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Simultaneous Formation and Micronization of Pharmaceutical Cocrystals by Rapid Expansion of Supercritical Solutions (RESS)

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Abstract

Purpose

We investigated the RESS process as a means of simultaneous micronization and cocrystallization of a model drug with poor aqueous solubility.

Methods

1:1 cocrystals of ibuprofen (IBU) and nicotinamide (NA) were produced with a pilot scale unit for RESS processing.IBU and NA were dissolved in scCO2 at 30 MPa and 50°C. After 24 h, the supercritical solution was expanded at a medium CO2 flow rate of 3.8 kg/h during 60 min into an expansion vessel kept at ambient conditions. Cocrystals were identified with DSC, XRD and confocal Raman microscopy (CRM) and further characterized by SEM, specific surface area, wetting ability, solubility and dissolution testing.

Results

Judging by DSC, XRD and CRM, cocrystals with high purity could be produced with the RESS technique. Micronization via RESS was successful, since the specific surface area of RESS cocrystals was increased almost tenfold in comparison to cocrystals produced by slow solvent evaporation. Due to the additional micronization, the mean dissolution time of IBU from RESS cocrystals was decreased.

Conclusions

RESS cocrystallization offers the advantage of combining micronization and cocrystallization in a single production step. For drugs with dissolution-limited bioavailability, RESS cocrystallization may therefore be a superior approach in comparison to established cocrystallization techniques.

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Abbreviations

IBU:

Ibuprofen

NA:

Nicotinamide

RCC 0.5:1:

RESS coprecipitates with a molar ratio of 0.5:1 (IBU:NA)

RCC 1:1:

RESS coprecipitates with a molar ratio of 1:1 (IBU:NA)

SCC 1:1:

Cocrystals produced by slow solvent evaporation

ScCO2 :

Supercritical carbon dioxide

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ACKNOWLEDGMENTS AND DISCLOSURES

A part of this work has been presented as a poster at the AAPS Annual Meeting in San Antonio, US, Nov. 10–14, 2013 and at the 9th PBP world meeting in Lisbon, Portugal, March 31—April 3.

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Authors and Affiliations

  1. Institut für Pharmazeutische Technologie und Biopharmazie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 8, 72076, Tübingen, Germany

    Katrin C. Müllers & Martin A. Wahl

  2. Departamento de Farmácia Galénica e Tecnologia Farmacêutica, Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003, Lisbon, Portugal

    Maria Paisana

Authors
  1. Katrin C. Müllers
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  2. Maria Paisana
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  3. Martin A. Wahl
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Correspondence to Martin A. Wahl.

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Müllers, K.C., Paisana, M. & Wahl, M.A. Simultaneous Formation and Micronization of Pharmaceutical Cocrystals by Rapid Expansion of Supercritical Solutions (RESS). Pharm Res 32, 702–713 (2015). https://doi.org/10.1007/s11095-014-1498-9

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  • DOI: https://doi.org/10.1007/s11095-014-1498-9

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