The analgesic effect of preventive administration of meloxicam in calves submitted to hot-iron dehorning / Efeito analgésico da administração preventiva de meloxicam em bezerros submetidos à descorna com ferro quente

Dehorning is a zootechnical practice that causes severe pain in cattle. Although there are several studies evaluating the effects of analgesics in calf dehorning, none of them used validated pain assessment instruments. We evaluated the analgesic effectiveness of meloxicam administered before dehorning, compared to a control group, using the Unesp-Botucatu, numerical, simple descriptive, and visual analogue scales for pain assessment before and 4, 8, and 24 hours after the dehorning in 44 female calves. All calves received 0.04 mg/kg of xylazine IM 20 minutes before dehorning and local anesthetic block with 2% lidocaine with a vasoconstrictor. Calves were divided into two groups: without (GX; n = 22) or with 0.5 mg/kg of meloxicam (GXM; n = 22) administered intravenously before the procedure. Dehorning was performed through the section of the base of the horn bud, followed by thermocautery disbudding. For comparisons over time, mixed linear or generalized mixed linear model were used. The interaction between groups and study phases was used as fixed effects and each calf as a random effect. Bonferroni post hoc test was used. There was an increase in the pain scores at 4h compared to baseline in both groups (GX and GXM) for the four scales. The scores at 4h were higher in GX compared to GXM for all scales. Meloxicam reduced, but did not eliminate, behavioral expressions of pain in calves submitted to hot-iron dehorning. Therefore, it should be included in the analgesic protocol to improve welfare in calves undergoing dehorning.

A descorna é uma prática zootécnica que causa dor intensa em bovinos. Há na literatura diversos estudos sobre os efeitos de analgésicos para mitigar a dor frente a descorna, mas nenhum usando escalas validadas. Avaliamos a eficácia do meloxicam administrado previamente à descorna, comparado a um grupo controle, utilizando-se as escalas Unesp-Botucatu, numérica, simples descritiva e analógica visual para avaliação da dor antes e 4, 8 e 24 horas após a descorna em 44 bezerros fêmeas tratadas com 0,04 mg/kg de xilazina IM 20 minutos antes da descorna e bloqueio anestésico local com lidocaína a 2% com vasoconstritor. Os bezerros foram alocados em dois grupos: sem (GX; n=22) ou com 0.5 mg/kg de meloxicam (GXM; n=22) administrado por via intravenosa antes do procedimento. Realizou-se a descorna por secção da base do botão cornual seguido de termocauterização. Para as comparações ao longo do tempo, empregou-se o modelo linear ou linear misto. Considerou-se a interação entre grupos e momentos como efeito fixo e cada bezerro como efeito aleatório. As alterações foram inferidas de acordo com o pós-teste de Bonferroni. Para as quatro escalas houve aumento dos escores às 4h comparado ao basal em ambos os grupos (GX e GXM). Os escores de todas as escalas às 4h foram maiores em GX que em GXM. O meloxicam reduziu, mas não aboliu, a expressão comportamental da dor em bezerros submetidos à descorna com ferro quente, o que sugere o uso de terapia antálgica multimodal para realizar tal procedimento e garantir o bem-estar animal.

Desenvolvimento de organogel injetável subcutâneo de Pluronic®-F127 e lecitina de soja (OPL) contendo meloxicam para uso veterinário / Development of a veterinary organogel formulation containing soy lecithin, Pluronic® F-127 and meloxicam for the treatment of acute and chronic pain in small animals

O organogel é formado por uma matriz tridimensional composta de filamentos que se auto-organizam em uma rede entrelaçada e que, por seu tipo de estrutura, pode ser utilizado com o objetivo de atuar como um implante que se forma in situ, sendo capaz de se comportar como uma forma farmacêutica de liberação prolongada. Esse trabalho tem, por tanto, o objetivo desse trabalho foi desenvolver, caracterizar, quantificar e traçar perfis de dissolução para formulações de organogel contendo meloxicam como principio ativo. O material está dividido em quatro capítulos, sendo apresentada inicialmente (I) revisão da literatura a respeito da lecitina de origem vegetal, com suas principais fontes de obtenção, como soja, girassol e colza, e também seu uso farmacêutico na obtenção de formulações como organogéis, microemulsões e lipossomas. Os demais capítulos abordam (II) desenvolvimento e otimização de uma formulação de organogel contendo lecitina de soja e Pluronic® F-127 como formadores da matriz tridimensional e meloxicam como principio ativo. (III) Desenvolvimento e validação de um método de quantificação do teor de meloxicam por cromatografia líquida de alta eficiência (CLAE). (IV) Desenvolvimento de um método de dissolução para formulações de organogel, que fosse capaz de ser utilizado na caracterização do perfil de dissolução de diferentes formulações. Com os resultados obtidos, foi possível desenvolver formulações de organogel contendo lecitina de soja, Pluronic® F-127 e meloxicam, assim como um método analítico validado para as analises de teor. Por fim, foram obtidos também os perfis de dissolução de duas formulações mais promissoras

