The Effect of Local Corticosteroid or Ketorolac Exposure on Histologic and Biomechanical Properties of Rabbit Tendon and Cartilage

Tendonitis, tenosynovitis, and the arthritides are clinical problems commonly encountered in daily orthopaedic practice. Systemic anti-inflammatories, physical therapy, and local corticosteroid injections all are used as nonoperative treatments of these conditions. Systemic anti-inflammatory agents and local corticosteroid agents, however, can be associated with adverse effects that render them intolerable to some patients. As a preliminary study assessing the feasibility of local injection of nonsteroidal anti-inflammatory medication, the histological and biomechanical effects of local exposure of rabbit cartilage and tendon to injectable steroidal (corticosteroid) and injectable nonsteroidal anti-inflammatory agents (ketorolac tromethamine, KT) were determined. Thirty rabbits underwent bilateral knee joint, patellar tendon, and Achilles tendon injections with either normal saline, corticosteroid, or KT. Mechanical and histologic evaluation of the tissues was performed at 6 and 15 weeks after injection. Gross tendon adhesions were observed in more corticosteroid-treated specimens than those exposed to normal saline or KT. Microscopic evaluation of tendons revealed no significant differences among the three groups. Mild cartilage degenerative changes were noted across all groups. Evidence of cartilage necrosis was noted for the corticosteroid-treated group only. Tendons exposed to corticosteroid or KT demonstrated increased load and energy to failure, but exhibited no difference in material stiffness or strain. The use of an injectable nonsteroidal anti-inflammatory agent may be safe and even pose less threat to local tissues after intra-articular and peri-tendinous administration.     

Preparation and evaluation of ketorolac tromethamine gel containing genipin for periodontal diseases

Ketorolac tromethamine gel (KT gel) and ketorolac tromethamine gel containing genipin (KTG gel) were prepared and their therapeutic effects on periodontitis were evaluated. The skin permeation rate of ketorolac from the KT gel and KTG gel was 5.75+/-0.53 and 5.82 +/- 0.74 microg/cm2/ h, respectively. The skin permeation rate of genipin from the KTG gel was 10.13 +/- 1.47 microg/ cm2/h. The tensile strength of the KTG gel was larger than the KT gel. After 4 weeks, the periodontal pocket depth of the KTG gel group (3.22 +/- 0.20 mm) significantly decreased compared with the non-treated group (4.50 +/- 0.25 mm) and the KT group (3.84 +/- 00.26 mm). The KTG gel did not induce separation of the stratum corneum and subcutaneous tissue, and the collagen layers of the corium were closer, more fibrous, and showed longer connections than in the other groups. The KTG gel appears to be effective against gingivitis in the periodontal pocket through its increased anti-inflammatory activity and the crosslinking of genipin with the biological tissue.     

Formulation and evaluation of ketorolac transdermal systems

The effects of pressure-sensitive adhesives and vehicles on the in vitro permeation of ketorolac and in vivo pharmacokinetics were studied. Duro-Tak 87-2196® showed the highest in vitro permeation profiles, and propylene glycol monolaurate-diethylene glycol monoethyl ether (DGME) (60:40, v/v) and propylene glycol monocaprylate-DGME (60:40, v/v) revealed the most favorable in vitro and in vivo results. The decreased C_max and prolonged T_max and half-life were obtained with the ketorolac transdermal systems compared with oral administration, indicating that the ketorolac transdermal systems may have a prolonged effect with reduced toxic event. There was an excellent relationship found between in vitro permeation flux and in vivo AUC_0-∞.     

Evaluation of ketorolac tromethamine microspheres by chitosan/gelatin B complex coacervation

Microspheres (MS) of Ketorolac Tromethamine (KT) for oral delivery were prepared by complex coacervation (method-1) and simple coacervation (method-2) methods without the use of chemical crossalinking agent (glutaraldehyde) to avoid the toxic reactions and other undesirable effects of the chemical cross-linking agents. Alternatively, ionotropic gelation was employed by using sodium-tripolyphosphate (Na-TPP) as cross linking agent. Chitosan and gelatin B were used as polymer and copolymer respectively. All the prepared microspheres were subjected to various physico-chemical studies, such as drug-polymer compatibility by Thin Layer Chromatography (TLC) and Fourier Transform Infra Red Spectroscopy (FTIR), surface morphology by Scanning Electron Microscopy (SEM), frequency distribution, encapsulation efficiency, in-vitro drug release characteristics and release kinetics. The physical state of drug in the microspheres was determined by Differential Scanning Calorimetry (DSC) and X-ray powder Diffractometry (XRD). TLC and FTIR studies indicated no drug-polymer incompatibility. All the MS showed release of drug by a fickian diffusion mechanism. DSC and XRD analysis indicated that the KT trapped in the microspheres existed in an amorphous or disordered-crystalline status in the polymer matrix. It is possible to design a controlled drug delivery system for the prolonged release of KT, improving therapy by possible reduction of time intervals between administrations.     

