Sequential design of a novel PVA-based crosslinked ethylenic homopolymer for extended drug delivery

A Box-Behnken Design was employed to study the influence of boric acid, sodium sulfate, ammonia and n-propanol in the formulation of crosslinked ethylenic homopolymeric (CEH) gelispheres from native polyvinyl alcohol (PVA). The dependent variables studied included the size of the spherical gelispheres, drug encapsulation efficiency, in vitro dissolution after 30 min and textural parameters, namely fracture force and matrix rupture energy. Based on these responses, an optimized CEH gelisphere matrix was formulated and thereafter incorporated as a powder into a candidate crosslinked zinc-pectinate multiple-unit device to assess its effect on modifying drug release. In the case of the CEH-loaded zinc-pectinate gelispheres, it was determined via constrained optimization that a maximum drug encapsulation efficiency of 28.63% could be obtained under the conditions of 0% (w/v) CEH, 13 h of crosslinking and drying temperature of 60 °C. On the other hand, initial drug release could be significantly retarded when 0.10% (w/v) of CEH was included in the formulation and crosslinked for 24 h at 40 °C. In this regard, CEH induced a 4 h lag phase. Furthermore, zero-order drug release was produced and could be maintained over several weeks. Kinetic analysis of drug release further supported that CEH inhibits polymer relaxation (k2 ≪ k1), and hence slows down drug diffusion. Based on these results, the CEH-zinc-pectinate drug delivery system appears to be a suitable carrier that may be employed for long-term administration for, e.g. via subcutaneous implantation.