Optimizing supercritical antisolvent process parameters to minimize the particle size of paracetamol nanoencapsulated in L-polylactide (original) (raw)
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International Journal of Nanomedicine, 2012
The reported work demonstrates and discusses the effect of supercritical fluid density (pressure and temperature of supercritical fluid carbon dioxide) on particle size and distribution using the supercritical antisolvent (SAS) method in the purpose of drug encapsulation. In this study, paracetamol was encapsulated inside L-polylactic acid, a semicrystalline polymer, with different process parameters, including pressure and temperature, using the SAS process. The morphology and particle size of the prepared nanoparticles were determined by scanning electron microscopy and transmission electron microscopy. The results revealed that increasing temperature enhanced mean particle size due to the plasticizing effect. Furthermore, increasing pressure enhanced molecular interaction and solubility; thus, particle size was reduced. Transmission electron microscopy images defined the internal structure of nanoparticles. Thermal characteristics of nanoparticles were also investigated via differential scanning calorimetry. Furthermore, X-ray diffraction pattern revealed the changes in crystallinity structure during the SAS process. In vitro drug release analysis determined the sustained release of paracetamol in over 4 weeks.
Langmuir, 2010
The present contribution investigates whether it is possible to form stable amorphous particles of ketoprofenpoly(lactic acid), naproxen-poly(lactic acid), and indomethacin-poly(lactic acid). Amorphization and micronization of these poorly water-soluble drugs offer a combined way to improve the solubility and enhance the dissolution rate. The particles were formed by pulsed rapid expansion of supercritical CO 2 solutions and characterized in the aerosol phase with rapid-scan infrared spectroscopy and after collection with scanning electron microscopy and X-ray diffraction. None of the three drug-poly(lactic acid) mixtures showed long-term stability on the order of weeks against the reversion from the amorphous to the crystalline state. Ketoprofen was the only drug that formed mixed amorphous particles with at least short-term stability. The long-term products turned out to be submicrometer-to micrometer-sized particles with a crystalline drug core and an amorphous poly(lactic acid) shell. Moreover, we found that the poly(lactic acid) coating stabilizes the particles against agglomeration.
The application of a supercritical antisolvent process for sustained drug delivery
Powder Technology, 2006
Supercritical processes for drug delivery system design have attracted considerable attention recently. This present work investigates the application of a supercritical antisolvent coating process for controlled drug release design. Hydrocortisone as the host drug particles and poly (lactide-co-glycolide) (PLGA) as the polymer carrier were selected as the model system for this purpose. In this research the drug particles were suspended in a polymer solution of dichloromethane. The suspension was then sprayed into supercritical CO 2 as an antisolvent. A parallel study of co-precipitation of the drug and polymer using the same supercritical antisolvent process at the same operating conditions was performed for comparison with the coating process. SEM images were used to characterize the drug particles before and after and the assay analysis was carried out using HPLC. The coated particles and co-precipitated particles were evaluated in terms of encapsulation efficiency and drug release profiles. The major advantage of this new approach is the ability to physically coat very fine (< 30 μm) particles without having to dissolve them in an organic solvent. It was found that higher polymer to drug ratios produced higher encapsulation efficiencies and the coated drug particles did show sustained release behavior. The co-precipitation of the drug and polymer (at the same operating conditions), however, did not exhibit any sustained release.
Drug encapsulation using supercritical fluid extraction of emulsions
Journal of Pharmaceutical Sciences, 2006
The current work was aimed at evaluating a new method, supercritical fluid extraction of emulsions (SFEE), for the production of composite (e.g., polymer-drug) micro- and nanoparticles, intended for application in sustained-release drug delivery formulations. Using the proposed method, composite particles were obtained, both in a continuous or batch manner by supercritical carbon dioxide extraction of oil-in-water (o/w) emulsions. Model drugs indomethacin and ketoprofen and biodegradable polymers poly(lactic/glycolic) acid and Eudragit RS were used in order to demonstrate the effectiveness of the SFEE process for producing these particles. Stable aqueous suspensions of composite micro and nanoparticles, having sizes ranging between 0.1 and 2 µm were consistently obtained. Emulsion droplet diameter was found to be the major size control parameter. Other parameters investigated included polymer and drug concentrations in solvent and emulsion solvent fraction. The residual solvent content in the particle suspension obtained was consistently below 50 ppm. Standard dissolution tests were used to observe the sustained release phenomenon of the composite particles. The dissolution profile was characterized in terms of the intrinsic dissolution kinetic coefficients taking into account the specific surface area and solubility of the particles. It was observed that the kinetic coefficient parameter for encapsulated drugs was reduced by 2–4 orders of magnitude when compared to the unprocessed drug particles. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:667–679, 2006
Journal of Drug Delivery Science and Technology, 2018
Poor aqueous solubility leading to poor oral bioavailability is a bottle neck in the development of many new drug candidates; particularly the BCS class II-IV drugs. These molecules are difficult to formulate using conventional approaches and are associated with numerous formulation related performance issues. To overcome this hurdle, formulation of nanosuspension can be one promising alternative. The purpose of this study was to develop nanosuspension using paracetamol as a model drug by antisolvent precipitation method. Nanoparticles were generated by incorporating drug solution into an antisolvent, which generated rapid nucleation leading to nanosuspension. Different stabilizers including PEG, HPMC, and Pluronic F68 were used to inhibit the particle size growth of nanosuspension. The prepared nanosuspension was evaluated in terms of particle size distribution, morphology and thermal properties. Dissolution study was also performed for nanosuspension and compared with the raw powder and commercially available paracetamol suspension (Ace ® suspension). Processing conditions and type of stabilizers showed marked impact on the average particle size, morphology and stability of nanosuspension batches. Although paracetamol is sparingly soluble in water, its nanosuspension formulation exhibited faster dissolution rate when compared with commercial microsuspension and raw powder.
