Nanocarrier manufacturing

Patent metadata

Field	Value
Publication number	US-12491482-B2
Application number	US-202319109456-A
Country	US
Kind code	B2
Filing date	Sep 1, 2023
Priority date	Sep 8, 2022
Publication date	Dec 9, 2025
Grant date	Dec 9, 2025

Abstract

Present invention relates to an apparatus ( 0 ) for producing nanocarriers and/or nanoformulation and a process for producing a nanocarrier and/or a nanoformulation by means of this apparatus ( 0 ). According to inventive preparation, a first liquid phase (A) and the second liquid phase (B) are mixed first to give the primary mixture (A+B) by means of a static mixer ( 4 ). In a subsequence mixing step primary mixture (A+B) is diluted with a third liquid (C). An important aspect of apparatus ( 0 ) is the arrangement of the static mixer ( 4 ) inside a linear pipe ( 7 ) conducting third liquid phase (C). Thus, the primary mixture (A+B) exiting the mixer ( 4 ) is instantaneously diluted with (C) to give secondary mixture (A+B+C). The volume flow of the third mixture (C) is chosen larger than the volume flow of the primary mixture (A+B). By these measures, nanocarriers with improved morphology and homogeneity are produced. Encapsulation efficiency was enhanced as well.

First claim

The invention claimed is:

1 . An apparatus for producing a nanocarrier and/or a nanoformulation, the apparatus comprising:
a static mixer having a contacting section and downstream of contacting section, a helically twisted channel extends; a linear pipe, whereby at least a distal section of the static mixer is surrounded by the linear pipe; a longitudinal mixing section, whereby the static mixer and the linear pipe establish the longitudinal mixing section, which extends downstream from the static mixer inside the linear pipe up to an end of the linear pipe; a first inlet of the static mixer for accommodating a first liquid phase from a first reservoir vessel via a first feed; a second inlet of the static mixer for accommodating a second liquid phase from a second reservoir vessel via a second feed; an inlet of the linear pipe for accommodating a third liquid phase to the longitudinal mixing section from a third reservoir vessel via a third feed; the linear pipe forming at least a part of said third feed and said longitudinal mixing section; wherein the first inlet and second inlet are in fluid communication with the contacting section, the contacting section is receiving the first liquid phase and the second liquid phase in absence of the third phase, and whereby the static mixer is providing an at least biphasic primary mixture by mixing the first liquid phase with the second liquid phase in absence of the third phase; the longitudinal mixing section is providing an at least triphasic secondary mixture by mixing said primary mixture with said third liquid phase; a collection vessel for accommodating the secondary mixture; a conduct, by which the longitudinal mixing section is in fluid communication with the collection vessel; wherein at least a distal section of the static mixer is arranged inside said linear pipe, wherein the static mixer has a conical contacting section.

2 . The apparatus as claimed in claim 1 , wherein conical contacting section comprises a restrictor.

3 . The apparatus as claimed in claim 1 , wherein the linear pipe and the static mixer are arranged vertically.

4 . The apparatus as claimed in claim 1 , wherein the static mixer comprises the helically twisted channel having a rectangular cross section and/or a staggered arrangement of static mixing elements.

5 . The apparatus as claimed in claim 1 , characterized by two inlet ducts arranged in parallel inside of the static mixer.

6 . The apparatus as claimed in claim 1 , wherein the static mixer has an extended dwelling section at the distal end.

7 . The apparatus as claimed in claim 1 , wherein the static mixer has a pinhole aperture projecting into the direction of a central axis of the linear pipe, wherein the pinhole aperture marks a most-narrow constriction of the static mixer, wherein a diameter of the pinhole aperture is from 0.1 to 1 mm.

8 . The apparatus as claimed in claim 1 , wherein the collection vessel for accommodating the secondary mixture and the third reservoir vessel for accommodating the third liquid phase are designed as a combined vessel.

9 . The apparatus as claimed in claim 8 , wherein the combined vessel, the third feed, the longitudinal mixing section, and the conduct form a circle line including a circulating pump for circulating the secondary mixture.

