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No abstract

The addition of a solute to a solvent is known to reduce the solubility of dissolved gases in solution which leads to gas oversaturation and outgassing of the solvent. The importance of the processes involved have received relatively little attention due to a limited capacity to elucidate their effects in real time. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) is a recently introduced acoustic approach which can monitor changes in the compressibility of a solvent due to outgassing. BARDS spectra show that a time dependent and quantitative reduction in gas oversaturation, following the dissolution of a simple salt, takes place over several hours. It is shown how vigorous agitation quickly equilibrates a solution, post dissolution, by removing gas oversaturation consistently. The level of oversaturation can be elucidated by further dissolving a marker compound into a solution consecutively. BARDS spectra indicate that the dissolution of a compound produces a consistent and quantifiable oversaturation of a solvent and a consistent and quantifiable outgassing. Low frequency sonication in an immersion bath is also shown to play no significant role in removing gas oversaturation post dissolution.

There is an increased trend towards the use of drug and enteric coated sugar spheres for controlled oral delivery of active pharmaceutical ingredients (API). This trend is driven by increased efficacy and ease of formulation of different dosage levels. However, difficulties exist in determining the thickness of drug and enteric coatings in a time efficient manner during manufacture, quality assurance and stability testing. The thickness of the coating determines the dosage of the API and the thickness of the enteric coating determines the release rate of the drug in the gastro-intestinal tract. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) offers a rapid new approach to characterising the enteric coating thickness and the raw materials used in their manufacture. BARDS applications are based on reproducible changes in the compressibility of a solvent during dissolution which is monitored acoustically due to associated changes in the speed of sound in solution. It is demonstrated how core delivery sugar spheres have unique acoustic spectra attributable to the mean size distribution of the spheres. A steady state acoustic lag time is associated with the disintegration of the enteric coating, in basic solution. This lag time can be manipulated by varying the concentration of the base which affects the rate at which the coating dissolves. It is anticipated that the thickness/loading of the spheres can be estimated from the lag time.

Enteric coatings are widely used in formulations of drug delivery spheres. The coating protects an active pharmaceutical ingredient (API) from acidic conditions in the low pH environment of the stomach. The coating breaks down readily at higher pH in the lower intestine to allow absorption of the API. The thickness of the enteric coating is one of the factors that determine the release rate of the drug in the gastrointestinal tract. It is difficult to determine the loading of the drug layer and enteric coating on the core support sphere without conventional dissolution testing during and post manufacture. Broadband acoustic resonance dissolution spectroscopy (BARDS) potentially offers a new, rapid approach to characterizing enteric coatings during their manufacture. BARDS applications are based on reproducible changes in the compressibility of a solvent during dissolution, which is monitored acoustically via associated changes in the frequency of induced acoustic resonances. Two drug sphere formulations that yield characteristic and reproducible data were investigated. A steady-state acoustic lag time is associated with the disintegration of the enteric coating and drug layer in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating and layers dissolve. BARDS analysis has the potential to characterize drug sphere formulations at-line in very short timescales. BARDS represents a complementary technique to conventional dissolution testing that could be used in precompliance testing for quality assurance during manufacture. BARDS data, in the future, may also be indicative of the likely performance of a formulation under USP dissolution testing. KEYWORDS:Hypromellose; enteric-coated spheres; dissolution; BARDS.