Development of controlled release dexketoprofen tablets and prediction of drug release using Artificial Neural Network (ANN) modelling

Dexketoprofen trometamol (DT) is an active S (+) enantiomer of ketoprofen, and a non-steroidal anti-inflammatory agent. DT has a short biological half-life and the dosing interval is quite short when there is a need to maintain the desirable effect for longer time periods. Consequently, a controlled release DT tablet was designed for oral administration aiming to minimize the number of doses and the possible side effects. Calculations of the parameters for controlled release DT tablets were shown clearly. Controlled release matrix-type tablet formulations were prepared using hydroxypropyl methylcellulose (HPMC) (low and high viscosity), Eudragit RS and Carbopol, and the effects of different polymers on DT release from the tablet formulations were investigated. The dissolution rate profiles were compared and analyzed kinetically. An Artificial Neural Network (ANN) model was developed to predict drug release and a successful model was obtained. Subsequently, an optimum formulation was selected and evaluated in terms of its analgesic and anti-inflammatory activity. Although the developed controlled release tablets did not have an initial dose, they were found to be as effective as commercially available tablets on the market. Dissolution and in vivo studies have shown that the prepared tablets were able to release DT for longer time periods, making the tablets more effective, convenient and more tolerable.

Manejo farmacológico del dolor en la odontología actual / Pharmacological management of pain in today´s dentistry

Una de las principales preocupaciones de los pacientes que van a ser sometidos a un procedimiento odontológico es el dolor que dicho procedimiento pueda ocasionar. Por lotanto, lograr un control eficaz y seguro de ese dolor es una parte esencial de la práctica odontológica diaria. Los fármacos de primera elección para el tratamiento del dolor y el edemason, sin lugar a dudas, los antiinflamatorios no esteroideos(AINEs). Principios activos como el ibuprofeno (y sus congéneres) o sus derivados permiten controlar simultáneamente el dolor y el edema posquirúrgicos de una forma eficaz y segura. En muchas ocasiones, el AINE prescrito para mantener al paciente asintomático o con síntomas tolerables es suficiente. Sin embargo, cuando esto no ocurre, debemos recurrir a otrosfármacos, o realizar asociaciones con fármacos que complementen el efecto analgésico y trabajen logrando un sinergismo de potenciación que incremente el efecto buscado y disminuya los efectos adversos de cada una de las sustancias por separado, utilizando menores dosis. Un ejemplo comprobado de esas asociaciones es la de ibuprofeno con paracetamol. En el presente artículo se sugieren diversas estrategias pre- y posoperatorias para el manejo del dolor de origen inflamatorio, y un protocolo para su tratamiento.

Possible pharmacodynamic interactions between the CNS stimulant [Nikethamide] and analgesic drugs in experimental animals

Recently, there has been striking increase in research on drug combinations that enhance analgesia in clinical populations as well as in experimental animals. These studies involve combinations of drugs that have been viewed, as effective analgesics in their own right, such as opioids and nonsteroidal anti-inflammatory drugs, and drugs that have not traditionally been viewed as analgesics. The purpose of this study was to investigate the possible pharmacodynamic interactions between a CNS stimulant [nikethamide] and opioid [morphine] and non-opioid [paracetamol] drugs. Also, this study assessed the rationale of these interactions in terms of efficacy and safety by using different models of analgesic and behavioral tests. Albino mice and rates were used, as experimental animals. The analgesic effect of drugs and their combination was evaluated using [hot-plate] [54 °C], [tail clip] and [writhing] [acetic acid, 1%. i.p.] tests. The behavioral effects of the drugs and their combinations were also determined. Nikethamide significantly diminished the analgesic effect of morphine [1-10 mg/kg, i.p.] in all tests [antagonism] and enhanced the analgesic effect of paracetamol [50-400 mg/kg. i.p.] in all tests [additive]. Coadministration of nikethamide [100 mg/kg, i.p.] with morphine [2.71 mg/kg, ED[50]] significantly decreased locomotor activity and impaired the acquisition on conditioned avoidance responses but did not affect motor coordination to any significant extent. On the other hand, coadministration of nikethamide [100 mg/kg, i.p.] with paracetamol [117.94 mg/kg, i.p, ED[50]] significantly increased locomolor activity and improved the acquisition on conditioned avoidance responses but did not affect motor coordination to any significant extent. We can conclude that the systemic coadministration of nikethamide significantely antagonized the analgesic effect of morphine and such combination was accompanied by increased side effects. In contrast, nikethamide significantly enhanced, the analgesic effect of paracetamol in an additive fashion and this combination was not accompanied by increased side effects

