DOCSLIB.ORG

Particle Generation for Pharmaceutical Applications Using Supercritical

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Particle Generation for Pharmaceutical Applications Using Supercritical Particle generation for pharmaceutical applications using supercritical fluid technology Jacques Fages, Hubert Lochard, Jean-jacques Letourneau, Martial Sauceau, Élisabeth Rodier To cite this version: Jacques Fages, Hubert Lochard, Jean-jacques Letourneau, Martial Sauceau, Élisabeth Rodier. Particle generation for pharmaceutical applications using supercritical fluid technology. Powder Technology, Elsevier, 2004, 141 (3), pp.219-226. 10.1016/j.powtec.2004.02.007. hal-01668423 HAL Id: hal-01668423 https://hal.archives-ouvertes.fr/hal-01668423 Submitted on 15 Mar 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Particle generation for pharmaceutical applications using supercritical fluid technology Jacques Fages*, Hubert Lochard, Jean-Jacques Letourneau, Martial Sauceau, Elisabeth Rodier E´ cole des Mines d’Albi-Carmaux, Chemical Engineering Laboratory for Particulate Solids, UMR-CNRS 2392, 81013 Albi, France Abstract Inthepharmaceuticalindustry,anevengreaternumberofproductsareintheformofparticulatesolids.Theirformation,formulationand thecontroloftheiruserpropertiesarestillnotwellunderstoodandmastered.Sincethemid-1980s,anewmethodofpowdergenerationhas appearedinvolvingcrystallisationwithsupercriticalfluids.Carbondioxideisthemostwidelyusedsolventanditsinnocuityand‘‘green’’ characteristicsmakeitthebestcandidateforthepharmaceuticalindustry.RapidExpansionofSupercriticalSolutions(RESS),Supercritical AntiSolvent(SAS)andParticlesfromGasSaturatedSolutions(PGSS)arethreefamiliesofprocesseswhichleadtotheproductionoffine andmonodispersepowders,includingthepossibilityofcontrollingcrystalpolymorphism.FortheRESSprocess,thesuddendecompression of the fluid in which a solute has been dissolved is the driving force of nucleation. CO2 is, however, a rather feeble solvent and this is obviouslythemainlimitationofthedevelopmentofRESS.IntheSASprocess,CO2actsasanon-solventforinducingthecrystallisationofa solutefromanorganicsolution.TheversatilityofSAS(thereisalwaysapropersolvent–antisolventcoupleforthestudiedsolute)ensures futuredevelopmentsforverydifferenttypesofmaterials.PGSSusesthefactthatitismucheasiertodissolveCO2 inorganicsolutions(or melted compounds) than the contrary. It presents very promising perspectives of industrial development. After almost 20 years of active research,andmorethan10yearsofprocessdevelopment,thistechnologyisreachingmaturity,andverysooncommercialdrugproducedby thesetechniquesarelikelytoappear. Keywords: Particle generation; Pharmaceutical application; Supercritical fluid technology 1. Introduction excipients or host molecules like cyclodextrins. In addition, several other advantages can be noted depending on the About two thirds of the products used in the pharmaceu- chosen process configuration: tical industry are in the form of particulate solids [1]. Consequently, a lot of effort has been put into research in high purity of products; particle generation processes. The standard processes, control of crystal polymorphism; crushing/milling and crystallisation/precipitation are still possibility of processing thermolabile molecules; the most used. However, supercritical fluid (SCF) technol- single-step process; ogy presents a new and interesting route for particle forma- easy downstream processing; tion, which avoids most of the drawbacks of the traditional environmentally acceptable technology. methods. Supercritical processes give micro- or even nano- particles with narrow size distribution, and can also be used Among these advantages, most of them due to the use of to achieve microencapsulation, surface coating of an active carbon dioxide (CO2) of which properties of nontoxicity and substance particle with a polymer or co-crystallisation with mild critical conditions make it an ideal substitute to organic solvents. Moreover, CO2 is gaseous at ambient conditions, * Corresponding author. Tel.: +33-563-49-31-41; fax: +33-563-49-30- which simplifies the problem of solvent residues. 