TY - JOUR

T1 - Assessment of drug salt release from solutions, suspensions and in situ suspensions using a rotating dialysis cell

AU - Parshad, Henrik

AU - Frydenvang, Karla

AU - Liljefors, Tommy

AU - Cornett, Claus

AU - Larsen, Claus

N1 - Keywords: Anesthetics, Local; Bupivacaine; Calorimetry, Differential Scanning; Dialysis; Diffusion; Rotation; Salts; Solubility; Solutions; Suspensions

PY - 2003

Y1 - 2003

N2 - A rotating dialysis cell consisting of a small (10 ml) and a large compartment (1000 ml) was used to study the release of drug salt (bupivacaine 9-anthracene carboxylate) from (i). solutions, (ii). suspensions and (iii). in situ formed suspensions. Initial release experiments from suspensions indicated that the release of drug salt in deionized water was predominantly limited by the diffusion across the membrane whereas it is essentially dissolution rate controlled in 0.05 M phosphate buffer (pH 7.40). Thus, the in vitro model appears to have a potential in formulation screening when phosphate buffer is used as release media. Generally, the initial release of the drug salt from in situ suspensions occurred faster as compared to conventional suspensions, probably due to incomplete precipitation of the drug salt, and hence formation of supersaturated solutions where the rate of release is predominantly determined by the concentration gradient. However, when an adequately concentrated solution of the drug salt was used to prepare the in situ suspension, the initial fast release was followed by a substantial sustained release indicating that the release had become dissolution rate limited.

AB - A rotating dialysis cell consisting of a small (10 ml) and a large compartment (1000 ml) was used to study the release of drug salt (bupivacaine 9-anthracene carboxylate) from (i). solutions, (ii). suspensions and (iii). in situ formed suspensions. Initial release experiments from suspensions indicated that the release of drug salt in deionized water was predominantly limited by the diffusion across the membrane whereas it is essentially dissolution rate controlled in 0.05 M phosphate buffer (pH 7.40). Thus, the in vitro model appears to have a potential in formulation screening when phosphate buffer is used as release media. Generally, the initial release of the drug salt from in situ suspensions occurred faster as compared to conventional suspensions, probably due to incomplete precipitation of the drug salt, and hence formation of supersaturated solutions where the rate of release is predominantly determined by the concentration gradient. However, when an adequately concentrated solution of the drug salt was used to prepare the in situ suspension, the initial fast release was followed by a substantial sustained release indicating that the release had become dissolution rate limited.

M3 - Journal article

C2 - 12885391

VL - 19

SP - 263

EP - 272

JO - Norvegica Pharmaceutica Acta

JF - Norvegica Pharmaceutica Acta

SN - 0928-0987

IS - 4

ER -