Improved bioavailability of aceclofenac from spherical agglomerates: development, in vitro and preclinical studies

The objective of present study was to improve the solubility, dissolution rate, micromeritic properties and bioavailability of aceclofenac [NSAID] by formulating its spherical agglomerates. They were prepared with different water soluble polymers [polyvinylpyrrolidone-K30, polyvinylpyrrolidone-K90 and sodium alginate] by using acetone-water-dichloromethane solvent system. The agglomerates were subjected to various physicochemical properties, DSC, IR spectroscopy, scanning electron microscopy [SEM], micromeritic properties and dissolution studies. The in vivo studies [anti-inflammatory, analgesic and pharmacokinetic studies] were conducted in Wistar rats and Swiss albino mice. SEM studies showed that agglomerates were spherical in structure and formed by cluster of small crystals. The agglomerates prepared with polyvinylpyrrolidone-K90 exhibited improved solubility, dissolution rate and micromeritic properties compared to those prepared with other polymers and pure drug. These optimized agglomerates showed rapid analgesic and anti-inflammatory activity besides exhibiting improved bioavailability of drug when compared to pure drug

Ketamina en el manejo del dolor refractario por cáncer / Ketamine in the handling of the refractory pain by cancer

Los pacientes con cáncer presentan dolor en el rango entre moderado e intenso durante del transcurso de su enfermedad, principalmente en la etapa terminal. La escalera analgésica de la Organización Mundial de la Salud (OMS) se ha empleado como guía terapéutica para tratar a estos pacientes; utiliza tres grupos de fármacos: opiáceos, antiinflamatorios no esteroideos (AINES) y coadyuvantes. Dentro de estos últimos se encuentra la Ketamina, un derivado frenociclidínico que interactúa con los receptores N-metil-D-aspartato (NMDA). Tradicionalmente ha sido utilizado como inductor de la anestesia general, y en dosis subanestésicas se emplea para el tratamiento del dolor refractario al uso de opioides. Descriptores: dolor, cáncer, analgesia, Ketamina.

Farmacología en el embarazo / Pharmacology in pregnancy

Hoy se sabe que se debe atender a una paciente embarazada en forma multi e interdisciplinaria si se quiere bajar la tasa de morbimortalidad infantil. Esto se debe a que dentro de sus multicausalidades se encuentra el mal estado bucodental. Así es que se debe encarar la atención odontológica en la gestante y la lactante desde el uso correcto de la medicación con las diferentes patologías que se puedan presentar. Se tendrá en cuenta la farmacodinamia en la paciente, la transferencia placentaria y la farmacocinética fetal, ya que se sabe que todas las drogas pueden ser tóxicas para el bebé si se abusa de ellas. La medicación analgésica será el paracetamol y como medicación antibiótica se utilizarán penicilinas, sus derivados y asociaciones, macrólidos y cefalosporinas. No debe ser atendida una paciente que presente signos de hpertensión arterial, diabetes gestacional no compensada o que su obstetra no se lo permita por algún motivo. A una urgencia odontológica se la tratará igual que una paciente no grávida, teniendo en cuenta la medicación permitida. Se tendrá en cuenta que se logrará un bebé saludable con una mamá saludable, eso significa que no sólo se cuidará la salud del bebé, sino que se controlará probables infecciones en la mamá

Método analítico para determinação de meloxicam em plasma humano por cromatografia líquida de alta eficiência (CLAE) / Determination of meloxicam in human plasma by HPLC