Organogels are formed by a three-dimensional matrix composed of filaments that selforganize in an interlaced network and that, due to its type of structure, can be used with the objective of acting as an implant that forms in situ, being able to behave as an extendedrelease dosage form. This work has, therefore, the objective of this work was to develop, characterize, quantify and trace dissolution profiles for organogel formulations containing meloxicam as active ingredient. The material is divided into four chapters, initially presented (I) review of the literature on lecithin of plant origin, with its main sources of production, such as soybean, sunflower and rapeseed, and also its pharmaceutical use in obtaining formulations such as organogels , microemulsions and liposomes. The remaining chapters address (II) development and optimization of an organogel formulation containing soy lecithin and Pluronic® F-127 as three-dimensional matrix formers and meloxicam as an active ingredient. (III) Development and validation of a method for quantification of meloxicam content by high performance liquid chromatography (HPLC). (IV) Development of a dissolution method for organogel formulations, capable of being used to characterize the dissolution profile of different formulations. With the results obtained, it was possible to develop organogel formulations containing soy lecithin, Pluronic® F-127 and meloxicam, as well as a validated analytical method for content analysis. Finally, the dissolution profiles of two more promising formulations were also obtained

Synergistic anti-inflammatory effect of NSAIDs plus B vitamins administered pre and postoperatively in third molar surgery: randomized clinical trial / Efeito anti-inflamatório sinérgico da associação de AINEs e vitaminas do complexo B administrada no pré e pós-operatório de cirurgia de terceiros molares: ensaio clínico randomizado

Objective : The aim of the present study was to evaluate the synergistic anti-inflammatory effect of Non-steroidal anti-inflammatory drugs (NSAIDs) plus B vitamins administered pre and postoperatively in surgeries of impacted mandibular third molars. Material and Methods : Double-blind randomized clinical trial, sixty-six patients participated and were randomized into 2 groups. The control group was administered meloxicam 15 mg intramuscularly plus placebo orally and to the experimental group, meloxicam 15 mg intramuscularly plus vitamins B [B1, B6, and B12] orally; both treatments were administered preoperatively. The anti-inflammatory effect was evaluated by pain intensity, facial swelling (facial contour measurements), and mouth opening (distance between the upper and lower incisors) during the post-surgical phase. Student's t-test was performed for independent samples. Results : In all the evaluated times (1 hour, 6 hours, 12 hours, 24 hours, 2 days, and 3 days after the end of the surgery) the experimental group presented a significantly lower intensity of pain compared to the control group (p<0.05). The highest pain intensity was recorded at 6 hours (17.7 ± 9.1 mm in the experimental group and 34.5 ± 21.3 mm in the control group). Swelling and mouth opening were similar in both groups, at all times evaluated (p>0.05). Conclusion : In the present study, the administration of NSAIDs plus B vitamins (B1, B6, B12) produced lower intensity of pain compared to the administration of only NSAIDs. Nevertheless, swelling and mouth opening were similar in all evaluations for both study groups (AU)

Objetivo : O objetivo do presente estudo foi avaliar o efeito anti-inflamatório sinérgico de anti-inflamatórios não esteroidais (AINEs) com vitaminas do complexo B administrados no pré e pós-operatório de cirurgias de terceiros molares inferiores impactados. Material e Métodos: Ensaio clínico randomizado duplo-cego, 66 participantesque foram randomizados em 2 grupos. O grupo controle recebeu Meloxicam 15 mg por via intramuscular + placebo por via oral e o grupo experimental, Meloxicam 15 mg por via intramuscular + vitaminas B [B1, B6 e B12] por via oral; ambos os tratamentos foram administrados no pré-operatório. O efeito anti-inflamatório foi avaliado pela intensidade da dor, edema facial (medidas do contorno facial) e abertura da boca (distância entre os incisivos superiores e inferiores) durante a fase pós-cirúrgica. Foi aplicado o teste t de Student para amostras independentes. Resultados: Em todos os tempos avaliados (1 hora, 6 horas, 12 horas, 24 horas, 2 dias e 3 dias após o término da cirurgia) o grupo experimental apresentou uma intensidade de dor significativamente menor em relação ao grupo controle (p <0,05). A maior intensidade de dor foi registrada em 6 horas (17,7 ± 9,1 mm no grupo experimental e 34,5 ± 21,3 mm no grupo controle). Edema e abertura bucal foram semelhantes nos dois grupos, em todos os momentos avaliados (p>0,05). Conclusão: No presente estudo, a administração de AINEs com vitaminas do complexo B (B1, B6, B12) resultou em menor intensidade de dor em comparação com a administração apenas de AINEs. No entanto, o edema e a abertura da boca foram semelhantes em todas as avaliações para ambos os grupos de estudo (AU).

Effects of flunixin meglumine, meloxicam, and firocoxib on the acute-phase proteins in horses following standing castration / Efeitos do flunixin meglumine, meloxicam e firocoxib na concentração de proteínas da fase aguda após em equinos após castração

