Development, characterization and evaluation of the dissolution profile of sulfasalazine suspensions / Desenvolvimento, caracterização e avaliação do perfil de dissolução de suspensões sulfasalazina

This paper reports the development, characterization and in vitrodissolution behavior of sulfasalazine suspensions for treatment of chronic intestinal inflammatory diseases. Three formulations were developed, from powdered sulfasalazine obtained from different suppliers. The sulfasalazine was characterized regarding concentration, Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), X-Ray Diffraction (XRD), particle size distribution, polydispersion and solubility. The suspensions were developed and characterized regarding pH, viscosity, density, particle size, sedimentation volume, concentration and dissolution. The pH values were slightly acidic. The method of preparing the suspensions reduced the particle sizes and made the size distribution more homogeneous. The dissolution studies showed that the sulfasalazine suspensions had low solubility in acidic media, but dissolve quickly, reaching levels of 85%, in neutral media or media containing 0.5% of surfactants such as polysorbate 80. Besides this, the sulfasalazine suspensions were classified as having immediate dissolution because they reached dissolution levels near 100% in 20 minutes...

O trabalho reporta o desenvolvimento, caracterização e estudo in vitro de dissolução de suspensões de sulfassalazina para uso em doenças inflamatórias crônicas intestinais. Desenvolveram-se três formulações baseadas em fornecedores diferentes de pó de sulfassalazina. A sulfassalazina foi caracterizada quanto a Teor, Infravermelho por Transformada de Fourier (FTIR), Calorimetria Diferencial de Varredura (DSC), Difração de Raios-X (XRD), distribuição de tamanho das partículas, índice de polidispersão e solubilidade. A suspensão foi desenvolvida e caracterizada quanto a pH, viscosidade, densidade, tamanho de partícula, volume de sedimentação, teor e estudo de dissolução. Os valores de pH determinados foram levemente ácidos. O método de preparo das suspensões reduziu o tamanho das partículas e tornou a distribuição de tamanho mais homogênea. Os estudos de dissolução mostraram que a suspensão de sulfassalazina tem problemas de solubilidade em meios de caráter ácido, entretanto, sofre dissolução rápida acima de 85% em meios neutros ou contendo 0,5% de tensoativos como Polissobato 80. Além disso, as suspensões de sulfassalazina foram classificadas como formulações de dissolução imediata porque a partir de 20 minutos sofrem dissolução em torno de 100%...

The Effects of Sulphasalazine on Urinary Excretion of the Hydroxypyridinium Crosslinks of Collagen in Patients with Rheumatoid Arthritis

Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent years, several attempts have been made to develop specific markers for monitoring connective tissue metabolism in arthritic diseases. Our purpose, in this study was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the activity of RA (changes related to sulphasalazine treatment). Fourty premenopausal female patients with active RA (mean age; 36.0 7.2 years), 20 postmenopausal women with active RA (mean age; 60.0 6.8 years), 23 postmenopausal women with OA (mean age; 56.1 6.6 years) and 17 premenopausal healthy subjects (mean age; 28.3 4.28 years) were enrolled in our study. All of the 40 premenopausal female patients with active RA were given sulphasalazine. The mean follow up period for these patients was 10.3 1.1 months. In all of these patients, urine samples were collected both in the active and in the inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD levels were significantly higher in the active period (14.01 3.16 nmol/mmol cr) than in the inactive (8.25 4.23 nmol/mmol cr) period in patients with premenopausal RA (p 0.05). Urine PYD levels were significantly high in postmenopausal active RA patients (19.06 3.26 nmol/mmol cr) compared to premenopausal active and ind inactive, postmenopausal inactive RA patients, osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients with premenopausal RA in the active (7.46 2.13 nmol/mmol cr) and inactive periods (5.08 0.87 nmol/mmol cr) (p 0.05). In active premenopausal RA patients, a correlation was found between PYD excretion and RAI, ESR, CRP and functional capacity (r=0.5729 p 0.01, r=0.5953 p 0.01, r=0.6125 p 0.01 and r=0.6232, p 0.01 respectively). But in the inactive period, no such correlation was was evident. In disease activity parameters did not correlate with DPYD excretion in either the active or the inactive period. As a result, urine PYD excretion was significantly high in patients with active RA. During sulphasalazine treatment, urine PYD levels decreased. This is attributed to improvement in bone destruction.

