celecoxib, Celebrex
Determination of celecoxib, a COX-2 inhibitor, in pharmaceutical dosage forms by MEKC.

Srinivasu MK, Sreenivas Rao D, Reddy GO.

Department of Analytical Research, Dr Reddy's Research Foundation, Miyapur, Hyderabad 500050, India.

A micellar electrokinetic chromatographic (MEKC) method was developed for the quantification of celecoxib, a COX-2 inhibitor in pharmaceutical dosage forms within the total analysis time of 7 min. The method has been validated and proven to be rugged. The quantification was carried out at 35 degrees C and 25 kV, using a 25 mM borate buffer (pH 9.3), 25 mM sodium dodecyl sulphate with an extended light path capillary (48.5 cm x 50 micro I.D., 40 cm to detector). Calibration curves were constructed for celecoxib (0.2-0.6 mg/ml) by the internal standard method with 2-nitro aniline as an internal standard (coefficient of correlation greater than 0.999). The intermediate precision (between day precision) of migration times and peak area ratios of celecoxib to internal standard were 1.44 and 1.58% R.S.D., demonstrates good reproducibility of the method. The method was applied to a commercial celecoxib formulation (Revibra, 100 mg) and the percentage recoveries were ranged from 93.0 to 98.4%.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12008128&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Determination of celecoxib in pharmaceutical formulations using UV spectrophotometry and liquid chromatography.

Saha RN, Sajeev C, Jadhav PR, Patil SP, Srinivasan N.

Pharmacy Group, Birla Institute of Technology and Science, Pilani 333 031, India. rnsaha bits-pilani.ac.in

A new UV spectrophotometric method (UV method) and a reversed phase liquid chromatographic method (LC method) for the quantitative estimation of celecoxib, a selective COX-2 inhibitor, in pure form and in solid dosage form were developed in the present study. The linear regression equations obtained by least square regression method, were Abs=4.949 x 10(-2).Conc. (in microg/ml)+1.110 x 10(-2) for the UV method and Area under the curve=5.340 x 10(1).Conc. (in ng/ml)+3.144 x 10(2) for the LC method, respectively. The detection limit, as per the error propagation theory, was found to be 0.26 microg/ml and 25 ng/ml, respectively, for the UV and LC methods. The developed methods were employed with a high degree of precision and accuracy for the estimation of total drug content in three commercial capsule formulations of celecoxib. The results of analysis were treated statistically, as per International Conference on Harmonisation (ICH) guidelines for validation of analytical procedures, and by recovery studies. The results were found to be accurate, reproducible and free from interference and better than the earlier reported methods.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12008154&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Chronic gastric ulcer healing in rats subjected to selective and non-selective cyclooxygenase-2 inhibitors.

Berenguer B, Alarcon de la Lastra C, Moreno FJ, Martin MJ.

Department of Pharmacology, Faculty of Pharmacy, University of Sevilla, Profesor Garcia Gonzalez Street, Seville, Spain.

The influence of different nonsteroidal anti-inflammatory drugs (NSAIDs) and of a proton pump inhibitor on the healing parameters of a chronic gastric ulcer was evaluated. Wistar rats were used after the induction of a chronic acetic acid ulcer. The animals were treated orally for 8 and 15 days, twice daily, with the conventional NSAID, piroxicam (0.35 mg/kg), the non-narcotic analgesic, metamizol (33 mg/kg), the selective cyclooxygenase-2 inhibitor, celecoxib (1.8 mg/kg) and the proton pump inhibitor, omeprazole (0.35 mg/kg). Macroscopic ulcer index, myeloperoxidase activity and prostaglandin E(2) content (both biochemical parameters were evaluated in ulcerated and in intact tissue) as well as histological and immunohistochemical evaluations were carried out at 8 and 15 days. Omeprazole accelerated ulcer healing at 8 and 15 days (P<0.05), while celecoxib delayed healing significantly at 15 days (P<0.01). At 8 days, the prostaglandin E2 content decreased with all NSAIDs at the ulcer site as well as in intact tissue. The same happened at 15 days except for celecoxib, which only diminished prostaglandins in intact mucosa. Immunohistochemistry showed differences in the location of cyclooxygenase-2 and -1. The highest cyclooxygenase-2 expression was found with piroxicam and the lowest expression was with celecoxib. CONCLUSIONS: Down-regulation of cyclooxygenase-2 expression as well as a possible involvement of the chemical structure of celecoxib, a 1,5-dirarylpirazole with a sulphonamide moiety, may account for the delay in ulcer healing.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12020690&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice.

