(624e) Vacuum Compression Molding As Screening Approach for Hot-Melt Extruded Dosage Forms

Hot melt extrusion (HME) is a continuous process with growing importance for the pharmaceutical industry [1]. It is a robust production process for solid dispersions. Solid dispersions can increase the solubility of the active pharmaceutical ingredient (API) in case of poor crystalline solubility or they can help to tailor a formulation to a certain API release behavior [2].

Often, HME supplies intermediates in form of pellets, which are processed via conventional tablet compaction or capsule filling to the final dosage form. Recently, injection molded dosage forms gained the interest since they offer several advantages [3]. They can have high hardness or high elasticity which are requested for example for abuse resistant formulations or implants. However, the effect of interactions between formulation, process parameters and product properties is not well understood. Thus, in general, HME formulation development usually requires a host of experimental attempts. In many cases, formulation screening is performed with small-scale extruders, for example with conical twin-screw extruders, which typically require 5 gram of material. The extruder delivers molten material which is typically collected as strand and cut into small pieces, which are then analyzed with respect to their suitability for the indented dosage form and release profile. However, many of the analyzed properties are impacted by several parameters concurrently. For example, the drug release profile is strongly impacted by the type of solid dispersion and the available exchange surface. Thus, for example defined geometries can simplify formulation screening since less parameters superimpose.

This work presents an alternative screening approach that requires less than 1 gram of material for the production of one sample tablet. A novel vacuum compression molding (VCM) tool has been developed. A powdery mixture of raw materials is filled into the sampling chamber. Subsequently, the tool is evacuated and heated above the melting point forming a homogeneous bubble-free tablet. Stickiness issues are prevented by the used PTFE coated release foils. Formulations consisting of matrix polymers and an API have been produced via the proposed method. The obtained tablets are analyzed by standard screening analysis tools (DSC, dissolution testing, etc.). The results are compared to results obtained from extruded material analyzed by the same methods. The comparison shows that similar results can be obtained with less effort. Thus, it has been demonstrated that VCM can be a useful tool in formulation development as it reduces workload and the required material amount.

References:

[1]       M. A. Repka, N. Langley, and J. DiNunzio, Melt Extrusion - Materials, Technology and Drug Product Design. New York, Heidelberg, Dordrecht, London: Springer, 2013.

[2]       E. Roblegg, E. Jäger, A. Hodzic, G. Koscher, S. Mohr, A. Zimmer, and J. Khinast, “Development of sustained-release lipophilic calcium stearate pellets via hot melt extrusion.,” Eur. J. Pharm. Biopharm., vol. 79, no. 3, pp. 635–45, Nov. 2011.

[3]        L. Zema, G. Loreti, A. Melocchi, A. Maroni, and A. Gazzaniga, “Injection Molding and its application to drug delivery.,” J. Control. Release, vol. 159, no. 3, pp. 324–31, May 2012.