Optimization of Supercritical CO2-Assisted Atomization: Phase

Jan 22, 2018 - The lack of phase behavior data with respect to CO2-assisted ... in their review, developments in particle design using supercritical f...
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Review Cite This: J. Chem. Eng. Data XXXX, XXX, XXX−XXX

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Optimization of Supercritical CO2‑Assisted Atomization: Phase Behavior and Design of Experiments Clarinda Costa, Teresa Casimiro,* and Ana Aguiar-Ricardo* LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade NOVA de Lisboa, Caparica, 2829-516, Portugal ABSTRACT: The use of supercritical fluid technology applied to the production of particles by atomization is an area of increasing interest. A wide variety of supercritical atomization techniques have been described in the literature. They have something in common: the importance of phase behavior governing the scCO2-assisted processes. This minireview intends to provide a critical overview of the supercritical CO2−assisted atomization process (SAA), the different systems already reported in the literature, and discuss the importance of phase equilibria and other parameters in the process optimization and hence in the final properties of the engineered particles.

1. INTRODUCTION In the last decades, there has been an intensive investigation on atomization techniques assisted by supercritical fluids. In the literature, we can find an increasing number of papers and reviews devoted to this subject, which undoubtedly prove that supercritical fluid technology has high potential in atomization presenting advantages over traditional techniques. A variety of SCF-based atomization techniques and their variations are reported in the literature.1,2 RESS (rapid expansion of supercritical solutions), SAS (supercritical anti-solvent), PGSS (particles from gas-saturated solutions), CPF (concentrated powder form), CAN-BD (carbon dioxide assisted nebulization with a bubble dryer) and DELOS (depressurization of an expanded liquid organic solution) are examples of the many reported techniques, and many processes have already arrived to the commercial stage. The use of different supercritical-based atomization techniques solely depends on phase behavior, on the solubility of the materials to be atomized, in the supercritical medium, typically supercritical CO2. Therefore, CO2 can be used as solvent, antisolvent, or cosolute. RESS is the simplest technique for which CO2 is used as solvent. However, it has a huge limitation which is precisely the lack of solubility of most materials in scCO2. For example, the solubility in mole fraction of most pharmaceutical drugs in scCO2 ranges from 10−7 to 10−3, with ibuprofen being one of the most soluble ones at 10−3.3 This lack of solubility has hampered the applicability of this technique to an industrial scale. When CO2 works as an antisolvent or cosolute typically more complex systems are involved, at least a ternary system such as CO2 + liquid solvent + material to atomize. In the case of SAS, a very well-known and established technique, the scCO2 works as antisolvent. The compound to be micronized is © XXXX American Chemical Society

dissolved in an appropriate solvent which is soluble in the scCO2. When the supercritical fluid is introduced the initial solvating capacity of the solvent is drastically reduced and the compound precipitates. In 2001, Reverchon patented a process for the production of microparticles and nanoparticles called supercritical assisted atomization (SAA).4 This process is indeed very similar to conventional spray-drying but assisted by scCO2, that is, a supercritical CO2-assisted spray drying (SASD) process that takes advantage of CO2 as cosolute dissolved in the liquid solution.5 Briefly a solution containing the substance to be atomized is mixed with a supercritical CO2 stream in a saturator which then passes through a nozzle where it is atomized, and instantly the droplets produced are dried by a hot air/nitrogen flow. A feature of all the above-mentioned micronization techniques is the requirement to bring about the atomization of multicomponent systems whose phase equilibria may be complex. The phase behavior of these systems is not easy to describe, nor is its interpretation or the assessment of its impact on the final particles’ properties. Nevertheless, this information is fundamental for the SAA/SASD process optimization to set the operating conditions in the saturator before the atomization step. While there has been an increasing number of published works, there is no following trend of papers studying the phase behavior of the systems involved in the atomization processes. While the binary systems CO2 + solvent, and ternary systems Special Issue: In Honor of Cor Peters Received: September 14, 2017 Accepted: January 8, 2018

A

DOI: 10.1021/acs.jced.7b00820 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Review

Figure 1. Schematic of the supercritical CO2-assisted spray drying (SASD) apparatus at NOVA’s laboratory: (1) HPLC pump; (2) temperature controller; (3) container with liquid solution; (4) saturator; (5) precipitator; (6) manometer; (7) high efficient cyclone.

