Design and evaluation of dental pastes Containing anti-inflammatory drugs

Abstract Periodontitis is an oral disease associated with inflammation and pain with swollen and bleeding gums. In the present study, dental pastes containing NSAIDs, namely, diclofenac sodium and nimesulide (1 % w/w) were prepared to treat periodontitis. Dental pastes of diclofenac sodium and nimesulide (1 % w/w) were prepared with/without mucoadhesive hydrocolloid polymers such as sodium carboxy methyl cellulose (NaCMC), hydroxyl ethyl cellulose (HEC) and methyl cellulose (MC) by conventional trituration method. The pH, drug content, viscosity, tube spreadability and tube extrudability of these prepared dental pastes were measured. These dental pastes of diclofenac sodium and nimesulide (1 % w/w) were characterized by FTIR analyses for drug-excipient compatibility. The in vitro drug releases from these dental pastes in 6.4 pH phosphate buffer solution displayed sustained release over longer period and the drug release rate was found to be decreased when the concentration of mucoadhesive polymer was increased. These dental pastes displayed good adhesion to the oral mucosa revealing more retention time in mouth when tested for ex vivo mucoadhesion using bovine cheek pouch. The stability study results reveal that the DC3 and NC3 dental paste formulations were found stable enough over a longer period in different storage conditions. The present study revealed that the prepared mucoadhesive dental pastes of diclofenac sodium and nimesulide (1 % w/w) had good adhesion with the oral mucosa to maintain consistent release of drugs over prolonged time.

Solid Phase Extraction and Simultaneous Chromatographic Quantification of some Non-steroidal Anti-inflammatory Drug Residues; an Application in Pharmaceutical Industrial Wastewater Effluent

Abstract Two sensitive and selective methods were developed for the simultaneous determination of four commonly used non-steroidal anti-inflammatory drugs (NSAIDs), namely; paracetamol (PCM), diclofenac sodium (DCF), ibuprofen (IBP), and indomethacin (IND) in wastewater effluents. The first method used HPLC for the determination of the studied drugs using a mobile phase consisting of phosphate buffer (pH 3.0) and acetonitrile at a flow rate of 1 mL/min. in gradient elution mode and detection at 220 nm. The separation process was performed on BDS Hypersil Cyano column (250 x 4.6 mm, 5 µm). The second method was a TLC-densitometric one which was performed using n-Hexane: ethyl acetate: acetic acid in the ratio (6:3.5:0.5) as a developing system. The proposed chromatographic methods were successfully applied for the selective determination of the four studied drugs in simulated and real pharmaceutical wastewater samples after their solid-phase extraction

Antinociceptive local activity of 4-allyl-1-hydroxy-2-methoxybenzene (eugenol) by the formalin test: an anti-inflammatory effect

Eugenol has been employed for decades as a condiment, an antimycotic, an antibacterial, an antiviral, and an antioxidant, and it is one of the natural analgesics most frequently utilized for pain and inflammation. Our objective was to determine the analgesic/anti-inflammatory effect of eugenol compared with diclofenac, naproxen, and tramadol using the formalin test. The formalin method was used in 6- to 10-week-old Wistar rats (weighing 250 g each) divided into six groups: saline (0.9%); formalin (5%); diclofenac (250 µg/kg); naproxen (400 µg/kg); tramadol (500 µg/kg), and eugenol (1,400 µg/kg), in the intraplantar part of the hind-end trunk of the rats, with n = 5 per group. Eugenol diminished 44.4% of nociceptive behavior in phase 1 and 48% in phase 2 (p ≤0.05 vs formalin). Eugenol was shown to be 1.14 times more effective than diclofenac, but 1.62 and 1.75 times less effective than naproxen and tramadol, respectively, in phase 1 and 1.45 times less effective than diclofenac and naproxen and 1.66 less effective than tramadol in phase 2 (p ≤0.05). These data suggest that eugenol possesses moderate activity in the acute pain phase and greater activity in inflammatory-type pain, and both effects are comparable to those produced by diclofenac and are less than the effects produced by naproxen and tramadol in the formalin test

