Compressibiliy and compactibility of pectin powders -A study of their potential as direct compression excipients in tablets

Papers 2 and 3 of this thesis are not available in Munin: 2. Salbu, L., Bauer-Brandl, A., Alderborn, G. and Tho, I.: 'Effect of degree of methoxylation and particle size on compression properties and compactibilty of pectin powders', Pharmaceutical Development and Technology (2011) 1–11. Available at http://dx.doi.org/10.3109/10837450.2010.535831 3. Salbu, L., Picker-Freyer, K. M., Schmid, W., Bauer- Brandl, A. and Tho, I.: 'Is one tablet sufficient? : Application of 3-D modelling to the compression of pectin powders' (manuscript)Pektinpulver med ulike prosentar metoksylering vart komprimert i ein komprimeringssimulator. Dette er ei avansert tablettmaskin som svært nøyaktig måler distansen tablettstempelet har gått (på mikrometernivå) og kor stor kraft som er involvert under komprimeringa (samantrykkinga av pulveret). Pektin med metoksyleringsgrad under 10% (også kalla pektinsyrer) gav dei mekanisk sterkaste tablettane, og er såleis den pektintypen det bør fokuserast på i framtidige forsøk med pektin som eit tabletthjelpestoff. Høgmetoksylert pektin, dvs. meir enn 50% metoksylering, var ueigna i tablttering ettersom dei ikkje gav samanhengande tablettar. Hovudsakleg skjedde det ein elastisk deformasjon med pektinpartiklane, og sidan dette generelt er ugunstig med hensyn på binding og mekanisk sterke tablettar vart det undersøkt kva mekanismar som bidreg til at tablettane heng saman. Det vart funne at ei viss grad av fragmentering skjedde i pektinsyrene. Plastisk deformasjon var det lite av. Avhandlinga viser at pektinsyrene og til dels andre pektintypar med metoksylering mindre enn eller lik 40% er veleigna som eit tabletthjelpestoff som kan fungere som ein bærar av ein aktiv substans til tjukktarmen.This thesis is dedicated to direct compression studies of pectin, a natural polysaccharide with potential as a pharmaceutical excipient due to its ability to act as a carrier for colon-specific drug delivery as well as for sustained drug release purposes. The main objective of this thesis was to study the suitability of pectin as a matrix former in tablets. The compressibility and compactibility of pectin powders were studied as a function of various degree of methoxylation (DM) grades and different particle sizes. Pectin powders with similar powder characteristics were compressed by direct compression on a compaction simulator and an instrumented tablet press, respectively. The results showed that pectin powders, irrespective of DM and particle size, were classified as class IIA powders, showing a low degree of particle rearrangement and a relatively low degree of fragmentation. The powders were relatively soft and resembled the deformation behaviour of pregelatinized starch, an elastically deforming material. The pectinic acids (DM ≤ 10%) were slightly more viscoelastic than the other pectin grades. However, in general terms, it should be emphasized that the DM had a limited effect on the compression behaviour (i.e. compressibility) although an increased DM gave slightly softer and slightly less brittle particles. On the contrary, the compactibility was strongly dependent on both DM and initial particle size. The low-methoxylated (LM) pectin (DM < 50%) and especially pectinic acids (DM ≤ 10%) produced mechanically strong tablets, whereas the high-methoxylated (HM) pectins did not produce coherent tablets. The tensile strength increased with decreasing initial particle size. Pectin also proved to have a high dilution potential as a binder/matrix former, as coherent tablets were produced even when 70% of an inert material was incorporated. To summarize, the results showed that pectins with DM ≤ 40% have potential as direct compression excipients in tablets

Direct Compression Behavior of Low- and High-Methoxylated Pectins

The objective of this study was to evaluate possible usefulness of pectins for direct compression of tablets. The deformation behavior of pectin grades of different degree of methoxylation (DM), namely, 5%, 10%, 25%, 35%, 40%, 50%, and 60% were, examined in terms of yield pressures (YP) derived from Heckel profiles for both compression and decompression and measurements of elastic recovery after ejection. All pectin grades showed a high degree of elastic recovery. DM 60% exhibited most plastic deformation (YP 70.4 MPa) whereas DM 5% (104.6 MPa) and DM 10% (114.7 MPa) least. However, DM 60% gave no coherent tablets, whereas tablet tensile strengths for DM 5% and DM 10% were comparable to Starch 1500®. Also, Heckel profiles were similar to Starch 1500®. For sieved fractions (180–250 and 90–125 μm) of DM 25% and DM 40% originating from the very same batch, YPs were alike, indicating minor effects of particle size. These facts indicate that DM is important for the compaction behavior, and batch-to-batch variability should also be considered. Therefore, pectins of low degree of methoxylation may have a potential as direct compression excipients