Sigthorsson G, Simpson RJ, Walley M, Anthony A, Foster R, Hotz-Behoftsitz C, Palizban A, Pombo J, Watts J, Morham SG, Bjarnason I.

Department of Medicine, Guy's, King's, St. Thomas' Medical School, London, England.

BACKGROUND & AIMS: The pathogenesis of nonsteroidal anti-inflammatory drug-induced enteropathy is controversial, but it is thought that cyclooxygenase-1 (COX-1) inhibition is of pivotal importance. We compared small intestinal function and morphology in untreated wild-type, COX-1- and COX-2-deficient mice and the effect of indomethacin, selective COX-1 (SC-560), and COX-2 (celecoxib) inhibition. METHODS: Intestinal permeability ((51)CrEDTA), inflammation (fecal granulocyte marker protein), prostaglandin E(2) (PGE(2)) levels, and macroscopic and microscopic appearances were assessed at baseline and after the drugs. RESULTS: COX-1(-/-) animals were normal except for a 97% decrease in intestinal PGE(2) levels. COX-1(+/+) and COX-1(-/-) animals reacted in a similar way to indomethacin. However, celecoxib, having caused no damage in COX-1(+/+) animals, caused small bowel ulcers in COX-1(-/-) animals. Selective inhibition of COX-1 decreased intestinal PGE(2) levels in COX-2(+/+) and COX-2(-/-) animals by 95%-97%, but caused only small bowel ulcers in the latter group. Dual inhibition of COX-1 and COX-2 in wild-type animals resulted in similar small bowel damage. Between 40% and 50% of untreated COX-2(-/-) animals had increased intestinal permeability and inflammation. Some had ileal ulcers that were distinctively different from indomethacin-induced ulcers. Furthermore, long-term celecoxib administration in wild-type animals was associated with similar damage as in the COX-2(-/-) mice. CONCLUSIONS: COX-1 deficiency or inhibition and short-term COX-2 inhibition are compatible with normal small intestinal integrity. Dual inhibition of the COX enzymes leads to damage similar to that seen with indomethacin. Long-term COX-2 deficiency or inhibition is associated with significant intestinal pathology despite normal intestinal PGE(2) levels, suggesting a role for COX-2 in the maintenance of small intestinal integrity in the mouse.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12055598&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer: a study in the hairless mouse model.

Orengo IF, Gerguis J, Phillips R, Guevara A, Lewis AT, Black HS.

Department of Dermatology, Baylor College of Medicine, Houston, TX 77030, USA. iorengo bcm.tmc.edu

OBJECTIVE: To assess the preventive effect of a cyclooxygenase 2 inhibitor, celecoxib (Celebrex; G.D. Searle & Co, Skokie, Ill), in UV-induced skin cancer in hairless mice. DESIGN: Randomized dose-response study. A total of 75 SKH-HR-1 female hairless mice, aged 2 months, were randomized into control, low-dose (200 mg twice daily human dose equivalent), and high-dose (400 mg twice daily human dose equivalent) celecoxib treatment groups. Animals received 1 J/cm(2) daily (5 d/wk) total irradiation. The animals were evaluated weekly for appearance of tumors, and the data were analyzed with respect to tumor latency period and tumor multiplicity using statistical software and Wilcoxon rank sum analyses, respectively. Prostaglandin E(2) levels in the blood and skin were assessed in each group. SETTING: Veterans Affairs Medical Center, Research and Dermatology Services. INTERVENTION: Animals received restricted diets containing the Food and Drug Administration-approved human equivalent doses of 200 mg (low dose) and 400 mg (high dose) of celecoxib twice daily. Controls received no drug. Tumors were induced in all animals with an equivalent UV dose. MAIN OUTCOME MEASURES: Animals were evaluated weekly for the appearance of tumors, and data were analyzed with regard to tumor latency period and tumor multiplicity. Constitutive prostaglandin E(2) levels in blood and epidermis were assessed in each group. RESULTS: Low doses and high doses of celecoxib significantly lengthened the tumor latency period (P<.03 and P<.003, respectively) and reduced tumor multiplicity (P<.005 and P<.001, respectively) compared with controls. There were no differences in the constitutive levels of blood or epidermal prostaglandin E(2) in the low- or high-dose treated animals compared with controls when analyzed at study termination. CONCLUSIONS: Celecoxib is an effective and safe chemopreventive agent in UV carcinogenesis. The epidemiologic, laboratory, and animal studies of the influence of celecoxib on cancer incidence and its low association with systemic adverse effects have led to a potentially new therapeutic approach for the prevention of skin cancer.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12056955&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Anti-implantation effects of indomethacin and celecoxib in rats.

