J Control Release. 2000 May 15;66(2-3):107-13.
Microencapsulation and characterization of tramadol-resin complexes.

Zhang ZY, Ping QN, Xiao B.

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, PR China.

Tramadol was complexed with a sulfonic acid cation-exchange resin by a column method. Microencapsulation of tramadol-resin complexes (TRC) was carried out by the spray-drying method. The effect of ethylcellulose (EC) of various viscosities, different solvent systems and addition of plasticizers on microencapsulation were investigated. The morphology of microcapsules was characterized by scanning electron microscopy (SEM). Selected solvents having similar toxicity levels while various physico-chemical properties resulted in greatly different microcapsules. Regular particle morphology and sustained-release behavior were obtained when dichloromethane or ethyl acetate was used as the solvent system, whereas ethanol produced a substantial number of coalesced microcapsules and acetone produced apparently surface-smooth monomicrocapsules with faster release behavior. Three kinds of plasticizers affected the drug release rate similarly. On the addition of plasticizer (DEP), the drug release rate from the microcapsule obtained from low viscosity-grade EC reduced, while there was no alternation for those obtained from middle viscosity-grade EC. Compared to EC with a viscosity of 100 cP, which produced multi-microcapsules and released 60% of the drug within 1 h, microcapsules prepared with 10, 20 and 45 cP viscosity-grade EC showed slower drug release and regular and smooth morphology.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10742572&dopt=Abstract tramadol Ultram

prius.jnj.com

A rapid and reliable analytical method is described for the simultaneous determination of RWJ-38705 (tramadol N-oxide) and several of its major metabolites in the plasma of Sprague-Dawley rats and Beagle dogs. Sample preparation using solid phase extraction was followed by reversed phase liquid chromatography (LC) coupled with tandem mass spectrometric (MS/MS) detection in the positive ionization mode. The assay was linear for all analytes over concentrations ranging from approximately 6 to 2000 ng/ml. The inter-assay reproducibility was generally less than 15% while accuracy values were within 13% of theoretical. The overall recovery of the analytes ranged from approximately 40 to 64% in rat plasma and 53-75% in dog plasma. This assay has proven to be sensitive, specific and reproducible, and it has been readily implemented in preclinical PK studies. Representative plasma concentration versus time profiles resulting from administration of TNO to rats and dogs are presented in this communication.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10766364&dopt=Abstract tramadol Ultram




Paediatr Anaesth. 2000;10(3):303-18.
Analysis of behavioural and physiological parameters for the assessment of postoperative analgesic demand in newborns, infants and young children: a comprehensive report on seven consecutive studies.

Buttner W, Finke W.

Clinic for Anaesthesiology and Surgical Intensive Care Medicine, Ruhr-University Bochum, Marienhospital Herne, Germany.

Many different systems for the assessment of pain in newborns and infants have been tested for validity, rarely for reliability but never for sensitivity or specificity. We aimed to determine whether the assessment of an analgesic demand in the lower age group during the postoperative period is possible by observational methods only. In an repetitive and sequential prospective process for identifying observationable behaviour and measurable physiological parameters as indicators of a postoperative analgesic demand, 584 newborns, infants and young children were studied (7 prospective studies, 4238 observations). Twenty-six items were selected as suggested by current literature and for reasons of economy and practicability. The factor analyses resulted in a two-factorial solution with the behavioural items loading on one factor and the physiological parameters on the other (principal component analyses). The physiological parameters blood pressure, respiratory rate and heart rate were found to be unreliable and had no discriminant power to detect an analgesic demand during the postoperative period (discriminant analyses, ROC-curves). In newborns and infants, nine observational items were identified as equally selective, reliable, sensitive and specific to the assessment of postoperative analgesic demand, whereas in young children only five items could be identified (discriminant analyses, ROC-curves). For economic reasons, these five items (crying, facial expression, posture of the trunk, posture of the legs, motor restlessness) were chosen as the basis of an additional pain scale ranging from 0=no pain to 10=maximal (Children's and Infants' Postoperative Pain Scale, CHIPPS). Its internal consistency yielded values for Cronbachs' alpha with 0.92 for toddlers and 0.96 for infants. The coefficient for interrater reliability was 0.93. The scale was validated constructively by the intravenous administration of metamizol, tramadol, nalbuphine, piritramide and ketamine (repeated measures analysis of variance). The Toddler-Preschooler Postoperative Pain Scale and CHIPPS equally identified painfree situations or analgesic demand in 87.4%. In cases with definite pain, the score of CHIPPS was never below 4 points. Seventy-one toddlers gave verbal comments on their pain intensity: in 29 painfree situations the CHIPPS score was 3.0 and in 29 painful situations it was 5.7. The values for sensitivity and specificity of CHIPPS were calculated to be 0.92-0.96 and 0.74-0.95, respectively (discriminant analyses). We conclude that it is possible to determine postoperative analgesic demand in the low age group of children by using an observational system such as CHIPPS alone.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10792748&dopt=Abstract tramadol Ultram

ulb.ac.be

Various monoolein-water systems containing tramadol HCl, a potent analgesic, were formulated to obtain sustained-release dosage forms which could be administered by subcutaneous, intramuscular or intrathecal injections. They were examined for their in vitro drug-release profiles and in vivo analgesic properties in rats in a 14 h period following intramuscular administration. In order to obtain a lower viscosity, we have substituted a part of monoolein by oleic acid and phospholipids. Both binary (monoolein-water) and quaternary (oleic acid-phospholipid-monoolein-water) formulations exhibited controlled drug-release profiles which were accelerated by surfactant adjunction. This surfactant action was probably due to structural changes in the lipid arrangement and was much more pronounced for the modified formulations. According to the results obtained in vitro, formulations with slower drug release (i.e. the native formulation and the modified one without surfactant) were selected for assessment of their in vivo properties. Both formulations demonstrated prolonged analgesic activities in the rat tail flick test manifested by stable pain relief during more than 10 h compared with the 3 to 4 h analgesia obtained with the commercially available tramadol HCl solution. The sustained-release capabilities were evaluated by using a modified half value duration (HVD) ratio and all sustained-released formulations exhibited a HVD ratio equal or superior to 3.9.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10823677&dopt=Abstract tramadol Ultram




Klin Khir. 2000;(3):33-5.
[Analgesia after orthopedic interventions]

[Article in Ukrainian]

Ternovyi MK, Kosiakov OM, Zazirnyi IM, Ievsieienko VH.

The efficacy of application of tramadol and naclofen for analgesia after performance of orthopedic operations was studied up. There were examined 112 patients, to whom were done total endoprosthesis of coxofemoral joint, 19--total endoprosthesis of the knee joint, 54--the knee joint arthroscopy. The analgesia efficacy was estimated according to visual-analogue scale and to the sensations index. High efficacy of the tramadol application for postoperative analgesia was established. In patients, to whom tramadol and naclofen were administered, maximal analgetic effect was noted.

Tramadol reference source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10857311&dopt=Abstract tramadol Ultram