Toothache, Associated Factors, and Its Impact on Oral Health-Related Quality of Life (OHRQoL) in Preschool Children

The aim of this study was to assess the prevalence of toothache, associated factors and impact of this condition on the Child Oral Health Related Quality of Life (COHRQoL) in preschoolers. The study was carried out in Santa Maria, Brazil, during the National Children's Vaccination Day, and 534 children aged 0 to 5 years were included. Clinical variables included dental caries and dental trauma. A questionnaire was responded by the parents and provided information about several socioeconomic indicators, dental service use and toothache. Toothache was collected by the question: "Has your child ever had a toothache - Yes or no?". Data on COHRQoL were assessed using the Brazilian version of the Early Childhood Oral Health Impact Scale (ECOHIS). Multivariable Logistic regression models were performed to assess the association between the predictor variables and outcomes. The prevalence of toothache was 10.11% (95% CI: 7.55% - 12.68%). Older children had a higher chance of presenting dental pain (OR 2.72; 95% CI: 1.01 - 7.56), as well as children with caries experience (OR 3.43; 95% CI: 1.81 - 6.52). Moreover, children who had not visited the dental service in the last 6 months were less likely to present toothache (OR 0.51; 95% CI: 0.28 - 0.95). The presence of dental pain negatively affects the COHRQoL; those with toothache presented a higher chance of having higher impact on the total scores of ECOHIS (OR 4.18; 95% CI: 1.76 - 9.95) than those without toothache. Similar observation was found for the child section of the questionnaire (OR 5.54; 95% CI: 2.15 - 14.24). Toothache negatively affects COHRQoL and is associated with caries experience, age and use of dental service.

O objetivo deste estudo foi avaliar a prevalência de dor dentaria, os fatores associados e seu impacto na qualidade de vida relacionada a saúde bucal de crianças pré-escolares. Esse estudo foi realizado em Santa Maria, Brasil, durante o dia nacional de vacinação infantil, e 534 crianças de 0 a 5 anos foram incluídas. As variáveis clinicas incluídas foram carie dental e traumatismo dentário. Um questionário foi respondido pelos pais, fornecendo informações sobre as condições socioeconômicas, uso de serviços odontológicos e dor dentaria. Dor de dente foi coletada através da pergunta: "Seu filho já teve dor de dente - Sim ou Não?". Os dados sobre qualidade de vida relacionada a saúde bucal foram obtidos através da versão brasileira do questionário "Early Childhood Oral Health Impact Scale" (ECOHIS). Modelos multivariáveis de regressão logística foram utilizados para avaliar a associação entre as variáveis preditoras e os desfechos. A prevalência de dor dentaria foi 10,11% (95% IC: 7,55% - 12,68%). Crianças mais velhas apresentaram uma maior chance de ter tido dor dentaria (OR 2,72; 95% IC: 1,01 - 7,56), assim como crianças com experiência de carie (OR 3,43; 95% IC: 1,81 - 6,52). Além disso, as crianças que não tinham visitado o dentista nos últimos 6 meses foram menos propensas a apresentar dor dentária (OR 0,51; 95% IC: 0,28 - 0,95). A presença de dor dentária afeta negativamente a qualidade de vida relacionada a saúde bucal das crianças; aquelas que tiveram dor de dente apresentaram uma maior chance de ter piores impactos nos escores totais do ECOHIS (OR 4,18; 95% IC: 1,76 - 9,95) quando comparadas àquelas que não tiveram dor dentária. O mesmo se pode observar para a seção do questionário correspondente aos impactos na criança (OR 5,54; 95% IC: 2,15 - 14,24. Dor dentaria afeta negativamente a qualidade de vida relacionada a saúde bucal e esta associada com experiência de carie, idade e uso de serviços odontológicos.

Evaluation of the analgesic and anti-inflammatory activity of fixed dose combination: Non-steroidal anti-inflammatory drugs in experimental animals.

