In-situ forming solvent-induced phase inversion (SIPI) implants for controlled drug delivery: Role of hydrophilic polymers

Abstract

In recent years, there has been a surge of research focused on in situ-forming implants as a method of localized drug delivery. Despite advancements, the predominant challenge in situ-forming solvent-induced phase inversion (SIPI) implants is significant burst release which typically occurs within the first 24 h post-administration. Another notable challenge is the real-time characterization of these implants, which is crucial for understanding their in situ formation and degradation mechanism. This study explores the impact of various hydrophilic polymers—hydroxypropyl methylcellulose (HPMC), hydroxypropyl cellulose (HPC), Carbopol, and carboxymethylcellulose (CMC) - on implant formation and drug release. SIPI systems, which are commonly composed of poly(lactic-co-glycolic acid) (PLGA) and N-methyl pyrrolidone (NMP), offer localized, controlled drug release but suffer from an initial burst within 24 h post-administration. The incorporation of hydrophilic polymers aims to modulate this release and improve implant properties. For first-time, optical coherence tomography (OCT) imaging was employed for non-invasive assessment of the rate of in situ phase inversion and the resulting implant morphology, whereas scanning electron microscopy (SEM) and digital microscopy provided further insights into the internal structure of the implants. The results demonstrated that the inclusion of polymers such as HPMC and Carbopol effectively reduced burst release, whereas polymers such as HPC and CMC exhibited faster phase inversion, resulting in a more porous implant morphology and greater burst release. Additionally, the mechanical properties and mucoadhesive capabilities of the formulations were tested, suggesting that Carbopol-enhanced implants are particularly suitable for applications requiring prolonged retention at mucosal sites. This investigation provides critical insights into the design and optimization of SIPI systems for drug delivery.