Sookvanichsilp N, Pulbutr P.

Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand. pynsw mahidol.ca.th

Pregnant Wistar rats were used to investigate the anti-implantation effect of cyclooxygenase (COX) inhibitors, indomethacin (nonselective COX-1/COX-2 inhibitor) and celecoxib (specific COX-2 inhibitor). Indomethacin at doses of 2.5 and 5 mg/kg/day and celecoxib at doses of 40, 80, and 160 mg/kg/day were orally administered once daily to each group (n = 8) on Days 3-5 of pregnancy (Day 1 = sperm detection). Indomethacin and celecoxib at anti-implantation dosages were further investigated for the effects on changes in endometrial vascular permeability in pregnant rats and uterine decidualization in pseudopregnant rats. The results demonstrated that indomethacin at a dose of 5 mg/kg/day as well as celecoxib at doses of 80 and 160 mg/kg/day could significantly reduce the proportion of pregnant rats. At the anti-implantation dosages, they exhibited no significant effect on proportion of rats with blue dye sites in the endometrial vascular permeability study, but they could significantly reduce the uterine decidualization. From these findings, the anti-implantation effect of the two COX inhibitors may principally be from decidualization defects, and COX inhibitors should, therefore, be used with caution in childbearing age women. On the other hand, specific COX-2 inhibitors with their good gastric safety profile may have a potential role in nonhormonal postcoital contraception.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12057792&dopt=Abstract celecoxib, Celebrex



celecoxib, Celebrex
Studies on the development of colon-targeted delivery systems for celecoxib in the prevention of colorectal cancer.

Krishnaiah YS, Satyanarayana V, Kumar BD, Karthikeyan RS.

Department of Pharmaceutical Sciences, Andhra University, India. krishnaysr112 rediffmail.com

The nonsteroidal anti-inflammatory drugs (NSAIDs) are found to be potential chemopreventive agents of colorectal cancer. Celecoxib, an NSAID with selective cyclooxygenase-2 inhibition, was proved to be effective for the prevention of colon cancer in patients with familial adenomatous polyposis (FAP) and sporadic polyps. In the light of this information, the present study was carried out to develop oral colon-targeting drug delivery systems for celecoxib using guar gum as a carrier. Matrix tablets containing various proportions of guar gum were prepared by wet granulation technique using starch paste as a binder. The tablets were evaluated for hardness, drug content and were subjected to in vitro drug release studies. The amount of celecoxib released from the matrix tablets at different time intervals was estimated by a HPLC method. Guar gum matrix tablets released only 2-4% of celecoxib in the physiological environment of stomach and small intestine depending on the proportion of guar gum used in the formulation. When the dissolution study was continued in simulated colonic fluids (rat caecal content medium), the matrix tablets containing 20% of guar gum released another 37% of celecoxib after degradation by the colonic bacterial action. The matrix tablets containing 30% of guar gum released about 24% of celecoxib in simulated colonic fluids indicating the susceptibility of the guar gum formulations to the rat caecal contents. The results of the study show that the matrix tablets containing either 20 or 30% of guar gum are most likely to target celecoxib for local action in the colon. The guar gum matrix tablets of celecoxib showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/RH 75% for 6 months. Differential scanning calorimetry (DSC) studies indicated no possibility of interaction between celecoxib and guar gum/other formulation excipients.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12075826&dopt=Abstract celecoxib, Celebrex