Solid Dosage Forms of Biopharmaceuticals in Drug Delivery Systems Using Sustainable Strategies.

Clarinda Costa,Teresa Casimiro,Maria Luísa Corvo,Ana Aguiar-Ricardo

doi:10.3390/molecules26247653

Abstract

Drug delivery systems (DDS) often comprise biopharmaceuticals in aqueous form, making them susceptible to physical and chemical degradation, and therefore requiring low temperature storage in cold supply and distribution chains. Freeze-drying, spray-drying, and spray-freeze-drying are some of the techniques used to convert biopharmaceuticals-loaded DDS from aqueous to solid dosage forms. However, the risk exists that shear and heat stress during processing may provoke DDS damage and efficacy loss. Supercritical fluids (SCF), specifically, supercritical carbon dioxide (scCO2), is a sustainable alternative to common techniques. Due to its moderately critical and tunable properties and thermodynamic behavior, scCO2 has aroused scientific and industrial interest. Therefore, this article reviews scCO2-based techniques used over the year in the production of solid biopharmaceutical dosage forms. Looking particularly at the use of scCO2 in each of its potential roles—as a solvent, co-solvent, anti-solvent, or co-solute. It ends with a comparison between the compound’s stability using supercritical CO2-assisted atomization/spray-drying and conventional drying.

Highlights

Biopharmaceuticals include enzymes, nucleic acids, monoclonal antibodies, and recombinant proteins that are either manufactured or isolated from biological sources for medical application [1]
The poor solubility of drugs and polymers in Supercritical CO2 (scCO2) hindered particle recovery leading to scale-up limitations and other disadvantages
PGSS presents easy scalability, requires no organic solvents, and can take place at low temperatures. Since it requires the solubilization of scCO2 in the melted compound, the technique is limited to pharmaceutical compounds in which CO2 is highly soluble

Summary

Introduction

Biopharmaceuticals include enzymes, nucleic acids, monoclonal antibodies, and recombinant proteins that are either manufactured or isolated from biological sources for medical application [1]. Biopharmaceutical-based drug delivery systems are usually formulated in aqueous forms [16] which require storage at temperatures between 2 and 8 ◦C or even below −70 ◦C to prevent chemical and physical destabilization [17]. Its polarity and solvation power are superior, and it offers the mass transfer properties of a low viscosity gas in association with high associated diffusivity [31].these properties are tunable near the critical point via minor temperature or pressure changes [32] For this reason, scCO2 can be used with different technologies, depending on its solvating behavior. 2. Supercritical CO2-Based Drying Techniques to Produce Solid Dosage Forms of Biopharmaceuticals in Drug Delivery Systems 2.1. PGSS can be more effective than RESS insofar as the compound (drug or polymer) does not need to be dissolved in scCO2 [52] and no organic solvents are necessary. Loaded liposomes are obtained in aqueous bulk rather than in dried form

Supercritical CO2 as Anti-Solvent

Findings

Conclusions and Future Perspectives