Preparation and characterization of pyrimethamine solid dispersions and an evaluation of the physical nature of pyrimethamine in solid dispersions

Pinak Khatri, Mansi Shah, Niketkumar Patel, Shashank Jain, Namrata Vora, Senshang Lin

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The objective of this investigation was to prepare, characterize pyrimethamine solid dispersions formulated with different carriers and to evaluate the physical nature of pyrimethamine in solid dispersion. Pyrimethamine solid dispersions were prepared by solvent evaporation technique using a rotary evaporator and characterized using intrinsic dissolution studies, differential scanning calorimetry (DSC), x-ray diffractometry (XRD), fourier transform infrared spectroscopy (FTIR), dissolution studies, and stability studies of selected solid dispersion. To further investigate the nature of drug, nuclear magnetic resonance was also performed. Intrinsic dissolution studies demonstrate that the dissolution rate of pyrimethamine could be markedly improved via solid dispersion technique. DSC studies show that PEG 6000 and poloxamer 188 could dissolve pyrimethamine up to 50% (w/w) in molten state. Results of XRD and FTIR suggest the presence of a different polymorphic form of pyrimethamine which might be due to the disruption of the supramolecular ribbon (synthon) formation of the original pyrimethamine polymorph. Significant improvement in dissolution rate from pyrimethamine solid dispersion using poloxamer 188 was achieved and pyrimethamine/poloxamer 188 ratio at 1:3 showing maximum dissolution rate enhancement of pyrimethamine. Furthermore, stability studies indicate no significant change in the physical nature of pyrimethamine in selected solid dispersion up to 5-month.

Original languageEnglish (US)
Pages (from-to)110-123
Number of pages14
JournalJournal of Drug Delivery Science and Technology
Volume45
DOIs
StatePublished - Jun 1 2018
Externally publishedYes

Fingerprint

Pyrimethamine
Poloxamer
Differential Scanning Calorimetry
Fourier Transform Infrared Spectroscopy
X-Rays
Magnetic Resonance Spectroscopy

Keywords

  • Intrinsic dissolution rate
  • Polymorph
  • Pyrimethamine
  • Solid dispersion
  • Supramolecular synthon
  • Thermogelling

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Preparation and characterization of pyrimethamine solid dispersions and an evaluation of the physical nature of pyrimethamine in solid dispersions. / Khatri, Pinak; Shah, Mansi; Patel, Niketkumar; Jain, Shashank; Vora, Namrata; Lin, Senshang.

In: Journal of Drug Delivery Science and Technology, Vol. 45, 01.06.2018, p. 110-123.

Research output: Contribution to journalArticle

@article{94ce1a3d2792497cb2ce4aae56aae1b6,
title = "Preparation and characterization of pyrimethamine solid dispersions and an evaluation of the physical nature of pyrimethamine in solid dispersions",
abstract = "The objective of this investigation was to prepare, characterize pyrimethamine solid dispersions formulated with different carriers and to evaluate the physical nature of pyrimethamine in solid dispersion. Pyrimethamine solid dispersions were prepared by solvent evaporation technique using a rotary evaporator and characterized using intrinsic dissolution studies, differential scanning calorimetry (DSC), x-ray diffractometry (XRD), fourier transform infrared spectroscopy (FTIR), dissolution studies, and stability studies of selected solid dispersion. To further investigate the nature of drug, nuclear magnetic resonance was also performed. Intrinsic dissolution studies demonstrate that the dissolution rate of pyrimethamine could be markedly improved via solid dispersion technique. DSC studies show that PEG 6000 and poloxamer 188 could dissolve pyrimethamine up to 50{\%} (w/w) in molten state. Results of XRD and FTIR suggest the presence of a different polymorphic form of pyrimethamine which might be due to the disruption of the supramolecular ribbon (synthon) formation of the original pyrimethamine polymorph. Significant improvement in dissolution rate from pyrimethamine solid dispersion using poloxamer 188 was achieved and pyrimethamine/poloxamer 188 ratio at 1:3 showing maximum dissolution rate enhancement of pyrimethamine. Furthermore, stability studies indicate no significant change in the physical nature of pyrimethamine in selected solid dispersion up to 5-month.",
keywords = "Intrinsic dissolution rate, Polymorph, Pyrimethamine, Solid dispersion, Supramolecular synthon, Thermogelling",
author = "Pinak Khatri and Mansi Shah and Niketkumar Patel and Shashank Jain and Namrata Vora and Senshang Lin",
year = "2018",
month = "6",
day = "1",
doi = "10.1016/j.jddst.2018.03.012",
language = "English (US)",
volume = "45",
pages = "110--123",
journal = "Journal of Drug Delivery Science and Technology",
issn = "1773-2247",
publisher = "Editions de Sante",