25. The bioavailability of pharmaceutical molecules depends E-mail address: [email protected] (J. Fages). on their absorption by the gastrointestinal tract, which is Fig. 1. Schematic flow diagram of the RESS process. governed by their dissolution and membrane permeation important role since a thermodynamic equilibrium may or rates. Micronisation techniques, and especially those using may not be reached in the extraction autoclave. In fact, the SC–CO2, which lead to an increase in the specific surface kinetics of the dissolution must not be neglected and diffusion 2 1 area (typically several tens of m gÀ for a nonporous limitations can occur. Additional problems may be encoun- solid), can significantly contribute to this improvement in tered when the solid to be extracted is not a pure component. bioavailability. The development of dry powder inhalers Indeed, fractionation of the load can lead to a variation in the (DPI) in which the drug is directly delivered to the lungs composition of the particles upon depressurisation. requires also fine powders with a mean particle size in the To understand what will happen during fluid expansion, range of 2 to 5 Am. phase diagrams are very useful. Fig. 2 shows the ( P, T) and Microencapsulation, coating and formation of composite ( P, h) diagrams for pure CO2. Phase diagrams and results particles are also extremely desirable for controlled delivery presented in this article have been simulated using multi- systems. Here again, supercritical technology may bring phase equilibrium calculations. The fluid phases are mod- new solutions to old problems. elled using the Peng-Robinson’s equation of state with Rapid Expansion of a Supercritical Solutions (RESS), various mixing rules. What can be noticed is that these phase Supercritical Anti-Solvent (SAS) and, to a lesser extent, equilibria involve pure solid constituents. The pure solid Particles from Gas Saturated Solutions (PGSS) are the chemical potential used in the model does not require the most studied processes. It is known that RESS can be value of the sublimation pressure. When the expressions of used with CO2-soluble molecules, while SAS can process the required properties are unknown, which is the case for nonsoluble molecules. However, the choice between these most of pharmaceutical molecules, this pure solid chemical two methods is not so simple in reality. To choose among potential expression is based on the measurements made these processes and the large domain of possible operating with a differential scanning calorimeter of the melting point (pure) conditions requires a good knowledge of the phase equi- of the solid. The fugacity coefficient ui,S in this chemical libria thermodynamics. potential is the following: pure lnuð Þ P; T 2. The RESS process i;S ð Þ fus fus std pure Tið Þ Dhið Þ Pð Þ lnuð Þ P; T 1 ð Þ 2.1. A two-step process: solubilisation and particle ¼ i;L ð Þþ À T fus ! RTið Þ formation P D vi u; T T L S ð Þ 1 T À du 1 fus RESS is a two-step process: after having solubilised a À P std RT À RT T ð Þ À u Z ð Þ Z i substance in an SCF, the mixture is suddenly depressurised std D cP Pð Þ; u du 1 in a nozzle causing fast nucleation and fine particle gener- Â L S i ð Þ ð Þ À ation (Fig. 1). In designing a RESS process, it is necessary to have the best possible understanding of what happens pure pure where: D vi P; T við;L Þ P; T við;S Þ P; T is the dif- upstream from the nozzle, that is to say during the extraction L S ð Þ¼ ð ÞÀ ð Þ ference betweenÀ pure liquid and pure solid molar volume step. Therefore, it is important either to collect data from the std pure pure (std) and D c P ; T cð Þ T cð Þ T (with P =1 literature when they exist, or to perform experiments or Pi ð Þ Pi;L Pi;S L S ð Þ¼ ð ÞÀ ð Þ modelling, about the solute solubility in the SCF [2,3]. atm)À is the difference between pure liquid and pure solid The key parameters of the extraction step are obviously the molar heat capacities. More details on the numerical calcu- operating T and P. The flow rate of the fluid may also play an lation of these phase equilibria are given elsewhere [4]. Fig. 2. Isenthalpic depressurisation of pure CO2 on P, T (pressure, temperature) and P, h (pressure, molar enthalpy) phase diagrams. An acceptable assumption is to consider that the depres- both phases (fluid and solid), which is related to the activity