Improvement of availability of allopurinol from pharmaceutical dosage forms I - suppositories.

Solid dispersion and crystallization of a very slightly water-soluble drug, allopurinol, were prepared using urea, sodium salicylate and beta-cyclodextrin (beta-CD) as carriers. The spectroscopic infra-red (IR), differential scanning calorimetry (DSC) and powder X-ray diffractometry (PXRD) data indicate a role of these carriers in decreasing the crystallinity of allopurinol and complexing abilities. Solid dispersion and crystallization of the drug with these carriers were used in suppository formulations to investigate their role in enhancement of drug release through the membrane barrier. The bases used included Suppocire AM and the mixture of polyethylene glycols (PEGs). The release rates of allopurinol from lipophilic and hydrophilic suppository bases were examined and compared with those obtained for their inclusion compounds incorporated in the same bases. The prepared suppositories were evaluated for in-vitro drug release, when fresh and on storage. The release of pure allopurinol from the lipophilic base was remarkably higher than that from the hydrophilic one. The release of allopurinol from lipophilic as well as hydrophilic bases was significantly enhanced by crystallization of the drug from 5% w/v of sodium salicylate. Allopurinol crystallized from sodium salicylate, showed enhanced release reaching about 100% in 1 h from the Suppocire AM base. The obtained data from these experiments proved the superiority of the PEG formulations containing coevaporates of the drug to sodium salicylate, ratio 1:1, or of the drug to beta-CD, ratio 1:2; T(90%),12 and 36 min, respectively. A significant decrease of uric acid excretion in rabbits was observed after rectal administration of suppositories containing allopurinol crystallized from sodium salicylate.

Accelerated stability of Ibuprofen-Eudragit RSPM sustained release tablets, IR and DSC solid stability testing.

Preformulated Ibuprofen-Eudragit RSPM sustained release tablets were subjected to accelerated stability testing at 25, 37 and 45 degrees C for 6 months. The stored tablets were evaluated for the intact drug in the formula, drug-polymer interaction and compatibility of the drug with the formulated excipients using infra red spectroscopy (IR) and differential scanning calorimetry (DSC). The IR spectrum of Ibuprofen in the tablets prepared by 15% w/v Eudragit RSPM as a granulating agent and containing 23% w/v Avicel pH 102 as an excipient is similar to the IR of standard Ibuprofen. There is no change in the IR spectra of the tablet components before and after storage of those tablets at the different investigated temperatures for 1, 3 and 6 months. The DSC thermograms of the Ibuprofen stored tablets show that the drug was still in the highly pure (> 98%) crystalline form and there was no significant degradation after storage indicating the stability of the drug on storage. In detecting Ibuprofen purity in the stored tablets, plotting of the sample temperature versus the reciprocal of the fraction of Ibuprofen melted showed deviation from Van 't Hoff linear plot.