Experimental data and thermodynamics modeling (PC-SAFT EoS) of the {CO2 + chloroform + PHBV} system at high pressures

https://doi.org/10.1016/j.supflu.2020.105140Get rights and content

Highlights

  • Phase Behavior Experimental data of the {CO2 + Chloroform + PHBV} System at High-Pressures.

  • The experimental data were modeled with the PC-SAFT equation of state.

  • Thermodynamic data are of great relevance for encapsulation of active ingredients in PHBV.

  • The carbon dioxide acted as an antisolvent, precipitating the PHBV.

Abstract

Herein, the influence of HV (hydroxyvalerate) addition (8.0 and 8.7 wt% HV) on the PHBV (poly(3-hydroxybutyrate-co-3-hydroxyvalerate)) composition from the perspective of phase equilibrium in high-pressure {(CO2 (1) + chloroform (2) + [PHBV - 8.0 wt%] (3) and (CO2 (1) + chloroform (2) + [PHBV - 8.7 wt%] (3)} systems was examined using the static synthetic method with a visual variable-volume view cell at temperatures ranging from 303.15 to 333.15 K, pressures approximately 10 MPa, and different concentrations of PHBV (HV = 8.0 and 8.7 wt%) in chloroform (0.01 and 0.02 g.cm−3). Transitions of the solid-vapor-liquid (SVL) were observed. The experimentally determined phase transitions were successfully modeled using the PC-SAFT equation of state.

Introduction

The controlled size distribution of micro-nano particles is essential for the optimal performance of controlled release of active particles [1], [2]. Studies of controlled drug delivery of micro-nano particle formulations composed of biocompatible and biodegradable polymers demonstrate that these formulations exhibit significant potential for efficiency [3], [4], [5]. The optimization and control of the particle size distribution have important applications in the food, agronomic, pharmaceutical, cosmetic, and veterinary industries [2], [4], [6], [7].

Traditional drug release methods often do not exhibit sustained release, maintaining dosages that, at times, can be elevated. However, the application of controlled size micro- or nano-particles, loaded on biodegradable polymers may provide suitable dosages [4], [5], [8]. In this manner, it is possible to increase the bioavailability period for metabolization and decrease the therapeutic drug dosage [4], [5], [8].

The profile and the mechanism of drug delivery are defined by polymer characteristics and the physicochemical properties of the incorporated substance [4], [5], [9]. The development of biodegradable systems requires the control of a significant number of variables, as the polymer degradation kinetics must remain constant to optimize controlled drug release [4], [5], [9].

Various techniques have been developed for the production of micro and nano particles of drugs. Most methods involve emulsification and solvent evaporation, solvent emulsification/diffusion, nanoprecipitation, salting-out, and interfacial polymerization [4], [5]. These techniques are excellent particle production strategies, but their application mostly involves the use of organic solvents. If the solvent removal is not performed correctly, the morphological quality and particle polydispersity can be compromised [4], [5], [10].

Supercritical fluids, such as carbon dioxide, have been used for the production of micro and nano particles from biodegradable polymers. The application of supercritical technology, using carbon dioxide as an anti-solvent, is an innovative process for the production of drug carrier particles. Particles with controlled size distribution, homogeneous morphology, high drug encapsulation efficiency in the polymer matrix, and solvent-free products are urgently needed [11].

The use of a compressible anti-solvent fluid is advantageous compared to that of liquid anti-solvents due to the ease of drying, purification of the precipitate, and recovery of the solvent and anti-solvent [4], [5], [12], [13].

In drug encapsulation or bioactive processes, compounds used as part of the coating film should be biodegradable and non-toxic. Polyhydroxyalkanoates (PHAs) are polymers that exhibit these desirable properties, with poly(3-hydroxybutyrate) (PHB) as the most common example. PHB exhibits properties similar to polypropylene (PP), including melting point, degree of crystallinity, and glass transition temperature [14]. In contrast, PHB copolymers with 3-hydroxyvalerate (PHBV) are less stiff and tougher. Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) is a thermoplastic copolymer that is semi-crystalline, biodegradable, and biocompatible with a linear chain containing hydroxybutyrate (HB) and hydroxyvalerate (HV) segments. The properties of this copolymer depend on its HV content, which determines polymer crystallinity [14]. Increasing the amount of HV in the PHB decreases the melting point and improves thermal stability [15]. The biodegradability of the polymer is promising for biomedical applications, including the controlled release of therapeutic drugs [16].

Information regarding the solubility behavior between drugs, organic solvents, and supercritical fluids is important for determining the success of many applications. In particular, vapor-liquid equilibrium data are required to appropriately design the precipitation/recrystallization process using antisolvent gas [17].

