Perspectives on the Wetting of Solids in Pharmaceutical Systems

Newman, Ann; Zografi, George

doi:10.1007/s11095-023-03491-3

Cited by 4 publications

(1 citation statement)

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“…At low L/S-ratio, a strong underdosing was detected in the 150–250 µm fraction and limited underdosing in the <150 µm fraction, whereas at high L/S-ratio only limited underdosing in both fractions was seen. As this effect of L/S-ratio on the API distribution over the different sieve fractions could not be attributed to the solubility of the fillers, other properties of the filler particles which affect the wetting behavior (e.g., contact angle, surface energy, particle size, porosity) will contribute to this effect [ 23 ]. The poor wetting of the material and subsequent hindered liquid distribution at low L/S-ratio could prevent part of the material from participating in the granulation process, resulting in a non-homogeneous API distribution over the sieve fractions.…”

Section: Resultsmentioning

confidence: 99%

Studying the API Distribution of Controlled Release Formulations Produced via Continuous Twin-Screw Wet Granulation: Influence of Matrix Former, Filler and Process Parameters

Denduyver,

Vervaet,

Vanhoorne

2024

Pharmaceutics

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Hydroxypropyl methylcellulose (HPMC) is a preferred hydrophilic matrix former for controlled release formulations produced through continuous twin-screw wet granulation. However, a non-homogeneous API distribution over sieve fractions with underdosing in the fines fraction (<150 µm) was previously reported. This could result in content uniformity issues during downstream processing. Therefore, the current study investigated the root cause of the non-homogeneous theophylline distribution. The effect of process parameters (L/S-ratio and screw configuration) and formulation parameters (matrix former and filler type) on content uniformity was studied. Next, the influence of the formulation parameters on tableting and dissolution behavior was investigated. Altering the L/S-ratio or using a more aggressive screw configuration did not result in a homogeneous API distribution over the granule sieve fractions. Using microcrystalline cellulose (MCC) as filler improved the API distribution due to its similar behavior as HPMC. As excluding HPMC or including a hydrophobic matrix former (Kollidon SR) yielded granules with a homogeneous API distribution, HPMC was identified as the root cause of the non-homogeneous API distribution. This was linked to its fast hydration and swelling (irrespective of the HPMC grade) upon addition of the granulation liquid.

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Section: Resultsmentioning

confidence: 99%