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Tailoring crystal size distributions for product performance, compaction of paracetamol

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dc.contributor.author Keshavarz, Leila
dc.contributor.author Pishnamazi, Mahboubeh
dc.contributor.author Khandavilli, U.B. Rao
dc.contributor.author Shirazian, Saeed
dc.contributor.author Collins, Maurice N.
dc.contributor.author Walker, Gavin M.
dc.contributor.author Frawley, Patrick J.
dc.date.accessioned 2021-03-15T12:54:57Z
dc.date.available 2021-03-15T12:54:57Z
dc.date.issued 2021
dc.identifier.uri http://hdl.handle.net/10344/9877
dc.description peer-reviewed en_US
dc.description.abstract Paracetamol crystals often exhibit poor compressibility properties, which results in capping issues. The Particle Size Distribution (PSD) of paracetamol was engineered to improve the compressibility of paracetamol crystals. This was accomplished by growing paracetamol crystals in the presence of additives. The active pharmaceutical ingredient Phenacetin and impurity 4-chloroacetanalide were used to modify the crystal properties of paracetamol. In solution, the phenacetin or 4-chloroacetanalide molecules adsorb onto the paracetamol crystal faces selectively (110 or 011) and inhibit the further growth of the paracetamol crystal and consequently, the paracetamol crystal growth is reduced substantially. For controlling the PSD of crystal to improve the compressibility of paracetamol crystals, a set of cooling crystallization experiments in the presence of additive was designed. According to a statistical experimental design, the cooling rate was the most effective parameter. The PSD was reduced when paracetamol crystallized from the controlled crystallization in the presence of less than 3 mol% of both additives. These smaller particles increased almost fourfold the compressibility of paracetamol in comparison to the commercial material. Moreover, tablets were prepared for each formulation using a direct compaction method. The results illustrated that a higher tablet hardness of paracetamol was achieved by tailoring the paracetamol crystal size distribution. In addition, the tablet disintegration time was higher for the formulation increased hardness. Overall, this work presents the potential use of structurally similar compounds as additives to alter the mechanical properties of an API. en_US
dc.language.iso eng en_US
dc.publisher Elsevier en_US
dc.relation.ispartofseries Arabian Journal of Chemistry;14, 103089
dc.subject Pharmaceutics en_US
dc.subject Crystallization en_US
dc.subject Paracetamol en_US
dc.title Tailoring crystal size distributions for product performance, compaction of paracetamol en_US
dc.type info:eu-repo/semantics/article en_US
dc.type.supercollection all_ul_research en_US
dc.type.supercollection ul_published_reviewed en_US
dc.rights.accessrights info:eu-repo/semantics/openAccess en_US


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