Continuous manufacture of polymeric cellular dosage forms

Abstract

The most prevalent pharmaceutical dosage forms at present are granular solids in the form of oral tablets and capsules. While effective in releasing drug rapidly upon contact with gastrointestinal fluid, their manufacture, which relies on particulate processing, is fraught with difficulties associated with the unpredictable inter-particle interactions. Such difficulties, however, could be easily overcome by transitioning to a liquid-based process. Therefore, we have recently introduced melt‐processed polymeric cellular dosage forms. The drug release behavior of the cellular forms was tailored by altering the microstructure; yet their preparation relied on an inefficient batch method comprising gas dissolution, and nucleation and growth of microscopic gas bubbles in the melt. In this study, therefore, we present a continuous microfluidic melt extrusion and molding process. The cellular dosage forms are produced by injecting gas bubbles directly into the melt stream in a micro‐ or milli-fluidic channel, followed by molding and solidification of the cellular structure. A model is developed to illustrate the effects of the width, frequency, and pressure of the gas injection pulses, and the flow rate and viscosity of the melt, on the microstructural parameters of the dosage forms produced. Experimental results show that the size and volume fraction of gas-filled cells (or voids) are predictable. They also confirm that the dosage form disintegration rate and density can be tailored by altering the volume fraction of voids. It is thus demonstrated that polymeric cellular dosage forms with predictable drug release properties, and density, can be readily manufactured by a continuous process.