The Evaluation of Meloxicam Nanocrystals by Oral Administration with Different Particle Sizes.

Meloxicam (MLX) is a non-steroidal anti-inflammatory drug used to treat rheumatoid arthritis and osteoarthritis. However, its poor water solubility limits the dissolution process and influences absorption. In order to solve this problem and improve its bioavailability, we prepared it in nanocrystals with three different particle sizes to improve solubility and compare the differences between various particle sizes. The nanocrystal particle sizes were studied through dynamic light scattering (DLS) and laser scattering (LS). Transmission electron microscopy (TEM) was used to characterize the morphology of nanocrystals. The sizes of meloxicam-nanocrystals-A (MLX-NCs-A), meloxicam-nanocrystals-B (MLX-NCs-B), and meloxicam-nanocrystals-C (MLX-NCs-C) were 3.262 ± 0.016 µm, 460.2 ± 9.5 nm, and 204.9 ± 2.8 nm, respectively. Molecular simulation was used to explore the distribution and interaction energy of MLX molecules and stabilizer molecules in water. The results of differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) proved that the crystalline state did not change in the preparation process. Transport studies of the Caco-2 cell model indicated that the cumulative degree of transport would increase as the particle size decreased. Additionally, plasma concentration-time curves showed that the AUC0-∞ of MLX-NCs-C were 3.58- and 2.92-fold greater than those of MLX-NCs-A and MLX-NCs-B, respectively. These results indicate that preparing MLX in nanocrystals can effectively improve the bioavailability, and the particle size of nanocrystals is an important factor in transmission and absorption.

The effect of meloxicam on neonatal dairy calves: Immunoglobulin G uptake and preweaning performance.

Objectives of this study were to determine effects of meloxicam administered in 2 forms on IgG uptake, growth, and health of preweaned calves. Sixteen Holstein bulls and 14 heifers with a body weight (BW) of 44.3 ± 5.24 kg were blocked by birth date in a randomized complete block design. Calves were removed from the dam before suckling, weighed, and randomly assigned to 1 of 3 treatments: (1) colostrum replacer (CR) at 0 h with no meloxicam (control; CON), (2) 1 mg/kg of BW of meloxicam in pill form before CR (PL), or (3) 1 mg/kg of BW of meloxicam mixed in solution with CR (SL). Calves were fed 675 g of dry matter of CR, providing a volume of 3 L and 180 g of IgG. Blood samples were collected at 0 h to analyze initial IgG and ketone concentrations, and at 6, 12, 18, and 24 h to analyze IgG uptake. At 24 h, calves were fed 432 g of dry matter of 24% crude protein milk replacer (MR) split in 2 feedings, and free choice starter and water until 42 d. Weekly blood samples were analyzed for glucose, plasma urea nitrogen, and ketone concentrations. Time of consumption of MR, BW, length, hip and withers height, and heart girth were recorded weekly. All calves achieved adequate transfer of immunity. Meloxicam did not affect apparent efficiency of absorption, serum total protein, or IgG uptake at 6, 18, and 24 h; however, meloxicam-treated calves had lesser IgG concentrations at 12 h (24.40 and 22.59 g/L for PL and SL, respectively) compared with CON (28.47 g/L). Meloxicam treatment did not affect BW. Calves that received PL tended to gain length at a faster rate (0.24 cm/d) than those that received SL (0.19 cm/d). Meloxicam treatment did not affect MR intake, time of consumption of MR, total dry matter intake, or feed efficiency. Meloxicam-treated calves tended to consume more starter (560.4 and 515.4 g/d for PL and SL, respectively) than those that received CON (452.6 g/d). Ketone levels tended to be greater in meloxicam-treated calves (0.15 and 0.17 mmol/L for PL and SL, respectively), suggesting improved rumen development compared with those that received CON (0.12 mmol/L). Meloxicam treatment did not affect plasma urea nitrogen . Glucose concentrations of calves that received PL (73.2 mg/dL) were less than those that received SL (83.3 mg/dL). Results of this study suggest that meloxicam given at 0 h offers positive effects on starter intake, and possibly rumen development, of preweaned dairy calves. Treatment PL, as compared with SL, offered positive results for rumen development, indicated by lower blood glucose levels.

Extra-abdominal aggressive fibromatosis treated with meloxicam and sorafenib: An encouraging option.

