(T1530-10-54) Development of Hot-Melt Extruded Implants Using Polycaprolactone as a Biodegradable Polymer

Purpose: Implantable drug delivery systems ensure patient compliance and enable controlled drug delivery over an extended period. The present study is intended to check the applicability of polycaprolactone (PCL) to develop biodegradable controlled release implants using various model drugs. PCL is chosen as a biodegradable polymer to prepare controlled and extended release implants because of its slower rate of biodegradation, great biocompatibility, non-toxicity, relatively low cost, and considerably lower melting and glass transition points, which favor easy processability, good stability at high processing temperatures.

Methods: The PCL implants were prepared using an 11 mm twin-screw corotating extruder (Process 11™, Thermo Fisher Scientific). The extruder consisted of 1 discharge zone, 3 mixing zones, 4 conveying zones, and 1 feeding zone. The physical mixture of drug and polymer is subjected to cryomilling to overcome the content uniformity issues. This cryomilled mixture was passed through the extruder at 25 rpm at different processing temperatures based on the API (Table 1). Following extrusion, the resulting filaments were allowed to cool before being cut to lengths determined by the drug loadings and subjected to physical characterization and in-vitro drug release studies.

Results: From the preliminary studies and previous experience, 30% and 50% of drug loaded PCL implants were extruded. Scanning Electron Microscopy revealed the smooth surface of the implants (Figure 1). FTIR and DSC studies revealed that there was no chemical interaction between polymers and the drug, and the drug was completely dispersed into the polymer. From the in-vitro drug release studies (Figure 2), PCL can produce the controlled release for a prolonged time for both drugs. With 50% PCL, both drugs exhibited not more than 60% cumulative drug release. Hence, future formulations are planned to reduce the PCL and combine it with other polymers to increase drug release.

Conclusion: In conclusion, developing hot-melt extruded implants using PCL as a biodegradable polymer could be vital to gain extended drug release in a controlled manner. By providing sustained release over an extended period may mitigate the clinical inconveniences and potential patient non-compliance resulting from daily drug administration.

References:
1. Muhindo D, Ashour EA, Almutairi M, Repka MA. Development and evaluation of raloxifene hydrochloride-loaded subdermal implants using hot-melt extrusion technology. International Journal of Pharmaceutics. 2022 Jun 25;622:121834.
2. Fan R, Chuan D, Hou H, Chen H, Xu J, Guo G. Development and evaluation of a novel biodegradable implants with excellent inflammatory response suppression effect by hot-melt extrusion. European Journal of Pharmaceutical Sciences. 2021 Nov 1;166:105981.

Table 1: Formulation of PCL implants

Figure 1. Surface morphology by SEM studies

Figure 2. Drug release profiles of PCL implants