surisation is an isenthalpic process provided the variation of of the solute in the solution at equilibrium. This supersat- kinetic energy can be neglected. This is, however, a better uration ratio, noted S, is defined as the concentration of the assumption for capillaries than for plain orifices [5]. There- solute divided by the solubility (the concentration at satu- fore, the expansion step will be a vertical line (dashed ration) provided the activity coefficients can be assumed to arrow) on the (P, h) diagram. Such a drop in pressure be close to 1 which is the case for low solubilities. S comes implies an important decrease in temperature, as shown in from the drop in density, which is very large especially near Fig. 2. In the example
Load more

Recommended publications
  • Colloidal Crystallization: Nucleation and Growth
    Colloidal Crystallization: Nucleation and Growth Dave Weitz Harvard Urs Gasser Konstanz Andy Schofield Edinburgh Rebecca Christianson Harvard Peter Pusey Edinburgh Peter Schall Harvard Frans Spaepen Harvard Eric Weeks Emory John Crocker UPenn •Colloids as model systems – soft materials •Nucleation and growth of colloidal crystals •Defect growth in crystals •Binary Alloy Colloidal Crystals NSF, NASA http://www.deas.harvard.edu/projects/weitzlab EMU 6/7//04 Colloidal Crystals Colloids 1 nm - 10 µm solid particles in a solvent Ubiquitous ink, paint, milk, butter, mayonnaise, toothpaste, blood Suspensions can act like both liquid and solid Modify flow properties Control: Size, uniformity, interactions Colloidal Particles •Solid particles in fluid •Hard Spheres •Volume exclusion •Stability: •Short range repulsion •Sometimes a slight charge Colloid Particles are: •Big Slow •~ a ~ 1 micron • τ ~ a2/D ~ ms to sec •Can “see” them •Follow individual particle dynamics Model: Colloid Æ Atom Phase Behavior Colloids Atomic Liquids U U s s Hard Spheres Leonard-Jones Osmotic Pressure Attraction Centro-symmetric Centro-symmetric Thermalized: kBT Thermalized: kBT Gas Gas Liquid Density Liquid Solid Solid Phase behavior is similar Hard Sphere Phase Diagram Volume Fraction Controls Phase Behavior liquid - crystal liquid coexistence crystal 49% 54% 63% 74% φ maximum packing maximum packing φRCP≈0.63 φHCP=0.74 0 Increase φ => Decrease Temperature F = U - TS Entropy Drives Crystallization 0 Entropy => Free Volume F = U - TS Disordered: Ordered: •Higher configurational
    [Show full text]
  • Entropy and the Tolman Parameter in Nucleation Theory
    entropy Article Entropy and the Tolman Parameter in Nucleation Theory Jürn W. P. Schmelzer 1 , Alexander S. Abyzov 2 and Vladimir G. Baidakov 3,* 1 Institute of Physics, University of Rostock, Albert-Einstein-Strasse 23-25, 18059 Rostock, Germany 2 National Science Center Kharkov Institute of Physics and Technology, 61108 Kharkov, Ukraine 3 Institute of Thermal Physics, Ural Branch of the Russian Academy of Sciences, Amundsen Street 107a, 620016 Yekaterinburg, Russia * Correspondence: [email protected]; Tel.: +49-381-498-6889; Fax: +49-381-498-6882 Received: 23 May 2019; Accepted: 5 July 2019; Published: 9 July 2019 Abstract: Thermodynamic aspects of the theory of nucleation are commonly considered employing Gibbs’ theory of interfacial phenomena and its generalizations. Utilizing Gibbs’ theory, the bulk parameters of the critical clusters governing nucleation can be uniquely determined for any metastable state of the ambient phase. As a rule, they turn out in such treatment to be widely similar to the properties of the newly-evolving macroscopic phases. Consequently, the major tool to resolve problems concerning the accuracy of theoretical predictions of nucleation rates and related characteristics of the nucleation process consists of an approach with the introduction of the size or curvature dependence of the surface tension. In the description of crystallization, this quantity has been expressed frequently via changes of entropy (or enthalpy) in crystallization, i.e., via the latent heat of melting or crystallization. Such a correlation between the capillarity phenomena and entropy changes was originally advanced by Stefan considering condensation and evaporation. It is known in the application to crystal nucleation as the Skapski–Turnbull relation.
