pH-sensitive polyvinylpyrrolidone-acrylic acid hydrogels: Impact of material parameters on swelling and drug release

In this study, we fabricated pH-sensitive polyvinylpyrrolidone/acrylic acid (PVP/AA) hydrogels by a free-radical polymerisation method with variation in the content of monomer, polymer and cross-linking agent. Swelling was performed in USP phosphate buffer solutions of pH 1.2, 5.5, 6.5 and 7.5 with constant ionic strength. Network structure was evaluated by different parameters and FTIR confirmed the formation of cross-linked hydrogels. X-ray crystallography showed molecular dispersion of tramadol HCl. A drug release study was carried out in phosphate buffer solutions of pH 1.2, 5.5 and 7.5 for selected samples. It was observed that swelling and drug release from hydrogels can be modified by changing composition and degree of cross-linking of the hydrogels under investigation. Swelling coefficient was high at higher pH values except for the one containing high PVP content. Drug release increased by increasing the pH of the medium and AA contents in hydrogels while increasing the concentration of cross-linking agent had the opposite effect. Analysis of the drug release mechanism revealed non-Fickian transport of tramadol from the hydrogels.

Nesse estudo, preparamos hidrogéis de polivinilpirrolidona/ácido acrílico(PVP/AA), sensíveis ao pH, por meio de método de polimerização de radical livre, com variações no conteúdo de monômero, de polímero e de agente de ligação cruzada. O inchamento foi realizado em soluções tampão fosfato USP pH 1,2, 5,5, 6,5 e 7,5, com força iônica constante. A estrutura reticular foi avaliada por diferentes parâmetros e o FTIR confirmou a formação de hidrogéis de ligação cruzada. A cristalografia de raios X mostrou dispersão molecular do cloridrato de tramadol. Realizou-se estudo de liberação do fármaco em soluções tampão fosfato pH 1,2, 5,5 e 7,5 para amostras selecionadas. Observou-se que o inchamento e a liberação do fármaco dos hidrogéis podem ser modificados mudando-se a composição e o grau de ligação cruzada dos hidrogéis em estudo. O coeficiente de inchamento foi alto em pH mais altos, exceto para um deles com alto conteúdo de PVP. A liberação do fármaco aumentou com o aumento do pH do meio e do conteúdo em AA nos hidrogéis, enquanto que o aumento na concentração do agente de ligação cruzada apresentou efeito oposto. A análise do mecanismo de liberação do fármaco revelou transporte não Fickiano do tramadol dos hidrogéis.

Effect of oral co-administration of frozen-dried grapefruit juice on pharmacokinetics of tramadol in dogs

Tramadol is a centrally acting analgesic drug extensively metabolized in animal species. Its clinical response is mainly due to the M1 metabolite, poorly produced in dogs. Grapefruit-juice can inhibit the metabolism of different drugs in animals and humans. The aim of the present study was to evaluate the pharmacokinetics of tramadol and its major metabolites after co-administration of tramadol and frozen-dried grapefruit-juice. A balanced cross-over study was used involving six male Beagle dogs. They were administered with tramadol alone [5 mg/kg] or with tramadol [5 mg/kg] plus frozen-dried grapefruit-juice [10 g]. The plasma concentration vs time curves showed significant differences during the first 4 h following drug administration. Tmax was at 1.33 and 1.70 h following tramadol and tramadol plus frozen-dried grapefruit-juice treatment, respectively. Significant differences were also shown in Cmax [490 vs 270 ng/ml] and AUC [11,610 vs 5,890 húhúng/ml]. Significant differences between the treatments were shown in all the M1 parameters reported. M2 and M5 did not show significant differences after both administrations. In conclusion, the frozen-dried grapefruit-juice was shown to affect the plasma concentrations of M1, despite them being well below those reported in humans

[Knowledge of Kerman general practitioners about Tramadol in 2004]

Tramadol is an opioid analgesic indicated for the management of moderate and severe pains. Its side effects, in parts are due to the activation of micro receptors and in parts to increasing central catecholamine and serotonin levels. In the case of long administration, tramadol has a potential to cause dependency, tolerance and also drug abuse. After prohibition of injective diclofenac, considering Iranian's tendency for rapid sedation of pain symptoms, tramadol has been prescribed widely. The aim of this study is to determine general practitioners knowledge about this new drug.This cross-sectional study was arranged by collecting data through a self-administrated questionnaire consisted of 25 questions related to different aspects of drug knowledge. Sample consisted of 244 general practitioners in Kerman and data analysis was performed by SPSS. Out of 173 general practitioners, 49.1% worked in clinics, 34.9% in private offices and 16% in Emergency Units. Mean knowledge score was 30.72 +/- 0.35 out of the maximum of [50]. From all subjects 49.7% had poor knowledge [Z<-1], while 39.3% had moderate knowledge [-11]. The poorest information was in regard to drug classification and pharmacokinetics, while in dosage and side effects subjects' knowledge was better. No correlation was observed between mean score and variables of job experience, duration, place and sex of practitioners. Considering serious side effects and drug interactions of tramadol and also the low level of knowledge of general practitioners about this drug, educational programs and limitation of distribution seems to be necessary