Rekristallisationsverhalten von teil-amorpher Laktose während und nach der Tablettierung
Susanne Ziffels1, Eugen Schwarz2, Hartwig Steckel1
1 Christian-Albrechts-Universität zu Kiel, Abteilung für Pharmazeutische Technologie und Biopharmazie, Kiel
Korrespondenz: Hartwig Steckel, Abteilung für Pharmazeutische Technologie und Biopharmazie, Gutenbergstr. 76, 24118 Kiel (Germany), e-mail: firstname.lastname@example.org
Recrystallization Behaviour of Partially Amorphous Lactose During and After Compression
The solid state properties of lactose, widely used as a pharmaceutical excipient, are of significant importance for the processing and stability of solid oral dosage forms. Alterations to the solid state properties, i. e. the creation or recrystallization of amorphous parts affect tablet properties like disintegration time and tensile strength. In the following study, the occurrence of phase transitions (solid-state transition from amorphous to crystalline and from crystalline to amorphous) have been investigated. The solid state properties of six different lactose qualities were investigated before and after direct compression. Fast Flo® 316 NF, FlowLac® 90, FlowLac® 100 as well as SuperTab® 11SD and SuperTab® 14SD were used as spraydried lactose qualities and compared to Tablettose® 80 as an example for an agglomerated lactose quality. At first the amorphous content of powders of all lactose qualities was determined by microcalorimetry prior to compaction. Straight after direct compression with a single-punch tablet machine at two different compaction forces, the amorphous content of the tablets as well as their tensile strength and disintegration time were investigated. The tablets were stored at 25 °C / 60 % rH and 40 °C / 75 % rH and reinvestigated after 1, 7, 28 and 56 days of storage. In these experiments, the amorphous content of the spray-dried lactose qualities was found to be between 1.7 and 3.0 %, but after seven days of storage amorphous parts were no longer detectable in all batches of tablets. Neither for the spray-dried lactose powders nor for the used agglomerated lactose type an increase of amorphous parts induced by the compression at the used compaction forces was found. However, tensile strength as well as disintegration time increased within 56 days due to the recrystallization of the amorphous parts during storage of the tablets. The amount of increased tensile strength and disintegration time depends on the lactose quality, the initial tensile strength and the chosen storage conditions. Maximum value for tensile strength was obtained for all batches between the first and seventh day of storage. In opposite to these findings, the results in disintegration time are more inhomogeneous. While FlowLac 100 tablets disintegrate quicker after one week of storage compared to their disintegration time directly after compression, all other produced batches show a slower disintegration time after one week. Even tablets stored at 40 °C / 75 % rH disintegrate slower after one week, however, disintegration time may decrease again during eight weeks of storage, depending on the used lactose quality.
Key words Amorphie • Bruchfestigkeit • Direkttablettierung • Laktose • Mikrokalorimetrie • Rekristallisation
pharmind 2010, Nr. 3, Seite 508