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Review
. 2022 Sep 6;14(9):1886.
doi: 10.3390/pharmaceutics14091886.

Review on the Scale-Up Methods for the Preparation of Solid Lipid Nanoparticles

Sakshi V Khairnar  1   2 , Pritha Pagare  1   3 , Aditya Thakre  1 , Aswathy Rajeevan Nambiar  4 , Vijayabhaskarreddy Junnuthula  5 , Manju Cheripelil Abraham  6 , Praveen Kolimi  7 , Dinesh Nyavanandi  8 , Sathish Dyawanapelly  1
Affiliations
Review

Review on the Scale-Up Methods for the Preparation of Solid Lipid Nanoparticles

Sakshi V Khairnar et al. Pharmaceutics. .

Abstract

Solid lipid nanoparticles (SLNs) are an alternate carrier system to liposomes, polymeric nanoparticles, and inorganic carriers. SLNs have attracted increasing attention in recent years for delivering drugs, nucleic acids, proteins, peptides, nutraceuticals, and cosmetics. These nanocarriers have attracted industrial attention due to their ease of preparation, physicochemical stability, and scalability. These characteristics make SLNs attractive for manufacture on a large scale. Currently, several products with SLNs are in clinical trials, and there is a high possibility that SLN carriers will quickly increase their presence in the market. A large-scale manufacturing unit is required for commercial applications to prepare enough formulations for clinical studies. Furthermore, continuous processing is becoming more popular in the pharmaceutical sector to reduce product batch-to-batch differences. This review paper discusses some conventional methods and the rationale for large-scale production. It further covers recent progress in scale-up methods for the synthesis of SLNs, including high-pressure homogenization (HPH), hot melt extrusion coupled with HPH, microchannels, nanoprecipitation using static mixers, and microemulsion-based methods. These scale-up technologies enable the possibility of commercialization of SLNs. Furthermore, ongoing studies indicate that these technologies will eventually reach the pharmaceutical market.

Keywords: drug delivery; high-pressure homogenization; nanomedicines; scale-up; solid lipid nanoparticles.

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Conflict of interest statement

The authors declare no conflict of interest. The company had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 3
Figure 3
Schematic representation of the sonication method for the SLN probe sonicator (A), bath sonicator used in academic labs (B) and SLN preparation by the sonication method (C). In this technique, the lipids will be melted and the aqueous phase with surfactants is then sonicated using probe sonicator to form emulsions with reduced droplet size. Gradual cooling of the emulsion below the crystallization temperature helps in formation of the SLN dispersions. Note: (A,B) figures are adapted with permission from Ref. [23]. Copyright 2014, Elsevier, and (C) is adapted from Ref. [24].
Figure 1
Figure 1
Advantages and disadvantages of SLN, data summarized from references [7,8].
Figure 2
Figure 2
Bibliographic search analysis of SLNs from the PubMed database [19]. Search term “Solid lipid nanoparticles [Title/Abstract]” (A) yielded 3143 publications; “Scale-up of solid lipid nanoparticles [Title/Abstract]” yielded 62 publications (B).
Figure 4
Figure 4
W/O/W double emulsion technique for the preparation of solid lipid nanoparticles. Reprinted from Ref. [35].
Figure 5
Figure 5
Supercritical fluid technique for the preparation of solid lipid nanoparticles. Reprinted from Ref. [17].
Figure 6
Figure 6
Scheme of the equipment used for supercritical fluid extraction of emulsions (SFEE). Reprinted with permission from Ref. [39]. Copyright 2016, Elsevier.
Figure 7
Figure 7
The spray-drying technique procedure is reproduced from [43].
Figure 8
Figure 8
Homogenization technique: hot homogenization technique and cold homogenization technique. Reprinted from Ref. [43].
Figure 9
Figure 9
Schematic representation of continuous SLN synthesis using HME-connected HPH. Reproduced with permission from Ref. [54]. Copyright 2014, Elsevier.
Figure 10
Figure 10
A microscopic view of a transparent microchannel showing vortices in the segmented gas-liquid flow (A) and microfluidic system with initial flow-focusing and subsequent Taylor flow (B) Reprinted from Ref. [58].
See this image and copyright information in PMC

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