Excessive infection and inflammation are the most common complications associated with castration. The objective of this study was to compare the efficacy of flunixin meglumine (FM), meloxicam (MX), or firocoxib (FX) for inflammation control after castration in horses using acute-phase proteins (APP) as markers of inflammation. Thirty healthy, unbroken, mixed-breed horses (body weight 358.62±45.57kg and age 4.99±2.63 years) were randomly (n=10 animals/group) allocated to receive one of three different post-castration anti-inflammatory medicines: Group 1 (FM 1.1mg/kg bwt, IV, s.i.d for 5 days); Group 2 (MX 0.6mg/kg bwt, IV, s.i.d for 5 days); and Group 3 (FX 0.1mg/kg bwt, IV, s.i.d for 5 days). All horses were castrated in standing position, using the open technique. Serum and peritoneal APP concentrations were measured by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and determined before castration (0), and 3, 5, 24, 48, 72, 120 and 168 hours after castration. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (p<0.05). Three animals from the MX group developed hyperthermia (with rectal temperatures of 39.8, 39.3 and 38.9°C on day 4, 5 and 6, respectively) and showed local clinical signs of inflammation (inguinal and excessive scrotal edema) and reluctance to walk, as well as a rigid gait of the hind limbs. The same complications were observed in one FX horse. No complications were observed among the FM animals. The castration resulted in significant changes in serum and peritoneal values of total proteins, ceruloplasmin (Cp), transferrin (Tf), albumin (Alb), haptoglobin (Hp) and α1-acid glycoprotein (Gp) in animals of all experimental groups. However, the animals of the MX and FX groups presented more intense acute phase response compared to the animals of the FM group. Changes in the APP were associated with the surgical trauma of castration, but the differences between groups were associated with the ability of the nonsteroidal anti-inflammatory drug to control the inflammation. In conclusion, and based on the findings of acute phase proteins, flunixin is more efficient to control the magnitude of inflammation following castration as compared to meloxicam and firocoxib.(AU)

Infecção e inflamação excessivas são as complicações mais comuns associadas à castração. O objetivo deste estudo foi comparar a eficácia do flunixin meglumine (FM), meloxicam (MX) ou firocoxib (FX) no controle da inflamação após a castração em cavalos usando proteínas da fase aguda (APP) como marcadores de inflamação. Trinta equinos saudáveis (358,62±45,57kg; 4,99±2,63 anos) foram em função dos anti-inflamatórios utilizados após as castrações aleatoriamente (n= 10 animais/grupo) alocados em três diferentes grupos: Grupo 1 (FM 1,1mg/kg de peso, IV, sid por 5 dias); Grupo 2 (MX 0,6mg/kg de peso, IV, s.i.d por 5 dias); e Grupo 3 (FX 0,1mg/kg de peso, IV, s.i.d por 5 dias). Todos os cavalos foram castrados em posição quadrupedal, utilizando a técnica aberta. As concentrações de APP sérica e peritoneal foram separadas por eletroforese em gel de poliacrilamida (PAGE) com dodecil-sulfato de sódio (SDS) e determinadas no momento 0 (antes da castração) e com 3, 5, 24, 48, 72, 120 e 168 horas após a castração. Os resultados foram submetidos à análise de variância pelo programa estatístico SAS e as médias foram comparadas pelo teste de Student-Newman-Keuls (p<0,05). Três animais do grupo MX desenvolveram hipertermia (com temperatura retal de 39,8, 39,3 e 38,9° C nos dias 4, 5 e 6, respectivamente) e mostraram sinais clínicos locais de inflamação (edema inguinal e escrotal excessivo) e relutância em andar, bem como marcha rígida dos membros posteriores. As mesmas complicações foram observadas em um cavalo do FX. Não foram observadas complicações entre os animais do FM. Independente do grupo, a castração resultou em alterações significativas nos valores séricos e peritoneais de proteínas totais, ceruloplasmina (Cp), transferrina (Tf), albumina (Alb), haptoglobina (Hp) e glicoproteína ácida α1 (Gp). No entanto, os animais dos grupos MX e FX apresentaram resposta de fase aguda mais intensa quando comparados aos animais do FM. Alterações na resposta de fase aguda deveram-se ao trauma cirúrgico da castração, mas as diferenças entre os grupos foram associadas à capacidade do anti-inflamatório em controlar a inflamação. Em conclusão, baseado da resposta de fase aguda, o flunixin em comparação com o meloxicam e o firocoxib é mais eficiente no controle da inflamação após a castração em equinos.(AU)

Effects of flunixin meglumine, meloxicam, and firocoxib on the acute-phase proteins in horses following standing castration

ABSTRACT: Excessive infection and inflammation are the most common complications associated with castration. The objective of this study was to compare the efficacy of flunixin meglumine (FM), meloxicam (MX), or firocoxib (FX) for inflammation control after castration in horses using acute-phase proteins (APP) as markers of inflammation. Thirty healthy, unbroken, mixed-breed horses (body weight 358.62±45.57kg and age 4.99±2.63 years) were randomly (n=10 animals/group) allocated to receive one of three different post-castration anti-inflammatory medicines: Group 1 (FM 1.1mg/kg bwt, IV, s.i.d for 5 days); Group 2 (MX 0.6mg/kg bwt, IV, s.i.d for 5 days); and Group 3 (FX 0.1mg/kg bwt, IV, s.i.d for 5 days). All horses were castrated in standing position, using the open technique. Serum and peritoneal APP concentrations were measured by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and determined before castration (0), and 3, 5, 24, 48, 72, 120 and 168 hours after castration. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (p 0.05). Three animals from the MX group developed hyperthermia (with rectal temperatures of 39.8, 39.3 and 38.9°C on day 4, 5 and 6, respectively) and showed local clinical signs of inflammation (inguinal and excessive scrotal edema) and reluctance to walk, as well as a rigid gait of the hind limbs. The same complications were observed in one FX horse. No complications were observed among the FM animals. The castration resulted in significant changes in serum and peritoneal values of total proteins, ceruloplasmin (Cp), transferrin (Tf), albumin (Alb), haptoglobin (Hp) and 1-acid glycoprotein (Gp) in animals of all experimental groups. However, the animals of the MX and FX groups presented more intense acute phase response compared to the animals of the FM group. Changes in the APP were associated with the surgical trauma of castration, but the differences between groups were associated with the ability of the nonsteroidal anti-inflammatory drug to control the inflammation. In conclusion, and based on the findings of acute phase proteins, flunixin is more efficient to control the magnitude of inflammation following castration as compared to meloxicam and firocoxib.

