Efficacy of Ibuprofen Lysine on First-Trimester AbortionRelated Pain and Hemorrhage: A Randomized TripleBlinded Clinical Trial.

BACKGROUND: Some recent trials have reported high efficacy for nonsteroidal anti-inflammatory drugs (NSAIDs) in relieving medical abortion-related pain. The aim of this study was to determine the beneficial effect of oral NSAIDs (ibuprofen lysine) in reduction of pain and hemorrhage in first-trimester medical abortion. METHODS: This randomized triple-blinded clinical trial was performed on 98 pregnant women who were candidate for medical abortion within the first-trimester period (gestational age<12 weeks). The participants were randomly assigned to receive ibuprofen lysine (684 mg orally every 4 hours) or placebo. All patients were initially treated with misoprostol (800 µg every 3 hours). Pain intensity and rate of hemorrhage were assessed every hour up to 15 hours after receiving the first dose of misoprostol by visual analogue scaling (VAS) and pictorial blood loss assessment chart (PBAC), respectively. RESULTS: Assessing the mean pain score within 15 hours of receiving misoprostol showed significantly lower pain intensity within the first 10 hours of assessment in the group receiving NSAID in comparison with the control group (P<0.001). The bleeding rate was also significantly lower in the NSAID group at the fifth (P=0.013) and ninth (P=0.040) hour of receiving misoprostol compared to the control group. We found no difference in abortion-related complication rate between the NSAID and placebo groups (8.3% versus 8.0%, P=0.952). CONCLUSION: The use of NSAIDs (ibuprofen lysine) is a good pharmacological analgesic option for relieving medical abortionrelated pain and hemorrhage.

A Randomized, Double-Blind, Placebo-Controlled Trial of Ibuprofen Lysinate in Comparison to Ibuprofen Acid for Acute Postoperative Dental Pain.

INTRODUCTION: Ibuprofen acid is poorly soluble in the stomach, thus reaching maximum plasma levels at approximately 90 min post-dose. Ibuprofen lysinate has been developed to accelerate absorption of ibuprofen to shorten the time to analgesic efficacy. This study compared analgesic efficacy and onset of effect of a single dose of ibuprofen lysinate or ibuprofen acid in patients undergoing third molar extraction. METHODS: Randomized, double-blind, placebo-controlled, multi-center, parallel-group single-dose study. Adults (18-60 years) undergoing extraction of ≥ 1 third molar were randomized 2:2:1 to ibuprofen lysinate, ibuprofen acid, or placebo postoperatively. Pain relief (PAR, 5-point scale, 0 = none to 4 = complete pain relief) and pain intensity (PI, 100 mm visual analog scale) were assessed between 15 and 360 min post-dose. The primary endpoint was the weighted sum of PAR scores at 6 h (TOTPAR). Time to onset of effect, global assessment of efficacy, and adverse events were also assessed. RESULTS: Overall, 351 patients received ibuprofen lysinate (N = 141), ibuprofen acid (N = 139), or placebo (N = 71). Both active treatments significantly reduced pain compared with placebo, from 15 min post-dose to 6 h (TOTPAR: ibuprofen lysinate: 19.57; ibuprofen acid: 19.96; placebo: 8.27). Ibuprofen lysinate was significantly more effective than placebo, but non-inferior to ibuprofen acid, at providing pain relief over 6 h. There was no significant difference between ibuprofen lysinate and ibuprofen acid for onset of analgesia. Both ibuprofen formulations were well tolerated; all adverse events were mild to moderate and considered unrelated to treatment. CONCLUSIONS: A single dose of ibuprofen lysinate is non-inferior to ibuprofen acid in terms of analgesic efficacy, onset of action, and tolerability in patients who have recently undergone dental surgery. TRIAL REGISTRATION: EudraCT No. 2006-006942-33. Plain language summary available for this article.

Characterization of alginate beads loaded with ibuprofen lysine salt and optimization of the preparation method.

The parameters influencing alginate ionotropic gelation and the production of alginate beads loaded with hydrosoluble ibuprofen lysine salt (IBU-L) were studied, as well as the optimization of the method for its attainment. A three-factor and three-level factorial design (3(3)) was carried out to determine the influence of three experimental variables: polymer concentration, CaCl2 concentration, and curing time on the dependent variables drug load and encapsulation efficiency. The effect of the pH used in the preparation bath was also evaluated. Concentrations of CaCl2 and pH of gelling bath were seen to affect bead formation and stability as well as their ability to properly entrap the drug. In this work, IBU-L was used as a model of a non-steroidal anti-inflammatory drug with good solubility in alginate solutions. IBU-L was successfully encapsulated in alginate beads obtained by the ionotropic gelation method. The obtained alginate matrixes are able to modify the release of the entrapped IBU-L and this occurs in a pH-sensitive way that can be correlated with the swelling behaviour of the alginate-produced beads. Morphological characteristics were evaluated by means of scanning electron microscopy.