CO2 + solvent + cosolvent are typically available in the literature, very limited data are available for the multicomponent systems involved in the real processes, where the content of the compound(s) to be atomized in the liquid solution can have a deep influence in the phase behavior. Works such as the one of Cor Peters and co-workers on the phase behavior determination of a ternary system of interest for a SAS process are scarce in the literature.6 In their paper, they have studied the system CO2 + methanol + prednisolone, a steroid that works as an immunosuppressant drug. These authors also pointed out in their paper, the serious lack of experimental data on the phase behavior of systems involved in this type of micronization techniques for process optimization. Their work reinforces the importance of having accurate information on phase equilibria to identify the phase diagram regions where the process works. Equations of state also play an important role since they are able to correlate and predict very accurately phase behavior data at conditions not experimentally measured.7 Excellent agreements have been found between the experimental and the predicted values of the bubble and dew points of the ternary systems. This modeling approach can reduce significantly the experimental effort to obtain the best VLE conditions in the saturator. The lack of phase behavior data with respect to CO2-assisted atomization processes means that trial-and-error approaches are typically used to identify the best operational conditions to obtain the desired particles.

The main improvements were the use of a saturator loaded with stainless steel perforated saddles instead of a micrometric volume tee and the elimination of the capillary tube to avoid the problem of pressure drop and possible capillary blockage of the CAN process. The phase equilibria include the solubilization of the scCO2 phase in the liquid solution. A near equilibrium solution is formed before depressurization thus leading to a much better control on nucleation within the droplets, and thus the formation of spherical microparticles is more easily achieved by SAA than by SAS.10 A schematic of a laboratory scale SASD system is shown in Figure 1. The resulting near equilibrium mixture outflowing from the saturator/static mixer is then atomized through the nozzle to the precipitation chamber. A N2/air heated flow from the top of the vessel dries the atomized particles that are collected after the high efficiency cyclone. A very precise control of the operation conditions assures the high efficiency and reproducibility of the micronization process. At least a ternary system is used comprising the CO2, solvent and material to be atomized, but much more complex systems are in reality atomized when nano- and microengineered particle dry powders are produced.11 The solubilization of scCO2 in the liquid solution, promoted in the saturator, is one of the key steps controlling the efficiency of the supercritical assisted atomization process.12 This solubility is governed by the p,T conditions at the saturator, and the system involved. Here the ratio between the CO2 flow and the liquid flow plays a key role in the vapor liquid equilibrium (VLE) of the CO2/solvent/solute(s) system. To take fully advantage of the technology, the operating point should fall in the one-phase liquid region, when all the CO2 is dissolved in the liquid solution, that would be ideal to boost the efficiency of the decompressive atomization. Since 2001, when the process was patented by Reverchon,4 many materials have been atomized using this technology. In 2003, Shariati and Peters13 reported in their review, developments in particle design using supercritical fluids. At that date,

2. SUPERCRITICAL CO2-ASSISTED ATOMIZATION/SPRAY-DRYING SAA/SASD takes advantage of the solubility of scCO2 into the liquid flow which is performed in a saturator which promotes the efficient contact between the solution containing the material to micronize and the scCO2 phase. The SAA process is in fact an improvement of the CAN-BD process patented in 1997 by Sievers and co-workers,8 and of the PGSS technique patented by Weidner and coauthors in 1994.9 B

DOI: 10.1021/acs.jced.7b00820 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

C

50% (v/v) ethanol aqueous solution ethanol methanol acetone water

water

Chitosan oligomers

α-cyclodextrin

Cromolyn sodium

Cholesterol

water

Chitosan hydrochloride

Chitosan

Chitosan

1% acetic acid aqueous solution 50% (v/v) ethanol aqueous solution 1% v/v acetic acid aqueous solution

water−ethanol

Cefadroxil

Chitosan

water

buffered water (pH 7) methanol ethanol methanol acetone acetone−water (9% v/v) methanol− water (4% v/ v) water

solvent

Bovine Serum Albumin

Bovine Serum Albumin

Beclomethasone dipropionate (BDP)

Ampicillin

system/compounds

1.8/75−150/70−90

1.8/90/85

1.0−2.4/60−100/40−80

1.2−1.8/85−113/70

1.0−2.4/80/40−90

1.2−1.8/85−120/50−90

1.0−2.4/80/40−90

1.8/80−150/70−90

n.a./ 60−140/50−70

1.0−1.4/80/60

2.0/90−120/50

1.8/90/80 1.3−1.8/80/90 1.2−2.0/80−83/82

1.8/120/90

Rb/ p(bar)/ T(°C)

nozzle (μm)