Effect of sulphasalazine and meloxicam on adjuvant - induced arthritis, clues to their action

This work was conducted to determine the possible in vivo effect of sulfasalazine and meloxicam on free oxygen radicals in adjuvant- induced arthritis in rats. Twenty-four male albino rats were used and divided into four equal groups. The first group consisted of non- arthritic rats [normal control] received normal saline orally for 21 days. The second group received intragastric saline for the same duration [arthritic control]. Third group consisted of arthritic rats treated with meloxicam in a dose of 0.12 mg/kg/d. The fourth group received sulfasalazine in a dose of 270 mg/kg/d orally for 21 days. The results suggested that sulfasalazine was as effective as meloxicam in the treatment of collagen II adjuvant-induced arthritis as both drugs exerted a free oxygen radical scavenging activity

Olsalazina / Olsalazine

En 1942 la reumatóloga sueca Dra. Nana Svartz comunicó los favorables resultados obtenidos con la administración de asulfidina a pacientes portadores de artritis y diarrea

The anti-inflammatory activity of some sulphonamides in albino rats.

Clinically equivalent doses of dapsone, sulphasalasine and sulphamethizole in albino rats showed significant (P < 0.05) anti-inflammatory activity in carrageenan and cotton pellet induced inflammation. Their activity was comparable to that of aspirin (200 mg/kg) and was confirmed by granuloma histology. Further, these compounds also showed significant (P < 0.01) analgesic activity which was comparable to that of aspirin. The ulcer index for sulphamethizole was comparable to that of control animals, whereas dapsone and sulphasalazine showed significant ulcerogenicity (P < 0.01). Other sulphonamides like sulphadiazine, sulphanilamide, sulphamoxole and cotrimoxazole did not show significant anti-inflammatory and analgesic activities.

Prostaglandin catabolism and ulcerative colitis: effect of sulphasalazine, 5-aminosalicylic acid and other drugs

1. Evidence is presented for the occurrence of type 1 prostaglandin 15-hidroxydehydrogenase in human rectal mucosa. No evidence of the presence of type 2 dnzyme was found. 2. A 15-keto-prostaglandin reductase, responsible for the breakdown of 13, 14-dihydro 15-keto prostaglandins to 13, 14-dihydro prostaglandins, was also present in human rectal mucosa. 3. Ulcerative colitis patients catabolized prostaglandins to the same extent as the control group. PGE was catabolized significantly better than PGF2 alfa. 4. 5-Aminosalicylic acid and sulphapyridine did not affect prostaglandin catabolism. Sulphasalazine, methilsulphasalazine, indomethacin, flurbiprofen, disodium cromoglycate, sodium salicylate and carbenoxolone sodium inhibited prostaglandin catabolism to the same extent in both groups.Salicylazosulphadimidine was a more potent inhibitor of PGE1 catabolism than of PGF2alfa. 5. The increased prostaglandin synthesis reported for ulcerative colitis patients was not paralleled by increased catabolism, a fact possibly contributing to the accumulation of such compounds in the diseased state

The effect of sulphasalazine on the in vitro activation of human peripheral blood mononuclear cells by phytohemagglutinin P

The in vitro action of sulphaslazine, BW 755-C and indomethacin on phytohemaglutinin P-induced human peripheral brood mononuclear cell activation was studied. Sulphasalazine increased, while indomethacin and BW 755-C decreased, prostaglandin E2 (PGE2) accumulation in activated cultures. When used together with indomethacin or BW 755-C, sulpjasalazine did not counteract the inhibiton of PGE2 caused by the other two. Sulphasalazine inhibited phytohemagglutinin P-induced cell activation in a concentration-dependent manner even when used together with indomethacin or BW 755-C. BW 755-C inhibited cell activation at 350 micronM, wehreas at 11, whereas at 11 micronM only increased sulphasalazine-induced inhibition. The implications of these findings on the etiopathology of inflammatory bowel disease are discussed