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. 2024 Dec 17;26(1):16.
doi: 10.1208/s12249-024-03004-4.

Formulation, Development, and Characterization of AMB-Based Subcutaneous Implants using PCL and PLGA via Hot-Melt Extrusion

Kshitij Chitnis  1 , Nagarjuna Narala  1 , Sateesh Kumar Vemula  1 , Sagar Narala  1 , Sivaram Munnangi  1 , Michael A Repka  2   3
Affiliations

Formulation, Development, and Characterization of AMB-Based Subcutaneous Implants using PCL and PLGA via Hot-Melt Extrusion

Kshitij Chitnis et al. AAPS PharmSciTech. .

Abstract

The hot-melt extrusion process is currently considered a prominent manufacturing technique in the pharmaceutical industry. The present study is intended to develop amlodipine besylate (AMB)-loaded subcutaneous implants to reduce the frequency of administration, thus improving patient compliance during hypertension management. AMB subcutaneous implants were prepared using continuous hot-melt extrusion technology using poly(caprolactone) and poly(lactic-co-glycolic acid) with dimensions of 3.70 cm (length) by 2.00 mm (diameter). The implants were characterized for thermal characteristics, drug-excipient incompatibilities, surface morphology, fracturability, in vitro drug release, and stability studies. Differential scanning calorimetry study confirmed the drug's crystalline state within the fabricated implants, while textural analysis demonstrated good fracturability in the lead formulation. Scanning electron microscopy revealed the smooth surface morphology of the lead subcutaneous implant. The lead formulation showed an extended drug release profile over 30 days (~ 2.25 mg per day) and followed zero-order release kinetics (R2 value to 0.9999) with a mean dissolution time of 14.96 days. The lead formulation remained stable for 30 days at accelerated stability conditions of 40°C and 75% relative humidity. In conclusion, developing hot-melt extruded implants could be an alternative to the conventional amlodipine besylate (AMB) formulation.

Keywords: Extended-release; Hot-melt extrusion; Subcutaneous implants; Textural analysis; Zero-order release kinetics.

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Conflict of interest statement

Declarations. Conflicts of Interest: The authors declare no conflicts of interest.

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