Effect of different surface active agents on the crystallinity of lyophilized diltiazem hydrochloride

Aqueous diltiazem hydrochloride solutions containing various amounts of sur face active agents, polysorbate 80 Texapon K-12 and Pluronic F-68, were fre eze-dried. The effect of non-ionic polysorbate 80, non-ionic Pluronic F-68 and anionic Texapon K-12 (sodium layryl sulfate) on the crystallinity of di ltiazem hydrochloride was investigated by the X-ray powder diffraction meth od. The moisture content and the reconstitution of the diltiazem hydrochlor ide plug were also studied. Lyophilization of pure water solution of diltia zem hydrochloride raw material resulted in a totally amorphous material. Th e effect of the surface active agent on the crystal properties of diltiazem hydrochloride can be revealed in formulations containing Pluronic or polys orbate 80 at concentrations as low as 0.1%. In such instances, the molecula r ordering of diltiazem hydrochloride was significantly increased. The degr ee of crystallinity was further increased when the concentrations of Pluron ic or polysorbate were increased to 1%. Texapon K-12, did not show any nota ble effect on the crystallinity of lyophilized diltiazem hydrochloride. The moisture content of the samples containing low amounts of polysorbate or P luronic Was approximately the same as in the lyophilized diltiazem hydrochl oride samples. When the concentration of the above-mentioned surface active agents was increased, the water content of the plugs decreased very signif icantly. Texapon did not influence the moisture content of lyophilized dilt iazem hydrochloride plug. The reconstitution time was dependent on the amou nt of surface active agent only in the cases of polysorbate 80 and Pluronic .