    [Show full text]
  • Heterogeneous Nucleation of Water Vapor on Different Types of Black Carbon Particles
    https://doi.org/10.5194/acp-2020-202 Preprint. Discussion started: 21 April 2020 c Author(s) 2020. CC BY 4.0 License. Heterogeneous nucleation of water vapor on different types of black carbon particles Ari Laaksonen1,2, Jussi Malila3, Athanasios Nenes4,5 5 1Finnish Meteorological Institute, 00101 Helsinki, Finland. 2Department of Applied Physics, University of Eastern Finland, 70211 Kuopio, Finland. 3Nano and Molecular Systems Research Unit, 90014 University of Oulu, Finland. 4Laboratory of Atmospheric Processes and their Impacts, School of Architecture, Civil & Environmental Engineering, École 10 Polytechnique Federale de Lausanne, 1015, Lausanne, Switzerland 5 Institute of Chemical Engineering Sciences, Foundation for Research and Technology Hellas (FORTH/ICE-HT), 26504, Patras, Greece Correspondence to: Ari Laaksonen ([email protected]) 15 Abstract: Heterogeneous nucleation of water vapor on insoluble particles affects cloud formation, precipitation, the hydrological cycle and climate. Despite its importance, heterogeneous nucleation remains a poorly understood phenomenon that relies heavily on empirical information for its quantitative description. Here, we examine heterogeneous nucleation of water vapor on and cloud drop activation of different types of soots, both pure black carbon particles, and black carbon particles mixed with secondary organic matter. We show that the recently developed adsorption nucleation theory 20 quantitatively predicts the nucleation of water and droplet formation upon particles of the various soot types. A surprising consequence of this new understanding is that, with sufficient adsorption site density, soot particles can activate into cloud droplets – even when completely lacking any soluble material. 1 https://doi.org/10.5194/acp-2020-202 Preprint. Discussion started: 21 April 2020 c Author(s) 2020.
    [Show full text]
  • The Role of Latent Heat in Heterogeneous Ice Nucleation
    EGU21-16164, updated on 02 Oct 2021 https://doi.org/10.5194/egusphere-egu21-16164 EGU General Assembly 2021 © Author(s) 2021. This work is distributed under the Creative Commons Attribution 4.0 License. The role of latent heat in heterogeneous ice nucleation Olli Pakarinen, Cintia Pulido Lamas, Golnaz Roudsari, Bernhard Reischl, and Hanna Vehkamäki University of Helsinki, INAR/Physics, University of Helsinki, Finland ([email protected]) Understanding the way in which ice forms is of great importance to many fields of science. Pure water droplets in the atmosphere can remain in the liquid phase to nearly -40º C. Crystallization of ice in the atmosphere therefore typically occurs in the presence of ice nucleating particles (INPs), such as mineral dust or organic particles, which trigger heterogeneous ice nucleation at clearly higher temperatures. The growth of ice is accompanied by a significant release of latent heat of fusion, which causes supercooled liquid droplets to freeze in two stages [Pruppacher and Klett, 1997]. We are studying these topics by utilizing the monatomic water model [Molinero and Moore, 2009] for unbiased molecular dynamics (MD) simulations, where different surfaces immersed in water are cooled below the melting point over tens of nanoseconds of simulation time and crystallization is followed. With a combination of finite difference calculations and novel moving-thermostat molecular dynamics simulations we show that the release of latent heat from ice growth has a noticeable effect on both the ice growth rate and the initial structure of the forming ice. However, latent heat is found not to be as critically important in controlling immersion nucleation as it is in vapor-to- liquid nucleation [Tanaka et al.2017].
    [Show full text]
  • Using Supercritical Fluid Technology As a Green Alternative During the Preparation of Drug Delivery Systems
    pharmaceutics Review Using Supercritical Fluid Technology as a Green Alternative During the Preparation of Drug Delivery Systems Paroma Chakravarty 1, Amin Famili 2, Karthik Nagapudi 1 and Mohammad A. Al-Sayah 2,* 1 Small Molecule Pharmaceutics, Genentech, Inc. So. San Francisco, CA 94080, USA; [email protected] (P.C.); [email protected] (K.N.) 2 Small Molecule Analytical Chemistry, Genentech, Inc. So. San Francisco, CA 94080, USA; [email protected] * Correspondence: [email protected]; Tel.: +650-467-3810 Received: 3 October 2019; Accepted: 18 November 2019; Published: 25 November 2019 Abstract: Micro- and nano-carrier formulations have been developed as drug delivery systems for active pharmaceutical ingredients (APIs) that suffer from poor physico-chemical, pharmacokinetic, and pharmacodynamic properties. Encapsulating the APIs in such systems can help improve their stability by protecting them from harsh conditions such as light, oxygen, temperature, pH, enzymes, and others. Consequently, the API’s dissolution rate and bioavailability are tremendously improved. Conventional techniques used in the production of these drug carrier formulations have several drawbacks, including thermal and chemical stability of the APIs, excessive use of organic solvents, high residual solvent levels, difficult particle size control and distributions, drug loading-related challenges, and time and energy consumption. This review illustrates how supercritical fluid (SCF) technologies can be superior in controlling the morphology of API particles and in the production of drug carriers due to SCF’s non-toxic, inert, economical, and environmentally friendly properties. The SCF’s advantages, benefits, and various preparation methods are discussed. Drug carrier formulations discussed in this review include microparticles, nanoparticles, polymeric membranes, aerogels, microporous foams, solid lipid nanoparticles, and liposomes.