RESUMO: Infecção e inflamação excessivas são as complicações mais comuns associadas à castração. O objetivo deste estudo foi comparar a eficácia do flunixin meglumine (FM), meloxicam (MX) ou firocoxib (FX) no controle da inflamação após a castração em cavalos usando proteínas da fase aguda (APP) como marcadores de inflamação. Trinta equinos saudáveis (358,62±45,57kg; 4,99±2,63 anos) foram em função dos anti-inflamatórios utilizados após as castrações aleatoriamente (n= 10 animais/grupo) alocados em três diferentes grupos: Grupo 1 (FM 1,1mg/kg de peso, IV, sid por 5 dias); Grupo 2 (MX 0,6mg/kg de peso, IV, s.i.d por 5 dias); e Grupo 3 (FX 0,1mg/kg de peso, IV, s.i.d por 5 dias). Todos os cavalos foram castrados em posição quadrupedal, utilizando a técnica aberta. As concentrações de APP sérica e peritoneal foram separadas por eletroforese em gel de poliacrilamida (PAGE) com dodecil-sulfato de sódio (SDS) e determinadas no momento 0 (antes da castração) e com 3, 5, 24, 48, 72, 120 e 168 horas após a castração. Os resultados foram submetidos à análise de variância pelo programa estatístico SAS e as médias foram comparadas pelo teste de Student-Newman-Keuls (p 0,05). Três animais do grupo MX desenvolveram hipertermia (com temperatura retal de 39,8, 39,3 e 38,9° C nos dias 4, 5 e 6, respectivamente) e mostraram sinais clínicos locais de inflamação (edema inguinal e escrotal excessivo) e relutância em andar, bem como marcha rígida dos membros posteriores. As mesmas complicações foram observadas em um cavalo do FX. Não foram observadas complicações entre os animais do FM. Independente do grupo, a castração resultou em alterações significativas nos valores séricos e peritoneais de proteínas totais, ceruloplasmina (Cp), transferrina (Tf), albumina (Alb), haptoglobina (Hp) e glicoproteína ácida 1 (Gp). No entanto, os animais dos grupos MX e FX apresentaram resposta de fase aguda mais intensa quando comparados aos animais do FM. Alterações na resposta de fase aguda deveram-se ao trauma cirúrgico da castração, mas as diferenças entre os grupos foram associadas à capacidade do anti-inflamatório em controlar a inflamação. Em conclusão, baseado da resposta de fase aguda, o flunixin em comparação com o meloxicam e o firocoxib é mais eficiente no controle da inflamação após a castração em equinos.

Integrated

The drug formulation design of self-emulsifying drug delivery systems (SEDDS) often requires numerous experiments, which are time- and money-consuming. This research aimed to rationally design the SEDDS formulation by the integrated computational and experimental approaches. 4495 SEDDS formulation datasets were collected to predict the pseudo-ternary phase diagram by the machine learning methods. Random forest (RF) showed the best prediction performance with 91.3% for accuracy, 92.0% for sensitivity and 90.7% for specificity in 5-fold cross-validation. The pseudo-ternary phase diagrams of meloxicam SEDDS were experimentally developed to validate the RF prediction model and achieved an excellent prediction accuracy (89.51%). The central composite design (CCD) was used to screen the best ratio of oil-surfactant-cosurfactant. Finally, molecular dynamic (MD) simulation was used to investigate the molecular interaction between excipients and drugs, which revealed the diffusion behavior in water and the role of cosurfactants. In conclusion, this research combined machine learning, central composite design, molecular modeling and experimental approaches for rational SEDDS formulation design. The integrated computer methodology can decrease traditional drug formulation design works and bring new ideas for future drug formulation design.

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.

Pharmacokinetics of cefquinome in goats after intramuscular administration alone and with meloxicam

Background: Nonsteroidal anti-inflammatory drugs and antibiotics are commonly prescribed together. We aimed to study the kinetic profile of cefquinome (2 mg/kg b.wt.) following intramuscular administration of it alone and co-administered with meloxicam (0.2 mg/kg b.wt.) in goats.Methods: Five Egyptian Baladi goats, each goat was injected intramuscularly at the dose rate of 2 mg/kg b.wt. Cefquinome into the deep gluteal muscle of hindquarter alone and then after fifteen days washout period, these animals also injected intramuscularly at the dose rate of 2 mg/kg b.wt. Cefquinome preceded with meloxicam at the dose rate of 0.2 mg/kg b.wt. The serum concentrations of cefquinome were detected by high performance liquid chromatography, two compartment model.Results: Following a single dose intramuscular administration of cefquinome alone, peak plasma concentration (1.71�0189 ?g/ml) was obtained at 1.59�0038 h. The absorption half-life (t1/2ab), total body clearance (Cltot), elimination half-life (t1/2el) and area under curve (area under concentration (AUC(0-inf)) of cefquinome were 0.4�0028 h, 0.068�78 l/h/kg, 9.21�178h and 29.36�78 礸.h.ml-1, respectively. Following a single dose intramuscular co-administration of cefquinome and meloxicam, peak plasma concentration (1.60�0124 ?g/ml) was obtained at 1.49�0092 h. The absorption half-life (t1/2ab), total body clearance (Cltot), elimination half-life (t1/2el) and area under curve (AUC(0-inf)) of cefquinome were 0.396�006 h, 0.094�25 l/h/kg, 6.5�221 h and 21.38�696 礸/h/ml, respectively. Non significant alters were reported in the parameters following co-administration of Cefquinome with meloxicam.Conclusions: From our results, may be concluded that intramuscular administration of meloxicam may be successfully co-administrated with cefquinome for combating bacterial infections with an inflammatory condition in goats without any antagonistic effect.

