An approach to engineer paracetamol crystals by antisolvent crystallization technique in presence of various additives for direct compression.
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.
Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB Kent, UK; Pharmaceutics and Pharmaceutical Technology Department, School of Pharmacy, University of Damascus, Syria. Electronic address: w.kaialy@kent.ac.uk.
Waseem
W
Kaialy
School of Applied Sciences, University of Huddersfield, Huddersfield, UK.
Hassan
H
Larhrib
Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB Kent, UK.
Brian
B
Chikwanha
Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB Kent, UK.
Saeed
S
Shojaee
Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent, ME4 4TB Kent, UK; Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz 51664, Iran. Electronic address: a.nokhodchi@kent.ac.uk.
Ali
A
Nokhodchi
D000082:Acetaminophen / Q000138:chemical synthesis*; D002616:Chemical Engineering / Q000379:methods*; D019245:Compressive Strength; D003460:Crystallization; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis; D012995:Solubility; D012997:Solvents / Q000138:chemical synthesis*
D011108:Polymers; D012997:Solvents; D000082:Acetaminophen
Additives; Antisolvent crystallization; Compactibility; Crystal habit; Paracetamol; Particle engineering