    [Show full text]
  • Thermodynamics and Kinetics of Binary Nucleation in Ideal-Gas Mixtures
    1 Thermodynamics and kinetics of binary nucleation in ideal-gas mixtures Nikolay V. Alekseechkin Akhiezer Institute for Theoretical Physics, National Science Centre “Kharkov Institute of Physics and Technology”, Akademicheskaya Street 1, Kharkov 61108, Ukraine Email: [email protected] Abstract . The nonisothermal single-component theory of droplet nucleation (Alekseechkin, 2014) is extended to binary case; the droplet volume V , composition x , and temperature T are the variables of the theory. An approach based on macroscopic kinetics (in contrast to the standard microscopic model of nucleation operating with the probabilities of monomer attachment and detachment) is developed for the droplet evolution and results in the derived droplet motion equations in the space (V , x,T) - equations for V& ≡ dV / dt , x& , and T& . The work W (V , x,T) of the droplet formation is calculated; it is obtained in the vicinity of the saddle point as a quadratic form with diagonal matrix. Also the problem of generalizing the single-component Kelvin equation for the equilibrium vapor pressure to binary case is solved; it is presented here as a problem of integrability of a Pfaffian equation. The equation for T& is shown to be the first law of thermodynamics for the droplet, which is a consequence of Onsager’s reciprocal relations and the linked-fluxes concept. As an example of ideal solution for demonstrative numerical calculations, the o-xylene-m-xylene system is employed. Both nonisothermal and enrichment effects are shown to exist; the mean steady-state overheat of droplets and their mean steady-state enrichment are calculated with the help of the 3D distribution function.
    [Show full text]
  • 4-Aza Steroids As Active Inhibitors of Testosterone
    Europäisches Patentamt *EP000880540B1* (19) European Patent Office Office européen des brevets (11) EP 0 880 540 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.7: C07J 73/00, A61K 31/59 of the grant of the patent: 12.06.2002 Bulletin 2002/24 (86) International application number: PCT/US97/00469 (21) Application number: 97901995.7 (87) International publication number: (22) Date of filing: 09.01.1997 WO 97/30069 (21.08.1997 Gazette 1997/36) (54) 17-BETA-CYCLOPROPYL(AMINO/OXY) 4-AZA STEROIDS AS ACTIVE INHIBITORS OF TESTOSTERONE 5-ALPHA-REDUCTASE AND C17-20-LYASE 17-BETA-CYCLOPROPYL(AMINO/OXY)4-AZA STEROIDE ALS TESTOSTERONE 5-ALPHA-RECTASE UND C17-20-LYASE HEMMENDE VERBINDUNGEN 17-BETA-CYCLOPROPYL(AMINO/OXY) 4-AZA STEROIDES UTILISES EN QUALITES D’INHIBITEURS DE 5-ALPHA-REDUCTASE ET DE C17-20-LYASE DE TESTOSTERONE (84) Designated Contracting States: (74) Representative: Minoja, Fabrizio, Dr. et al AT BE CH DE DK ES FI FR GB GR IE IT LI LU MC Bianchetti Bracco Minoja S.r.l. NL PT SE Via Rossini, 8 Designated Extension States: 20122 Milano (IT) AL LT LV RO SI (56) References cited: (30) Priority: 14.02.1996 US 601278 WO-A-93/15104 WO-A-93/23053 WO-A-94/28010 (43) Date of publication of application: 02.12.1998 Bulletin 1998/49 • JOURNAL OF MEDICINAL CHEMISTRY, vol. 38, no. 7, 31 March 1995, WASHINGTON US, pages (73) Proprietor: Aventis Pharmaceuticals Inc. 1158-1173, XP002030536 XUN LI ET AL: Bridgewater, NJ 08807-0800 (US) "Synthesis and in Vitro Activity of 17.beta.-(N-Alkyl/arylformamido)- and (72) Inventors: 17.beta.-[(Alkyl/aryl)alkyl/arylamido]-4-m • PRIBISH, James R.