Ketorolac-induced irreversible renal failure in sickle cell disease: a case report

 Nonsteroidal anti-inflammatory drugs are often used in the management of those with acute pain secondary to sickle cell disease due to potent analgesic effects along with a lack of addictive potential, respiratory depression, and central nervous system effects, as may occur with narcotics. Caution should be observed in the use of nonsteroidal anti-inflammatory drugs in patients with compromised renal function. We present a case of a 17-year-old sickle cell disease patient with an acute painful episode and normal renal function indices who subsequently developed irreversible renal failure and a perirenal hematoma following the administration of ketorolac, despite adequate hydration. Due to its inhibitory effect on prostaglandin-mediated vasodilation, we advise caution in the use of ketorolac for the pain management of sickle cell painful episodes. We recommend following the administration guidelines for ketorolac for renal-compromised patients in those with painful episodes of sickle cell disease, and if used in this patient population, renal function must be very closely monitored. Received: 24 March 1998 / Revised: 5 June 1998 / Accepted: 10 June 1998     

Crystal forms of ketorolac

Four crystal forms of ketorolac have been obtained by recrystallization in organic solvents under variable conditions. Different ketorolac polymorphs and pseudopolymorph were characterized by X-ray powder diffraction crystallography (XRD), Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). In the dissolution studies in water at 37 +/- 0.5 degrees C, four crystal forms showed different patterns. The solubility of Form I were the highest. The solubility decreased in rank order: Form I > Form II > Form III > Form IV. Form land Form III were shown to have a good physical stability at room temperature for 60 days. However, Form II is converted to Form III and Form IV is converted to Form I after 60 days storage. Therefore, these observations indicate that crystalline polymorphism for ketorolac is readily inter-convertible and the relationship may have to taken into consideration in the formulation of the drug.     

纳布啡联合酮咯酸氨丁三醇预防性镇痛对鼻内镜手术患者术后疼痛及恢复质量的影响

目的 观察纳布啡联合酮咯酸氨丁三醇预防性镇痛对鼻内镜手术患者术后疼痛及恢复质量的影响.方法 选取2019年6月-2020年4月该院择期行鼻内镜下鼻中隔偏曲矫形术治疗的患者46例,随机分为纳布啡联合酮咯酸氨丁三醇组(NK组)和酮咯酸氨丁三醇对照组(C组),每组23例.两组患者均于麻醉诱导前10 min行预防性镇痛,NK组...     

Ketorolac after congenital heart surgery: does it increase the risk of significant bleeding complications?

BACKGROUND: The routine use of ketorolac after congenital heart surgery in infants and children is limited by concerns for postoperative bleeding complications. The object of this study was to determine if the use of ketorolac is associated with an increased risk of significant postoperative bleeding after congenital heart surgery in infants and children. METHODS: A retrospective chart review was performed. The exposure of interest was postoperative use of ketorolac after congenital heart surgery in infants and children. The outcome measured was postoperative bleeding requiring surgical exploration. The patients who received ketorolac were compared with an age- and diagnosis-matched comparison group who did not receive ketorolac. RESULTS: Records of 842 infants and children who underwent congenital heart surgery between July 2001 and October 2002 were reviewed. 94 (11.1%) patients were treated with ketorolac postoperatively. The comparison group consisted of 94 matched subjects selected from the patients that did not receive ketorolac. The mean age of patient in the ketorolac group was 8.5 (+/-6.1) years. No (0%) patients in the ketorolac group and four (4.2%) patients in the nonketorolac group developed postoperative bleeding requiring surgical exploration. The relative risk for postoperative bleeding that required surgical exploration in the ketorolac group compared with the nonketorolac group was 0.2 (95% CI 0.02-1.67). CONCLUSIONS: The use of ketorolac after congenital heart surgery in infants and children does not significantly increase the risk of bleeding complications requiring surgical exploration.     

Formulation and optimization of a sustained-release tablet of ketorolac tromethamine

The objective of our study was to formulate a sustained-release tablet of Ketorolac tromethamine, which is a nonsteroidal anti-inflammatory agent. A 2 3 full factorial design (8 runs) was selected. The variables studied were the amount of drug (30 and 40 mg), ratio of hydroxypropyl methylcellulose (HPMC)/sodium carboxymethylcellulose (NaCMC) (240/40 and 140/140 mg), and amount of ethylcellulose (140 and 180 mg). Swelling-controlled matrix tablets were manufactured by direct compression of formulation ingredients using a Stokes single punch tablet press. Dissolution tests were performed using USP apparatus 3 (Bio-Dis II), at various pHs to mimic the conditions that exist in the gastrointestinal tract. Responses studied included time for 50% of the drug to dissolve ( T 50 ), diffusional exponent ( n ) that characterizes the release mechanism, and percent friability of the tablets. Analysis of variance indicated that the release rate ( T 50 ) was affected by the HPMC/NaCMC ratio, amount of drug, and two-way and three-way interactions; whereas the amount of drug, HPMC/NaCMC ratio, ethylcellulose, and the interaction between drug and HPMC/NaCMC and HPMC/NaCMC and ethylcellulose and also three-way interactions were significantly affecting the diffusional exponent ( n ). The release mechanism was found to be super-case II transport. The friability of the tablets was significantly affected by all three factors: amount of drug, HPMC/NaCMC ratio, and amount of ethylcellulose. The formulation giving the best release characteristics was identified.