Aspirin-Loaded Polymeric Films for Drug Delivery Systems: Comparison between Soaking and Supercritical CO2 Impregnation

Abstract

Polymeric implants loaded with drugs can overcome the disadvantages of oral or injection drug administration and deliver the drug locally. Several methods can load drugs into polymers. Herein, soaking and supercritical CO2 (scCO2) impregnation methods were employed to load aspirin into poly(l-lactic acid) (PLLA) and linear low-density polyethylene (LLDPE). Higher drug loadings (DL) were achieved with scCO2 impregnation compared to soaking and in a shorter time (3.4 ± 0.8 vs. 1.3 ± 0.4% for PLLA; and 0.4 ± 0.5 vs. 0.6 ± 0.5% for LLDPE), due to the higher swelling capacity of CO2. The higher affinity of aspirin explained the higher DL in PLLA than in LLDPE. Residual solvent was detected in LLDPE prepared by soaking, but within the FDA concentration limits. The solvents used in both methods acted as plasticizers and increased PLLA crystallinity. PLLA impregnated with aspirin exhibited faster hydrolysis in vitro due to the catalytic effect of aspirin. Finally, PLLA impregnated by soaking showed a burst release because of aspirin crystals on the PLLA surface, and released 100% of aspirin within 60 days, whereas the PLLA prepared with scCO2 released 60% after 74 days by diffusion and PLLA erosion. Hence, the scCO2 impregnation method is adequate for higher aspirin loadings and prolonged drug release.

Screening of the Supercritical Impregnation of Olea europaea Leaves Extract into Filaments of Thermoplastic Polyurethane (TPU) and Polylactic Acid (PLA) Intended for Biomedical Applications

“…They observed an increase in the swelling degree at higher pressures and temperatures as a result of the higher scCO 2 density and solvent diffusivity. Coutinho et al measured a swelling degree of 14% for PLLA and 6% for LLDPE films using scCO 2 at 80 °C and 300 bar after 3 h. The differences were attributed to the presence of ester groups in PLLA that can interact with CO 2 , increasing the chain mobility and swelling [ 16 ].…”

“…PLA is a synthetic biopolymer belonging to the family of aliphatic polyesters that has been extensively used for the supercritical impregnation of bioactive compounds [ 12 ]. PLA foams have been employed for the supercritical impregnation of cinnamaldehyde [ 13 ], and thymol [ 14 , 15 ]; it was also employed for the loading of aspirin in film form [ 16 ] and as a particle it was used for nitrendipine [ 17 ], ketoprofen and carvone [ 18 ], diclofenac [ 19 ], dihydroquercetin and α-tocopheryl succinate [ 20 ].…”

Green Processing of Neat Poly(lactic acid) Using Carbon Dioxide under Elevated Pressure for Preparation of Advanced Materials: A Review (2012–2022)

“…This technique can improve polymer impregnation due to the low viscosity and good transport properties of sc-CO 2 as well as the high solvent power shown to organic molecules at moderate temperatures [ 4 , 126 ]. For instance, Trindade Coutinho et al [ 128 ] reported that the SSI process of 3 h enabled 2.6 times higher drug loading into PLA film compared with the conventional soaking method that lasted 10 days. An additional advantage of SSI is that the BCs’ load and distribution through a polymer matrix can be easily tuned by changing the process conditions [ 15 , 25 , 129 ].…”

“…PLA materials impregnated with BCs by sc-CO 2 can be used for the preparation of drug delivery systems [ 66 , 133 ]. For instance, PLA was impregnated with aspirin used as an anti-inflammatory drug [ 128 ], triflusal used in the prevention of cardiovascular events [ 66 ], and paclitaxel used in cancer therapy [ 124 ]. In addition, sc-CO 2 has been widely used for the preparation of bioactive medical devices such as intraocular lenses, sutures, and scaffolds for tissue engineering.…”

3D-Printed Alginate/Pectin-Based Patches Loaded with Olive Leaf Extracts for Wound Healing Applications: Development, Characterization and In Vitro Evaluation of Biological Properties

“…This parameter is highly useful since it indicates the type of release mechanism involved. For polymeric delivery systems characterized by a slab geometry, if n ≤ 0.5, a Fickian diffusion is observed, and this suggests that the drug diffuses through the hydrogel matrix [ 52 , 53 ]. In the other cases, if n = 1.0, the release is referred to as Case-II transport caused by system swelling, while if 0.5 < n < 1.0, the mechanism indicates an anomalous transport corresponding to a superposition of both diffusion and polymer relaxation.…”