of organic buffers are incorporated in oral tablets. This addition increases the tablet size, making them difficult to swallow for pediatric and geriatric patients. In this research project, cohesive, flexible and water insoluble silicone pressure sensitive adhesive was evaluated for the first time as a polymer matrix for oral controlled release of ionizable drugs without the use of organic buffers. The effect of dissolution medium pH on the release rate of weak base verapamil and weak acid diclofenac from silicone adhesive tablets was tested. Ethyl cellulose, a widely used polymer in oral controlled release system, was studied for direct comparison. It was shown that pH-independent release of ionizable drug verapamil was achieved from silicone adhesive matrix. In addition dissolution stirring conditions had no effect on the drug release rate. As expected, ethyl cellulose matrix failed to achieve pH-independent release. This finding suggests that the unique properties offered by silicone adhesive can be useful for controlled release matrix of ionizable drugs to reduce the variability in drug release due to the changing dissolution conditions encountered in vivo.
Oral controlled delivery systems such as tablets are exposed to a wide range of pH conditions and mechanical agitation along the gastrointestinal tract, which leads to undesirable fluctuations in drug release rates and variable drug plasma concentrations in vivo. Due to the pH-dependent solubility of ionizable drugs, oral tablets containing ionizable drugs are particularly prone to these release rate fluctuations. In order to achieve pH-independent release, large amounts of organic buffers are incorporated in oral tablets. This addition increases the tablet size, making them difficult to swallow for pediatric and geriatric patients. In this research project, cohesive, flexible and water insoluble silicone pressure sensitive adhesive was evaluated for the first time as a polymer matrix for oral controlled release of ionizable drugs without the use of organic buffers. The effect of dissolution medium pH on the release rate of weak base verapamil and weak acid diclofenac from silicone adhesive tablets was tested. Ethyl cellulose, a widely used polymer in oral controlled release system, was studied for direct comparison. It was shown that pH-independent release of ionizable drug verapamil was achieved from silicone adhesive matrix. In addition dissolution stirring conditions had no effect on the drug release rate. As expected, ethyl cellulose matrix failed to achieve pH-independent release. This finding suggests that the unique properties offered by silicone adhesive can be useful for controlled release matrix of ionizable drugs to reduce the variability in drug release due to the changing dissolution conditions encountered in vivo.
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Copyright 2023 TERC.
Presented by IGERT.org.
Funded by the National Science Foundation.
Copyright 2023 TERC.
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