Bead cellulose products with film formers and solubilizers for controlled drug release

Flowable bead cellulose (BC) coprecipitates were prepared for controlled release, consisting of spherical BC as carrier, the film former hydroxypropyl methylcellulose (HPMC), the hydrophilic solubilizers polyethylene glycol 6000 (PEG 6000) or Poloxamer, the plasticizers dimethyl phthalate and dioctyl phthalate and the model drugs prednisolone and griseofulvin. Coprecipitates of BC/HPMC/drug or BC/HPMC/plasticizer/drug without solubilizer showed fast and complete release of prednisolone due to the dispersed crystalline state and sufficient solubility of the drug and retarded release of griseofulvin due to poor solubility. The drugs crystallized during coprecipitation and were partially incorporated as well as HPMC and plasticizer into the pores of the beads and precipitated on the bead surface. IR-dried coprecipitates of BC, high solubilizer content and low HPMC content (or absence of HPMC) showed high release rates due to the amorphous or solid dispersed state of the drugs in the coprecipitates, therefore fast dissolution due to the solubilizing effect of PEG 6000 or Poloxamer. On the other hand, with increasing HPMC content and decreasing solubilizer content the release rates were diminished due to increasing crystallinity of the drugs and therefore slow dissolution, reduced solubilization, swelling of HPMC and hindered drug diffusion. The IR-dried coprecipitates with solubilizers were flowable and consisted of spherical particles. Freeze-dried coprecipitates of similar composition consisted of beads and separate HPMC and solubilizer particles. The advantages of the BC coprecipitates are the variation of the release rates in a wide range by changing the ratio of solubilizer, HPMC and drug and their favourable physical and flow properties.