OBJECTIVE: Aggressive fibromatosis (AF), also called desmoid tumor, is an uncommon soft-tissue neoplasm. Characteristically, it expands locally without metastatic potential. However, its tendency of relapse after curative resections has been well documented. Effective treatment options have been limited and there is a clear need for novel treatment strategies. METHODS: We used combination therapy including multikinase tyrosine kinase inhibitor for treating AF. RESULTS: We presented a case of an extra-abdominal AF who was successfully treated with meloxicam and sorafenib combination in our clinic. She tolerated this therapy well with only mild side effects. To our knowledge, this is the first case report of an extra-abdominal AF with a major partial response to sorafenib and meloxicam combination. CONCLUSION: Due to the favorable toxicity profile of sorafenib and meloxicam, this combination might be an effective treatment option for patients with locally aggressive and inoperable AF.

Randomized control trial assessing the efficacy of pain control strategies for caustic paste disbudding in dairy calves younger than 9 days of age.

Disbudding is a common procedure practiced in the dairy industry and is known to cause pain when performed without pain control. Dairy producers who disbud calves with caustic paste are less likely to provide pain control than those using cautery. Little research has been conducted on pain control for caustic paste disbudding and no studies have specifically examined calves under 9 d of age. The objective of this study was to evaluate the efficacy of local anesthesia and nonsteroidal anti-inflammatory drug analgesia on indicators of pain and inflammation in dairy calves disbudded using caustic paste. One hundred forty Holstein heifer calves 1 to 9 d of age were enrolled in 28 blocks and randomly allocated to 1 of 5 treatments: sham control (SH); positive control (POS); lidocaine cornual nerve block (LC); meloxicam (MEL); and lidocaine cornual nerve block plus meloxicam (LCM). We measured outcomes including serum cortisol and haptoglobin, pressure sensitivity, and lying behavior. Data were analyzed using mixed linear regression models with treatment as a fixed effect, baseline values as a covariate, and trial block as a random effect. Compared with the POS group, the LCM group had reduced serum cortisol at 15, 30, 45, and 60 min post-disbudding; cortisol values were not different between LC, LCM, and SH calves at these time points. At 60, 90, 120, and 180 min post-disbudding, LCM calves had reduced cortisol compared with LC calves, whereas, values did not differ between LCM and SH calves at these time points. At 3 to 4 d post-disbudding, the LCM group tended to have reduced haptoglobin, but no differences were found between groups at 180 min and 7 d post-disbudding. At 60, 90, and 120 min post-disbudding, LC and LCM treated calves had decreased pressure sensitivity compared with other groups. No differences were seen in pressure sensitivity between groups at 180 min, 3 to 4 or 7 d post-disbudding. No differences in lying behavior were found between treatment groups on any of the 7 d following disbudding. These findings demonstrate that the combination of a local anesthetic with a nonsteroidal anti-inflammatory drug is beneficial for reducing indicators of pain and inflammation in young calves disbudded with caustic paste.

Effects of Oral Meloxicam and Topical Lidocaine on Pain associated Behaviors of Piglets Undergoing Surgical Castration.

The objective of this study was to find a practical means of reducing pain associated with surgical castration by evaluating the effects of oral meloxicam and topical lidocaine, separately and in combination, on behavioral indicators of pain in piglets. Two hundred thirty-five piglets were surgically castrated between three and seven days of age. Immediately following castration, piglets received one of four treatments: (1) No pain mitigation (C; control; n = 58); (2) NSAID only (M; meloxicam; n = 59); (3) Topical anesthetic (L; lidocaine spray; n = 60); or (4) NSAID and topical anesthetic (X; meloxicam and lidocaine spray; n = 59). Behaviors were recorded by direct observation of individual piglets using five-minute scan samples over a five-hour period, for three days post-castration. Results of the experiment demonstrate the administration of oral meloxicam and topical lidocaine spray at the time of castration under the current methods did not mitigate pain associated with the procedure (P = 0.09; C: 2.1 ± 0.1, L: 2.4 ± 0.1, M: 2.1 ± 0.1 and X: 2.1 ± 0.1).

Effects of omega-6/3 and omega-9/6 nutraceuticals on pain and fertility in peritoneal endometriosis in rats.

