The present work reports the study of different ketoprofen:excipient formulations, in order to determine the effect of the polymer substitution and type of diluent on the drug-release mechanism. Substituted cellulose-methylcellulose, hydroxypropylcellulose and hydroxypropylmethylcellulose were used as polymers, while lactose monohydrate and beta-cyclodextrin were tested as diluents. Distinct test formulations were prepared, containing 57.14% of ketoprofen, 20.00% of polymer, 20.29% of diluent, and 1.71% of talc/0.86% of magnesium stearate as lubricants. The tablets were tested for their drug content, weight variation, hardness, thickness, tensile strength, friability, swelling and release ratio. Polymers MC25 and HPC were found not to be appropriate for the preparation of modified release ketoprofen hydrophilic matrix tablets, while HPMC K15M and K100M showed to be advantageous. The analysis of the release profiles in the light of distinct kinetic models (zero-order, first-order, Higuchi and Korsmeyer-Peppas) led to the conclusion that the type of polymer did not influence the release mechanism of the drug. The mean dissolution time (MDT) was determined, the highest MDT value being obtained for HPMC formulations. Moreover, the drug-release process was found to be slightly influenced by the type of diluent, either lactose or beta-cyclodextrin.

A thorough conformational analysis of ibuprofen [2-(4-isobutylphenyl) propionic acid] was carried by out, using density functional theory (DFT) calculations coupled to optical vibrational spectroscopy (both Raman and FTIR). Eight different geometries were found to be energy minima. The relative orientations of the substituent groups in the ibuprofen molecule, which can be considered as a para-substituted phenyl ring, were verified to hardly affect its conformational stability. The internal rotations converting the calculated conformers of ibuprofen were studied and the intramolecular interactions governing the conformational preferences of the molecule were analyzed by quantitative potential energy deconvolution using Fourier type profiles. The harmonic vibrational frequencies and corresponding intensities were calculated for all the conformers obtained, leading to the assignment of the spectra, and evidencing the sole presence of one of the lowest energy conformers in the solid state. Vibrational spectroscopic proof of intermolecular hydrogen bonds between the carboxylic groups of adjacent ibuprofen molecules, leading to the formation of dimers, was also obtained. ß

A conformational study of ketoprofen was carried out by both density functional theory (DFT) calculations and Raman spectroscopy. Nine different geometries were found to correspond to energy minimum conformations but only one of them was experimentally detected in the condensed phase spectra. Those rotations which interconvert the five most stable conformers were studied and the intramolecular interactions governing the corresponding conformational preferences were assessed. A thorough vibrational analysis was performed, leading to the assignment of both the solid and liquid spectra. Evidence for formation of intermolecular hydrogen bonds between carboxylic groups of adjacent ketoprofen molecules, leading to dimeric entities, was obtained.

Cellulose derivatives are the most frequently used polymers in formulations of pharmaceutical products for controlled drug delivery. The main aim of the present work was to evaluate the effect of different cellulose substitutions on the release rate of ibuprofen (IBP) from hydrophilic matrix tablets. Thus, the release mechanism of IBP with methylcellulose (MC25), hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K15M or K100M) was studied. In addition, the influence of the diluents lactose monohydrate (LAC) and beta-cyclodextrin (beta-CD) was evaluated. Distinct test formulations were prepared containing: 57.14% of IBP, 20.00% of polymer, 20.29% of diluent, 1.71% of talc lubricants, and 0.86% of magnesium stearate as lubricants. Although non-negligible drug-excipient interactions were detected from DSC studies, these were found not to constitute an incompatibility effect. Tablets were examined for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, swelling, and dissolution performance. Polymers MC25 and HPC were found to be unsuitable for the preparation of this kind of solid dosage form, while HPMC K15M and K100M showed to be advantageous. Dissolution parameters such as the area under the dissolution curve (AUC), the dissolution efficiency (DE(20 h)), dissolution time (t 50%), and mean dissolution time (MDT) were calculated for all the formulations, and the highest MDT values were obtained with HPMC indicating that a higher value of MDT signifies a higher drug retarding ability of the polymer and vice-versa. The analysis of the drug release data was performed in the light of distinct kinetic mathematical models-Kosmeyer-Peppas, Higuchi, zero-, and first-order. The release process was also found to be slightly influenced by the kind of diluent used.

The influence of cellulose ether derivatives on ibuprofen release from matrix tablets was investigated. Raman spectroscopy and differential scanning calorimetry (DSC) experiments were used, in order to examine the compatibility between the matrix components: both excipients and ibuprofen. While both the DSC and Raman results did not detect any incompatibilities, DSC revealed the existence of some drug:excipient interactions, reflected by variations in the hydration/dehydration processes. Formulations containing mixtures of polymers with both low and high viscosity grades-methylcellulose (MC25) or hydroxypropylcellulose (HPC), and hydroxypropylmethylcellulose (HPMC K100M), respectively--were prepared by a direct compression method (using 20, 25, and 30% of either MC25 or HPC). The tablets were evaluated for their drug content, weight uniformity, hardness, thickness, tensile strength, friability, porosity, surface area, and volume. Parameters such as the mean dissolution time (MDT) and the dissolution efficiency (DE) were calculated in all cases. The solid formulations presently studied demonstrated a predominantly Fickian diffusion release mechanism.