Background: In India, a number of fixed dose drug combinations of non-steroidal anti-inflammatory drugs (NSAID's) are available, often as over-the-counter products. These combinations are being prescribed too. Evidence for efficacy of NSIAD fixed dose combination is lacking. Objectives: The current study was undertaken to assess the analgesic and anti-inflammatory efficacy of these combinations over their individual components. Materials and Methods: The study used three NSAIDs viz; paracetamol, ibuprofen and diclofenac sodium, alone or in combination with paracetamol. Animals were divided into six groups with six animals in each group. Analgesic activity was tested by writhing test and paw edema model was used to assess the anti-inflammatory activity. The test drugs were administered orally 30 min prior to injecting 0.6% solution of glacial acetic acid intraperitoneally for writhing test. For paw edema test, after 30 min of drugs administration, animals were injected with 0.1 ml of 1% carrageenan in subplanter region for inducing inflammation. Paw volume was again measured at baseline and after 3 h of subplanter injection of 1% carrageenan. Results: The analgesic and the anti-inflammatory activity of paracetamol and ibuprofen combination were significantly greater than the individual agents when used alone. However, no significant difference in the analgesic or anti-inflammatory activity was found between diclofenac sodium and its combination with paracetamol. It was observed that diclofenac sodium was the most efficacious of the analgesics tested. Combining paracetamol with diclofenac did not show superior analgesic activity compared to diclofenac alone (P = 0.18). Conclusion: Combining paracetamol with ibuprofen enhances analgesic/anti-inflammatory activity over their individual component but potentiation of analgesic activity of diclofenac was not seen when paracetamol was added to it.

Efeito de anti-inflamatórios não esteroidais na apoptose de células epidermais lamelares de equinos com laminite / Effect of nonsteroidal anti-inflammatory drugs on apoptosis of epidermal lamellar cells of equines with laminitis

O objetivo deste trabalho foi avaliar a influência da administração dos anti-inflamatórios não esteroidais (AINEs) cetoprofeno, fenilbutazona e flunixin meglumine sobre o índice apoptótico de células epiteliais do tecido lamelar de cavalos com laminite induzida por administração de amido. Foram empregados 20 equinos hígidos, divididos em quatro grupos experimentais (n=5): solução salina, cetoprofeno, fenilbutazona e flunixin meglumine. O tecido lamelar foi coletado por biópsia, fixado e corado pela técnica de TUNEL. À marcação positiva por essa técnica adicionou-se a avaliação morfológica celular para identificação da apoptose. Não houve diferença significativa no índice apoptótico entre os grupos tratados com anti-inflamatórios e o controle (P>0,05). Os anti-inflamatórios não interferiram sobre o índice apoptótico possivelmente porque foram administrados após a fase prodrômica da laminite e/ou porque não são eficazes em alterar a dinâmica da apoptose. Concluiu-se que a administração de anti-inflamatórios não esteroidais após a fase prodrômica da laminite não contribui para uma intervenção no curso da apoptose no tecido lamelar de cavalos com laminite quando comparados ao grupo controle não tratado. Outros estudos, com diferentes períodos de avaliação, são necessários para esclarecer os efeitos dos anti-inflamatórios não esteroidais na fisiopatologia da laminite em equinos, especialmente no que concerne à participação da apoptose.

The aim of this study was to evaluate the influence of the administration of anti-inflammatory drugs (NSAIDs) ketoprofen, phenylbutazone and flunixin meglumine on the apoptotic index of the epithelial cells of lamellar tissue of horses with induced laminitis. 20 healthy horses were employed and underwent induction of laminitis by administration of starch, divided into four groups with induced laminitis (n = 5): saline, ketoprofen, phenylbutazone and flunixin meglumine. The lamellar tissue was collected by biopsy, fixed and stained with the TUNEL technique. All that were stained positive by this technique were added to the cell morphological identification of apoptosis. No significant difference was found in the apoptotic index between the groups treated with anti-inflammatory and controls (P> 0.05). It was concluded that the administration of NSAIDs after the prodromal phase of laminitis does not contribute to an intervention in the course of apoptosis in the lamellar tissue of horses with laminitis when compared to the untreated control group. Other studies with different evaluation periods are needed to clarify the effects of anti-inflammatory non-steroidal drugs in the pathophysiology of laminitis in horses, especially regarding the role of apoptosis.