}

TY - JOUR

T1 - Preparation and characterization of pyrimethamine solid dispersions and an evaluation of the physical nature of pyrimethamine in solid dispersions

AU - Khatri, Pinak

AU - Shah, Mansi

AU - Patel, Niketkumar

AU - Jain, Shashank

AU - Vora, Namrata

AU - Lin, Senshang

PY - 2018/6/1

Y1 - 2018/6/1

N2 - The objective of this investigation was to prepare, characterize pyrimethamine solid dispersions formulated with different carriers and to evaluate the physical nature of pyrimethamine in solid dispersion. Pyrimethamine solid dispersions were prepared by solvent evaporation technique using a rotary evaporator and characterized using intrinsic dissolution studies, differential scanning calorimetry (DSC), x-ray diffractometry (XRD), fourier transform infrared spectroscopy (FTIR), dissolution studies, and stability studies of selected solid dispersion. To further investigate the nature of drug, nuclear magnetic resonance was also performed. Intrinsic dissolution studies demonstrate that the dissolution rate of pyrimethamine could be markedly improved via solid dispersion technique. DSC studies show that PEG 6000 and poloxamer 188 could dissolve pyrimethamine up to 50% (w/w) in molten state. Results of XRD and FTIR suggest the presence of a different polymorphic form of pyrimethamine which might be due to the disruption of the supramolecular ribbon (synthon) formation of the original pyrimethamine polymorph. Significant improvement in dissolution rate from pyrimethamine solid dispersion using poloxamer 188 was achieved and pyrimethamine/poloxamer 188 ratio at 1:3 showing maximum dissolution rate enhancement of pyrimethamine. Furthermore, stability studies indicate no significant change in the physical nature of pyrimethamine in selected solid dispersion up to 5-month.

AB - The objective of this investigation was to prepare, characterize pyrimethamine solid dispersions formulated with different carriers and to evaluate the physical nature of pyrimethamine in solid dispersion. Pyrimethamine solid dispersions were prepared by solvent evaporation technique using a rotary evaporator and characterized using intrinsic dissolution studies, differential scanning calorimetry (DSC), x-ray diffractometry (XRD), fourier transform infrared spectroscopy (FTIR), dissolution studies, and stability studies of selected solid dispersion. To further investigate the nature of drug, nuclear magnetic resonance was also performed. Intrinsic dissolution studies demonstrate that the dissolution rate of pyrimethamine could be markedly improved via solid dispersion technique. DSC studies show that PEG 6000 and poloxamer 188 could dissolve pyrimethamine up to 50% (w/w) in molten state. Results of XRD and FTIR suggest the presence of a different polymorphic form of pyrimethamine which might be due to the disruption of the supramolecular ribbon (synthon) formation of the original pyrimethamine polymorph. Significant improvement in dissolution rate from pyrimethamine solid dispersion using poloxamer 188 was achieved and pyrimethamine/poloxamer 188 ratio at 1:3 showing maximum dissolution rate enhancement of pyrimethamine. Furthermore, stability studies indicate no significant change in the physical nature of pyrimethamine in selected solid dispersion up to 5-month.

KW - Intrinsic dissolution rate

KW - Polymorph

KW - Pyrimethamine

KW - Solid dispersion

KW - Supramolecular synthon

KW - Thermogelling

UR - http://www.scopus.com/inward/record.url?scp=85043524474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85043524474&partnerID=8YFLogxK

U2 - 10.1016/j.jddst.2018.03.012

DO - 10.1016/j.jddst.2018.03.012

M3 - Article

AN - SCOPUS:85043524474

VL - 45

SP - 110

EP - 123

JO - Journal of Drug Delivery Science and Technology

JF - Journal of Drug Delivery Science and Technology

SN - 1773-2247

ER -