Continuous manufacture of hydroxychloroquine sulfate drug products via hot melt extrusion technology to meet increased demand during a global pandemic: From bench to pilot scale

Margerie, Victoire de; McConville, Christopher; Dadou, Suha; Shu, Li; Boulet, Pascal; Aranda, Lionel; Walker, Andrew; Mohylyuk, Valentyn; Jones, David S.; Murray, Brian M.; Andrews, Gavin

doi:10.1016/j.ijpharm.2021.120818

Cited by 6 publications

(4 citation statements)

References 32 publications

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“…The reduced variation of process parameters with the vertical extruder will enable high performance continuous manufacturing with minimum waste of (expensive) raw materials. [19] Other recent examples include the common work between Rondol, Seqens and Institut Jean Lamour on acetylsalicylic acid (ASA) (Figure 2). It shows that ASA can be fully amorphous at loadings of up to 45% w/w (Figure 3) and remains so more than 6 weeks after the manufacture which is promising for their long-term stability.…”

Section: New Developments Thanks To Vertical Extrusionmentioning

confidence: 99%

“…For example as explained below, we recently started to work on Camostat and found that it melts 10 C lower when it is previously mixed with 30% Soluplus. Taking account on our studies on HCQ, [19] ASA, and Camostat, the most important effect of the extruder is to increase the interaction of the API and excipient. First due to the precise mixing along the screw, the dispersion of the nanoparticles into the excipient progressively increases.…”

Section: New Developments Thanks To Vertical Extrusionmentioning

confidence: 99%

“…[15] Despite the potential of HME as an innovative technology and the advantages it offers, still few marketed drug-containing pharmaceutical products have been successfully manufactured while using HME, [16] mostly amorphous solid dispersions (ASD) that comprise blends of drug and polymer and that demonstrated improved bioavailability in vivo as compared to crystalline systems. [17][18][19] Table 1 describes the various types of biocompatible polymers with their main characteristics desired and undesired for extruded pharmaceutical products.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Extrusion for pharma applications: An update

Gallas

Boulet

Margerie³

2023

SPE Polymers

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This paper aims to give an overview of our current research and development on hot-melt extrusion (HME) for pharmaceutical formulation and drug delivery.Unfortunately, a large percentage of marketed drugs (40%) and those in the development pipeline (90%) are poorly water soluble. We use a few examples to show that solubility of APIs can be drastically improved by using HME to mix them with different biocompatible polymers and playing with the various process parameters (extrusion temperature, screw speed, screw configuration, etc.).The advantages of this technique are then presented as well as the further development needed to make this process fully industrial for pharmaceutical purposes.

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Section: New Developments Thanks To Vertical Extrusionmentioning

confidence: 99%

Section: New Developments Thanks To Vertical Extrusionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Extrusion for pharma applications: An update

Gallas

Boulet

Margerie³

2023

SPE Polymers

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“…Present work is focused on the both solubility measurement and modelling of hydroxychloroquine sulfate (HCQS) in scCO 2 . This drug was originally developed in United States (US) to counter malaria in the year 1949 9 , 10 . HCQS is considered as better alternate to chloroquine, due to less toxicity.…”

Section: Introductionmentioning

confidence: 99%

Solubility measurement and modeling of hydroxychloroquine sulfate (antimalarial medication) in supercritical carbon dioxide

Sodeifian

Garlapati

Nooshabadi

et al. 2023

Sci Rep

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A supercritical fluid, such as supercritical carbon dioxide (scCO2) is increasingly used for the micronization of pharmaceuticals in the recent past. The role of scCO2 as a green solvent in supercritical fluid (SCF) process is decided by the solubility information of the pharmaceutical compound in scCO2. The commonly used SCF processes are the rapid expansion of supercritical solution (RESS) and supercritical antisolvent precipitation (SAS). To implement micronization process, solubility of pharmaceuticals in scCO2 is required. Present study is aimed at both measuring and modeling of solubilities of hydroxychloroquine sulfate (HCQS) in scCO2. Experiments were conducted at various conditions (P = 12 to 27 MPa and T = 308 to 338 K), for the first time. The measured solubilities were found to be ranging between (0.0304 × 10–4 and 0.1459 × 10–4) at 308 K, (0.0627 × 10–4 and 0.3158 × 10–4) at 318 K, (0.0982 × 10–4 and 0.4351 × 10–4) at 328 K, (0.1398 × 10–4 and 0.5515 × 10–4) at 338 K. To expand the usage of the data, various models were tested. For the modelling task existing models (Chrastil, reformulated Chrastil, Méndez-Santiago and Teja (MST), Bartle et al., Reddy-Garlapati, Sodeifian et al., models) and new set of solvate complex models were considered. Among the all models investigated Reddy-Garlapati and new solvate complex models are able to fit the data with the least error. Finally, the total and solvation enthalpies of HCQS in scCO2 were calculated with the help of model constants obtained from Chrastil, reformulated Chrastil and Bartle et al., models.

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