Muhammad Sajid Hamid Akash, Ikram Ullah Khan, Syed Nisar Hussain Shah, Sajid Asghar, Asif massud, Muhammad Imran Qadir, Atif akbar
Hydrophilic matrices of xanthan gum and hydroxypropyl methylcellulose were prepared by direct compression using diclofenac sodium as model drug. All formulations were subjected to physical tests, FTIR studies and dissolution studies at pH 1.2 and 6.8, to evaluate drug release kinetics. In vivo studies were carried out in rabbits using single latin cross over design and pharmacokinetic parameters were analyzed by using one way ANOVA and LSD. Physical parameters of all formulations were within limits with stability of drug during direct compression and absence of drug polymer interaction as evident by FTIR spectra. In vitro release studies showed that both polymers were able to retard the drug release but matrices containing XG showed initial greater burst release in acidic media (pH 1.2) which was absent in HPMC matrices due to delayed hydration and pH independent gelling mechanism in HPMC. XG matrices showed greater sustained release pattern in phosphate buffer solution (pH 6.8) over twenty-four hours of study due to formation of gel and viscous solution around matrices. All the formulation followed Higuchi kinetics and Korsmeyer-Peppas equation confirms the involvement of multiple drug release mechanisms release from hydrophilic matrices. Plasma drug concentration in rabbits after oral administration was used to calculate different pharmacokinetic parameters, which showed the inverse relationship of the AUC, AUMC and Cmax of the drug with polymer concentrations. Statistical evaluation confirms the role of polymer concentration on delayed release. XG matrices demonstrated fewer time to reach Tmax, higher Cmax and AUC0-∞ values as compared to batches formulated with HPMC, owing to burst release of drug from XG matrices in acidic media. Both formulations showed poor IVIVC due to in vitro and in vivo difference of pH and ionic strength.