    [Show full text]
  • Spinodal Lines and Equations of State: a Review
    10 l Nuclear Engineering and Design 95 (1986) 297-314 297 North-Holland, Amsterdam SPINODAL LINES AND EQUATIONS OF STATE: A REVIEW John H. LIENHARD, N, SHAMSUNDAR and PaulO, BINEY * Heat Transfer/ Phase-Change Laboratory, Mechanical Engineering Department, University of Houston, Houston, TX 77004, USA The importance of knowing superheated liquid properties, and of locating the liquid spinodal line, is discussed, The measurement and prediction of the spinodal line, and the limits of isentropic pressure undershoot, are reviewed, Means are presented for formulating equations of state and fundamental equations to predict superheated liquid properties and spinodal limits, It is shown how the temperature dependence of surface tension can be used to verify p - v - T equations of state, or how this dependence can be predicted if the equation of state is known. 1. Scope methods for making simplified predictions of property information, which can be applied to the full range of Today's technology, with its emphasis on miniaturiz­ fluids - water, mercury, nitrogen, etc. [3-5]; and predic­ ing and intensifying thennal processes, steadily de­ tions of the depressurizations that might occur in ther­ mands higher heat fluxes and poses greater dangers of mohydraulic accidents. (See e.g. refs. [6,7].) sending liquids beyond their boiling points into the metastable, or superheated, state. This state poses the threat of serious thermohydraulic explosions. Yet we 2. The spinodal limit of liquid superheat know little about its thermal properties, and cannot predict process behavior after a liquid becomes super­ heated. Some of the practical situations that require a 2.1. The role of the equation of state in defining the spinodal line knowledge the limits of liquid superheat, and the physi­ cal properties of superheated liquids, include: - Thennohydraulic explosions as might occur in nuclear Fig.
    [Show full text]
  • A Review on Micronization Techniques JALAY T
    Jalay T. Joshi / Journal of Pharmaceutical Science and Technology Vol. 3 (7), 2011,651-681 A Review on Micronization Techniques JALAY T. JOSHI Department of Pharmaceutics and Pharmaceutical Technology, Sardar Patel University, A. R. College of Pharmacy and G. H. Patel Institute of Pharmacy, Motabazar, Vallabh Vidyanagar-388120, Anand, Gujarat, India Abstract: Drug powders containing micron-size drug particles are used in several pharmaceutical dosage forms. Many drugs, especially newly developed substances, are poorly water soluble, which limits their oral bioavailability. The dissolution rate can be enhanced by using micronized drugs. Small drug particles are also required in administration forms, which require the drug in micron-size size due to geometric reasons in the organ to be targeted (e.g., drugs for pulmonary use). The common technique for the preparation of micron-size drugs is the mechanical commination (e.g., by crushing, grinding, and milling) of previously formed larger particles. In spite of the widespread use of this technique, the milling process does not represent the ideal way for the production of small particles because drug substance properties and surface properties are altered in a mainly uncontrolled manner. Thus, techniques that prepare the drug directly in the required particle size are of interest. Because physicochemical drug powder properties are decisive for the manufacturing of a dosage form and for therapeutic success, the characterization of the particle surface and powder properties plays an important role. This article summarizes common and novel techniques for the production of a drug in small particle size. The properties of the resulting products that are obtained by different techniques are characterized and compared.
