| Mark Hall and his colleagues at The Dow Chemical Company discuss hot melt extrusion as a means to produce compositions that contain high API loads and exhibit-controlled release behaviour
Preparing formulations that contain high active pharmaceutical ingredient (API) loads and exhibit controlled API-release via conventional pharmaceutical processing technologies has proven to be difficult. As the amount of API increases, the quantity of dissolution rate-controlling additives and other excipients must be reduced. This often has a negative impact on dosage form preparation processes, and/or results in dosage forms with poor mechanical properties. The conventional solution is to increase the dosage size, but there is a practical limit to this approach.
The authors have found that hot melt extrusion (HME) can be used to produce these types of dosage forms. Formulations containing 50 weight per cent acetaminophen (APAP) and ketoprofen were produced exhibiting the desired controlledrelease behavior. Hypromellose (HPMC), ethylcellulose (EC) and polyethylene oxide (PEO) are polymeric excipients that can be used in HME (1). These polymers, in addition to a proprietary development product, were used in the APAP and ketoprofen formulations. Tablet physical properties (hardness and friability) of the extruded formulations were found to be quite acceptable.
In addition to being able to produce the desired high drug-loaded dosage forms, there are benefits to using HME over traditional processing techniques. These include fewer unit operations, good content uniformity, an anhydrous process, a dispersion mechanism for poorly soluble drugs, a low energy alternative to high shear granulation, and less processing time compared to conventional wet granulation (2). |
