Investigating in Vitro Drug Release Mechanisms Inside Dosage Forms
The internal mechanisms that drive drug release underpin both the in-vitro and the in-vivo performance of oral dosage forms and therefore underlie any derived in-vivo/in-vitro relationships. Until relatively recently, it has been difficult to directly observe the processes inside dosage forms, and drug release mechanisms have been largely inferred from analyses of in-vitro release kinetics. It is still extremely difficult to obtain information about release mechanisms in-vivo, but methologies using imaging microscopies are currently being developed at Nottingham that enable us to directly visualise the changes taking place inside dosage forms in-vitro as they hydrate and perform. Techniques such as cryogenic SEM, NMR microscopy and laser scanning confocal microscopy have given valuable insights into the changing internal patterns of hydration, drug dissolution, and water and solute diffusion in, for example, hydrophilic matrix 1–4 and pellet5,6 extended release systems. In the present work, confocal laser scanning microscopy has been used to provide evidence for a difference in release mechanism between two complex HPMC hydrophilic matrix formulations which showed unexpectedly different release profiles in-vivo. In a wider context this work exemplifies how advanced imaging technologies may be used to provide some understanding of the complex phenomena that may underlie the process of drug release inside controlled release devices.
KeywordsDrug Release Dosage Form Liquid Penetration Release Dosage Form Drug Release Mechanism
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