The influence of crystallization inhibition of HPMC and HPMCAS on model substance dissolution and release in swellable matrix tablets

Tajarobi, Farhad, 1971 (författare): Chalmers tekniska högskola,Chalmers University of Technology

Larsson, Anette, 1966 (författare): Chalmers tekniska högskola,Chalmers University of Technology

Matic, Hanna, 1970 (författare)

Abrahmsén-Alami, Susanna (författare)

(creator_code:org_t)

2011
2011
Engelska.
Ingår i: European Journal of Parenteral and Pharmaceutical Sciences. - 1740-6277 .- 0964-4679. ; 78, s. 125-133

Abstract Ämnesord

Stäng

Poorly soluble compounds are mainly released in particulate form from swellable matrixtablets. If the bioavailability of the drug substance is limited to dissolution, it can be advantageous toformulate the dosage form in a way, which promotes release of molecular form of the drug. In thisstudy, the solid state and dissolution behaviour of amorphous solid dispersions of a model crystallinesubstance, butylparaben in HPMC and HPMCAS was investigated. In addition, the suitability of HPMCASboth as effective solid solution carrier and as extended release matrix forming polymer was examined.The release from all systems investigated showed extended release capacity with release similar tomatrix erosion. However, a detailed study of the factors affecting the release mechanism revealed thatupon hydration, the model substance crystallized in the gel layer of the HPMC based formulation,whereas it remained in amorphous form in the HPMCAS tablets. In the case of HPMCAS formulationthis effect was attributed to i) the ability of this polymer to keep the model substance in asupersaturated state and ii) the very slow matrix hydration, resulting in a steep concentration gradientof the drug substance and a short diffusion path through the matrix into the dissolution bulk.

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