Tprecipitation Csolute

packed contactor

packed contactor

HCM

Csolute Tsaturator Psaturator Tprecipitation

Tprecipitation Csolute

packed contactor

Cpolymer Tsaturator RCO2/liquid flow

HCM

HCM

Csolute Tsaturator Psaturator Tprecipitation RCO2/liquid flow

Tsaturator Psaturator Tprecipitation RCO2/liquid flow

packed contactor

Cpolymer Tsaturator RCO2/liquid flow

mixing vessel

Tsaturator Psaturator Csolute Solution feed rate

packed contactor

packed contactor

Tprecipitation RCO2/liquid flow

Tprecipitation Csolute

80

HCM

Psaturator Tprecipitation Csolute

thin wall 80 or 100 80

200

thin wall 200

130

thin wall 200

130

80

n.a.

200

packed contactor

180

Single Component packed contactor 80 and 100

homogenizerc

Liquid solvent mixture

Influence of the solvent RCO2/liquid flow Csolute dnozzle

studied parameters

Table 1. SAA/SASD Works Reported in the Literature from 2002 to 2017a

n.a.

n.a.

n.a.

n.a.

80%

n.a.

80%

95%

n.a.

n.a.

n.a.

56%

n.a.

yield

SAA-HCM could be a promising technique to micronize bioactive macromolecules Vacuum system implemented possibilities to operate at lower temperatures The most effective parameters were pressure in the mixer and the feed solution concentration A CHT-drug composite was micronized Micrometric chitosan particles produced can be used as drug carriers The micronization of chitosan with different MWs via SAA-HCM technique was successful The presence of ethanol enhances the second atomization The SAA-HCM can be applied to the successful micronization of chi-tosan oligomers The interaction between alcohols and scCO2 is weaker than acetone and scCO2 Particles suitable for aerosol delivery Amorphous particles were obtained whereas raw αCD was crystalline

hollow spherical θ 0.3−5 μm

mass-weighted mean size 0.223−0.515 μm

distinct morphology θ 0.2−5.0 μm

spherical dv: 1−5 μm spherical θ 0.1−5 μm

spherical/plate-like θ 0.2−2.5 μm

spherical θ 0.5−3.0 μm

mean particle size 0.21−0.40 μm

spherical θ 0.1−1.5 μm

concave particles 5< 3 μm

spherical θ 1.0 μm

Reproduction of laboratory results on a pilot scale

SAA produced particles suitable for aerosol

outputs

crystalline particles θ 0.2−4.7 μm (acetone−water)

spherical θ 0.5−5 μm

particle morphology

2006

2007

2012

2014

2015

2014

2015

2006

2009

2011

2011

2010

2003

year

12

24

10

23

22

21

20

19

18

17

16

15

14

ref.

Journal of Chemical & Engineering Data Review

DOI: 10.1021/acs.jced.7b00820 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

1.8/95/70

ethanol

methanol

water acidic and alkaline solution methanol

Ginkgo flavonoids

HMR1031 (Antiasthma drug) Insulin

water

water

acetone ethanol iso-propanol acetone

Lysozyme

NaCl, KI, NH4Cl

Palmitoyl-ethanolamide

D

acetone

acetone

chloroform

PEG 10000

Pigment red 60

PLA−PEG copolymer

PEG 6000

Lysozyme

water buffered water (pH 6.2) water−ethanol aqueous solution

Lysozyme

Levofloxacin hydrochloride

1.8/70−90/70−90

acetone

Griseofulvin

1.8/90/80

0.9−1.8/76/40−80

3.5/67/40

3.5/67/40

1.0−3.5/70−92/55−80

1.8/100−120/65−95

0.9−2.2/85−125/40−120

0.84/250/150

1.8/104−114/84

0.9−2.2/95−125/40−120

1.5−2.3/80−120/40−80

1.2−1.9/70−90/70−90

0.9−1.6/80−90/40−85

methanol

Dexamethasone Dexamethasone acetate

1.8/75−150/70−90

Rb/ p(bar)/ T(°C)

water

solvent

Hydroxypropyl-β-cyclodextrin

system/compounds

Table 1. continued

RCO2/liquid flow Tprecipitation Csolute Relative content of copolymers

80

200

packed contactor packed contactor

80

80

thinwall 100 thin wall 80

thin wall 200

120

80

packed contactor

packed contactor

Csolute Tprecipitation Csolute Tprecipitation

packed contactor

packed contactor

Tprecipitation Csolute n.a.

