Development of a New Dissolution Test Method for Soft Chewable Dosage Forms.

Soft chewable dosage forms are a new approach to improve the compliance of medication for special patient populations. Based on their texture, they are chewed several times before they get swallowed. A suitable dissolution method based on in vivo chewing data was developed. The method covers parts of dissolution within the oral cavity (simulation of chewing) as well as the dissolution of the swallowed bolus within the gastrointestinal tract. Chewing was simulated by the help of a steel tooth assembled to a texture analyzer and wedge gliding on an inclined plane, imitating the occlusal glide. Chewing cycles of non-brittle, elastically deformable foods were predicted by a multiple linear regression (R adj = 0.985) using hardness, stickiness, fat/water content, and softening behavior as independent variables. Cross-validation of three sets of chewing data led to a root mean square error of prediction of 0.408 or 0.658 chewing cycles, respectively. The new method is able to distinguish between different soft chewable formulations which had been approved as similar by the dissolution method of the European Pharmacopoeia. Furthermore, it provides information about the drug content released within the time of chewing (7-15%).

Solid lipid extrusion with small die diameters--electrostatic charging, taste masking and continuous production.

The aim of this work was to develop a continuous solid lipid extrusion process that includes post-process milling of the extrudates. Die diameters smaller than 0.5 mm should be used for taste masking of the bitter tasting anthelmintic praziquantel. During lipid extrusion with small die diameters, electrostatic charging of the extrudates occurred. This could be avoided by adding liquid polyethylene glycol (PEG) as antistatic agent. Further, extrusion with PEG as antistatic agent was possible with small diameter down to 0.2 mm and with up to 80% praziquantel load. Dissolution of praziquantel extrudates was shown to be faster with smaller extrudate diameter due to surface enlargement. Anyhow, different praziquantel extrudates with small diameter, drug load up to 70% and PEG content up to 20%, were proven to be sufficiently taste masked in a randomised palatability study with 40 cats. Within a scale-up experiment, lipid extrusion and milling of the extrudates in a centrifugal mill afterwards were conducted continuously. Extrudates from continuous and batchwise production revealed small differences in terms of size distribution and surface habit, but were similar in drug dissolution rate.

Controlled release of active as a consequence of the die diameter in solid lipid extrusion.

The aim of the study was the investigation of dependency of the release profile on the original diameters of milled extrudates manufactured by solid lipid extrusion. Different die diameters in the range of 0.3 mm to 5.0 mm were used. The extrudates were milled and sieved. The fractions between 315 microm and 400 microm were investigated within their shape, surface area and dissolution profiles by using the dissolution tester and the disintegration tester for short-time dissolution tests. Different pH-media were used for the release tests: pH 1.2 to imitate release conditions in the stomach and pH 7.4 to imitate conditions in the mouth. The chosen active enrofloxacin, a derivate of 3-quinolinecarboxylic acid, offers different solubilities in these release media. Two conclusions of this study were obtained: In the case of slightly solubility of active in the medium there was no dependency of the released active on the die diameter. If the active was very slightly soluble in the release medium a dependency between the two parameters was found. Having bad tasting actives like enrofloxacin, this achievement has an enormous impact on the manufacturing processes: a reduction of die diameters and therefore reduction of released amount of active will lead to taste masking.