Controlled drug release from a coprecipitate with a biodegradable polymer is a possible method for prolonging release characteristics. Giufrida et al. [5] studied the encapsulation of nano particles with PHBV using supercritical fluid extraction of emulsions (SFEE). Giufrida et al. [4] reported the synthesis of particles based on a PHBV polymer impregnated with progesterone using supercritical CO2 anti‐solvent expansion (SAS). Costa et al. [14] produced PHBV microparticles from organic solutions using the SAS technique. Franceschi et al. [10] investigated the application of solution enhanced dispersion by supercritical fluids (SEDS) for precipitation of pure β-carotene and PHBV copolymer. Boschetto et al. [18] encapsulated grape seed in PHBV using the SEDS technique. Machado et al. [19] investigated the effectiveness of supercritical carbon dioxide as an anti-solvent for the encapsulation of astaxanthin from Haematococcus pluvialis in PHBV using dichloromethane as an organic solvent via SEDS.

Although some studies involving the encapsulation of micro or nanoparticles using PHBV have been reported in the literature, it is necessary to perform studies regarding the phase behavior in high-pressure systems involving CO2, organic solvents, and PHBV. The PHBV composition was modified via addition of hydroxybutyrate (HB) and hydroxyvalerate (HV). The addition of HV modified the physico-chemical properties of the polymer and may alter the drug encapsulation process.

Thus, the influence of HV addition (8.0 and 8.7 wt% HV) on PHBV composition in terms of phase equilibrium at high pressures in {(CO2 (1) + chloroform (2) + [PHBV - 8.0 wt%] (3) and (CO2 (1) + chloroform (2) + [PHBV - 8.7 wt%] (3)} systems was examined using an equilibrium cell at temperatures ranging from 303.15 to 333.15 K and with different concentrations of PHBV (HV = 8.0 and 8.7 wt%) in chloroform (0.01 and 0.02 g.cm−3). PHBV’s with 8 and 8.7 wt% of HV are products of the production line of the company PHB Industrial S.A (Brazil), lots FE110 and FE113, respectively. The obtained thermodynamic data can contribute to the establishment and elucidation of optimum operating conditions of drug encapsulation in PHBV.

Section snippets

Material

PHBV’s (>95 wt%), with 8.0 and 8.7 wt% of HV was kindly donated by PHB Industrial S.A (Brazil). Chloroform (99.8 wt%) were purchase fron and VETEC (Brazil). Carbon dioxide (99.9 wt% - liquid phase) was purchased from White Martins S.A (Brazil). All chemicals were used with no further purification. Critical properties of the pure components were obtained from DIPPR database [20] (Table 1).

Apparatus and experimental procedure

The experiments were conducted using the visual static synthetic method at high pressures using a

PC-SAFT equation of state for copolymers

The original PC-SAFT model [29] for polymers was extended to copolymers [30]. In this model different segment types, i.e. types α and β, are introduced in the molecular chain. A schematic of the interactions between segments and solvent molecules is shown in Fig. 2.

PC-SAFT includes several pure-component parameters for non-associating ((mi, σI, and εi are the number of segments, segment diameter, and energy parameter, respectively) or associating compounds ((mi, σi, εI, κAiBj, and εAiBj, where

Experimental

To check the reliability of the apparatus and experimental procedure presents the phase equilibrium data was obtained in this study for the {CO2 (1) + acetone (2)} system at 303.15 and 313.15 K (see Fig. 3), which are compared to the experimental data reported in the literature [36], [37], [38]. One can see that the data obtained in this work are in good agreement with those presented in the literature for both isotherms (303.15 and 313.15 K).

The experimental data from the binary system {CO2

Conclusions

The experimental data obtained in this study for the ternary {CO2 (1) + chloroform (2) + [PHBV – 8.0 wt%] (3)} and {CO2 (1) + chloroform (2) + [PHBV – 8.7 wt%] (3)} systems were similar to the data reported by Favareto [25] for the phase transition of the binary {CO2 (1) + chloroform (2)} system. The phase transitions were relatively suppressed, but the system showed significantly increased turbidity with increasing molar composition of CO2. That is, CO2 acted as an antisolvent, precipitating

Funding

We thank the following agencies for financial support: CAPES (Ministry of Education), CNPq (National Council for Scientific and Technological Development). LF-P thanks the financial support of the Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP (Brazil), through the grant 2018/23063-1. PFA thanks the financial support of the Fundação de Amparo à Pesquisa do Estado de São Paulo, FAPESP (Brazil), through the grants 2015/05155-8 and 2018/03739-0 and CNPq by financial support of the

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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