title: Study of the Transformations of Micro/Nano-crystalline Acetaminophen Polymorphs in Drug-Polymer Binary Mixtures.
abstract: This study elucidates the physical properties of sono-crystallised micro/nano-sized acetaminophen/paracetamol (PMOL) and monitors its possible transformation from polymorphic form I (monoclinic) to form II (orthorhombic). Hydrophilic Plasdone® S630 copovidone (S630), N-vinyl-2-pyrrolidone and vinyl acetate copolymer, and methacrylate-based cationic copolymer, Eudragit® EPO (EPO), were used as polymeric carriers to prepare drug/polymer binary mixtures. Commercially available PMOL was crystallised under ultra sound sonication to produce micro/nano-sized (0.2-10 microns) crystals in monoclinic form. Homogeneous binary blends of drug-polymer mixtures at various drug concentrations were obtained via a thorough mixing. The analysis conducted via the single X-ray crystallography determined the detailed structure of the crystallised PMOL in its monoclinic form. The solid state and the morphology analyses of the PMOL in the binary blends evaluated via differential scanning calorimetry (DSC), modulated temperature DSC (MTDSC), scanning electron microscopy (SEM) and hot stage microscopy (HSM) revealed the crystalline existence of the drug within the amorphous polymeric matrices. The application of temperature controlled X-ray diffraction (VTXRPD) to study the polymorphism of PMOL showed that the most stable form I (monoclinic) was altered to its less stable form II (orthorhombic) at high temperature (>112°C) in the binary blends regardless of the drug amount. Thus, VTXRD was used as a useful tool to monitor polymorphic transformations of crystalline drug (e.g. PMOL) to assess their thermal stability in terms of pharmaceutical product development and research.
authors: Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Arundel Building, Falmer, Brighton, BN1 9QG, UK. M.Maniruzzaman@sussex.ac.uk.
authors: Mohammed
authors: M
authors: Maniruzzaman
authors: Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Arundel Building, Falmer, Brighton, BN1 9QG, UK.
authors: Matthew
authors: M
authors: Lam
authors: Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Arundel Building, Falmer, Brighton, BN1 9QG, UK.
authors: Carlos
authors: C
authors: Molina
authors: Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Arundel Building, Falmer, Brighton, BN1 9QG, UK. A.Nokhodchi@sussex.ac.uk.|Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran. A.Nokhodchi@sussex.ac.uk.
authors: Ali
authors: A
authors: Nokhodchi
mesh_terms: D000082:Acetaminophen / Q000737:chemistry / Q000493:pharmacokinetics; D018712:Analgesics, Non-Narcotic / Q000737:chemistry / Q000493:pharmacokinetics; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D053758:Nanoparticles / Q000737:chemistry; D011109:Polymethacrylic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D011205:Povidone / Q000737:chemistry / Q000493:pharmacokinetics; D011759:Pyrrolidines / Q000737:chemistry / Q000493:pharmacokinetics; D013696:Temperature; D014753:Vinyl Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D018712:Analgesics, Non-Narcotic; D004337:Drug Carriers; D011109:Polymethacrylic Acids; D011759:Pyrrolidines; D014753:Vinyl Compounds; C402301:poly(vinylpyrrolidone-co-vinyl-acetate); C038300:methylmethacrylate-methacrylic acid copolymer; D000082:Acetaminophen; D011205:Povidone; C011566:vinyl acetate
keywords: monoclinic; nano-sized crystals; orthorhombic; sono-crystallisation; variable temperature XRPD