An approach to engineer paracetamol crystals by antisolvent crystallization technique in presence of various additives for direct compression

Waseem Kaialy, El Hassanne Larhrib, Brian Chikwanha, Saeed Shojaee, Ali Nokhodchi

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Paracetamol is a popular over-the-counter analgesic and a challenging model drug due to its poor technological and biopharmaceutical properties such as flowability, compressibility, compactibility and wettability. This work was aimed to alter the crystal habit of paracetamol from elongated to polyhedral-angular via particle engineering whilst maintaining the stable polymorphic form (form I: monoclinic form). The engineered paracetamol crystals obtained in the present investigation showed better technological and biopharmaceutical properties in comparison to the commercial paracetamol. Engineered paracetamol crystals were obtained using antisolvent crystallization technique in the presence of various concentrations (0.1, 0.5 and 1%, w/w) of additives, namely, polyvinyl alcohol (PVA), Avicel PH 102 (microcrystalline cellulose), Brij 58, methylcellulose (MC) and polyethylene glycol having different molecular weights (PEGs 1500, 6000 and 8000). Paracetamols crystallized in the presence of Avicel (or physically mixed with Avicel), Brij 58 and PEG 6000 demonstrated the best compactibility over a range of compaction pressures. Brij-crystallized paracetamol provided the fastest dissolution rate among all the paracetamol batches. Paracetamols crystallized in the presence of PVA or Avicel, or physically mixed with Avicel demonstrated a reduced degree of crystallinity in comparison to the other paracetamols. This study showed that the type, the grade and the concentration of additives could influence the physical stability such as flow, crystallinity and polymorphic transformation of paracetamol, the technological and biopharmaceutical properties of paracetamol. Stable polymorphic form of paracetamol with optimal tableting characteristics can be achieved through particle engineering.

Original languageEnglish
Pages (from-to)53-64
Number of pages12
JournalInternational Journal of Pharmaceutics
Volume464
Issue number1-2
DOIs
Publication statusPublished - 10 Apr 2014

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Acetaminophen
Crystallization
Cellulose
Cetomacrogol
Polyvinyl Alcohol
Wettability
Methylcellulose
Habits
Analgesics
Molecular Weight

Cite this

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title = "An approach to engineer paracetamol crystals by antisolvent crystallization technique in presence of various additives for direct compression",
abstract = "Paracetamol is a popular over-the-counter analgesic and a challenging model drug due to its poor technological and biopharmaceutical properties such as flowability, compressibility, compactibility and wettability. This work was aimed to alter the crystal habit of paracetamol from elongated to polyhedral-angular via particle engineering whilst maintaining the stable polymorphic form (form I: monoclinic form). The engineered paracetamol crystals obtained in the present investigation showed better technological and biopharmaceutical properties in comparison to the commercial paracetamol. Engineered paracetamol crystals were obtained using antisolvent crystallization technique in the presence of various concentrations (0.1, 0.5 and 1{\%}, w/w) of additives, namely, polyvinyl alcohol (PVA), Avicel PH 102 (microcrystalline cellulose), Brij 58, methylcellulose (MC) and polyethylene glycol having different molecular weights (PEGs 1500, 6000 and 8000). Paracetamols crystallized in the presence of Avicel (or physically mixed with Avicel), Brij 58 and PEG 6000 demonstrated the best compactibility over a range of compaction pressures. Brij-crystallized paracetamol provided the fastest dissolution rate among all the paracetamol batches. Paracetamols crystallized in the presence of PVA or Avicel, or physically mixed with Avicel demonstrated a reduced degree of crystallinity in comparison to the other paracetamols. This study showed that the type, the grade and the concentration of additives could influence the physical stability such as flow, crystallinity and polymorphic transformation of paracetamol, the technological and biopharmaceutical properties of paracetamol. Stable polymorphic form of paracetamol with optimal tableting characteristics can be achieved through particle engineering.",
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An approach to engineer paracetamol crystals by antisolvent crystallization technique in presence of various additives for direct compression. / Kaialy, Waseem; Larhrib, El Hassanne; Chikwanha, Brian; Shojaee, Saeed; Nokhodchi, Ali.

In: International Journal of Pharmaceutics, Vol. 464, No. 1-2, 10.04.2014, p. 53-64.

Research output: Contribution to journalArticle

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AU - Larhrib, El Hassanne

AU - Chikwanha, Brian

AU - Shojaee, Saeed

AU - Nokhodchi, Ali

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