Desenvolveu-se e validou-se método analítico simples, rápido e específico para quantificação de meloxicam (inibidor do COX-2) em plasma humano através da cromatografia líquida de alta eficiência, para aplicação em estudos de bioequivalência. Piroxicam foi utilizado como padrão interno. Empregou-se cromotografia em fase reversa com coluna modelo Synergi RP-MAX (150 X 4,6 mn0, à temperatura de 30 ºC e fase móvel constituída por mistura de acetonitrila e tampão fosfato 0,025 mol/L pH 4,5 (40:60, v/c4.v), a um fluxo de 1,0 mL/min. Os analitos foram detectados por UV a 364 nm. As amostras de plasma foram acidificadas com ácido clorídrico 1 mol/L, extraídas utilizando-se éter terc-butil metílico e, após filtração e secagem, o resíduo foi reconstituído em 250 mL de fase móvel para injeção em CLAE...

Solubilization of certain Analgesics by cetomacrogol 1000

Solubilization of certain nonsteroidal anti-inflammatory drugs, viz., phenacetin, ibuprofen and indomethacin by Cetomacrogol 1000 [Cetomacrogol] has been investigated. The values of the ratio of mole drug solubilized per mole micellar Cetomacrogol revealed that the solubilizing power of Cetomacrogol towards ibuprofen is higher than that for phenacetin or indomethacin. One Cetomacrogol micelle solubilizes 38, 17 and 6 molecules of ibuprofen, phenacetin and indomethacin, respectively. Spectrophotometry as well as solubility measurements in different solvents have been used to provide evidence on the environment of the solubilizate molecule in the micelle. On the basis of the results obtained, it was concluded that these drugs are solubilized as follows: Phenacetin and ibuprofen are solubilized in the hydrocarbon core and in the polyoxyethylene region adjacent to the hydrocarbon core. Indomethacin is wholly solubilized in the polyoxyethylene layer adjacent to the hydrocarbon core. The ability of the surfactants to accelerate the dissolution rate of the drug was also investigated. The dissolution profiles of these drugs in Cetomacrogol revealed marked enhancement of dissolution and there is a good correlation between the dissolution efficiency of the three drugs and their solubility in Cetomacrogol at the same temperature

Analgesia postoperatoria II: técnicas analgésicas / Postoperative analgesia II: analgesic techniques

La remisión del dolor es una labor importante para beneficio del paciente desde el punto de vista psicológico y fisiológico, en el presente trabajo se revisan las difernetes técnicas y vías de administración de fármacos para proporcionar analgesia al paciente en el postoperatorio. Se realiza una revisión de las siguientes técnicas y vías de administracíon: Vía de administración bucal, sublingual, oral, rectal, transnasal, transdérmica, intramuscular, intravenosa, analgesia controlada por el paciente, local, tópica, regional, peridural, subaracnoidea, crionalgesia y estimulación eléctrica transcutánea de nervio.

Quaternary ammonium salt derivatives of allylphenols with peripheral analgesic effect

Ammonium salt derivatives of natural allylphenols were synthesized with the purpose of obtaining potential peripheral analgesics. These drugs, by virtue of their physicochemical properties, would not be able to cross the blood brain barrier. Their inability to enter into the central nervous system (CNS) should prevent several adverse effects observed with classical opiate analgesics (Ferreira et al., 1984). Eugenol (1) O-methyleugenol (5) and safrole (9) were submitted to nitration, reduction and permethylation, leading to the ammonium salts 4, 8 and 12. Another strategy applied to eugenol (1), consisting in its conversion to a glycidic ether (13), opening the epoxide ring with secondary amines and methylation, led to the ammonium salts 16 and 17. All these ammonium salts showed significant peripheral analgesic action, in modified version of the Randall-Sellito test (Ferreira et al. 1978), at non-lethal doses. The ammonium salt 8 showed an activity comparable to that of methylnalorphinium, the prototype of an ideal peripheral analgesic (Ferreira et al., 1984).