{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T13:14:07Z","timestamp":1747746847351,"version":"3.28.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2002,6,1]],"date-time":"2002-06-01T00:00:00Z","timestamp":1022889600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The aim of this study was to develop an in-vitro release method suitable for injectable slow-release lipid formulations of local anaesthetics (or other drugs). We also aimed that the results of the in-vitro measurements should have a clear relationship to duration of action in-vivo. Six formulations of bupivacaine base in medium-chain triglyceride-glyceryl dilaurate mixtures were developed. A new apparatus was constructed for determination of their in-vitro release profiles. A bulbous glass tube was fixed inside a standard glass bottle, which was then filled with release medium. A stirring magnet was enclosed in the perforated polypropylene cylinder holding the glass tube. The stirring created a continuous, rotating downward flow of medium inside the tube, which kept the lipid phase, introduced by means of a syringe, suspended as a single, free drop. Release profiles were obtained by sampling of the release medium for up to 72 h and analysis by gas-liquid chromatography. The duration of action in-vivo of the respective formulations was tested by the hot-plate method in rats. The release profiles of bupivacaine in-vitro were mono-exponential for four formulations and bi-exponential for the other two. There was a positive correlation between the proportion of glyceryl dilaurate in the formulation and the slow half-life of release of bupivacaine. All formulations showed prolonged duration of action in-vivo, median values within the range 4.5\u201312 h, as compared with a 2-h effect of bupivacaine hydrochloride solution. A comparison of in-vitro release curves and durations of action in-vivo suggested that to maintain nerve blockade in-vivo the formulations must release bupivacaine at a rate of approximately 350 \u03bcg h\u22121 under the in-vitro conditions. To conclude, we designed and tested a novel apparatus for measuring release of a local anaesthetic (or other drug) from a fluid or semi-solid formulation in-vitro. Release rates obtained in-vitro by means of this technique may be used to guide the development of formulations with suitable durations of action in-vivo. The apparatus is, however, as yet a prototype. Rigorous evaluation of performance should be carried out on devices built to specific standards according to their intended application.<\/jats:p>","DOI":"10.1211\/0022357021779087","type":"journal-article","created":{"date-parts":[[2002,10,11]],"date-time":"2002-10-11T20:14:04Z","timestamp":1034367244000},"page":"747-755","source":"Crossref","is-referenced-by-count":8,"title":["In-vitro release of bupivacaine from injectable lipid formulations investigated by a single drop technique \u2014 relation to duration of action in-vivo"],"prefix":"10.1093","volume":"54","author":[{"given":"Lars","family":"S\u00f6derberg","sequence":"first","affiliation":[{"name":"Hospital Pharmacy, Malm\u00f6 University Hospital , SE-205 02 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Dyhre","sequence":"additional","affiliation":[{"name":"Department of Anaesthesia, Malm\u00f6 University Hospital , SE-205 02 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bodil","family":"Roth","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, Malm\u00f6 University Hospital , SE-205 02 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sven","family":"Bj\u00f6rkman","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, Malm\u00f6 University Hospital , SE-205 02 Malm\u00f6,","place":["Sweden"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2002,6,1]]},"reference":[{"key":"2024103109375862100_cit1","first-page":"609","article-title":"Rates of transfer of organic protolytic solutes between an aqueous and an organic phase","volume":"8","author":"Brodin","year":"1971","journal-title":"Acta Pharm. 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