Characteristics of lipid micro- and nanoparticles based on supercritical formation for potential pharmaceutical application

Abstract

The interest of the pharmaceutical industry in lipid drug delivery systems due to their prolonged release profile, biocompatibility, reduction of side effects, and so on is already known. However, conventional methods of preparation of these structures for their use and production in the pharmaceutical industry are difficult since these methods are usually multi-step and involve high amount of organic solvent. Furthermore, some processes need extreme conditions, which can lead to an increase of heterogeneity of particle size and degradation of the drug. An alternative for drug delivery system production is the utilization of supercritical fluid technique. Lipid particles produced by supercritical fluid have shown different physicochemical properties in comparison to lipid particles produced by classical methods. Such particles have shown more physical stability and narrower size distribution. So, in this paper, a critical overview of supercritical fluid-based processes for the production of lipid micro- and nanoparticles is given and the most important characteristics of each process are highlighted.

Figure 1

Schematic representation of the apparatus utilized by Frederiksen et al. [27]. Composed of a (I) CO₂ pump, (II) modifier pump, (III) high-pressure recycling pump, (IV, 4) pulse dampener capillary, (V) low-pressure recycling pump, (1) CO₂ cylinder, (2) cooling device, (3, 11) manometer, (5) waste flask, (6) measuring cylinder, (7) pump T-piece, (9) dynamic mixer, (10) filter, (12, 20, 24) T-piece, (13) cartridge guard column, (14) UV detector, (15) Plexiglas water bath, (16) high-pressure recycling system, (17) pressuring transducer, (18) back-pressure regulator, (19) pressure controller, (21) checking valve, (23) encapsulation capillary, (25) static mixer, (26) liposomal suspension reservoir, (27) low-pressure recycling system, and (28) fume cupboard to remove CO₂; a, b, c, d, e, f, g, h, i, k, j, l, m, n, and o are valves.

Figure 2

Schematic representation of the RESS apparatus used by Wen et al. [28]to produce liposomes. In this apparatus, the following are found: (1) CO₂ cylinder, (2) heat exchanger, (3) refrigerating machine, (4, 8) syringe pump, (5) reactor, (6) coaxial injector, (7) collector, (9) storage tank, (10) rotameter, and (11) volumetric cylinder.

Figure 3

Apparatus utilized for DESAM process developed by Meure et al. [29].

Figure 4

Representation of the SEDS process apparatus utilized by Li et al. [31].

Figure 5

The SAS apparatus utilized for the production of liposomes[35].

Figure 6

Schematic representation of the CAS apparatus utilized by Lesoin et al.[40]. In this apparatus, the following are found: (1) cooler, (2) volumetric pump, (3) heater, (4) flow indicator transmitter, (5) temperature indicator, (6) back-pressure valve, (7) safety valve, (8) release valves, (9) stirring, (10) control valve, and (11) dryer.

Figure 7

Schematic representation of the scRPE apparatus.

Figure 8

Schematic representation of the coating process developed by Ribeiro dos Santos et al.[58]. (A) Filling step: BSA crystals (white) and lipid material (black). (B) Solubilization of lipid in scCO₂ with dispersion of insoluble BSA crystals. (C) Decompression phase with lipid deposition on BSA. (D) Coated particles are obtained.

Figure 9

Extraction system used in the SFEE process developed by Chattopadhyay et al.[59].

Figure 10

The supercritical co-injection process. (Left) Schematic representation of the supercritical co-injection process: (1) CO₂cylinder, (2) cooler, (3) pump, (4) heater, (5) saturation vessel, (6) high-pressure vessel, (7) valve, (8) pneumatic conveying, (9) co-injection advice, (10) gas/solid separation filter, (PI) pressure indicator, (PIC) pressure indicator and controller, (TIC) temperature indicator and controller, and (VENT) Venturi. (Right) The co-injection device [60].

Figure 11

Example of PGSS plant for particle formation for drug-loaded particles [46].

Figure 12

Different results obtained under different operation conditions in a PGSS method for production of PEG-600 particles. Adapted from Kappler et al. [95].

Figure 13

Schematic of the modified PGSS apparatus adapted from Vezzù et al. [71]. MO, electric motor; AM, stirrer; MC, mixing chamber; U, nozzle; CE, expansion chamber; F, filter; R1 to R4, electric resistances; SC, heater exchanger; P1, pump; P2, manual syringe pump; V1 to V6, on-off valves; PR, pressure reducer; C, air compressor; D, synthetic air or nitrogen cylinder; TIC, temperature indicator and controller.