10 . The apparatus as claimed in claim 1 , fulfilling at least one feature selected from the group consisting of features (i), (ii), and (iii):
(i) the first feed comprises a metering device for dosing the first liquid phase into the static mixer; (ii) the second feed comprises a metering device for dosing the second liquid phase into the static mixer; and (iii) the third feed comprises a metering device for dosing the third liquid phase into the longitudinal mixing section.

11 . A process for producing a nanocarrier and/or a nanoformulation, the process comprising:
a) providing an apparatus according to claim 1 ; b) providing the first liquid phase in the first reservoir vessel, wherein the first liquid phase comprises a first liquid dispersion medium and at least one component selected from the group consisting of a precursor to the nanocarrier, an active ingredient, and a precursor to an active ingredient; c) providing the second liquid phase in the second reservoir vessel, wherein the second liquid phase comprises a second liquid dispersion medium and at least one component selected from the group consisting of a precursor to the nanocarrier, a precursor to an active ingredient, and an active ingredient; d) providing the third liquid phase in the third reservoir vessel, wherein the third liquid phase comprises a third liquid dispersion medium; e) establishing a first liquid flow from the first reservoir vessel via the first feed into the static mixer; f) establishing a second liquid flow from the second reservoir vessel via the second feed into the static mixer; g establishing a third liquid flow from the third reservoir vessel via the third feed into the longitudinal mixing section, wherein a volume flow of the third liquid flow is larger than a sum of a volume flow of the first liquid flow and a volume flow of the second liquid flow; h) mixing the first liquid phase and the second liquid phase in the static mixer in absence of the third phase so as to obtain an at least biphasic mixture containing the nanocarrier and/or a nanoformulation or precursors thereof; i) mixing the biphasic mixture with the third liquid phase in the longitudinal mixing section so as to obtain an at least triphasic mixture containing the nanocarrier and/or nanoformulation and the third liquid dispersion medium; k) conducting the triphasic mixture from the longitudinal mixing section to the collection vessel through the conduct; l) Collecting the triphasic mixture in the collection vessel; m) withdrawing the triphasic mixture from the apparatus; n) optionally working up the triphasic mixture.

12 . The process as claimed in claim 11 , wherein a pH of the first liquid phase is between 3 and 5; wherein a pH of the third liquid phase is either between 6 and 8 or between 3 and 5; all pH values are as measured at a temperature of 25° C. by a glass electrode.

13 . The process as claimed in claim 12 , wherein the first dispersion medium is water or an aqueous buffer, the second dispersion medium is an organic substance, and the third dispersion medium is water or an aqueous buffer.

14 . The process as claimed in claim 13 , wherein the organic substance is a monohydric or polyhydric alcohol.

15 . The process as claimed in claim 13 , wherein the second liquid phase comprises at least one precursor to the nanocarrier, wherein said precursor to the nanocarrier is a natural or artificial lipid.

16 . The process as claimed in claim 15 , whereby the natural or artificial lipid is selected from the group consisting of cholesterol, 1,2-dioleyloxy-3-dimethylaminopropane (DODMA), 1,2-Dimyristoyl-rac-glycero-3-methoxypolyoxyethylene (PEG-DMG), dilinoleylmethyl-4-dimethylaminobutyrate (Dlin-MC3-DMA), and 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC).

17 . The process as claimed in claim 11 , wherein the third liquid phase comprises a buffer.

18 . The process as claimed in claim 11 , wherein the collection vessel for accommodating the secondary mixture and the third reservoir vessel for accommodating the third liquid phase are designed as a combined vessel, and wherein the third liquid phase is circulated before or during a metered addition of the first liquid phase and the second l

Assignees

• Evonik Operations Gmbh

Inventors

• Lang Jürgen Erwin
• Gomez Mario
• Arndt Marcel

Classifications

• B01F2215/0486

  Material property information · CPC title

• B01F2215/0431

  Numerical size values, e.g. diameter of a hole or conduit, area, volume, length, width, or ratios thereof · CPC title

• A61K9/5192

  Processes · CPC title

• A61K9/5123

  Organic compounds, e.g. fats, sugars · CPC title

• B01F23/45

  using flow mixing · CPC title