The possibility of a pH-controlled drug release mechanism applying to silicone microspheres containing nicotinamide (NAM) and Polycarbophil (PCP), a pH-sensitive hydrogel, is evaluated. NAM-medicated PCP in the 4:1 PCP-NAM wt ratio is dispersed, at the 20% or 40% concentration, in silicone in the form of osmotically active particles of around 15 μm mean volume diameter, and encapsulated in microspheres in the 105–710 μm size range by a modified emulsion vulcanization technique, with a 100% entrapment efficiency. The external and internal morphology of microspheres, and the size distribution of PCP-NAM particles dispersed therein are evaluated by scanning electron micrography. Microspheres are eluted 9 h with simulated GI fluids (pH 1.2–7.4). Assessment of the time exponent characterizing the release kinetics, together with release and swelling data from planar matrices of same formulation as the microspheres, substantiate the following release mechanism. Due to their small size, the osmotically active particles have a limited ability to crack the silicone polymer and interconnect upon swelling, so the hydrogel route of release is of a minor relevance, and so is the hydrogel pH-sensitivity. Drug release is mainly governed by partitioning-diffusion in the silicone continuum of microspheres, therefore it is pH-independent and the time exponent is close to the value typical of Fickian release. It is concluded that encapsulation of hydrogel particles of larger size is a necessary condition for a pH-controlled release pattern.