Continuous Release of rh-Interferon α-2a from Triglyceride Implants: Storage Stability of the Dosage Forms

Tristearin implants containing polyethylene glycol 6000 (PEG) were shown to be a promising platform for the delivery of pharmaceutical proteins for periods up to 1 month. The objective of this study was to investigate the storage stability of the lipid devices, as long-term storage stability ensuring acceptable shelf-life can be considered the most important parameter for commercially viable sustained-release dosage forms. Rh-Interferon α-2a was stabilized by a lyophilization process using either trehalose or hydroxypropyl-β-cyclodextrin as stabilizer. Tristearin implants containing the lyophilized protein material and 10% PEG were stored over 3 months and 6 months, both at 4°C and room temperature, before release studies were initiated. Data from stored implants demonstrated trehalose not to be effective to provide full protein stabilization during long-term storage of the lipid matrices, this was apparent from both the reduced total drug level liberated and the release of aggregated specimen compared to the situation immediately after implant manufacture. In contrast, hydroxypropyl-β-cyclodextrin (HP-β-CD) exhibited a high potential for protein stabilization within the matrices during both storage and release. Generally, 95% of the incorporated protein was delivered continuously within 1 month in monomeric form, even after 6 months' storage of the implants at room temperature.