Meloxicam Inhibit the Growth of Oral Squamous Cell Carcinoma Induced by Benzopyrenes

@#Introduction: Meloxicam is a NSAID which able to inhibit the cyclooxygenase 2 (COX-2). The purpose of this research is to explain the effect of Meloxicam in inhibit the growth of oral squamous cell carcinoma (OSCC) induced by benzopyrenes. The apoptosis and proliferation of OSCC, the p53, Ras and COX-2 expression used as indicator. Methods: male mice were induced by benzopyrene 10 mg/kg body weight was given topically on buccal mucosa 2 times a week for 4 weeks for induced the OSCC. Meloxicam was given orally with 3 different doses was 50mg/kg, 100mg/kg, and 200mg/kg.b.w given once a day for 60 days. The control groups were given with CMC-1% 0.1ml/10g body weight. The buccal mucosa then biopsy and staining with immunohistochemistry to analyzed the p53, Ras, COX-2 expression, apoptosis and proliferation of OSCC. Results: The increase of Meloxicam dose is proportional to the increase in wild p53 expression and apoptosis, and inversely proportional to the expression of mutant race, cox-2 and the proliferation of OSCC. Conclusion: Meloxicam able to inhibit the growth of OSCC induced by benzopyrenes.

Loading and evaluation of meloxicam and atorvastatin in carrageenan microspherical aerogels particles

In this work, the potential of using microspherical aerogel particles based on commercial carrageenan as a drug vehiclewas evaluated. Carrageenan hydrogel microparticles were prepared following the emulsion gelation approach. Afterthe successive solvent exchange, supercritical CO2 drying procedure was employed to obtain aerogel microsphericalparticles. Meloxicam and atorvastatin (class II drug) were loaded into the aerogel matrix by adsorption from theircorresponding supercritical CO2 solution. All preparations were characterized by their physicochemical properties. Invitro drug released was investigated for the drug-aerogel formulation to assist the effect of aerogel technology on therelease profile of the targeted drug. Meloxicam and atorvastatin model drugs maintained their crystalline structure.Significant enhancement in the release profile of meloxicam after loading in the carrageenan aerogel can be related tode-aggregation of meloxicam inside the particle, while no enhancement in atorvastatin release was observed. Resultswere indicative of a failure in the loading of atorvastatin inside the carrageenan particle at the selected experimentalprocessing parameters.

Clinical efficacy of resveratrol as an adjuvant with meloxican in the treatment of knee osteoarthritis patients: A double-blind, randomised, placebo-controlled trial

The present study aimed to evaluate the effect of the adjuvant use of resveratrol with meloxicam on the clinical scores of knee OA patients. This was a double-blind placebo-controlled randomised trial involving 100 patients with knee osteoarthritis performed at the Shar Teaching Hospital, Sulaimani General Hospital and Specialised Rheumatology Center, Sulaimani City from December 2016 to September 2017. The efficacy of the treatment was evaluated by measuring the changes from baseline in the KOOS score, WOMAC index, and VAS-100 score after 90 days of treatment. Resveratrol significantly improves the knee OA pain and associated symptoms compared with placebo, and both clinical scores were found to be eligible for following treatment outcomes. In conclusion, resveratrol, when used in combination with meloxicam, improves pain and symptom scores in patients with mild-to-moderate knee OA compared with placebo. The intervention with a dietary supplement may significantly impact the pain and overall quality of life in patients with knee OA.

Pedometria e acompanhamento bioquímico no pós-operatório de bovinos Nelore com onfalopatias / Pedometer and biochemistry monitoring on postoperative from Nelore cattle with umbilical diseases

A analgesia pós-operatória em bovinos, por vezes, é negligenciada, frequentemente por falta de métodos quantitativos para seu diagnóstico e dimensionamento. Os objetivos deste trabalho foram: avaliar a pedometria e o acompanhamento bioquímico no pós-operatório de bovinos Nelore com onfalopatias e comparar a eficiência anti-inflamatória e analgésica entre diferentes doses de flunixin meglumine e meloxicam nesses animais. Foram utilizados 24 bovinos; deste total, 18 animais foram submetidos a laparotomia para tratamento das onfalopatias e, posteriormente, divididos em três grupos de animais: G1, que recebeu 1,1mg/kg flunixin; G2, 2,2mg/kg flunixin; G3, 0,5mg/kg meloxicam. A via de eleição para os tratamentos foi a IM, uma vez ao dia, totalizando seis aplicações. Outros seis bovinos saudáveis compuseram o grupo controle (GC). As coletas do sangue total para mensuração do cortisol plasmático foram realizadas antes e depois da cirurgia, assim como a leitura do pedômetro e o exame clínico. As concentrações plasmáticas de cortisol diferiram apenas no M0, entre o GC e os grupos tratados. O flunixin meglumine em diferentes doses e o meloxicam foram equivalentes no tratamento da dor pós-operatória e no efeito anti-inflamatório em bovinos submetidos à laparotomia para tratamento das onfalopatias.(AU)

