Controlled initial surge despite high drug fraction and high solubility

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Polymer Chemistry

Background:

• Poly (d, l-lactide-co-glycolide) (PLGA) is widely used for controlled drug release.
• Understanding factors affecting drug release kinetics is crucial for effective drug delivery.
• Tetracycline hydrochloride is an important antibiotic with potential for controlled release applications.

Purpose of the Study:

• To investigate the relationship between polymer chemistry, solvent evaporation rate, and the release profile of tetracycline hydrochloride from PLGA films.
• To elucidate how these factors influence drug release, particularly at high drug loading.
• To identify parameters that can be manipulated to control the early stage of drug release.

Main Methods:

• Preparation of poly (d, l-lactide-co-glycolide) (PLGA) films with varying lactic acid content (50:50 and 85:15) and high drug fractions (50%, 30%, 15%) of tetracycline hydrochloride.
• Fabrication of films using two distinct solvent evaporation rates.
• Analysis of early release rates and release profiles under different conditions.
• Evaluation of surface characteristics related to drug distribution.

Main Results:

• At high tetracycline concentrations (50%), early release rates were generally low (≤0.5 μg/min).
• Release profiles varied: linear for lower lactic content/slower evaporation, bimodal for higher lactic content/faster evaporation.
• Polymer chemistry and evaporation rate significantly altered surface drug distribution and early release, especially for 50:50 PLGA at slower evaporation rates, leading to reduced release.

Conclusions:

• The interplay between polymer chemistry and solvent evaporation rate critically determines the microstructure and early release characteristics of high-drug-loaded PLGA systems.
• These parameters offer a means to modulate and control the initial drug release phase.
• Tailoring PLGA composition and processing conditions is key for optimizing tetracycline hydrochloride delivery.