HCM

packed contactor

Cenzyme Liquid solvent mixture

Csolute Tsaturator Psaturator Tprecipitation

hydrodynamic cavitation mixer (HCM)

Csolute RCO2/liquid flow

mixer

200

HCM

Dissolution method Csolute Tprecipitation

n.a.

thin wall 200

packed contactor

Tprecipitation Csolute dnozzle 100

HCM

thinwall 80 200

packed contactor

spherical θ 0.25−0.45 μm

quasi-spherical crystals θ 0.5−2.5 μm

≥95% n.a.

spherical θ 1.95−3.32 μm

spherical θ 1.0−1.5 μm

quasi-spherical θ 2−5 μm

well-defined cubic crystals

spherical θ 0.2−5.0 μm

⌀ 1−3 μm

spherical θ 0.1−4.0 μm

spherical θ < 2 μm

distinct morphology θ 1.4−2.7 μm

The reduced pressure produce microparticles with low glass transition temperature

It was difficult to control Palmitoyl-ethanolamide tendency to crystallize. Production of PEG microparticles under reduced pressure The use of atmospheric pressure and at low temperatures was successful in avoiding particles coalescence phenomena. Comparison between SAS and SAA processes

The heated airflow decreases the probabilities of particles agglomeration. SAA-HCM exhibits advantages in maintaining the bioactivity of lysozyme Mechanism of crystal formation was proposed

SAA-HCM was expected to be a promising technique for producing microparticles The successful use of mixtures H2O/EtOH further broadens the possibilities of application of SAA

Improved drug absorption in the body SAA was proposed to micronize antiasthma drugs SAA−HCM allows the control of morphology and size of insulin microparticles

spherical θ 0.2−3 μm spherical θ 1−3 μm

SAA presented advantages over conventional jet-mill

Production of micronized drug/CD complexes using SAA Drug performance improved

outputs

spherical θ 0.5−2.5 μm

spherical θ 0.5−1.2 μm

spherical θ < 5 μm

particle morphology

n.a.

n.a.

n.a.

n.a.

94.5%

n.a.

70−83%

n.a.

83−95%

n.a.

n.a.

95%

95%

100

packed contactor

yield n.a.

nozzle (μm)

Single Component packed contactor 80

homogenizerc

Csolute RCO2/liquid flow

Csolute RCO2/liquid flow Liquid solvent Tprecipitation Csolute

Tprecipitation Csolute

studied parameters

2012

2005

2012

2012

2015

2004

2011

2010

2009

2008

2013

2005

2010

2004

2006

2006

year

38

37

36

36

35

34

33

32

31

30

29

28

27

26

25

12

ref.

Journal of Chemical & Engineering Data Review

DOI: 10.1021/acs.jced.7b00820 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

E

water

water

Lincomycin hydrochloride

water water−ethanol

Sodium cellulose sulfate

Gentamicin sulfate

water

methanol methanol

Rifampicin Rifampicin

Yttrium acetate

water−acetone

Polyvinylpyrrolidone

water

acetone

Poly(methyl methacrylate)

Zyrconil nitrate hydrate

acetone

Poly(methyl methacrylate)

water aqueous solution

chloroform

Poly-L-lactide

Tetracycline Trypsin

acetone

solvent

Poly-L-lactide

system/compounds

Table 1. continued

1.8/96−110/83−86

1.8/100−105/80−90

0.7−2.0/80−115/60−80

1.8/110/80

1.8/80−150/80

1.8/97/85 0.55/260/160

1.8/94/80 1.8/80/80

1.8/70−165/40−85

0.8−2.8/65/40−90

0.9−1.6/70−90/70−90

1.0−1.4/80/100

1.2−2.0/80/80

Rb/ p(bar)/ T(°C)

nozzle (μm)

packed contactor

n.a.

n.a.

