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

IF 3.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

AAPS PharmSciTech Pub Date : 2024-12-17 DOI:10.1208/s12249-024-03004-4

Kshitij Chitnis, Nagarjuna Narala, Sateesh Kumar Vemula, Sagar Narala, Sivaram Munnangi, Michael A. Repka

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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.

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来源期刊

AAPS PharmSciTech 医学-药学

CiteScore

6.80

自引率

3.00%

发文量

264

审稿时长

2.4 months

期刊介绍： AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.