Incorporation of polymeric nanoparticles into solid dosage forms.

Abstract

Besides parenteral delivery, polymeric nanoparticles have been used for oral drug delivery. In this study, model polymeric nanoparticles (aqueous colloidal polymer dispersions: Eudragit(R) RL 30D, L 30D, NE 30D, or Aquacoat(R)) with different physicochemical properties were incorporated into various solid dosage forms (granules, tablets, pellets or films). The compatibility of the nanoparticles with commonly used tabletting excipients and the redispersibility of the nanoparticles after contact of the solid dosage forms with aqueous media were investigated. Ideally, the nanoparticles should be released from the solid dosage forms with their original properties. The addition of polymeric binders (e.g. polyvinylpyrrolidone, Na carboxymethylcellulose or hydroxypropyl methylcellulose) to the aqueous nanoparticle dispersions prior to wet granulation resulted in phase separation (depletion or bridging flocculation) for many nanoparticle/binder systems. Two critical parameters for the complete redispersibility/release of the nanoparticles with the original particle size properties from the solid dosage forms were a (1) high minimum film formation temperature (MFT) of the polymer dispersion and (2) a good wettability of the dried polymeric nanoparticles. Nanoparticle dispersions with a low MFT were not redispersible, they coalesced into larger agglomerates/films during the drying step. Contact angle measurements correlated well with the redispersibility of the nanoparticles, with ethylcellulose particles having high contact angles and poor redispersibility and Eudragit(R) RL, a polymer stabilized with quaternary ammonium groups, having low contact angles and good redispersibility.