Authors:G. Perlovich, Tatyana Volkova, and Annette Bauer-Brandl
The thermodynamic relationship between crystal modifications of paracetamol was studied by alternative methods. Temperature
dependence of saturated vapor pressure for polymorphic modifications of the drug paracetamol (acetaminophen) was mea sured
and thermodynamic functions of the sublimation process calculated. Solution calorimetry was carried out for the two modifications
in the same solvent. Thermodynamic parameters for sublimation for form I (monoclinic) were found: ΔGsub298=60.0 kJ mol−1; ΔHsub298=117.9�0.7 kJ mol−1; ΔSsub298=190�2 J mol−1 K−1. For the orthorhombic modification (form II), the saturated vapor pressure could only be studied at 391 K. Phase transition
enthalpy at 298 K, ΔHtr298(I→II)=2.0�0.4 kJ mol−1, was derived as the difference between the solution enthalpies of the noted polymorphs in the same solution (methanol). Based
on ΔHtr298 (I→II), differences between temperature dependencies of heat capacities of both modifications and the vapor pressure value
of form II at 391 K, the temperature dependence of saturated vapor pressure and thermodynamic sublimation parameters for modification
II were also estimated (ΔGsub298=56.1 kJ mol−1; ΔHsub298=115.9�0.9 kJ mol−1; ΔSsub298=200�3 J mol−1 K−1). The results indicate that the modifications are monotropically related, which is in contrast to findings recently reported
found by classical thermochemical methods.
Authors:F. Giordano, A. Rossi, R. Bettini, A. Savioli, A. Gazzaniga, and Cs. Novák
The thermal behavior of binary mixtures of paracetamol and a polymeric excipient (microcrystalline cellulose, hydroxypropylmethylcellulose
and cross-linked poly(vinylpyrrolidone)) was investigated. The physical mixtures, ranging from 50 to 90% by mass of drug,
were submitted to a heating-cooling-heating program in the 35–180C temperature range. Solid-state analysis was performed
by means of differential scanning calorimetry (DSC), hot stage microscopy (HSM), micro-Fourier transformed infrared spectroscopy
(MFTIR), and scanning electron microscopy (SEM).
The polymeric excipients were found to address in a reproducible manner the recrystallization of molten paracetamol within
the binary mixture into Form II or Form III. The degree of crystallinity of paracetamol in the binary mixtures, evaluated
from fusion enthalpies during the first and second heating scans, was influenced by the composition of the mixture, the nature
of the excipient and the thermal history. In particular, DSC on mixtures with cross-linked poly(vinylpyrrolidone) and hydroxypropylmethylcellulose
with drug contents below 65 and75%, respectively, evidenced the presence only of amorphous paracetamol after the cooling phase.
Microcrystalline cellulose was very effective in directing the recrystallization of molten paracetamol as Form II.
Authors:P. Di Martino, P. Conflant, M. Drache, J. -P. Huvenne, and A. -M. Guyot-Hermann
The polymorphic forms II and III of paracetamol were obtained by melting the marketed form I. Under the melting and cooling conditions used, it was possible to obtain forms I, II and III. The recrystallization conditions and the physical properties of forms II and III were investigated by means of various techniques: thermomicroscopy, DSC analysis, infrared microspectrometry and X-ray powder diffraction at room temperature and as a function of temperature. Form III was found to be very unstable. However, its formation seems to be an important intermediate step in the preparation of form II.
Authors:Almas Arage, Thomas Layloff, Ariaya Hymete, and Ayenew Ashenef
as an important tool in routine analysis for pharmaceuticals.
Paracetamol (PCM) chemically is N-(4-hydroxyphenyl) acetamide; commonly known as acetaminophen ( Fig. 1a ). PCM exhibit absorption maxima at 257 nm. It is used as
Authors:Nafiu Aminu, Siok-Yee Chan, Nasir Hayat Khan, Ahmed Bassam Farhan, Muhammad Nura Umar, and Seok-Ming Toh
, and minimize the development of resistance to antibiotics [ 2 ].