Postoperative analgesia in cattle is sometimes overlooked, frequently due to the lack of quantitative methods for diagnosis and measurement. The objectives of this study were: to analyze the pedometric and biochemistry alterations of postoperative period in Nelore bovines with umbilical diseases; compare the anti-inflammatory and analgesic efficiency between different doses of flunixin meglumine and meloxicam in the postoperative of umbilical diseases in these animals. Twenty four bovines were used. From this total, 18 animals were submitted to laparotomy for treatment of umbilical diseases and subsequently divided into three groups of animals: G1, which received 1.1mg/kg flunixin, G2 2.2mg/kg flunixin, G3 0.5mg/kg meloxicam. Six other healthy cattle were allocated to the control group (CG). Total blood samples for plasma cortisol clinical examination was performed on standardizer times. Plasma cortisol concentrations differed only in the M0 between GC and treated groups. Flunixin meglumine in different doses and meloxicam were equivalent in the treatment of postoperative pain and anti-inflammatory effect in cattle submitted to laparotomy for the treatment of umbilical diseases.(AU)

Clinical therapeutic effects on rheumatoid arthritis treated with the assisted therapy of acupuncture at the points detected with thermosensitive moxibustion in medicine / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the clinical therapeutic effects and safety on rheumatoid arthritis (RA) treated with acupuncture at the points detected with thermosensitive moxibustion in medicine combined with western medication.</p><p><b>METHODS</b>A total of 168 RA patients in compliance with the inclusive criteria were collected and randomized into an observation group and a control group, 84 cases in each one. In the control group, in reference to the updated guideline of new drugs by the European League Against Rheumatism (EULAR) in 2013, the medication scheme was formulated for oral administration, methotrexate tablet 7.5 mg, once a week; salazosulfapyridine enteric-coated tablets, 100 mg, twice a day; hydroxychloroquine sulfate tablets, 20 mg, twice a day; and meloxicam tablets, 15 mg, once a day. In the observation group, besides the treatment as the control group, the acupuncture therapy at the points detected with thermosensitive moxibustion in medicine was given. The mild moxibustion was applied near to the affected joint with the moxa material of herbal medicine to detect the sensitization points. Afterwards, the acupuncture technique of medicine was given on those points, without any manipulation applied. The needles were retained for 30 min, once daily. The treatment for 2 weeks was as one course, continuously for 2 courses. The indexes were observed before and after treatment in the two groups including gripping power, the time of morning stiffness, the swollen joint count 28 (SJC 28), the tender joint count 28 (TJC 28), the disease activity score 28 (DAS 28), the score of patient global assessment of disease activity (PtGA) and the score of provider global assessment of disease activity (PhGA), as well as rheumatoid factors (RF), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and anti-cyclic peptide containing citrulline (A-CCP). The clinical therapeutic effects were evaluated in the two groups.</p><p><b>RESULTS</b>After 4-week treatment, a total of 163 patients accomplished the clinical trial, 81 cases in the observation group and 82 cases in the control group. The results of gripping power, the time of morning stiffness, SJC 28, TJC 28, PtGA, PhGA, DAS 28, RF, CRP, ESR and A-CCP were all improved as compared with those before treatment (all <0.05). In 4 weeks of treatment, the results of gripping power, the time of morning stiffness, SJC 28, TJC 28, PtGA, PhGA, DAS 28, as well as CRP and ESR in the observation group were better than those in the control group (all <0.05). The results of RF and A-CCP were not different significantly between the two groups (both >0.05). The total effective rate was 85.19% (69/81) in the observation group, higher than 70.73% (58/82) in the control group (<0.05).</p><p><b>CONCLUSION</b>The acupuncture therapy at the points detected with thermosensitive moxibustion in medicine achieves the satisfactory clinical effects with few adverse effects.</p>

Physicochemical characterization, the Hirshfeld surface, and biological evaluation of two meloxicam compounding pharmacy samples / 药物分析学报

Meloxicam (MLX) is an anti-inflammatory drug susceptible to variations and crystalline transitions. In compounding pharmacies, the complete crystallographic evaluation of the raw material is not a routine procedure. We performed a complete crystallographic characterization of aleatory raw MLX samples from compounding pharmacies. X-ray diffraction indicated the presence of two crystalline forms in one sample. DSC experiments suggested that crystallization, or a crystal transition, occurred differently be-tween samples. The FTIR and 1H NMR spectra showed characteristic assignments. 13C solid-state NMR spectroscopy indicated the presence of more than one phase in a sample from pharmacy B. The Hirshfeld surface analysis, with electrostatic potential projection, allowed complete assignment of the UV spectra in ethanol solution. The polymorph I of meloxicam was more active than polymorph Ⅲ in an experi-mental model of acute inflammation in mice. Our results highlighted the need for complete crystal-lographic characterization and the separation of freely used raw materials in compounding pharmacies, as a routine procedure, to ensure the desired dose/effect.