Use of in-die powder densification parameters in the implementation of process analytical technologies for tablet production on industrial scale.

The use of process analytical technologies (PAT) to ensure final product quality is by now a well established practice in pharmaceutical industry. To date, most of the efforts in this field have focused on development of analytical methods using spectroscopic techniques (i.e., NIR, Raman, etc.). This work evaluated the possibility of using the parameters derived from the processing of in-line raw compaction data (the forces and displacement of the punches) as a PAT tool for controlling the tableting process. To reach this goal, two commercially available formulations were used, changing the quantitative composition and compressing them on a fully instrumented rotary pressing machine. The Heckel yield pressure and the compaction energies, together with the tablets hardness and compaction pressure, were selected and evaluated as discriminating parameters in all the prepared formulations. The apparent yield pressure, as shown in the obtained results, has the necessary sensitivity to be effectively included in a PAT strategy to monitor the tableting process. Additional investigations were performed to understand the criticalities and the mechanisms beyond this performing parameter and the associated implications. Specifically, it was discovered that the efficiency of the apparent yield pressure depends on the nominal drug title, the drug densification mechanism and the error in pycnometric density. In this study, the potential of using some parameters derived from the compaction raw data has been demonstrated to be an attractive alternative and complementary method to the well established spectroscopic techniques to monitor and control the tableting process. The compaction data monitoring method is also easy to set up and very cost effective.

Preparation of Ibuprofen Lysine Sustained-release Liquid Suppository and Its Evaluation in vivo and in vi-tro / 中国药房

OBJECTIVE:To prepare Ibuprofen lysine sustained-release liquid suppository,and conduct the evaluation in vivo and in vitro. METHODS:Ibuprofen lysine sustained-release liquid suppository was prepared by using Poloxamer solution as main matrix,carbomer as bioadhesive agent,laurocapram as penetrant. The ratios of poloxamer 407(P407)-poloxamer 188(P188)and carbomer content were screened by using gel temperature,gel intensity,biological adhesion and release rate in vitro as indexes, and the concentration-time curves and pharmacokinetic parameters of prepared liquid suppository and common solid suppository af-ter rectal administration in Beagle dogs in vivo were compared. RESULTS:When the P407-P188 ratio was 1:1.2,the gel tempera-ture of sustained-release liquid suppository was 30.4-38.1 ℃,which was the nearest to the rectal temperature;when the content of carbomer was 0.8%,the in vitro release of sustained-release liquid suppository was in zero-order model,with favorable correlation (R2=0.996). The tmax of common solid suppository was 3.206 h,then plasma concentration decreased significantly,release time did not exceed 12 h,AUC0-∞ was 501.826 mg·h/L;tmax of sustained-release liquid suppository was 8.814 h,then plasma concentration decreased,release time exceeded 24 h,AUC0-∞ was 715.489 mg·h/L. CONCLUSIONS:Ibuprofen lysine sustained-release liquid suppository is successfully prepared,which shows better sustained-release effect and excellent correlation in vivo and in vitro than common solid suppository.

Physical Compatibility of Ibuprofen Lysine Injection with Selected Drugs During Simulated Y-site Injection.

PURPOSE: To study the physical compatibility of ibuprofen lysine injection (NeoProfen, Ovation Pharmaceuticals Inc., Deerfield, IL) with medications commonly used in the premature neonatal population during simulated Y-site administration. MATERIALS AND METHODS: Commonly used intravenous medications in preterm infants were evaluated for physical compatibility with ibuprofen lysine injection. A 20-mL sample of ibuprofen lysine drug product solution was mixed with a 20-mL sample of each of the 34 medications at concentrations used clinically. The mixtures were stored at room temperature and each sample was evaluated for turbidity and physical appearance at time 0 (immediately after preparation) and at 4 hours after preparation. RESULTS: THE FOLLOWING DRUGS WERE DEEMED COMPATIBLE WITH IBUPROFEN LYSINE: ceftazidime, epinephrine, furosemide, heparin lock flush, diluted insulin, morphine sulfate, phenobarbital, potassium chloride, and sodium bicarbonate. Diluted dopamine was initially compatible at time 0 but showed a small precipitate at the 4-hour time point. CONCLUSION: Of the 37 drug solutions tested, 14 preparations (10 medications; several with more than one diluent) showed physical compatibility with ibuprofen lysine, 1 was compatible at time 0 and incompatible at 4 hours, and 1 could not be evaluated. The remaining preparations were considered to be incompatible.