Supercritical Antisolvent Process for Pharmaceutical Applications: A Review
Processes
The supercritical antisolvent (SAS) technique has been widely employed in the biomedical field, including drug delivery, to obtain drug particles or polymer-based systems of nanometric or micrometric size. The primary purpose of producing SAS particles is to improve the treatment of different pathologies and to better the patient’s compliance. In this context, many active compounds have been micronized to enhance their dissolution rate and bioavailability. Aiming for more effective treatments with reduced side effects caused by drug overdose, the SAS polymer/active principle coprecipitation has mainly been proposed to offer an adequate drug release for specific therapy. The demand for new formulations with reduced side effects on the patient’s health is still growing; in this context, the SAS technique is a promising tool to solve existing issues in the biomedical field. This updated review on the use of the SAS process for clinical applications provides useful information about the...
Chemical engineering transactions, 2021
The manufacture of functionalized bioabsorbable polymeric implants is gaining attention in recent years. These devices administer gradually and locally drugs or biomolecules to treat several diseases and they disappear once they perform their function. In this work, ketoprofen, an anti-inflammatory drug with analgesic and antipyretic effects, was loaded by supercritical solvent impregnation (SSI) in polylactic acid (PLA) filaments, and the initial stage of its in vitro release was explored. Impregnation experiments were carried out in a range of pressure and temperature of 25-40 MPa and 328-348 K. Different drug loading values were obtained (up to 9 % respecting the polymer mass) depending on the operating conditions.The ketoprofen release profile and the mathematical modelling (Korsmeyer-Peppas and Peppas-Sahlin models) showed an initial release governed by diffusion and with different kinetics depending on the impregnation conditions. Thus, this study reveals that SSI could be use...
Disease-a-Month, 2005
The objective of this work was to develop sustained release formulation for hydrophilic drugs with minimal burst effects. For this purpose, nanoparticles of a hydrophilic drug were produced using supercritical CO 2 , which were then encapsulated into polymer microparticles using an anhydrous method, followed by studying their sustained in-vitro drug release. A hydrophilic drug, dexamethasone phosphate, was dissolved in methanol and injected in supercritical CO 2 with ultrasonic field for enhanced molecular mixing (SAS-EM technique). Supercritical CO 2 rapidly extracts methanol leading to instantaneous precipitation of drug nanoparticles of 150 nm. These nanoparticles, on encapsulation in poly(lactideco-glycolide) polymer using anhydrous s/o/o/o technique, resulted in the well-dispersed encapsulation of drug nanoparticles in polymer microspheres of ~70 µm. Their invitro drug release showed sustained release of dexamethasone phosphate over a period of 700 hours with almost no initial burst release.
Journal of Supercritical Fluids, 2009
The manufacturing and stability of composite nanoparticles of the non-steroidal anti-inflammatory drug Ketoprofen (KET) and the amorphous biodegradable polymer poly-lactic-co-glycolic acid (PLGA) has been investigated. Co-formulation particles ranging between 100 and 200 nm in size were produced by supercritical CO 2 extraction of emulsions. During 1 week of storage in aqueous suspension, the composite particles were isolated and analyzed in order to determine the evolution of drug content. In suspensions equilibrated with crystals of racemic KET, particles were observed to approach a KET level of approximately 5 wt.%, independent of their initial drug content. Only in the absence of KET crystals, clearly higher drug levels of up to 10 wt.% were maintained during storage. This behavior is rationalized assuming a solubility of approximately 5 wt.% for KET in PLGA together with a metastable zone extending to levels of at least 10 wt.%. Using a simple lattice model, a negative value of the dimensionless Flory-Huggins interaction parameter lying in between −0.17 and −0.26 was determined from the solubility, indicating the presence of strong molecular interactions between drug and polymer.