Optimization of Meloxicam Nanosuspensions Fast Dissolving Sublingual Films (MLX-NS-Fdsfs) by Box-Behnken Response Surface Methodology / 中国药学杂志

OBJECTIVE: To prepare and optimize meloxicam nanosuspensions fast dissolving sublingual films (MLX-NS-FDSFs) and to evaluate its in vitro dissolution characteristics. METHODS: Meloxicam nanosuspensions (MLX-NS) were prepared by pH-dependent dissolving-precipitating/high speed shearing method and then transformed into fast dissolving sublingual films (FDSFs). The formulations of MLX-NS-FDSFs were optimized by employing Box-Behnken design-response surface methodology with the amount of HPMC-E30, PEG-400 and MLX-NS as investigation factors, and particle size of reconstituted nanoparticles from MLX-NS-FDSFs, disintegration time and stretch length as indexes. The morphology, content uniformity and in vitro dissolution of the optimal formulation were also evaluated. RESULTS: The MLX-NS-FDSFs prepared by optimized formulation (35 mg·mL-1 HPMC-E30, 40 mg·mL-1 PEG-400, 10 mL MLX-NS) could fast disintegrate in (26.08±1.76) s, the tensile length was (1.51±0.13) mm, and the particle size of reconstituted nanoparticles from MLX-NS-FDSFs was (186.4±6.3) nm. There was a little deviation between the theoretically predicted value and the measured value. It showed that this model had a good prediction. Morphological analysis showed that well-dispersed MLX nanoparticles embedded in MLX-NS-FDSFs. The conformity of drug content was up to standard. MLX could be released in vitro as much as (91.75±8.05)% within five minutes. CONCLUSION: Using Box-Behnken design and response surface method to optimize MLX-NS-FDSFs is effective and feasible. MLX-NS-FDSFs can significantly increase the cumulative dissolution of MLX.

Selective COX-2 Inhibitor (Meloxicam) and Tooth-Supporting Bone Quality. A Histomorphometric Study in Rats

Abstract The effects of the non-steroidal anti-inflammatory drugs (NSAIDs) on bone quantity and quality were investigated for years. However, there is lack of information on the impact of NSAIDs on the quality of tooth-supporting alveolar bone in absence of periodontal inflammation. Thus, the aim of this study was to evaluate histometrically the influence of a selective COX-2 NSAID (Meloxicam) on the inter-radicular bone mineral density in rats. Forty-nine adult male Wistar rats were randomly divided into four experimental groups: Subcutaneous injection of 0.9% sterile saline for 15 days (G1; n=12) and 45 days (G2; n=11); and subcutaneous injection of Meloxicam for 15 days (G3; n=13) and 45 days (G4; n=13). Mineral density was histometrically determined in the inter-radicular area of the 1st mandibular molars and data analysis performed by two-way ANOVA (a=5%). Results showed no interaction between time and treatment (p>0.05) and that meloxicam did not affect the alveolar bone density. In contrast, it was found that inter-radicular alveolar bone density increased with time (91.88±3.08% and 92.86±2.38% for groups 15 and 45 days, respectively) (p<0.05). Within the limits of this study, daily administration of a selective COX-2 inhibitor (Meloxicam) did not affect the quality of the inter-radicular alveolar bone in absence of periodontal infection.

Resumo Os efeitos dos fármacos anti-inflamatórios não esteroidais (AINEs) sobre a quantidade e qualidade óssea tem sido investigados ao longo dos anos.Entretanto, há falta de informação sobre o impacto dos AINEs na qualidade do osso alveolar de suporte na ausência de inflamação periodontal. Assim, o objetivo deste estudo foi avaliar, histometricamente, a influência de um AINE seletivo para COX-2 (Meloxicam) na densidade mineral óssea inter-radicular em ratos. Quarenta e nove ratos Wistar, machos e adultos foram divididos aleatoriamente em quatro grupos experimentais: injeções subcutâneas de 0,9% de solução salina estéril por 15 dias (G1, n=12) e 45 dias (G2, n=11); e injeções subcutâneas de Meloxicam por 15 (G3, n=13) e 45 dias (G4, n=13). A densidade mineral foi determinada histometricamente na área inter-radicular dos primeiros molares mandibulares e a análise dos dados realizada por meio de ANOVA (a=5%). Os resultados mostraram nenhuma interação entre tempo e tratamento (p>0,05) e que o meloxicam não afetou a densidade óssea alveolar. Em contraste, foi encontrado que a densidade óssea alveolar inter-radicular aumentou ao longo do tempo (91,88±3,08% e 92,86±2,38% para os grupos 15 e 45 dias, respectivamente) (p<0,05). Dentro dos limites deste estudo, a administração diária de um inibidor seletivo para COX-2 (Meloxicam) não afetou a qualidade do osso alveolar inter-radicular na ausência de infecção periodontal.

Study on bioequivalence of Meloxicam Chewable Tablets / 药物评价研究

Objective To investigate in vivo pharmacokinetics and bioequivalence of Meloxicam Chewable Tablets in healthy Beagle's dogs.Method Twelve healthy adult Beagle's dogs were randomized into two groups.Using the double-preparation,double-cycle,cross-over method and administering orally of testing and reference tablet (2 mg) respectively.The plasma concentration of meloxicam was determinated by RP-HPLC.The 3P97 software was adopted to calculate the pharmacokinetic parameters and evaluate the bioequivalence of two preparations.Results The area under the curves (AUC0-96 h) of the testing tablets and innovator tablets were (2.85±0.64) and (2.79±0.48) μg/mL·h.The peak time (Tmax) was (4.33±0.65) and (4.16±0.71) h.The peak concentration (Cmax) was (0.091±0.017) and (0.086±0.021) μg/mL.The half time (t1/2) was (26.08±3.64) and (26.94± 4.21) h.After the double unilateral t test,there was no statistical significance in the difference of lnAUC and lnCmax between the testing tablets and innovator tablets.Conclusion The testing tablets and innovator tablets are bioequivalent.The relative bioavailability of generic tablet is (98.0±9.76)％.