Confirmación de dexametasona y diclofenaco por LC-MS-MS como adulterantes en un producto herbolario / Dexamethasone and diclofenac by LC-MS-MS as herbal product adulterants

Objetivo. Confirmar la presencia de dexametasona y diclofenaco como adulterantes de un producto comercializado como de origen natural. Material y métodos. Para la identificación y confirmación de la presencia de los fármacos se utilizó un método de análisis instrumental por cromatografía de líquidos de alta presión acoplado a espectrometría de masas en tándem. Resultados. En el análisis de 11 frascos de Reumofan Plus obtenidos de pacientes y médicos de la localidad se confirmó la presencia de dexametasona y diclofenaco. La metodología utilizada permitió separar los esteroisómeros dexametasona y betametasona, las abundancias relativas de iones productos 237.2 y 279.2 m/z permiten diferenciar espectralmente un compuesto de otro. Conclusiones. Se confirmó la presencia de dexametasona y diclofenaco en muestras de un producto comercializado como "100% natural" obtenidas de diferentes pacientes o médicos en el periodo enero a diciembre de 2011.

Objective. To confirm the presence of dexamethasone and diclofenac as adulterants of an herbal product. Materials and methods. For identificaction and confirmation of drugs a method of instrumental analysis by liquid chromatography coupled with high pressure tandem mass spectrometry was used. Results. The presence of dexamethasone and diclofenac was confirmed in samples of 11 bottles of Reumofan Plus obtained from patients and/or physicians. The methodology used, allowed separation of stereoisomers dexamethasone and betamethasone, the relative abundances of product ions 237.2 and 279.2 m / z spectrally differentiate the compounds. Conclusions. The presence of dexamethasone and diclofenac was confirmed in samples of a product marketed as "100% natural" obtained from patients and / or physicians in a period from January to December, 2011.

Planejamento, síntese e avaliação biológica de derivados pirrólicos com potencial atividade antiinflamatória / Design, synthesis and evaluation of biological derivatives pyrroles potentially antiinflamatory activity

Os antiinflamatórios não-esteróides (AINEs) estão entre os fármacos mais prescritos e utilizados do mundo. Estes fármacos inibem as ciclooxigenases, enzimas responsáveis pela transformação do ácido araquidônico em prostaglandinas flogísticas, pela ação da fosfolipase A2. A síntese de compostos antiinflamatórios contendo núcleo pirrólico em suas estruturas vem sendo um tópico muito atrativo e bastante estudado, que somado ao conhecimento do sítio de interação do fármaco ao receptor possibilita o planejamento de estruturas de novas substâncias candidatas a protótipos de novos fármacos, por meio da modificação molecular. Nesse contexto, o presente trabalho teve como objetivo o planejamento, síntese e avaliação biológica de derivados pirrólicos com potencial atividade antiinflamatória, com base nas estruturas da indometacina, protótipo da classe dos derivados de ácido arilalcanóico e dos diarilheterociclos (COXIBES). Sendo assim, foram obtidos cinco compostos em rendimentos satisfatórios, a partir de acetoacetato de etila, via metodologia de Hantzsch e ciclofuncionalização, utilizando ultrassom, que resultou na redução do tempo de reação e do consumo de solvente, seguindo os princípios da Química Verde. Os compostos 5a e 5b mostraram-se promissores, a partir de ensaios "in vitro"

