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Effect of intragranular porosity on compression behaviour of and drug release from reservoir pellets
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaci.
2003 (Engelska)Ingår i: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 19, nr 5, s. 333-344Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

In this study, reservoir pellets were prepared and their compression behaviour as well as the importance of their porosity for compression-induced changes in drug release was investigated. Pellets of three different porosities, consisting of microcrystalline cellulose and salicylic acid, were prepared by extrusion-spheronisation and spray-coated with ethyl cellulose (ethanol solution). Lubricated reservoir pellets were compressed and retrieved by deaggregation of the tablets. The retrieved pellets were analysed regarding porosity, thickness, surface area, shape and drug release. It was found that the coating did not significantly affect their compression behaviour. Compaction of pellets of high original porosity considerably affected densification and degree of deformation, whereas the effect on drug release was minor. For low porosity pellets the influence of compaction on drug release was appreciable, but only slight regarding densification and degree of deformation. In conclusion, the porosity of pellets is a potential factor that the formulator can use to optimize drug release and one that can affect the robustness of a formulation during manufacture. Moreover, the coating may be able to adapt to the densification and deformation of the pellets.

Ort, förlag, år, upplaga, sidor
2003. Vol. 19, nr 5, s. 333-344
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
URN: urn:nbn:se:uu:diva-90382DOI: 10.1016/S0928-0987(03)00106-4PubMedID: 12907284OAI: oai:DiVA.org:uu-90382DiVA, id: diva2:162714
Tillgänglig från: 2003-04-23 Skapad: 2003-04-23 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
Ingår i avhandling
1. Preparation of Tablets from Reservoir Pellets with an Emphasis on the Compression Behaviour and Drug Release
Öppna denna publikation i ny flik eller fönster >>Preparation of Tablets from Reservoir Pellets with an Emphasis on the Compression Behaviour and Drug Release
2003 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

The preparation of multiple unit tablets was investigated in this thesis with the intention of gaining a deeper understanding of some of the factors that influence the properties of such tablets.

Initially, three different types of pellets (drug, soft and disintegrant pellets) were combined as a model to investigate the ability of the mixture to form disintegrating tablets. The proportions of the different pellets and the type of disintegrant used were factors that independently influenced the tablet properties. Furthermore, the properties of tablets containing drug pellets barrier-coated with an aqueous polymer dispersion were also found to depend on the coating thickness and the compaction pressure.

When compacting pellets barrier-coated with a solvent-based polymer solution without incorporating excipient particles in the tablet formulation, a high pellet porosity was advantageous to preserve the original drug release profile, even though highly porous pellets became more densified and deformed than pellets of lower porosity.

The influence of the properties of excipient particles on the deformation of the reservoir pellets was also studied and, although the amount of flattening of the pellets was only slightly affected, changes in the pellet shape (irregularity) with alterations in the porosity and size of the excipient particles were more substantial. In contrast, the properties of the excipient particles did not affect the pellet densification.

The solvent-based coating used was able to adapt to the changes in volume and shape that the pellets underwent during compaction. The coating structure appears to be changed by compaction and it is proposed that the final structure of the coating is the net effect of two parallel processes, one reducing and one prolonging the transport time of the drug across the coating. Thus, the drug release could be maintained or even prolonged after compaction, despite extensive structural changes of the reservoir pellets.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2003. s. 65
Serie
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 288
Nyckelord
Pharmaceutics, multiple unit tablets, extrusion-spheronisation, barrier-coating, modified drug release, pellet types, compaction, tablet properties, deformation, densification, Galenisk farmaci
Nationell ämneskategori
Farmaceutiska vetenskaper
Forskningsämne
galenisk farmaci
Identifikatorer
urn:nbn:se:uu:diva-3411 (URN)91-554-5601-4 (ISBN)
Disputation
2003-05-16, B22, Uppsala Biomedical Centre, Uppsala, 12:15
Opponent
Handledare
Tillgänglig från: 2003-04-23 Skapad: 2003-04-23 Senast uppdaterad: 2022-03-11Bibliografiskt granskad

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Gråsjö, JohanAlderborn, Göran

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