Production of protein- pharmaceutical composites

spherical θ 0.3−3.0 μm

High drug content encapsulation efficiency The microspheres showed a controlled release of the drug over about 6 days

SAA technique was proposed

spherical θ 1−2.0 μm

spherical θ 1.0−2.0 μm

spherical θ 0.32−0.77 μm

spherical θ 0.5−1.2 μm ⌀ 1−3 μm

No chemical degradation A modification was proposed: heated airflow directed counter the spray torch SAA was a flexible and easily scalable process

No chemical degradation SAA was a flexible and easily scalable process

spherical θ 0.5−3 μm spherical θ 0.3−0.4 μm

spherical θ 0.5−2.12 μm

Lower concentrations of polymer and higher saturator temperatures contributes for the decrease of the particle size. When ethanol is used as solvent, smallest particles are produced

spherical θ 0.82−0.176 μm

doughnut-like spheres θ 0.05−1.6 μm

The vacuum system is more efficient when an organic solvent was used, with respect to water. Microparticles showed a depen-dence on the R.

spherical θ 1.0−1.5 μm

Rprotein/drug

n.a. n.a.

n.a. 91%

n.a.

n.a.

n.a.

n.a.

Valid alternative to conventional processes

outputs

doughnut-like spheres θ 0.1−3.5 μm

particle morphology

spherical θ 1.3−2.5 μm

packed contactor

Csolute

thin wall 60, 40 and 80 100 80 (lab scale) 200 (pilot scale) 80 120

130

80

80

n.a.

yield

80 (lab 91% scale) 200 (pilot scale) n.a. Csolute dnozzle Liquid solvent packed contactor 80 and 100 Tsaturator Psaturator Csolute HCM thin90% wall RCO2/liquid flow 200 Bovine Serum Albumin as Excipient Single Component packed contactor 80 n.a. RBSA/drug

saturator mixer

Csolute n.a.

saturator packed contactor

Csolute Csolute

packed contactor

Tprecipitation Tsaturator Spray angle of nozzle

packed contactor

packed contactor

Tprecipitation Csolute RCO2/liquid flow

Solvent

packed contactor

Single Component packed contactor 80

homogenizerc

Tprecipitation RCO2/liquid flow

Tprecipitation Csolute RCO2/liquid flow

studied parameters

2017

2010

2010

2002

2005

2003 2010

2003 2005

2015

2011

2007

2011

2007

year

47

46

45

44

43

42 32

42 43

41

40

39

17

39

ref.

Journal of Chemical & Engineering Data Review

DOI: 10.1021/acs.jced.7b00820 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

1% acetic acid aqueous solution 1% acetic acid aqueous solution with 18.6% (v/v) of ethanol 50% (v/v) aqueous ethanol water

water 1% v/v acetic acid and 1 mm HCL aqueous solutions

Ampicillin trihydrate

Trypsin

F

Salmon calcitonin+ Trehalose/Inulin

Poly(methyl methacrylate)- coethyl methacrylatee POxylated AuNPs

ethanol: water (8:2)

1% acid water 18.6% (v/v) of ethanol

1% v/v acetic acid aqueous solution 1% v/v acetic acid aqueous solution acetone

Fe3O4 NPs+ Tween 80

Hydroxyapatite+ Tween 80

1% acidic water and ethanol (3:2)

Ibuprofen+ POxylated strawberry-like partially Fe@AuNPs

Insulinf

Indomethacine

Ibuprofen

solvent

system/compounds

Table 1. continued

6.0/85/40

Powder aerosolization characteristics Cumulative release profile of the nanoparticles Enzymatic degradation Kind of absorption enhancers and stabilizers

Csolute Tsaturator RCO2/liquid flow

0.8−2.8/65/40−90

7.14- 12.5/100/70

Cpolymer Chydroxyapatite Tprecipitation RCO2/liquid f low

mixer chamber loaded with glass beads

static-mixer

packed contactor

packed contactor

100

150

130

80

Design of experiments was applied on SAA process

The crystal form of Indomethacin was altered The particle morphology was influenced by polymer/ protein ratio SAA-HCM process was demonstrated to be a promising technique for production of labile protein microparticles

dv,50d 2.1−2.4 μm

⌀ 0.516−1.0 μm spherical θ 1−5 μm

n.a.

spherical θ 0.47−0.50 μm

Approach to an improvement of nasal absorption of biopharmaceuticals

The extremely fast process of SAA minimizes the possibility of degradation by heat

aerodynamic size 3.2−3.8 μm

⌀d 0.09−0.17 μm ⌀e 0.17−0.26 μm 80%a 70%b 57−75%

spherical θ 0.6 μm

spherical θ 1.2−2 μm

System candidate for pulmonary administration of therapeutic agents for local cancer theragnosis Encapsulation of nanoin microparticles suitable for biomedical applications The surface roughness can improve the NPs linkage with the human bone Primary nucleation was found dominant in the process

aerodynamic size 2.6−2.8 μm

noncoalescing spherical θ 0.2−3 μm

Successful polymer/drug coprecipitates

outputs

spherical θ 0.1−6 μm

particle morphology

n.a.

n.a.

thin wall 80

packed contactor

n.a.

n.a.

