Preparation of nanoparticles consisting of methacrylic polymers and drugs by an aerosol flow reactor method

Dissertation

Hannele Eerikäinen

Research output: ThesisDissertationCollection of Articles

Abstract

Drug-containing polymer nanoparticles are submicron-sized particles consisting of drug and stabilising or functional polymer. In this experimental study, methacrylic polymer nanoparticles with and without incorporated model drug were prepared using a novel method, namely, aerosol flow reactor method. This method involves first preparing a solution containing the drug and the polymer, followed by spraying the solution as nanosized droplets into a carrier gas stream, then drying the nanoparticles in a tubular laminar flow reactor tube, and finally collecting the nanoparticles. Model polymers used in this study were Eudragit L, Eudragit E, and Eudragit RS, which are commonly used methacrylic polymers in the pharmaceutical industry. Model drugs studied were beclomethasone dipropionate, ketoprofen, and naproxen. Various properties of the prepared nanoparticles were studied, such as particle size and size distribution, morphology, crystallinity, thermal properties, drug content, and drug release. It was found that this method could be used to produce amorphous, spherical, homogeneous matrix-type drug-polymer nanoparticles. The size of the particles was adjusted between 90 and 200 nm by the concentration of the solution. The morphology of the particles varied as a function of the properties and composition of the starting solution. The nanoparticles were collected as dry powders, but the stability of the powders in an amorphous form was found to be dependent on the interactions between the drug and the polymer. When the amount of the drug in the nanoparticles was below the solubility limit of the drug in the polymer, the amorphous nanoparticles were found to be stable and no crystallisation of the drug took place. When the amount of the drug was larger than the solubility limit, large crystalline structures were formed due to crystallisation of the drug. The crystallisation was also dependent on the thermal properties of the drug, as amorphous nanoparticles consisting of a drug having a high glass transition temperature could be collected at room temperature. A low glass transition temperature of the drug led to crystallisation of the drug at ambient conditions, when the drug amount in the nanoparticles was larger than the solubility limit. Drug release from the nanoparticles could be modified by using polymers having specific solubility properties.
Original languageEnglish
QualificationDoctor Degree
Awarding Institution
  • University of Helsinki
Supervisors/Advisors
  • Kauppinen, Esko, Supervisor, External person
  • Tenhu, Heikki, Supervisor, External person
Award date3 Jun 2005
Place of PublicationEspoo
Publisher
Print ISBNs951-38-6443-X
Electronic ISBNs951-38-6444-8
Publication statusPublished - 2005
MoE publication typeG5 Doctoral dissertation (article)

Fingerprint

Aerosols
Polymers
Nanoparticles
Pharmaceutical Preparations
Crystallization
Solubility
Powders
Thermodynamic properties
Beclomethasone
Ketoprofen
Functional polymers
Naproxen

Keywords

  • methacrylic polymer nanoparticles
  • preparation of drug nanoparticles
  • aerosol flow reactor method
  • drug release
  • solubility properties
  • particle size
  • morphology
  • crystallinity
  • thermal properties
  • drug content

Cite this

Eerikäinen, Hannele. / Preparation of nanoparticles consisting of methacrylic polymers and drugs by an aerosol flow reactor method : Dissertation. Espoo : VTT Technical Research Centre of Finland, 2005. 116 p.
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Preparation of nanoparticles consisting of methacrylic polymers and drugs by an aerosol flow reactor method : Dissertation. / Eerikäinen, Hannele.

Espoo : VTT Technical Research Centre of Finland, 2005. 116 p.