The fixed-dose combination of paracetamol (PCM) and caffeine (CF) is primarily employed in conditions such as a migraine headache [ 4 ], which is a chronic and common disorder
Authors:Antonilêni Medeiros, Ana Santos, F. de Souza, J. Procópio, Márcia Pinto, and R. Macêdo
Stability of drugs
and products has a great practical interest, which is facing to strict regulation.
Thermal studies, besides the determination of the thermal properties of the
investigated product allow the verification of possible interactions between
the drug substances and excipients. The objective of this work was to obtain
solid pre-formulates of paracetamol (PC) by spray drying (SPDR), as well as
to investigate their thermal behavior. Dynamic and isotherm TG, conventional
DSC and DSC-photovisual coupled methods were used to characterize the conventional
and pre-formulated mixtures obtained by SPDR. The results of both DSC investigations
showed slight alterations in melting temperatures, which suggests incompatibilities.
The TG decomposition data of the mixtures evidenced that the dry process via
SPDR leads to stability enhancement of the pre-formulated mixtures.
Authors:V. K. Mahajan, S. B. Bari, A. A. Shirkhedkar, and S. J. Surana
A new simple, accurate, precise, rapid, and selective densitometric TLC method has been established for simultaneous analysis of aceclofenac, paracetamol, and chlorzoxazone in tablets. Identification and quantification were performed on 10 cm × 10 cm aluminium-backed TLC plates coated with 0.2 mm layers of silica gel 60 F254, previously washed with methanol, and using toluene-2-propanol-ammonia 4:4:0.4 (υ/υ) as mobile phase. Detection was performed at 274 nm. The RF values of aceclofenac, paracetamol, and chlorzoxazone were 0.28 ± 0.01, 0.72 ± 0.02, and 0.51 ± 0.02, respectively. Calibration plots were linear in the range 400–1400 ng per band for aceclofenac, 2000–7000 ng per band for paracetamol, and 1000–3500 ng per band for chlorzoxazone, with correlation coefficients, r, 0.9995, 0.9993, and 0.9996, respectively. Recovery of aceclofenac, paracetamol, and chlorzoxazone were 99.54–100.44, 100.02–100.47, and 99.39–99.84%, respectively. The suitability of densitometric TLC for quantitative analysis of these compounds was proved by validation in accordance with the requirements of ICH Guidelines.
Authors:S. Romero, P. Bustamante, B. Escalera, M. Cirri, and P. Mura
Differential scanning calorimetry (DSC), supported by hot stage microscopy, IR spectroscopy and X-ray powder diffractometry,
was used to investigate the characteristics of the solid phases of mefenamic, niflumic, and flufenamic acids and of paracetamol,
before and after equilibration with saturated solutions in different solvents. Mixtures of Lewis base (dioxane and ethyl acetate)
and amphiprotic solvents (ethanol and water) were prepared for evaluating the influence of both nature and polarity of the
solvents. Solid-state analysis performed on the original samples (commercial products) made it possible to establish that
paracetamol, mefenamic acid and flufenamic acid were in their respective Form I. No polymorphic modifications are known for
niflumic acid. Paracetamol, niflumic and mefenamic acids did not show any change after equilibration with the various solvents
or solvent mixtures, regardless of their different chemical nature. In contrast, DSC, IR and X-ray analyses revealed the partial
recrystallization of flufenamic acid into its polymorphic Form III in solid phases at equilibrium with ethanol, ethyl acetate
and their blends, as well as in dioxane-water mixtures containing 30 to 100% dioxane and in ethanol-water mixtures with a
water content less than 50%.
Authors:Ricardo Picciochi, Hermínio Diogo, and Manuel Minas da Piedade
Combustion calorimetry, Calvet-drop sublimation calorimetry, and the Knudsen effusion method were used to determine the standard
(po = 0.1 MPa) molar enthalpies of formation of monoclinic (form I) and gaseous paracetamol, at T = 298.15 K:
were used to assess the predictions of the B3LYP/cc-pVTZ and CBS-QB3 methods for the enthalpy of a isodesmic and isogyric
reaction involving those species. This test supported the reliability of the theoretical methods, and indicated a good thermodynamic
consistency between the