80%

n.a.

38

thin wall 200

n.a.

n.a.

150

95%

yield

Multicomponent static-mixer 150

HCM

MWpolymer Rpolymer/protein Csolution

saturator

static mixer

HCM

Powder aerosolization characteristics Cumulative release profile of the nanoparticles Csolute Csurfactant Tsaturator Psaturator Kind of polymer

nozzle (μm)

Chitosan as Excipient Single Component packed contactor 80

homogenizerc

Csolute Tsaturator Psaturator Cdrug RCO2/liquid flow

Rpolymer/drug

Cdrug RCO2/liquid flow Tprecipitation

Rpolymer/drug

studied parameters

1.5−2.5/90/80

1.8/95/85

7.14- 12.5/90−110/70

1.8/95/50−70

1.5−2.1/80−120/50−90

n.a./ 80/40−90

5.3- 8.9/100/60−80

1.8/105/85

Rb/ p(bar)/ T(°C)

2015

2017

2014

2013

2012

2017

2015

2016

2016

2016

2007

year

57

11

56

55

54

53

52

51

50

49

48

ref.

Journal of Chemical & Engineering Data Review

DOI: 10.1021/acs.jced.7b00820 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

G

ethanol

ethanol

Curcumin (CUR)

Dexamethasone

ethyl-acetate

1-monoacyl-glycerol

ethanol+ water

Phenolic compounds

acetone

buffer solution

Ampicillin trihydrate

Rifampicin

70:30 (%v/v) water+ ethanol

Luteolin+ FITC

acetone

water

Fe3O4 NPs+ Tween 80

Rotenoneh

ethanol: water (8:2)

solvent

Salmon calcitonin+ Trehalose/Inulin

system/compounds

Table 1. continued

1.8/76/40

0.8−1.8/93−99/80

n.a./ 110/80

0.7/85/80

3/81/40

n.a./ n.a./ 75

1.8/80−150/70−90

1.8/92/85

1.8/88−125/83−87

6.0/85/40

Rb/ p(bar)/ T(°C)

Rpolymer/drug

Rpolymer/drug

Rpolymer/lipid Emulsion method

Rpolymer/drug

Rpolymer/rotenone

Maltodextrin amount Rmaltodextrin/TSEg Tprecipitation

Rpolymer/drug

Kind of absorption enhancers and stabilizers

n.a.

packed contactor

80

n.a.

Poly(vinylpyrrolidone) as Excipient Single Component packed contactor thin wall n.a. 80

Poly(vinyl alcohol) as Excipient Single Component packed contactor thin wall n.a. 80

Polyethylenoglycol as Excipient Single Component packed contactor thin wall n.a. 80 Poly-L-lactide as Excipient Single Component packed contactor 80 n.a.

Hydroxypropyl Cellulose as Excipient Single Component packed contactor thin wall 95% 80 Maltodextrin as Excipient Single Component packed contactor 80 65.3%

thin wall 80

packed contactor

yield

Csolute Rdrug/polymer

nozzle (μm)

Csolute Csurfactant Tsaturator Psaturator Kind of polymer

homogenizerc β-Cyclodextrin as Excipient Multicomponent mixer chamber 100 n.a. loaded with glass beads Dextran as Excipient Multicomponent packed contactor thin wall n.a. 80

studied parameters

Dextran 60 demonstrated to be unsuccessful for the encapsulation. Production of fluorescent microparticles for cells drug delivery and imaging carriers

spherical θ 1.2−2 μm

spherical θ 0.8−1 μm

⌀ 0.24−0.38 μm

Best dissolution rate of curcumin particles produced by SAA then the physical mixture SAA process was very efficient in the micronization of drug-PVP composite particles

Production of microparticles of hydrophobic APIs and hydrophilic polymeric carriers

Preparation of smooth and sphe-rical composites

spherical θ 0.123−0.148 μm

spherical θ 0.5−3 μm

Very high encapsulation efficiency

Efficient encapsulation of natural bioactive compounds at relatively low temperatures

⌀ 0.712 μm

spherical θ 1.5 μm

Production of drug/polymer composite materials

spherical or doughnut-like θ 0.05−5.2 μm

noncoalescing spherical