Formulering av granulat med mekanisk styrke til å tåle coating i fluid bed

SAMANDRAG Den mekaniske styrken til eit granulat er ein viktig eigenskap når det gjeld den vidare behandlinga av granulatet. Enten granulatet skal fyllast i kapslar eller coatast, må det ha ein mekanisk styrke som tåler desse operasjonane. Coating i fluid bed er ein coatingprosess som stiller ekstra store krav til granulatet. I ein slik prosess gjennomgår granulatet ei røff behandling, og dette krev at granulatet har høg mekanisk styrke. I denne oppgåva skulle det utviklast eit granulat med mekanisk styrke til å tåle coating i fluid bed. Det var også ynskjeleg å coate granulatet slik at ei tidskontrollert frisetjing kunne oppnåast. Preparatet skulle ha ei lagtid på tre timar og deretter ei lineær frisetjing av virkestoffet over tre timar. Ved hjelp av eksperimentelt design og multivariat analyse, vart det utvikla eit granulat som hadde tilstrekkeleg mekanisk styrke til å tåle coating i fluid bed. Undervegs i arbeidet vart det funne ut at brotstyrken ikkje var ein eigna parameter for måling av den mekaniske styrken. Slitetapet derimot, viste seg å vere ein eigna parameter til dette føremålet. Det var ingen samanheng mellom slitetap og brotstyrke. Ucoata granulat hadde T90% = 5 minutt. Coatinga av granulatet gav derimot ikkje den ynskjelege frisetjingsprofilen. Enten hadde formuleringa inga lagtid, eller så var lagtida minst 6 timar. Frisetjingsprofilane viste også at frisetjingshastigheita var for låg, og at det skjedde ei ikkje-lineær frisetjing av virkestoffet. Dette viser at coatingprosessen må optimaliserast, og fleire in vitro frisetjingar må utførast

Characterization of uranium and plutonium containing particles originating from the nuclear weapons accident in Thule, Greenland, 1968

To improve long-term radioecological impact assessment for the contaminated ecosystem of Bylot Sound, Greenland, U and Pu containing particles have been characterized with respect to particle size, elemental distribution, morphology and oxidation states. Based on scanning electron microscopy with XRMA, particles ranging from about 20 to 40 microm were isolated. XRMA and mu-XRF mapping demonstrated that U and Pu were homogeneously distributed throughout the particles, indicating that U and Pu have been fused. Furthermore, mu-XANES showed that U and Pu in the particles were present as mixed oxides. U was found to be in oxidation state IV whereas Pu apparently is a mixture of Pu(III) and Pu(IV). As previous assessments are based on PuO2 only, revisions should be made, taking Pu(III) into account

Use of 3-D modelling in early development phase of pectin tablets

This study examines the contribution of the 3-D model in an early development set-up for pectin tablets. Therefore, the aim of this work is to extract as much information on the compression behaviour from as few tablets as possible. Pectins with various degrees of methoxylation (DM) were studied (4-72%). The compressibility was evaluated by classical “in-die” Heckel and Kawakita analyses in addition to the 3-D modelling. For validation purposes well-known reference materials were included. 3-D modelling applied on data of single tablets yielded a certain degree of information on the compressibility. When several tablets with different maximum relative densities were included, no additional information was gained in the classical evaluation, whereas the 3D-model provided additional information through the shape of the 3-D parameter plot: pectins with a DM ? 25% consolidated predominantly by elastic deformation similarly to the 3-D parameter plot of pregelatinized starch (PGS). The 3-D analysis also suggests some degree of fragmentation, and for some of the low-methoxylated pectins (DM ? 10%) viscoelastic deformation. This study showed that by application of 3-D modelling it is possible to differentiate elastic and viscoelastic materials, if tablets of different maximum relative densities are evaluated