Repeated bowel perforations with Ibuprofen lysine: a case report.

Non-steroidal anti-inflammatory drugs (NSAID) have been used to close the patent ductus arteriosus in neonates for over two decades. Ibuprofen lysine, a parenteral NSAID, is labeled for the treatment of patent ductus arteriosus in neonates who do not respond to conventional medical management. While sharing many of the same adverse effects as indomethacin, spontaneous bowel perforation has not been reported. We describe a premature infant that experienced isolated bowel perforations after treatment with ibuprofen lysine for symptomatic patent ductus arteriosus.

Clinical experience with intravenous Ibuprofen lysine in the pharmacologic closure of patent ductus arteriosus.

Patent ductus arteriosus (PDA) is the failure of the ductus that arises from the distal dorsal aortic arch to close during the first few days of life. The treatment options for PDA include "watchful waiting," pharmacologic therapy with cyclooxygenase (COX) inhibitors (COX-1 and COX-2), such as indomethacin or intravenous (IV) ibuprofen lysine, and surgery when medical interventions have proved ineffective. The clinical trials evaluating the utilization of IV ibuprofen lysine focus on either preventing the persistence of a PDA or treating the PDA in premature infants in whom the ductus does not close within 48 hours of birth. Although the role of COX inhibitors in prophylaxis of PDA has been studied, it has not been clearly delineated. Treatment of PDA in preterm low birth weight infants from the second day of life on with IV ibuprofen lysine has been studied in 4 major and 3 smaller clinical trials. Overall, in 7 studies with 492 patients, the closure rate of PDA was 75.1% with IV ibuprofen lysine compared to 73.5% with indomethacin. In addition, neonates treated with IV ibuprofen lysine had significantly better creatinine clearance, urine output, serum creatinine, and blood urea nitrogen (BUN) profiles than indomethacin-treated patients. Overall, IV ibuprofen lysine is as effective as indomethacin for closure of PDA, yet is associated with a better safety profile with fewer negative side effects when compared to indomethacin.

Common clinical and practical questions on the use of intravenous Ibuprofen lysine for the treatment of patent ductus arteriosus.

Cyclooxygenase inhibitors have proven efficacy in the treatment of patent ductus arteriosus (PDA). Intravenous indomethacin has been the only approved treatment for PDA available in the United States for the past 20 years. The armamentarium has recently been expanded with the approval of intravenous ibuprofen lysine in 2006. Ibuprofen lysine has been used for years in Europe, and the author reviews the extensive published literature. This review addresses common questions about ibuprofen lysine, summarizes the available literature, and discusses the data submitted to the Food and Drug Administration (FDA) in support of its approval. Three major trials served as the approval basis for the safety and efficacy of ibuprofen lysine. The author has summarized these studies and, where appropriate, presents pooled results from additional analyses that have not been previously published. Many practical questions regarding the drug, including dosing, administration, and storage are addressed. The results of recently completed but unpublished tests on stability and compatibility with commonly used drugs in the neonatal setting are also reviewed. Ibuprofen lysine now represents an alternative pharmacological option to surgery for the treatment of PDA.

Patent ductus arteriosus: an overview.

Patent ductus arteriosus (PDA) is one of the most common congenital heart defects, accounting for 5%-10% of all congenital heart disease in term infants. The occurrence of PDA is inversely related to gestational age and weight, with an even greater incidence in preterm infants. The maintenance of ductal patency is essential for the normal development of the fetus. In the neonate, however, persistent patency of the ductus arteriosus (DA) is associated with significant morbidity and mortality. Normally, at birth, the DA constricts, resulting in intraluminal ischemic hypoxia, which eventually leads to closure and remodeling of the ductus. PDA in term infants is usually associated with a functional defect, whereas in preterm infants it is associated with immaturity. Normal physiologic mechanisms contributing to closure - oxygen tension and decreased prostaglandins-are altered in prematurity. Clinical signs of ductal patency include murmur, tachycardia, bounding peripheral pulses, and congestive heart failure and associated symptoms. Symptoms are not always present; therefore, diagnostic imaging is critical if a PDA is suspected on clinical grounds. Three management strategies are currently available for PDA: fluid restriction and diuretics (as clinically appropriate), medical intervention, and surgical ligation. Pharmacologic closure can be achieved via administration of intravenous indomethacin or ibuprofen lysine. While both agents have shown similar efficacy, ibuprofen lysine has demonstrated an improved safety profile, particularly in terms of renal effects, compared to indomethacin.