PURPOSE: To evaluate the effects of the nutraceuticals omega-6/3 and omega-9/6 on endometriosis-associated infertility and pain. METHODS: Controlled experimental study, with each group composed of eight female rats. Fertility groups: sham-operated control (0.9% saline solution); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); and meloxicam (0.8 mg/kg/day). Pain groups: sham-operated control (0.9% saline); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); medroxyprogesterone acetate (5 mg/kg/every 3 days); and meloxicam (0.8 mg/kg/day). Peritoneal endometriosis was surgically induced. Pain was evaluated with the writhing test. Fertility was evaluated by counting the number of embryos in the left hemi-uterus. RESULTS: The mean number of writhings was as follows: sham-operated, 11.1 ± 2.9; control with endometriosis, 49.3 ± 4.4; omega-6/3, 31.5 ± 2.7; omega-9/6, 34.1 ± 4.5; medroxyprogesterone acetate, 2.1 ± 0.8; meloxicam, 1 ± 0.3. There was a significant difference between both controls and all drugs used for treatment. Regarding fertility, the mean values were as follows: sham-operated, 6.8 ± 0.6; control with endometriosis, 4.2 ± 0.7; omega-6/3, 4.7 ± 1; omega-9/6, 3.8 ± 0.9; and meloxicam, 1.8 ± 0.9. CONCLUSIONS: The omega-6/3 and omega-9/6 nutraceuticals decreased pain compared to the controls. There was no improvement in fertility in any of the tested groups.

Eutexia for enhanced dissolution rate and anti-inflammatory activity of nonsteroidal anti-inflammatory agents: Caffeine as a melting point modulator.

Fast dissolution of nonsteroidal anti-inflammatory drugs (NSAIDs) is a prerequisite from patient perspective. However, most NSAIDs are slowly dissolving acidic compounds. Caffeine, a commonly used analgesic adjuvant with NSAIDs showed high potential as eutectic co-former for acidic compounds. The study investigated eutectic forming potential of caffeine with meloxicam, aceclofenac and flurbiprofen. Each drug was co-ground with caffeine in various ratios and the products were characterized by thermal analysis to determine the optimum eutectic composition from phase diagram and Tamman's triangle. The optimum systems were subjected to X-ray powder diffraction (XRPD), Fourier-transform infrared (FTIR) and dissolution studies. Co-ground systems at dose ratio were also assessed for drug dissolution and anti-inflammatory effect using carrageenan induced rat paw edema method. Eutexia was confirmed by thermal analysis with the optimum composition being 1:1, 1:1 and 1:2 (NSAID: caffeine) for aceclofenac, flurbiprofen and meloxicam, respectively. Eutexia did not alter FTIR spectra with minor changes being recorded in XRPD patterns. The eutectic systems underwent fast liberation of drugs with fast dissolution being retained even at dose ratios. Dissolution enhancement was associated with enhanced anti-inflammatory response. The study introduced caffeine as eutectic forming analgesic for fixed dose combination with NSAIDs to enhance drug dissolution and anti-inflammatory effect.

Effects of omega-6/3 and omega-9/6 nutraceuticals on pain and fertility in peritoneal endometriosis in rats

Abstract Purpose: To evaluate the effects of the nutraceuticals omega-6/3 and omega-9/6 on endometriosis-associated infertility and pain. Methods: Controlled experimental study, with each group composed of eight female rats. Fertility groups: sham-operated control (0.9% saline solution); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); and meloxicam (0.8 mg/kg/day). Pain groups: sham-operated control (0.9% saline); control with endometriosis (0.9% saline); omega-6/3 (1.2 g/kg/day); omega-9/6 (1.2 g/kg/day); medroxyprogesterone acetate (5 mg/kg/every 3 days); and meloxicam (0.8 mg/kg/day). Peritoneal endometriosis was surgically induced. Pain was evaluated with the writhing test. Fertility was evaluated by counting the number of embryos in the left hemi-uterus. Results: The mean number of writhings was as follows: sham-operated, 11.1 ± 2.9; control with endometriosis, 49.3 ± 4.4; omega-6/3, 31.5 ± 2.7; omega-9/6, 34.1 ± 4.5; medroxyprogesterone acetate, 2.1 ± 0.8; meloxicam, 1 ± 0.3. There was a significant difference between both controls and all drugs used for treatment. Regarding fertility, the mean values were as follows: sham-operated, 6.8 ± 0.6; control with endometriosis, 4.2 ± 0.7; omega-6/3, 4.7 ± 1; omega-9/6, 3.8 ± 0.9; and meloxicam, 1.8 ± 0.9. Conclusions: The omega-6/3 and omega-9/6 nutraceuticals decreased pain compared to the controls. There was no improvement in fertility in any of the tested groups.