Ultralong Peripheral Nerve Block by Lidocaine:Prilocaine 1:1 Mixture in a Lipid Depot Formulation

Abstract

The pharmaceutical properties of these formulations compare favorably with those of other depot preparations. The high-percentage ones showed the longest duration of action yet reported for sciatic nerve block in rats. The possibility of using a high-concentration local anesthetic depot formulation as an alternative to ethanol or phenol for long-term nerve blocks in chronic pain merits further investigation.

Do surface active parenteral formulations cause inflammation?

“…Oshida et al 56 investigated approximately 300 different preparations used in 57 Japan in the late 1970s, by measuring physico-chemical param-58 eters such as the pH and the osmotic properties (Oshida et al, 59 1979). They found wide ranges in relative osmotic pressure from 60 0.2 to 36 (relative to that of physiological saline solution) and pH findings from previous studies on cell cultures (Söderberg et al, 84 2009;Lanbeck et al, 2004), a rat model (Söderberg et al, 2006) and 85 observations in the clinic (Lanbeck et al, 2002). Pharmacopoeia quality, and were supplied by Apoteket AB (Sweden).…”

“…Erythromycin was found 233 to be the most potent antibiotic in terms of interfacial activity 234 followed by dicloxacillin. tension (g) (SD) and relative interfacial pressure (P rel ) obtained in the present study at three different interfaces, using a lidocaine:prilocaine depot formulation of different concentrations, and scores indicating nerve inflammation in rats, reported by Söderberg et al (2006). Individual scores of nerve inflammation (pathological changes) were graded as follows: 0: not observable; 1: minimal; 2: slight; 3: moderate and 4: marked.…”

“…These systems were used as 149 reference systems (giving values of g 0 ). The results obtained in vitro150 were compared with reported effects in cell models(Söderberg 151 et al, 2009;Lanbeck et al, 2004), effects seen in an animal model 152(Söderberg et al, 2006) and clinical investigations(Lanbeck et al, 153 2002). The relative interfacial pressure was used as the preferred 154 independent parameter for comparison, provided that the concen-155 trations in the corresponding in vivo experiment were known.…”

“…At levels above 19 normal physiological concentrations, FFAs can induce morphological 20 changes in erythrocytes both in vitro and in vivo (Kamada et al,1987;21 Söderberg et al, 2009), and several diseases are associated with 22 elevated concentrations of FFAs (Dhainaut et al, 1987;Lefevre et al, 23 1988; Roden et al, 1996;Egan et al, 1999;Kurien and Oliver, 1966;24 Oliver, 1972;Mozaffarian et al, 2006). 25 In a previous study, injectable anesthetic depot formulations 26 (lidocaine-prilocaine 1:1) were tested on rats to induce ultra-long 27 nerve blockades by administration directly next to the sciatic nerve 28 (Söderberg et al, 2006). Below a concentration of 20% active Abbreviations: C, concentration; EC50 in vitro , concentration required to obtain 50% of the maximal attainable effect in terms of measured interfacial pressure in vitro; n H , Hill coefficient; P, interfacial pressure; P max , maximal attainable interfacial pressure; P rel , relative interfacial pressure; g 0 , interfacial tension of the pure fluid/solution (reference system); g, interfacial tension of the pure fluid/ solution including the active substance; C 2:0 , acetic acid; C 6:0 , caproic acid; C 8:0 , caprylic acid; C 10:0 , capric acid; C 12:0 , lauric acid; C 16:0 , palmitic acid; AP, ampicillin; BP, benzylpenicillin; CE, cefuroxime; CX, cloxacillin; DC, dicloxacillin; ER, erythromycin; EDTA, edetate dipotassium; FFAs, free fatty acids; HSA, human albumin; PBS, phosphate-buffered saline solution; EaHy926, endothelial hybrid cell line; HUVEC, human umbilical vein endothelial cell; ICAM, intercellular adhesion molecule.…”

Long-term effect of ropivacaine nanoparticles for sciatic nerve block on postoperative pain in rats

“…As has been mentioned by Polakovic et al, 32 two main mechanisms determining the lidocaine release from the PLA matrix are diffusion and solid drug dissolution, but the drug release varies strongly with the parameters such as the molecular weight of nanoparticles, particle size, or drug content. Söderberg et al 33 found that the high percentage formulations showed the longest duration of action yet reported for sciatic nerve block in rats. The researchers 34 also indicated that increasing initial lidocaine content proportionately increased the duration of functional sciatic nerve block and single treatment with a slow-release lidocaine sheet (30%, w/w) inhibited hyperalgesia caused by paw incision for 1 week.…”