    [Show full text]
  • About Nucleation
    Nucleation • Nucleation: localized formation of a distinct thermodynamic phase. • Nucleation an occur in a gas, liquid or solid phase. Some examples of phases that may form via nucleation include: 1) in gas: Creation of liquid droplets in saturated vapor; 2) in liquid: formation of gaseous bubbles, crystals (e.g., ice formation from water), or glassy regions; 3) in solid: Nucleation of crystalline, amorphous, and even vacancy clusters in solid materials. Such solid state nucleation is important, for example, to the semiconductor industry. • Most nucleation processes are physical, rather than chemical. • Nucleation normally occurs at nucleation sites on surfaces contacting the liquid or vapor. Suspended particles or minute bubbles also provide nucleation sites. This is called heterogeneous nucleation (Lecture 12). • Nucleation without preferential nucleation sites is homogeneous nucleation (Lecture 10-11). Homogeneous nucleation occurs spontaneously and randomly, but it requires superheating or supercooling of the medium. Ref. wikipedia website Homogeneous Nucleation • Compared to the heterogeneous nucleation (which starts at nucleation sites on surfaces), Homogeneous nucleation occurs with much more difficulty in the interior of a uniform substance. The creation of a nucleus implies the formation of an interface at the boundaries of a new phase. • Liquids cooled below the maximum heterogeneous nucleation temperature (melting temperature), but which are above the homogeneous nucleation temperature (pure substance freezing temperature) are said to be supercooled. This is useful for making amorphous solids and other metastable structures, but can delay the progress of industrial chemical processes or produce undesirable effects in the context of casting. • Supercooling brings about supersaturation, the driving force for nucleation. Supersaturation occurs when the pressure in the newly formed solid is less than the vapor pressure, and brings about a change in free energy per unit volume, Gv, between the liquid and newly created solid phase.
    [Show full text]
  • Solubility of Progesterone in Supercritical Carbon Dioxide and Its Micronization Through RESS
    Powder Technology 258 (2014) 66–77 Contents lists available at ScienceDirect Powder Technology journal homepage: www.elsevier.com/locate/powtec Solubility of progesterone in supercritical carbon dioxide and its micronization through RESS Zhen Huang ⁎, Yu-hua Guo, Hui Miao, Li-jun Teng Department of Packaging Engineering, Institute of Materials & Chemical Engineering, Tianjin University of Commerce, Tianjin 300134, China article info abstract Article history: To investigate the formation of progesterone fine particles with rapid expansion of supercritical solution (RESS), Received 16 September 2013 it is vital to determine the solubility of progesterone under various equilibrium pressure and temperature Received in revised form 6 February 2014 conditions and to correlate the solubility data with a well-performed model. In this study, the solubility of Accepted 1 March 2014 progesterone in supercritical CO was measured using a dynamic apparatus at pressure ranging from 120 to Available online 11 March 2014 2 260 bar, and temperature from 313.15 to 338.15 K. The determined solubility in mole fraction is in the range −5– −4 – Keywords: of 5.3 × 10 8.9 × 10 and correlated with three empirical density-based models and the Peng Robinson Progesterone equation of state model. The latter model has better correlation effects than the other density-based models Supercritical CO2 and provides an overall average absolute relative deviation of 11.6% between the calculated and experimental Solubility data correlation solubility. Then, the performances of RESS under different conditions are evaluated by analyzing the particle RESS characteristics, and the effects of extraction temperature, extraction pressure, and nozzle diameter on the particle Particle micronization size and particle size distribution of the formed particles are discussed.
    [Show full text]
  • Nucleation and Condensation in Gas-Vapor Mixtures of Alkanes and Water
    Nucleation and condensation in gas-vapor mixtures of alkanes and water Citation for published version (APA): Peeters, P. (2002). Nucleation and condensation in gas-vapor mixtures of alkanes and water. Technische Universiteit Eindhoven. https://doi.org/10.6100/IR559332 DOI: 10.6100/IR559332 Document status and date: Published: 01/01/2002 Document Version: Publisher’s PDF, also known as Version of Record (includes final page, issue and volume numbers) Please check the document version of this publication: • A submitted manuscript is the version of the article upon submission and before peer-review. There can be important differences between the submitted version and the official published version of record. People interested in the research are advised to contact the author for the final version of the publication, or visit the DOI to the publisher's website. • The final author version and the galley proof are versions of the publication after peer review. • The final published version features the final layout of the paper including the volume, issue and page numbers. Link to publication General rights Copyright and moral rights for the publications made accessible in the public portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from the public portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain • You may freely distribute the URL identifying the publication in the public portal.
    [Show full text]