Study on the clinical effect of Tuina therapy for knee osteoarthritis patients / 国际中医中药杂志

Objective To explore the clinical effect of Tuina therapy for knee osteoarthritis (KOA) patients and their musculus quadriceps fexoris strength. Methods The 114 patients with KOA who met the inclusion criteria were randomly divided into the observation group and the control group (57 in each group). The patients in observation group were treated with Tuina therapy, and the control group were treated with Meloxicam. All the patients were treated for 30 days. The Isokinetic muscle strength test was used to evaluate the strength of the four biceps femoris muscle, and HSS score and pain score were observed before and after treatment. Results The total effective rate of the observation group was 91.2% (52/57), and the control group was 71.9% (41/57). The difference between 2 groups was statistically significant (χ2=3.971, P=0.018). After treatment, the HSS scores (79.0 ± 2.0 vs. 66.3 ± 1.4; t=3.121, P<0.01) in observation group were significantly higher than that in control group, and the pain scores (1.7 ± 1.1 vs. 3.2 ± 1.1; t=2.953, P<0.01) in observation group were significantly lower than that in control group. The PT (59.91 ± 25.90 Kgm vs. 55.17 ± 25.88 Kgm, t=2.652), AP (30.04 ± 12.59 W vs. 28.02 ± 17.03 W, t=3.618), TW (496.47 ± 257.26 Nm vs. 466.19 ± 225.70 Nm, t=3.227) of 60/s isokinetic muscle strength test and PT (37.22 ± 18.73 Kgm vs. 32.54 ± 15.22 Kgm, t=2.511), AP (39.43 ± 18.02 W vs. 36.14 ± 23.88 W, t=2.183), TW (326.03 ± 159.38 Nm vs. 267.66 ± 156.93 Nm, t=2.073) of 180/s isokinetic muscle strength test in observation group were significantly higher than those in control group (P<0.05). Conclusions Tuina therapy could improve KOA patients' musculus quadriceps fexoris strength, which curative effect were better than oral treatment of Meloxicam.

Preparation and physicochemical characterization of meloxicam orally fast disintegration tablet using its solid dispersion

ABSTRACT Meloxicam (MLX) is a non-steroidal, anti-inflammatory drug that is prescribed in the treatment of rheumatoid arthritis and osteoarthritis. MLX is practically insoluble in water and exhibits a slow onset of action. In this study, MLX solid dispersions (MLX SDs) were prepared to improve the water solubility of this poorly water-soluble drug. Then orally disintegrating tablets (ODT) of MLX were developed using MLX SD to decrease the onset of action of this drug. MLX, poloxamer 188, and crospovidone of different ratios were melted in molten poloxamer 188 as a hydrophilic carrier. The optimum SD with the highest saturation solubility in water (13.09±0.34 microgram/mL) consisting of MLX: poloxamer 188: crospovidone in the ratio of 1:2:0 was used for the preparation of MLX ODTs. MLX ODTs were prepared by the direct compression method and optimized by the 23 factorial design. The effect of the superdisintegrant concentration, the mannitol-avicel ratio, and the level of compression force on the disintegration time, hardness, and percent of dissolved MLX from MLX ODTs after 30 min was evaluated. DSC and XRD analysis approved an amorphous form of MLX in SDs. The optimized ODT formulation containing 10% of superdisintegrant, and mannitol and avicel in the ratio of 4:1 respectively was compressed using a high level of compression force. The optimized ODT showed hardness (34.37±2.1 N) and friability (1.26±0.04%). This formulation showed a rapid disintegration in 12.66±2.5 seconds, which 82.66±5.1% of the MLX released within 30 min. MLX ODTs, prepared from MLX SD, could be introduced as a suitable dosage form of MLX with improved solubility and the onset of action.

A Simple and Sensitive HPLC/UV Method for Determination of Meloxicam in Human Plasma for Bioavailability and Bioequivalence Studies.

An HPLC/UV method to monitor meloxicam (MX) in human plasma was developed and properly validated. This method was based on a reversed-phase chromatographic analysis using C18-Symmetry column and a mobile phase consisting of acetonitrile: deionized water [50:50 (% v/v)] adjusted to pH 3 with glacial acetic acid. The detection wavelength was 360 nm using piroxicam as an I.S. The developed HPLC method was linear, sensitive, accurate, precise, selective and stable. This method exclusively provided a LLOQ of 5 ng/mL and ULOQ of 3000 ng/ml which could be considered as an excellent and economical method for carrying-out BA/BE studies. The determination of pharmacokinetics of single oral dose (15 mg/tablet) administered to healthy human male volunteer was carried-out to compare the bioavailability of three different MX products with a washout period of 8-days between treatments. Moreover, a comparative in vitro dissolution study of the three products using USP#4 (the Flow-through cell, FTC) has been carried-out prior to the in vivo test. The pharmacokinetic data revealed that the developed HPLC method was sensitive enough to monitor the multiple-peak phenomena characterized for MX absorption. Where, the first Cmax appeared at 4.5–5.5 hrs and the second at 10–12 hrs, for the tested products. Abbreviations: MX: Meloxicam, I.S.: Internal Standard, Q: Amount Dissolved, IR: Immediate Release, LOQ: Lower limit of quantification, ULOQ: Upper limit of quantification, BA: Bioavailability, BE: Bioequivalence.