The nonsteroidal antiinflammatory drugs (NSAIDs) are among the most prescribed and used drugs in the world. These drugs inhibit the cyclooxygenases, enzymes responsible for conversion of arachidonic acid into phlogistic prostaglandins, by the action of phospholipase A2. The synthesis of compounds containing pyrrole nucleus in their structures has been a topic very attractive and well studied, that knowledge added to the site of interaction of the drug to the receptor enables the planning of new structures of substances candidates for prototypes of new drugs through of molecular modification. In this context, this work aimed at the design, synthesis and biological evaluation of pyrrole derivatives with potential antiinflammatory activity, based on the structures of indomethacin, the prototype of arylalkanoic acid class and diarylheterocycles (coxibs). Thus, five compounds were obtained in good yields from ethyl acetoacetate, route of Hantzsch and cyclofunctionalization methods, using ultrasound, which resulted in the reduction of the reaction time and consumption of solvent, following the principles of Green Chemistry. The 5a and 5b compounds were shown to be promising, from tests in vitro

Estudo da encapsulaçäo do diclofenaco sódico em lipossomas unilamelares e avaliaçäo da toxicidade tissular após administraçäo intramuscular / Study of the encapsulation of diclofenac sodium in unilamellar liposomes and assessment of tissue toxicity after intramuscular injection

Foi estudada a encapsulaçäo do diclofenaco sódico em lipossomas unilamelares compostos por fosfatidilcolina, colesterol e `ALFA'-tocoferol (40:10:0,04 nM). Os ensaios de liberaçäo in vitro demonstraram que a liberaçäo do fármaco encapsulado nos lipossomas foi mais lenta em comparaçäo à do fármaco livre. As preparaçöes foram administradas via intramuscular em ratos Wistar machos e a atividade sérica da creatina fosfoquinase (CPK) foi utilizada como parâmetro para avaliaçäo da lesäo celular no sítio de injeçäo. Enquanto que as preparaçöes contendo diclofenaco livre provocaram aumento significativo na atividade da CPK, o fármaco encapsulado em lipossomas causou reaçäo insignificante, semelhante ao grupo controle...

Técnica analítica para el control de calidad de las tabletas de Ribofen 80 mg / Analytical technique for the quality control of ribofen tablets 80 mg

Se desarrolló una técnica para el control de calidad de las tabletas de ribofen, con el empleo de la espectrofotometría UV y la cromatografía líquida de alta resolución, que incluye la identificación, disolución, uniformidad de dosis y valoración. Las tabletas cumplen con los índices de calidad establecidos en la técnica. Se estudio la especificidad, linealidad, precisión, exactitud y se corroboró la validez de estos parámetros en ambos métodos

Estudo comparativo do mecanismo de açäo e dos efeitos farmacológicos do Tenoxicam, Indometacina, Dexametasona e Metotrexato no processo inflamatório agudo e crônico / Comparative study of mechanism of action and the farmacological effects of Tenoxican, Indomethacin, Dexamethazone and Methotrexate in acute and chronic inflammatory process

Aprofundamos o estudo dos efeitos farmacológicos da dexametasona, indometacina e tenoxicam e de uma droga citostática (metotrexano), assim como a análise dos mecanismos envolvidos na estimulaçäo flogógena causada por agentes de intensidades fraca, média e forte. Para isso, empregamos o teste edemogênico, que demonstrou serem os fármacos antiinflamatórios näo esteróides (tenoxicam e indometacina), os de maior potência na inibiçäo da exsudaçäo plasmática induzida pela paracoccidioidina. Todavia, com agentes flogógenos de intensidade média (carragenina), o metotrexano foi o medicamento mais potente, enquanto que com a placa microbiana dental (agente forte), a dexametasona e a indometacina foram os de maior potência antiinflamatória. Por meio da análise histomorfométrica relativa dos granulomas induzidos por esse último agente, verificamos até 14 dias, a maior potência antiinflamatória apresentada pelo tenoxicam, comparativamente a indometacina, pois inibiu mais acentuadamente a regiäo central de necrose supurativa, demonstrando efeito semelhante ao da dexametasona, näo obstante, em relaçäo à inibiçäo da densidade do volume do tecido granulomatoso, os fármacos mais potentes terem sido a indometacina e a dexametasona. Após os 14 dias näo foi constatada diferença significativa entre o efeito apresentado pelo tenoxicam e o da indometacina. O acentuado efeito apresentado pelos NSAIDs em relaçäo à inibiçäo da densidade de volume dos macrófagos, semelhante ao efeito do metotrexato, sugeriu que os NSATDs inibiram a proliferaçäo das células progenitoras mielóides dos monócitos/macrófagos. Também agiram tanto aumentando (21 dias) como inibindo (28 dias) a densidade de volume ocupada pelas fibras colágenas, enquanto que a dexametasona apresentou efeito contrário. Tais resultados indicaram que no processo inflamatório induzido por agentes flogógenos de intensidade forte (PMD) estimulores da acentuada produçäo Lts e PGs, o emprego de antiinflamatórios esteróides e näo esteróides foi vantajosa em relaçäo ao fármaco citostático