Research output: ThesisDissertationCollection of Articles

TY - THES

T1 - Preparation of nanoparticles consisting of methacrylic polymers and drugs by an aerosol flow reactor method

T2 - Dissertation

AU - Eerikäinen, Hannele

PY - 2005

Y1 - 2005

N2 - Drug-containing polymer nanoparticles are submicron-sized particles consisting of drug and stabilising or functional polymer. In this experimental study, methacrylic polymer nanoparticles with and without incorporated model drug were prepared using a novel method, namely, aerosol flow reactor method. This method involves first preparing a solution containing the drug and the polymer, followed by spraying the solution as nanosized droplets into a carrier gas stream, then drying the nanoparticles in a tubular laminar flow reactor tube, and finally collecting the nanoparticles. Model polymers used in this study were Eudragit L, Eudragit E, and Eudragit RS, which are commonly used methacrylic polymers in the pharmaceutical industry. Model drugs studied were beclomethasone dipropionate, ketoprofen, and naproxen. Various properties of the prepared nanoparticles were studied, such as particle size and size distribution, morphology, crystallinity, thermal properties, drug content, and drug release. It was found that this method could be used to produce amorphous, spherical, homogeneous matrix-type drug-polymer nanoparticles. The size of the particles was adjusted between 90 and 200 nm by the concentration of the solution. The morphology of the particles varied as a function of the properties and composition of the starting solution. The nanoparticles were collected as dry powders, but the stability of the powders in an amorphous form was found to be dependent on the interactions between the drug and the polymer. When the amount of the drug in the nanoparticles was below the solubility limit of the drug in the polymer, the amorphous nanoparticles were found to be stable and no crystallisation of the drug took place. When the amount of the drug was larger than the solubility limit, large crystalline structures were formed due to crystallisation of the drug. The crystallisation was also dependent on the thermal properties of the drug, as amorphous nanoparticles consisting of a drug having a high glass transition temperature could be collected at room temperature. A low glass transition temperature of the drug led to crystallisation of the drug at ambient conditions, when the drug amount in the nanoparticles was larger than the solubility limit. Drug release from the nanoparticles could be modified by using polymers having specific solubility properties.

AB - Drug-containing polymer nanoparticles are submicron-sized particles consisting of drug and stabilising or functional polymer. In this experimental study, methacrylic polymer nanoparticles with and without incorporated model drug were prepared using a novel method, namely, aerosol flow reactor method. This method involves first preparing a solution containing the drug and the polymer, followed by spraying the solution as nanosized droplets into a carrier gas stream, then drying the nanoparticles in a tubular laminar flow reactor tube, and finally collecting the nanoparticles. Model polymers used in this study were Eudragit L, Eudragit E, and Eudragit RS, which are commonly used methacrylic polymers in the pharmaceutical industry. Model drugs studied were beclomethasone dipropionate, ketoprofen, and naproxen. Various properties of the prepared nanoparticles were studied, such as particle size and size distribution, morphology, crystallinity, thermal properties, drug content, and drug release. It was found that this method could be used to produce amorphous, spherical, homogeneous matrix-type drug-polymer nanoparticles. The size of the particles was adjusted between 90 and 200 nm by the concentration of the solution. The morphology of the particles varied as a function of the properties and composition of the starting solution. The nanoparticles were collected as dry powders, but the stability of the powders in an amorphous form was found to be dependent on the interactions between the drug and the polymer. When the amount of the drug in the nanoparticles was below the solubility limit of the drug in the polymer, the amorphous nanoparticles were found to be stable and no crystallisation of the drug took place. When the amount of the drug was larger than the solubility limit, large crystalline structures were formed due to crystallisation of the drug. The crystallisation was also dependent on the thermal properties of the drug, as amorphous nanoparticles consisting of a drug having a high glass transition temperature could be collected at room temperature. A low glass transition temperature of the drug led to crystallisation of the drug at ambient conditions, when the drug amount in the nanoparticles was larger than the solubility limit. Drug release from the nanoparticles could be modified by using polymers having specific solubility properties.

KW - methacrylic polymer nanoparticles

KW - preparation of drug nanoparticles

KW - aerosol flow reactor method

KW - drug release

KW - solubility properties

KW - particle size

KW - morphology

KW - crystallinity

KW - thermal properties

KW - drug content

M3 - Dissertation

SN - 951-38-6443-X

T3 - VTT Publications

PB - VTT Technical Research Centre of Finland

CY - Espoo

ER -