Intiinflamatorios no esteroideos en pacientes de edad avanzada: cómo utilizarlos sin riesgo

Estos medicamentos son muy útiles e incluso, algunas veces, esenciales en los pacientes de edad avanzada, pero pueden ser peligrosos por sus efectos gastrointestinales y renales. Por lo tanto su prescripción debe ser cuidadosa y basada en adecuados controles y seguimiento

Tenoxicam venoso para prevençåo da dor pós-operatória em cirurgia abdominal superficial / Prevention of postoperative pain after abdominal dermoliprctomy with intravenous tenoxicam

Intravenous tenoxicam, a non-steridal anti-inflammatory drug (NSAID), was evaluated for postoperative pain relief after abdominal dermolipectomy. All patients received epidural anesthesia with 0,5 por cent bupivacaine with epinephrine 1:200,000. Twenty patients received 2 ml of saline, Group A1 (N=10) before and group A2 (n=10) after surgery. Twenty patients, Group B (N=20), received 20 mg (2 ml) of intravenous tenoxicam before the epidural , while the rest of them received the same dose after completion of surgery (Group C, N=20). Duration of postoperative analgesia, intensity of pain, supplementary analgesic requirement and adverse side effects were assessed. Patients who received tenoxicam had longer duration of postoperative analgesia (p<0,05), lower pain scores at 6 and 12 hours (p<0,01) and request less supplemental analgesics (p<0,05) compared to Group A. Analgesic requirements were less in Group B compared to Group C. Administration of tenoxicam before surgery produced better results suggesting an actual preempitive pain relief. Our data demonstrate that the better postoperative analgesia achieved using epidural bupivacaine and intravenous tenoxicam may reflect a synergistic pharmacologic interection between NSAIDS and local anethetics

Hombro doloroso: evaluación del tratamiento con infiltraciones de orgoteína / Painful shoulder treated by subacromial orgoteine infiltration: assessment of treatment

El hombro doloroso es la tercera causa de consulta por dolor en la práctica médica general, por detrás de la cefalea y el dolor de espalda. El objeto de este trabajo es sentar las bases para la terapéutica de este síndrome mediante infiltraciones locales con orgoteína. Se han seguido 48 pacientes con hombro doloroso. El seguimiento se extiende desde enero de 1989 a diciembre de 1990, con una media de 17 meses. La media de edad entre los pacientes fue de 33 años con un limite entre 19 y 61 años. De los 48 pacientes, 16 eran hombres y 32 mujeres. Tras un estudio protocolizado prospectivo se pudo apreciar cómo todos los pacientes mejoraron su sintomatología y en períodos muy similares: el dolor nocturno desapareció en la segunda semana, mientras que el diurno lo hizo a la tercera semana. La rigidez matutina era de 10 minutos de duración ya a la primera semana y desapareció a partir de entonces. La movilidad en abducción alcanzó los 90-100 grados hacia la sexta semana del tratamiento. La orgoteína como sustancia aplicada en infiltración local cumple su misión de disminución de radicales libres de oxígeno contribuyendo a la acción antiflogística y en definitiva aliviando los síntomas generales del hombro doloroso.